synthesis of heterocycli compoundc sir.amu.ac.in/370/1/t 1233.pdf · 2015. 6. 30. · 1. 0at«3crti...
TRANSCRIPT
SYNTHESIS OF HETEROCYCLIC COMPOUNDS
ABSTRACT
THESIS
SUBMITTED FOR THE DEGREE O^
DOCTOR OF PHILOSOPHY IN CHEMISTRY
TO THE ALIGARH MUSLIM UNIVERSITY
ALIGARH
JANUARY 1972 MAHENDRA PRATAP SAXENA
A B S t EACT
tfaia thesl* e^nslflt* ef tvci jpaittt
%&the0li aai eli»siQ«l r«tetioii8 at
P«jri I ^ e t i b d t th* «j>iiih«tit of
with i^lMmasfli^lcit^ vz^ nt):^
toVbcmA I9- d^l iMtien in the prssane* of «iin(i« fteo b«aasflo9Qr
p^admlnio lM tier* eoi«trtirt«di to oorretpeaiditig l drosQr dwriirativss.
th» ir« nv aud mr ngixaetzm of tfamt oocpounit wero Also stndiod*
FoUoviDg ohwdeal rtaetiontt of
1,4-<lioxop7i«tliio(ttS-a)lado3l« tmro ttudiodt
1. 0At«3crtio l]|)rtljros«n*tim or«r pi«tiiiuii oaddo*
2. aoduotlon with lithism oIuainiixM tignirldit*
3. jOkiOiat hordroSjraia,
4. MtrttagrUtion with
5* BMotloD with bonsaldotg^*
(ti)
Part tl d»mrlh»9 tht of inaoSjo-S^cerbesainl esi
end and
•9ter* Thft Xattttx* vert ^ thss ived th t eiaidfaiMtimi of ehla^Oftefftspl
ipiioaa m^ tirtiMr with neti^l tollowad Isf oyoUs^tion In
th# ^«sttne« 0t mAim m^tmM9 audi soitos tMmagrloaddft r«fl|)eotivi^«
tbo oeiu!tn«kti(m of ib* eoxrtn^imdlsig et>|joxid« vitb
SYNTHESIS OF HETEROCYCLIC COMPOUNDS
THESIS
SUBMITTED FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY IN CHEMISTRY
TO
THE ALIGARH MUSLIM UNIVERSITY
ALIGARH
JANUARY 1972 MAHENDRA PRATAP SAXENA
nil
T1233
A C K N 0 M I, , D g B M ^ H g 3
eoithor expraAMs bis ddep a«ae« o£ gratitude to
Siiafeti fi./a^ed for tser guMaoes mi. coaatant
mGrnru imnt fchrougfemit tlii«
fflsthoy igmteftaiy «cta0wl«(if08 tlie h&lp in vorioae
reMereS to Mm Bur, Prcf.it.R.fldiwidii Dr.S.M.F Robasm,
mi Mr,P*L»G!«ptift.
Thanks are to C.S.I,R. and for finaBciaX Rssistance,
Kfthssaiya Pmtaip Serena,
Shis tbi»tl« eoiosiifca of ivo pcrtfts
I . eHmaixiwX v««otiont of
Psrt I d«seflli«s %im mpAim^M of
witli aM H-Stffelispi^oin* •tii^I osttra^
fc Xowcd iQr egcHmUm ia tlit fimsene* of tri«tf9r& Mini* fiM li«a8ijf!l03Qr
pyrtili»d»lol«o tmr* eolxvoHodi to tkt oowoaptai^ae ti^eaur d«i^iratlvii«.
tlMi w tmA tmt ii^aetra of thwm ooi|potiRaa mm also stini^ttl*
feUxnAng eltiiidoaJ. raaetlona of
1^4*^iexop3nm8ii»>(t»2*a}l»iola vara ata<Uadii
1 # Cataljrtie bjNbrogaaatlAO owr
platlmui oxida.
Radttotion tfiili l i thim altt«tt^a ti dxida,
3* AlkaXliia
4. ItetliorlaUon vith Ciy^aDKa*
5* Raaotioa vitb baoaaldatorda.
( i i )
JP«rt ZX dtseribee tht ipathtslG df
eater* fHa lat ter wero f^tliosiatd lyr tho eoadonsation of dfalorots^gtjri
asinds «ikl «8tcar idth nt t l^ l antiienmil«t« l^llovtd ejreiiflntloit In
tbir pt0tmtm oi oodSxai imthoxid* ftnS aodltoi IxiiimrioxMo
mm prti^sin^
th« o<i»d«Mnttio& of the tilth
varieiit e«tiaa.
C OB f 8 » f 3
f A R f « I
X. XMIROMt lOlj
• • • •
*
0OKII ohAHieaX rMotitm of
II, BIOTSSiOlS
a^lmtie 0f B*bom I«ii&3io iisM «steri
1,4r.di(aoigr»iiiiio{1,«**)iraJoil.et . . .
S^bMia of 8»trifiib8tittttiid 1«i^oxopstrniOmi 1 , A ) indolot • • •
Sjnntlwait of 6*tri«itwtitQt«d 1 p 4Niiox9p3miiiiio( 1, Indoltt . • • Zfi trv gxd vm of
triwbititiitod . . .
f f t p T ^ U m mod t^o««nation of
Ch««ieal rMotionc CAtalytio l:grdrof«B«tloo Uiak^Lim. with Alkali
Em&L
1
a
IS
29
34
36
41
46
48
51
56 5$
( i i )
Etdueticm with y . 10. B/ ••• ••• 5? 4
B«*etion vltH tMOitsMtt^d*
ni*
B|vithaiia of »stttr« •••
of eta^ ••• ••« fD
S^ttMsls of
f^pmrfttimi ffiid eatttJ^ie of
ChwdUwl ro&otloas
hsr^semt im «•• ••« ••• 9? with 14 A1 B^ «•• •*• ••• 9?
Bittotioa of MkaXi ••• . . . «•« 99 ••• ••• too
nti^iiotl vith l>eneiL]4«!isttd* ••• fOt »«£itr«no»t 4 • i l l
IIID0l>Br2»CimBaXMg08S
I. israoDomoB . . . 103
• •• .«. ••• 104
107
(iAi)
fhAimadologliial «oMvity of lnita»<»2*»e«rl)oiEiiiM«s
n . siaoisstoB
IH iijectri, of In!lol»«2-carl503iasl4»»
i n . m m i m m .
IC9
110
114
l i s
iai
m
129
m
141
1 - i i i
ypBUCAyioirs
ami £st«r
2. CfttiO ifii of Zf^&^tro-p^ttiml
Smuit c»d S.B«« lad* 37 (1971)*
X K f E O O V G t l O l i
X l i f R O B t l C t X O I l
Pm21BQ{ XKOQLES
Keraaelc* Perkln^ and RoMnaon (1) ^ r s t i^^heoiaed th is ring
^ s t e a naised i t as lsdoX»odiAzi^(ti4) inidl6(ti4)diaslae with
iKialMHrifig 00 in X. £At«r Johnson «nd his ooworksrs used the name
pyraeii»(%2»a)lndoXtt for this ring syetras (2)* this nem has also
bean adopted in the ring iMm (1959) with nuDbering at in XX. (Bavlssd
Bing Xi est Sjrstewi
\o
I N2
Mgpo-ox9"pyrf»iw( 11 g' ft) Iftdfflff I *
Xn an attaiqpit to prapara noiliariBan (XXX), a ooe^ound related to
- 2 -
hanilno «lkeIoi^ (X¥), Kormssk et aX. <ep« e l t , ) eoadmsed
cfeaoridA idLth ftigL^i«ti]isrl4C«taX to obtadn iitdoXo-SS-etrboiqraofttatX*
Affiide <V).
•N H
III rv
thi« sttbataeen c;y«li80dl in m eJLoohoMe soltition satai«t«ii with
ehlorid9, with the loss of t m isol«eiiles of aloohol* fhe eyt^c product
VM not tho Ic«to*aiMt^»orbarffiQn (VI)* slnea i t oould not Im
converted to noriunrm»n ,
K / ^ onHCM^cHtotiO, Q NH
O
V VI
- 3 -
flid eoi^^M oHtdnvd gem a poaitim raeetiozi i«dth SHrll,$h*9
r«ftg«at (dimtbyl§minolmnz»ld0l9yde Aiaoolv&i in nloohol ia tta«
preseset ot i^roohloric aiei4)| iaslicatiiig t it@& ponition on the
indtol« mielous. This eotiM onljr be the >-pe«itlo% sSme indol«s,
wbieh hevt 2 or 3 poKLtion give those rveetions* fber«f<a'e
this product ccm3d not b0 1,2-ai}iiy?Sr©-1-oxo-p^Sd(3#4^b)li«lolo ( t t ) .
Pf«9«BC9 of -^OHIi-gm^ toad pheaolie pr^mrtima ruled <%it th« 6orr«8pend'-
Ing ^aeelct stmctiiro (VH).
on N H < O^ci-f
N- c h
yii
7he onljr poaslbillty for tl)» eoapmnd obtainwl bar tboaa taithors
to b* 1|2''dihy<iro*1->o}i^pjrra8iao(1»S*ft)iiMloXa (VHZ).
•IM 0
NH
Vlll
•m m
Aeeording; to Xeraack^ Fomn «ad AoMnson " The fomation
of ring ^ r i n g th« action of aleofaolie t rdlrogon ehloridi* en
iniol«-l3-earbojiytte«tftl<ioM« (?) hA» taJw» iplaee with th» help of
fcQrdrogen atom of th* -NH-groap in the indole imeXaus*'. Actually
th«s« reaetio&a em het d«pict«d aat
(OEt)HC\^ MH
HCi Q - H
.N + -H
0 -H^o
Z
V\U
Latur on, John»cn et a l . (3) fbimd that lndole-2-carboxyacotalaialdo (V)
on e;yeliMtion in th« pres<me« of athanolio l^irogtn ehlorida or etharaal
ealphurlo aoid actually yielded an isoeorie sdacture of 1,a->dllQrdro-1«oxo->
- 5 -
pyr««i«o(t,2-«)indol« (mi) B0% a»d 'l,2-dlhy<lr 1-03«ipyrld(3^4-b)indole
• eo NHCH^CHCoEt)
V
HCWtOH
n •IM' o
NH
D s - ^ v H 0
VIU 6 0 % V f 20%
fhiqr aoparat^ tbsst tiro iaoners and establic^tfd thtt atruoiurt of
both thest eos^trnda \3gr ecH^parison of thair \iltr«viol49t absoi^stion
iq)ectra vith thoss of the oynth«tie isodtX eoe -ounds IX and X, {vrtparvdi
m ^
bgr blocking t- or 3- poslticm of the indoU itael«tts with a sietliyl
grmp, 90 tfcat tho ring cloaare oonH takA pltuse only mt one tbt
two potsitloBS <3- or 1- reap«ctivo3y).
Hd iJTOH ^
C H : hdiEvoH^ Or— ^ ^
0
iH
X
Sffect of mhetit^mtAa en ring forgatlom
SGUlkio and Forkln (4) and later on Jotmaon ot «!• (op. ol t . )
found tb@t tb» preaanee of «n alk^i group on tha nitrogen ato» of the
MBlnoQoatAl s t r m i ^ disfavours the fonsatlon of tlw pTresinolndole
iaoaart jrliadlng the oorrespod'Hng p^dindole .
- 7 -
«ffe«t of aiffftrant substituwita on thd onlitf »itrog«(it
«e wen es in tba indole ring, on tho ring eloear® was studlM lay
awasiy workers (^6) * This ie smanerlaed b«lowt
Xll
R
IK
M
R» » 331 yield XUX Yield
4-OGH C83 In traces Mtjor product (4) 5-OCB CHy 50 50 M 5-0C«3 B 100 m «
CH 50 50 0 \ 1 H 100 tt
20 m 11
6.CB B tyolisfttion does not oeottr« s^moost CHgPh m 100 <6)
- 21 -
fh9 rnhcm re&etjbns em so^pomA to JtoUow threugls tHe intoitiadiat««
Jda and Xlb laading to ihs formation of HI ai^ HXI raapdetiiraiy*
XI
0=HC NR
xiai
x\\
XDl
Jotmton and bis eoworkara obtaittod a mi&bMr of dM-ivatiiroa of
dioasvand t]rioxo-p3rraeino(t,£'<>a)indtola« during their work on tha atruotura
of tha antibiotic* mold aatabolita, gUotosdn (XIV). Taylor at aX. (7)
axanlnad tha cultures of PanieilHun terliHowakii for the presence of
1,2,3,4-tatrahgrdro-1,4-dioxojyraeiiio(1,2-a)lndolea. According to thaa©
- 9 -
e»thor9 ttuKCo are theoroticaX reasons for aasuaii^ thes! to be the
interao^ietee in the tjiosjmtheele of antlbiotios like fliotosdn*
riieae autlsora have also postulated 1,2,3»VtetrAlyf?Sre~t*4-3i©«»-a-
(XV) as the Moaynttaetie
ifitei^9sdU.ate of gliotoxic*
H^s KO 1 S
a ^CHt,
CHJLO H
XIV
u HO
N O
CH
xv
OliotoxLn (XIV) gave
(lf2oa}indolo (XVZ) on wariaing with Iqrdriotiie aoid eM redi phosphorus (2).
•N o
O-K^HCH^ CH,
XY|
- 10 -
Johnson et al* (op; eit«)
4iiB9t};Qrl*t#4-dio:>i39pyrasin0(1»2->a)ind0l0 (IVl) tgr eonci«xtsing thd
etlgrl •stffT of dl<»K-»fl(tt^lalaniiia with inSole-S-OdOCboityl ohXoildt
following a astbod usod •afliftt Isty Porkin et al* asltor
(XVH) pfo^dad tfi8 eyclifi^ on waming in th# pmBmc» of th« «thyl
Aoter of dL'l^awthjrlalanino (2,9) with tha loss of a asoleimlo of
athanol. 7hs ring eloeuro oouM oeeur at elthar ot 3-positioa of
the indole isioX^aa to promee th® p^ra«i2X>(1,2»a)indol« (XVI) or tha
i«MB0rie pyridijKlola (XVIII),
Q
cHj
N CH3
CO NCHCOOtl-CHa
^vrr
0 .CH
^ 0
Xviii
- 11 -
fhe ultravlelest absorption apectrua of tha coogpoand obtidnai by
eyclisetion of tho ©star (X/II) wa© found to bo striltlag3^ •iadlftr
to tbst of the eoJol coRpound (HX) In which ring <Sb8ap« at 3*poaltion
m» blocked tgr « notb^rl group. TMa modal eotipoimd wma pr^arad £ro»
3-ffletbyliiKiol«-2-oarbo3grli« acid aa follows (10)t-
|. S0d<2. '3
COOH NH CH Ch3 CHj
CH3
Johnaon at al* (op* e l t . ) found tliat the cjn:lisation of the cos^otrnds
related to XVXX tal»it placa in the preaenQe of a base, aminoaoid esters
and even anaionla ha* bean tmrA to catalyse this eyolisatlon. These
authors have also fovmd that alkylaticn at the aaidio nitrogen i s
- 12 -
absolutely •seontial for this eyoXiaation to take pXeee* In the
ftbaemse of the ftlkyi group on the ftmidlo nitrogcRi oycliaatlon does
not take place and th/» uiKi^xllsed starting omteriid i s reoovered*
Xhe steohanism of thia base oatail^sedi dyolisation can be represented
as followss
o
O
O
NCVA-CH3
8 " - H D N-
CH3
I
CHa
Johnson and Mmmw (11) obtained
3-B«thyl«n<i-'l>^ioxo-pyra8iao(1«2-ft)i{^ole (XX) passing a ohloroform-
hexane solution of ^iotoxin over a eoluioR of untfatOied alunina.
- 13 -
,fh« abevo c0ii|)0tiM was aynthaslsed (ic^. elt») by condensing indolu-^
eart^aaijrl ehlorld® with th? isHfe^l cator of 1-nstb5rlanslao-2-!!5stho3^y-
prepionie mM fblloued by cyellsation of the r0salti»g (XH).
Ihl« cyclic prodwtct eav« 1,Z,3,Vtetriil^ro-2-!80tl^l»>-a»ttsyl«na-
t»4!-^io3cop3rraj8ino{l,2*a}indole (M) \ihm passed ov^ a Qdlwrn of
unwashed alsaniiui.
Q H' H +
N H c h COOC Hj (LhjOCH^
c o d
XX
XX\
D N
SCH3 CH20CHJ
f«ylor et al* (7) bave dlreotljr coxarexted indolo-S<-oarb03^1*o( •jsatl^laitdao*
ra^thoxypropimije acid eater (XXI) into XX tgr treatiaent with aeetio ai^ydxlde
and sodlua acetate.
- 14 -
John908 oti aX*
(12) have eyntheaisad IjS^J^Vtetrslqfdro-gpJ-
disubstlti«t«i 1C-i?j'urosy'*1,4«dlosopyrflaino(1,2-a)iiKlel«a (XXll) Ibgr
tvQ differ<mt osthods.
(a) Cyolisfttion oi" the correapoMlng dl-^c«rboi8®thojqyph«Rylgl^cyel-
—U-setl^lamino aeM-aatara gava the iSaaired-prodiacts-jte'tha-praaaraBa
of wsdiun eabhoxida.
C00CH3
'N H
-0
^ o o C v ^ ^ N c n ^
NaQCHj
<;b) >Matl)03t^iiidola-2*earbosQirI ehlorid* vaa eonianaea vith H-itattiylattifio
acid astor and tha resnltlng eos{)ouni£l waa oyeliaod In tfea praaan^a of a
- 15 -
base (uaualV N-iBfftliylajBlta> acid eater i t so l f ) . The IC-ffisthoaq^
pyraainoindoles were doinatbyleted with Hl/P'ta give tha 10-bydroay-
pyrfi sine {1,2-a) Isrsdol® s,
•N H
OCH3
C-Onc Kcooy-CH3
U
.OCH-j
R
Hl/P
It {11 M ^ l n t
Fareed (13) ooMvnead diothyl 2'-eftrb03g^nd0le-1*Gus&tat« with enosda
and idth different diiuiinos. 7h« bisdiemides ( m i l ) on heating eyollsed
Q ts^^COOth I
-V RNH2
Q CHaco IHR
XXiiL-
1 6 .
y-ri exo»r>yr&gi»Q( 1. tndoXes
Johnscm ®t a l . (11) ofcSiainadi
hefttSjii; gliotojcin witfe sol^aiia®, mi also by
8rick«r airi Roberts (14) oxidation of
»etl:\ylatio-1jVt3ioxopyra»lfloi1,2-a)lMole (XX).
O ^ X ^ N C H t , o
fh t Above co8|ionnd wm synthealeed (loe* c i t . ) ^ eontonslng K-mibylaBildo
of lndoXiN'2HS«rbo9^Xio aeid with otl^xalyl eblorMe in th» prasonco of
PITidinOt Th® condonaation product (XSVI), which was mot isoXated, oyoUsod
to give 1,jJ,3f4-tetrabydrc*2*n»t^X-1,3f4-trio3reqp7ra8dno(t,a*a)iM (XXV)»
Py. C0iHUC>\3 D
c i - c o c o o a
• N-^COHCOcooa
XXV )
XXV
- 17 -
fh« fiact that the ring elosuro takes place exclusively at position -J-
of the indole melms in this ease mlso, was confirm)^ in a lais •ifidlar
to that for the dioaro co3!po'aa4B.
hm^-pm^M 11 grf ?
Reeently Btavedov et a l . (15-17) have pfvpared a smher of
1-aiyl-10-^liy2|5yra8lnoinaol«« (OTSII) trom 2^aroyl-3-aliQai»dioles
(35XVII),
R 1 By
XXVll)
R - U, Ke, OKe, CI.
R « H, (Ke, CI.
» le .
8QHS CfliiSMICAL umQUmS or
%drog«&fttion over Adan^s eaial^at (and also reduction viith
«laBSsitta-*aM^ga» in ethenol) (11) radueea tbo ^-carlxMayl ip?oup In t l»
1,Sescop^yraainoiMolet- to -give ifc ydx©- ooagpooisS; (XXIX), on"
del^'drfttim with aeetie anl^dridla givas th» iacmo-o}co*i3oirivG iva (tXJL).
•N
0
EVOH
MCH3 CH-
'N'
V O CH3
Ac o
- 19 -
Johnson's { op. c i t . ) 3-mthylea8 coapound, which gives a
positive t»st for unaatua^tion get reduicoS to IVI on li»it4sd hydrogen&ticMi
at low iiraosuro &cd tc XXIX on ibrthar bydrogonation.
h2 h a Hz
'N'
Chr
HCV\3 CH-
h'oedi (13) tea symtheaised a vmbeT oi I^Jkdioxopyraaijaoi^g-m)-
indoles end reduosd them with lithlua aluminiiia hydrido (1s2.8) in
tetraii3rd3*ofuren for 24 hours, ths fivo a»inbor«d pyrrol® ring i s not
rodneod. thmly th» two k«to gronps in tho pyr««ln® ring are r tduo^.
u
v 0
(e) JReaoetioa. wli:t>„ ^odltm aetiCl tn n . i^lcejaol t
ie reiSticed wHh
sodiuta in boiHaB tjutauol to
Ixiiole (1).
:0
NH
Sh^ddoir «t al» (15-17) ra^esd l-eryl-IO-el^lpS^msiaolaiole*
to th« conresjponling 1,S?,3,Vt«tr»l^K>pyr««laoina©l«s (XXSl) with oodium
in othanoX.
-N Na tJi-oH
X X X I
- 21 -
(ltS*a)i»(iol« ie roadlljr oxMiaed gr petassitiD pomenganate and also
radueas Tollan^a raagent (10).
H'
CH^
MCH3
1»S*Pil ]r!iit>*1*oxopyraaino(l*J?-a}lndiolea polyiwriaa lAian
heatod with eoneantrated hjrdrochloric acid (1). Thia peilymrimtion
Inirolvaa {K>8ition-10 posaihlyf as th« lOmattijirl eoa^tind doea tue/t
palymriBm but glvas a eryataXXintt h^roohloi>i<la (8).
HcJ? Poi^
1«4»0ioxDpyra8ino(1,£-a}lndol«8 do not raact with atrcHOg aclda (2).
• 22
ly^ with alkali t
(a) yK»nc-oycHt>yrft>lno( 1 .g-aHniolea:
i s soluble in
ocoieentrated potassium l^roxidn stiowing a possible toiitoi^orisfttion
into the stjolic form (l) .
.R i-
^^
1«4^0i(m>pyrft8l»oCl|2«»a)indole8 «r« reiy 8m»itiv» to i^kaXi*
These ooi^tmda are l^rolysed in aXeoholie potaasiua hjrdrojdda to a
nonobasie aeid which gets fUrthar hiydlro2yaodl to iadol9->2-carbox7Uo aoid(2),
Q Q V. ACe. KOH ^ 2.. HcP
CH3
• S ' T
h ^ o O v ^ N C H j CHjj
Qcy. KOH
H
- 83-
The dii^i^dariVttUva (XXIX) of X?I tinclergoos an intersating
r9»rtmgmm% whan hsattd tfitl3|aqueou8 alkeXi (18)* This appartntljr
tak«s piacs through tho openlog of pjrraxine ring subse^ent
rocyolisatioa of 'tlt« open cbain eildQligrde at po8itio»-3 of indole to * —
t,2-diI^o-2,3-diij»tiyX-1-o«opyrid(3,Vb)linJol« (XXXII)|
^•satli^Xatloii fitvtmri»g3hd^fo»s&tioi} of pyridindole (4) ^ f f i tlw
opm obaifi intdmradiato*
o^. KOH
CHi
Nc
i l l . Mrs^Eirm^d I i
Xbe trioxopyrasiiio(1»a-a)indolQ i s l^drol^aei witb sethanoUe
pot&sait® i^roxidn to give {XMlll). m&
©x&Mc neM. Th« former givaa inAolt^-earteagrlle aeia oetlyrl aaslna
oa vigorouB l^ ro lys i s (t9)«
NCH3
-f eoovi 1
AlS^rlfttlon of or i to
IC-fflsfelqrl d«riwtive by aagr of thi convantionia SKittooda M©gSO /lKaC38t|«,
CU t/MeB an! etren with ohloroaoatie aoid in allsaline i^dittm givaa only t i ^
K-aUgrl dariimtiiraa (3). 0-All^lation tliough tfeooraticiOly poaaibla haa
fM>t baen obaanraii.
•N
ClcH^cocH ,0 oIIOAAI
H c H2.C00H
25
cm trefttttimt with
sine glirott an orange eolourM eo^potmci. A immber of eoXour raaotioii9
hffiva also bedn diacmiSd^ Koimek ot al«{!)*
1 f 3, 3-diiBattiylL* 1, d dUiccfpyM^mim (1, iisdoija
i« indiifferant to ooM aqiiaoaa aci^a audi baaae* and 4oae not reaot idtb
reagantfl or with aeylailng ireageRta.It naSargioos ^oi ^Xing with
diaiBOtlaad sulphir-ilic acid a«i redtucas acjueout p9f!aiiRg«iMito and fQll«n*a
reagent* Failura to raaot with acyiatini; aganta a»f. loiir mM»9 for
aetlva i ^ r o ^ aug^aat that tbo i^earboiijrl group S» m t aasSXy
enolia^ (IS),
o i a c o s s i o i
«
f t 1 aio3cop;iKr«iSjtQC 1, indiolot
h9m ijossible i»t»iiie<li«tei in tfct MoijRtliosit ftt
«iitil»i$>tiea Uk« eXidioxin (?)• Jelmtati a l . (10,12) Ihkv* iipit&osistdi
ft rRiiBl»r ef d«riv«tiir»a of
(JDCXI?) in odmectiea ttatir work m tbii itniet^urai of
'Kl'
0
,0
R fL<= H, O H .
For th« of tiais* mn^mxdtk tti* Imnl to H*iait!^iiaiieo
iffiids htvt to l)a uftid. teidtt «r« wteb Aaeiar to s^iBti^^tiM*
Thtrofor*! in tho prvacmt votk, i t us* p ropoaetS to w^imMim
ina^lAs Sa taGosits unoMi t thait »mm of
thgdr eboaietl roactioiui eati
Tim only l]gnilfoa y| iiJd.fioitidQ3,«« qynthttiaai by Sohnmm ot
hat* tho hjdrca^ g^oap |3otltioi^10 (loe. <rit.)« fbato iutbora wort
- 27 -
in th i s eonqpcnand beeaase th«y originally tliea^it
«ntliy<trGd«thlegXiotoxtn to be ths tOt 11-dllsgr^ro of
Taylor et a l . (7) hav« lso3iitei
>»0tl^Xon«-1#4^i©*opyr«8iiMf{1,2-a)l«iSol« froa tli« cultures of
Pwaicilllam tarlikowsidi* Tbsjr hsvo alao eiSFnthstdsei tli« 7-aM
9'-ia0thct3(y aRAlogu«i8 of thl a in eonaeetlon with thei r work
on biosynthficde of gHotoxla. In suu^ doriv'Ativvd of iiidoXe^
iBtroSuetlon of ii j drosgr ^oup at podition^5 leads to Intorsstlfig
pharsaecolof^ciil proportt«s. Serotoaln aid bufotdniiaa ar® botfc
5-ti^roMy dorivativoa of tryptaMiio. A nuafesr of awt
dorivativaa of ttyptaalB© &« w«li as lawtryptaajiBe haw
b««a e^Athvslood with a vl«w to tholr pharisaoolioglcftl pr(^«rtl««
(20). HarcholU at a l . (21) hova iQmthasisod 4,5,6 atsS
analogaoa of inaol<i->carb03grlic aeid for tba sama parpoB», In vlaw
of thla, I t waa pw^osad to aynthaalea pyraeinoltdolao with liydroagr
group at poaltion 6,7 and 8«
oi' 1 ' i . s - p i s i r s g r i T i n ' g D t. ^sioxot agRAzrao* >itn?oi»a5i illSPI'
The9« eoittpouRds vsre sjmthosised by tbe eondonaatlon of
etn.oridQ and H-alkylfiucdjao aeid eaters i» thd prassnoo
o^ a
H' H
COCL
HVA CVA CO0£)r 0
0
ft
ll-B<m«y3ji»lno aeid ostara wer# sy»tli«8isod Ijy th® foUoidng •eheiMi
KHg - CH - 0OOH +
PhCBO
1 »H - CH - GOOH CHgPh
NH - CH - COOSt ki, ,Ph
R,- B,CHyCiy>h.
- 29 -
m m Mtids mt« tri^tetl tdth fk^asbly bsnswlitltl^ft
(1sl) in eotiitaa liy4rG;Kiad soluti^^n «ndi th« r«»etion miigtam ms troAtftd
mAim besrohjr^rtd* in with stirring, this prm&dmm wa*
witb wm &f oodiuts
Attar tlrta stiirrinf f«sr ttwthar two lnwra, tht vm w«st»iti
wltti oth«r ensJ naiifepaliaed witli Jn^s^hlufle 1© mutitil il Bomi X-
asiise eci40 tfsuo obtitinwi ware fiXtAmt, Etilod.
KH - CH - CCXHI -fr 0,H.CH - 0 1. HM-CH-COOB 8Ci CHgfb
^Pfwgy^ffp tot ...Ml*?., I
«oida if«r« tato thdip itlsisrl ••tftr* Igr
aaturating tht i r suspanalona in ftbso'JLut* othftcol with dry laiyraroehXorifi
aoidt gas. After sfituration, atbanol «nd b;y4roehlorie acid gat wtra
reaovad imdiar racluosd praegure on a atw^aotial^ mai tha a«iw> aeid atlQ^
obtainai as thidi: li smSd (to sons oaoaa tbi^ uera sapmratad
- 30 -
fiiidisg /Sry ethdr to the aleolioUe •olution) • fiMi •• tcr lgrdr«ohloH.49a
vem then dissoivdd in a sdnltatia iq^tantitsr of Mater an! eovarisd with a
of f^tasslws earbonat* (vx&^irma) mn added in portiona
t i l l tfea aquaoea l ^ a r beoana a «tah* Tha atharaiA l ^ e r vm dacantail
audi the suah was waahad iiith f!re8b ethar. fha etheraal axfcract was
dried ovar ani^ydmia poteaeiitus carboaata* i i l terod and tlmn othar waa
r«aoT0d at low irascwre. A thick liquid waa obfcairusd which waa uead
iBsnsedifttal .
R - CB - OO0H 1. CiltOH/HGl ^ • CH - COOSt
Tha «th«r axtroct,' afbar tha daootopoaition of tha h'oatathjrl^lyoina
othyl oarUr hydroehXoride <«« daataribed abova) waa coisjaatratad to about
150 aO.. at atnoapherie prftssoraj, and tt«ad aa auotv baeausa of i ta high
Tolatility.
Indol9-2-oarb6niyl efeXoridd was aeecrding to th«
followiRg «chiod;
o N O L
^ HCH cDOH
C0CH3 I
C-=0
CH3
This Asslftotocs tf«s pr«£ikre!& heaiins a Kixtur^ of
B&etyigiyeim, lUsod eo 'tiun Aoetftt« &e«tlo ashydrldl* Ibr two
aaS « half hours on a atean l>atb. Alter cooling, tba yollow ctyiriialXim
• 32 -
8sa«s vfts filtorfti* «a«iio«i with ica eoM wfttor aM drtM in • vacuMa
<3efieeator.
Q c h o C h ^ c o o h MaO Ae
^ Q ^ 1^HCOCH3 AdO " f-L o
CU3
axXaoton® to
o-.nitro|;heiigrlpyTUVic aoid Iqr roflaxing >tfith IK iJiiRirochloPic iwia for
two a httlf hfflirs. The fa^^roa^sddl prodxtct c ry s t a l l i s e out cm oooling
«fc and soratohing.
Q .CH= c — c^ O
^vo•2. T cv\
H a Q ch^cocooH
Inm^-P-fisrhomrlie neid (l)t
i>-Mtrqph«r»ylpyr»vic aeM wan eommrted^ to iMoio-S*
«arboiE; lie field V roduetlon with imrmo ao}|>bftto asd wnonlA.
Indol<N-2-eartsE»3QrHo ieid m» extraetai )«Lth hot dilut* MHoniii
aolsttioRf which <m eomiontration aoidilfieatloii ^ttlAnd th«
deslTfld product.
COC^OH
u VA
ludoliKlt^earboagrlic aold In «th«r wm traatad with firesbl^
di«tiXl«d ttiicBsyl ohlflrid* Aftar kiMping the raaetlon mSjxtara
for one hour at roos ttte^amtura, the excaae of thioi^X ohloilda and!
l^fdroohloric acid gae were renoved tinder r^tueed predsore* fha aeai*
crystalline acid ehloriilNi was taken up in drjr ether and ueed i«»aedietely.
s o d .
•N' h
C06W -V
cod
-
li^oXo-S-cafbofQrl «»t\oxl<S9 tr®at®d with tbe M-benagrl*
asdis® ©at®r tiad trietfegrl isdne (tstj£) in etfeur «t rmm t»ie»!^oratitre.
Tb» eoRt«nt« ©f th» fl»9fc w«r© r»flujE«d geatl^ for § Isewt, Th® raiuBtloit
i^Kiwe was t!iii& takwn in tiwnsdPt mO, vashtd with dilXist«
lisM und ifftter. fho I«ijr«ir vas dried temat {lodtoa
fKtlpt)at@« tetatie vim m^ovsdi ami tbs residua w&s oiystalliasd ITOB »thtt»Gl.
u •N H N
CV\2?V>
ohXoiride ooi»S<ms«ii with m «Ke99« of
K*>ffi9tl)arlel;rein9 etfc X enttrj, unj^ir ttis sase eoMitions m dtsoxlbed abov*
to giv« tha eyolie product.
H x^Cocl^
- 35 -
th» e©)R<l«n®&ti$ii |>if0ll«ot of «feloriidt dl-
^btns^lpbenjrlala&ine to oyeUee In t l» i iresimeo of mslrn*
u h
cooei-
Iw^PVs
CON-cVcOO-i ^
^m^mim
CendttDsation of i3»iol«-2*o&rtM3dnyl c!Mi»x-i<t« with li-iwtls^iifljrolntt
otfc^l •otor ( is sxoess) CTOliSfttioa of the f^asdmmd product vittout
addition of ftti^ othar Imiso IxidicAtos that oth i'l «ift«r
itaolf «cts «• the protcm noesptor fttm th« indole nltrogm. Bat in t l»
o u t of N*b*niQrIcnlno noid eycXisttlon doot not tindtr
this* oonlltionsf m stronftr tMue Ilk« t r io t t^ l «0in« hue to b« addlid to dl-
OAtftljfM the 0ji«lia&ti0n* Condonaation proiuot ofA-b«aiylph«iyl»lani*ai
do»« ts>t ojoliso ovwn in the prosoneo of trietfeQrl mlm, Froa thoM
obMnratlona, i t «ay bo conoludodi tbat K-b«Da!yl«iilno «eld «st«r« ar« not
batio mxngh to act as proton acoaptora In tbia raaotion*
- 3 6 .
ggflilttftf 1 i tiUMoAta*
5-Bonnylo^indiolj9»2«Cftrboi^l wae eoiia«ns«d with
il-«lkylefflino «teid» foUowad W tba eyeiloation to
iMoh on
i^regenolljreis yi^dad th« eoiTAi^nding h^i ta^ eoc^pomls. ajn^thoMa
warn ®arrie4 out tbreui^ follov^ing a t^s t
H O o CH WO n •HOi
o .CW-, ^ V -Q
cu COCoOH
Q h '
o codi ^
B j o -
U •N ho Q
-R
. 37 •
ve@ treated vlth sodiuft n i t r i ta in salplimrie acid
to giv g-nitroso-S-l^roagrtolaena whieh OR oadLdaitlozi with ni t r ic «cid
g&v® tho t i t l o coa|)mn<i.
H 0
u NOx
2oNitro>5*l^iIroxyt(»Ii3ene vaa tMme^latad vdl^ benigrl eldoride
in tha presence of sodiuta @thoxid«. Th© axcftas of chlorida irat«
reaoved Isgr stea^ disti l lation and tben the reaetion oixtura ma takan
in ethor, and the atharaal layer waa washed with dilute sodium hydroxida
and vatar. Froa tha atharaal tha banigrlosiy eoapound tiaa iaolatad.
ho
U
CH-
MO L- Q CH:,
N02_
- 3 8 -
i^e eecdtnswl with 09tal«t«
in t)i9 proaenee of potftsaitiii Athoxidit in ftt room ta^ankturt* th»
pota«slia» ial t ef ott url filtArcd «a«i
faifilrol^aod iidth aquecus ftlkall to ijivs tbft sodiuit aelt of ths
«old vhich on acidlifieiitioii with iigrdbroohXorie ftoid ^^eXded ths t i t l e
oo pofimd in tb0 foxu of & tar* this on eeratehii:^ anS pooling lMK>f»« «
solid.
cootv Nc OH 3 Kcl NOi.
3«re«l mt ftl. hava oHsinM S-b^z/loiQr-indiols-S-Gwrboi^llo
aoid bgr reiluxlng « oisetur* 2»nitro~5-^aiirlo3gfpN»^lpyrttVio iyeid with
r«rrottS tulphftte and amonia for om hour, (25) • In tho prasent votk,
i t WAS found naoasaary to ineraasa tha reaction tina to ona and a half
hours* Sodiun hgrdrosdda solution ($%) waa uoad In plaea of amaonia to
- 39 -
• ^ f t o t 5*b»ns^lo3^»lol»^<-eirbo3QrUe aett)* Ii«v«rtii«lMt,
ths yi«M Ikildd to go ftbe^ 555. Stoll ti«v» fediieod th« f
Vboria^loj^toesisrlpyrevie with oodiuti and iodiuiB
bgrAroxid* In yielA <26), &u« to nonavailablUty of aodiiiw l?yposalp1»lt«
thia r«aetion eoxM not ba foUotiiad
• C H ^ C O C O O H
•NO2. NH^OH COOH
S*8iiniCTlexyindol»-g«cerboi«rl ehlertda*
Schlndler (£7) baa raporfead tha pyaparatloB of 5-baiiagrlojg?^
i»3oIa<*2*eejrbozi9rI eMLorlda tegr rafltKi»g 5-b9ntgrXo;;^j'iadola-2-carb®)i5riic aoid
with thici^l chlerlda {1i3j7) in hmtmn and tha for«at4os of the dtaetfearl
a»lda ftWB i t in 80I jriald. Whan 5-i3«aj5ylo3iyinclola-»2-cii?b©«yllc aeld
WIS treated vith thJ^nyl ehlorldt in ather at rooKi tas^eraturai tha
eyolla pKJdaot of * two step r«aetio» was olstainod in 62%
sod X eo6v\ O
H •cocH
- 40 •
iM^AEi
ebXosldItt vftt with
^•eU^lAffilno mida in tht pr«seiict of tintiiir th« s«a»
•sqpffriswii^at O0iutitl<m8 as daseribad bolbr*.
H
Cod-
MH V a
-CH-cooO-
uiOKpouttdi E w CH , « H mB synthtsistd in tfeo 0C aa aaetattml
Imea Hke trietl^jrl luaind but in the presonce of <»retB8 of Kointthylig^Ljroltia
ethyl aster.
S-aiii8jflojiy|i^iraalno(1f2-a)iii!iolaa wara traated «itb PdMJ(103t)
undar bordrog»ii at 45 pad for Ibur hxmm to give ttia conrasponsiine t jftpoxiy
pjnra»ii3o( 2-a) ii^olast
u HO-
Hx
D Tbl-c: u •N 0
i
ftosso eostpounda wwb syntbssised by tho foXlowini eobtM -
OU
CVA3
D O HO
c II o /
V • CH-
4
^30 n
g j o •H' H C O O H
4 n • H-H
CocJ
>0 Q R,
In an «tt«sipt to i ^ t h t t l t s oft to
positKai to ih» t ydbrasy group or p->cr®sol, was «l»»ctlirat«d by m»%ylMttm
of l><»erosol, this adiftjl iti«rlv»tiin» vas nltarixtti, CoUowkI iQrdro^ftls
to obtain t t ^ t l t l « oossmnd. &it ttui eoi iOtt&d aotualji^ obtainsd ma
i<ld»ti£itd as 2^6-dinitre p-er®tol, (Ulaeusaod on p8g»53).
Than wae pmp&tH by a» il t«mat«
QMltbod, Fboagai^ gm wna passed i»to an a l ' ^ i n d of |>*exi>0oX at
th@ otarhm&t p vhich saparatad aa a I i# i t Ixronm praolpitata
was filtftrsd, waabeA ax:d 4xlail. t lda driod p*tolyl oairbonata %ma sltratad
witb nitr ic aei^l in olatm foUowat) t^ IngrdroSj'aia with eoneantrato^
l^roelblArio acid. Tba isoffisT waa rcnovad Ijy steaa &latillatS«8»
ac^ t t m tha raaidua tha ti t ' ia eospound vaa iaoXatad*
D OH
NaOH DO HMO 3
b 0 s.
5
HO HO l
S*Nitro>4»b«nz7lo)Qrtoludntt was prt^ftrad %or tho bwmgrlttioji
of with benzyl otOjorMfli In alcohelle aodluit
tqriroxidtt aoXution.
(vicv OH o
2-Nitro-4^1»n05flojgitolu«n« visa eondenaod with dlet!^! oxal«to
In the prsssnco of potasailiata ett^idda in toluene. 1?h» potadfduia salt of
2«Mtre«4rb0iiJiylo3igrph<!SQyl: pyruvate was Isiy^lysad with aquaotto
so<9iut lardroxia® tiolution md th« acid procipitafcad with feySrochlwic acid.
U cooyr I. K O U -
H02_ cOOU- 2.NaOH •5 Htil
^CH2.C0C00V\
N02.
- 4 4 -
9ttrto« ot a l (29a) feav® re^ccKS 2«nitiM>.4)»bimfyIoaiypht!Qrl,-
pj^nivle aoid with ferrous aulphata aikI sodiim %<ire3dd« to 5-!»ni^l03gr-
iij!iol®-2-earboj^lle acid In yieW. How0V«ar| in oar hauda this
r09«5tion gave V0P2r poer yitM, Conasquently
pyruvte acid was redtucdtS to 6-benjgrlo»yin4ol®-SS-Cflrt)©5ylie acid imaer
tho ssBrti eouflltloaa as i t s J^bensgrloxy iacsaer l a yioM.
^.^^CHiCOGOOU
6-a9ai?yloagrlMol9-2-c<srb03^2rlie acid tias convortedi to i t a acid
chloride by thioiiy ehlorids in aihsr. The oxcoao of thioisrl chloride vm
reotcved under reduced pressure and the aoid ehloride wat uaad innediately.
H O
H LOdl
- 45 -
Ukrmm-lr]
ohloridw eo«a»K««d with
^tmi^latalno aoid Agt«rs in th* pfaom9 of tr i«t l^l m im and aIoo
with «xc«8i ©f ttbyl »at«r to f l v t
on ljy«irog^noay»la with p«ll«ilM» und®!' Jns«lro«iii i t
45 pai tbs oozraajjof^ing tj^oxsr coa wsuBKla.
C o d B
WH-CH COO£l
R R.
nn O
0
Hx
R
Pol-C
Hd' u • N
o'
R . CU^PU^ ^^ , H. CW3
* is"
In ordleir to synthttSise
oat with som» tDodifioatlons in ttie efmditioiSia.
B-CrssoX Mfts n i t r a t e vith fitntas: nitric aei^ axA salphurie
mid in * of ol«aa asd milphurio aaid (30). After th«
roaotion nlxtur* a t roon teapffiraturs for 24 hoara, i t «ma steas diatiUad
with 8up«« • ltat®d atean at 1S0-170®. S-NltaPo-^a-craeol earn a« a bottar
Hko &mX$ion along with othor isoaera. the dist i i lata traa axtraotad with
ether, tha etheraal extract w«» driftdi owr anhydrcoa aoSiua 8a2|>bata wad
ather vBue rewovad laavlng a thick 1.iq!iia behind. Xhia was rafluxsd with
•xcaaa of aeotio anl^rida eod the acdiyi darivatiira of Si-iiitro-jp->eraaol
waa fractiouaiay diat inad at 132-35® ttnd!?r 5 tm, praaaura
Ol HNO3 jhzSOif SVeck-wx P\»AV»
O H
Q OH
CU3
NOi McxOH o
|so-W>e S MO2,
?vadUoviaS. ciUobv>.
• CH 3 N02
ORc
- 4 7 -
Thl<» *js) flqtteou« aodhm l^drosdde
solution gavft £»nitr<»>o-cr«8ol as a single product.
Kobin«oa 6t nl. (29b) b«»^l«t«d 2«nltr©-i!Msr©8ol with beni;^
br<>fi(l<t« p>tiit8lufB earbonat*, in fielA* due to tlKi BonavtiXftbiXity
of bsnsgrl brosldo, tbt bemer^^ion w«a eaxiriad wxt with hmwyl ctiloriiia
tiniiier th« wstn* eonSitioas «o (S«aarlb8<l Isiy Btixton aX.C^a)
in yi©M.
M OH
CH,
NO'
PW C \ i 2 d
N a O^ o M02
S-Nitro->b»iufyXQ3^Xttttrio wet trMtadi with ai«tbyX o}»Xat» in
tlM prosene* o£ potMoitiK ettioxldt. lha rtaetion vas carried out iimiar
•jeaotXjr thi atsA •s^arimntaX eoaditioas a« ^aaeribad bsfora ibr tha
S«iiitro*4>-ban«^Xo37 iamar. 2»Rltro*3-banfgrXo>i7pbQi\ P7risvie aeid vat
obtained aa a tumim tar^ tihieh eoidd not ba puriliad. Tba abova procadura
vaa r i^atad tfaras tiieaa but tba daai r^ product coaXd not ba iaoXatad.
4000 3000 2000 ISQQ cM-< 1000 900 8 0 0 lOOF I — , , 700
7 8 9 10 II
WAVELENGTH (MICRONS )
N-CHJ pi N-CHzCeHs
P|G^ \
5 P P M 6 4 I ' ~r-
«OHC HMD (COCI|)
5 PPM T 4
r ic, 2
- ^
ShSmSa:*!
Ch«s*aetcristie peaks of fM3«0 oni ssddic earboiyrl.
olMiervdd fei^imi 1700 and l jSOciT^ r«sp«jtiviajr, fheso tuo iNmtls
at 1700 m& 1650 c*"^ md tlwi «b3enc« of pmaks eimmi 54DO c which
woiHd ba rAH^niiliilA for indol* IfH) «on£ira thA o^lisaticm at |>o<iitio»-1
of fabl« 1).
SQ'mmn 9% (to) gi ® * t Slid tt f&t
1 » 3 , 1 0 - t rimst i^yl-l $ 11
also give two in th» rmig^ T^wk* £39*240 nyU.
{TabU n ) .
{1»^a)iBdtoltt tftk«n in oarboa t«tiniishlorM« oa » 60 KC initnueent.
It shewa tht folXowing f«atur«»» (Fig. £)*
PIG,. 3 .
4 <.6
230 240 250 260 270 280 290 ' 00 310
Wavalangth (m n )
iVo efettrp at 5.81 C^) iiriiisftt*
pTmmm oi tm grmip®, is^iefe e.W5 mt jaewjt
th& i3p£i«M aiagl^t cofrtapoa^Ja t o
wh©r#®s dmm tinM aiisglei nm'tmpoMa to to i i » eeupfeoasrl
gfw^, fftiltipl«t,s utT" g,7(9p) «is3 1»S<1p) cerr»i|50»d t o tii» WBmdmim
aspomtio pmtmB*
tnkozi after diRitori'yni it»lio«it#9 tlia «l>senee
&t mast «eilir« in tii« cexpotmi*
[timm*:
In " s® {7/8)-t)0Rssylei«y eoJ!!f>o*m{i»# along with tfee etear«et®ri»ti<j
baiKfa for indole IM/»0 aad earJsoisgrl asmmdi t70© md to$G em
mspwotivwlsr, hmd@ hatmm cisT^ w»r» «bf»rv»di for
fhs ooiT#i|ioiid[ii3g tgriSrosy cosfjoyoad® ggm ft ehmrp btudl bttvsvn 3300-3100 ciT^
iMcb is I w Sbr • phtnolie i^drtt:^!, l.s9oelatieii I>®tii0»» th«
eiqr «0ootint for t h i s , f be coddic earboaisirX l^nds Aim ebammi «t l o t ^
f5p«q(U«nci«». (Fig, 3,5} T«bl« 1).
5 6 7 8 9 10 II 12 13 14 15
WAVELENGTH (MICRONS)
f iG, ST
F i ^ . 6
- 50 -
jsbe
In the S^tesg'loa^' and S-bydiro]^ two vsmdmm
mrm obaerrod in the nmga ^8a r. 255-257 mj^ and X «a*. £$0-294
in the T^mhatitutttS derivatives on* leiodSMi was ot^serred
in the range 315-3S! jy^ . (Fig, 4,6j Table I I ) .
• 51 -
•(Si ilijtiolo
f A B L E ^ I
I R, Rg KC«0 (indolo)
car*
C*© Ca«ido)
cvr^
IMoltf ring etr^ Fh i^ l i e 01
cur^
1. M H 1?O0 1650 1610,1570,1440
2. GHgFfe R 1715 1635 1580,1560,1440 -
3. B 1700 1650 1625,1575,1460 1235,1210
4. CBj 8 -QCl^Fh 16&5 1640 1600,1585,1435 1240,1210
S. CH H 8 -OOigPh 1645 1590,1440 1^62,1240
H 7 -OCSigPh 1700 1650 1600,1575,1430 1240
7. CRgPli CI^ 7 -OCHgPh 17C0 1630 1600,1585,1440 1250,1200
8« CE, H 7 -Om^Ph 1705 1620,1590,1440 1240
% (M^Ph n a -6E l a o 1615 3150
10. ci^m 8 -OH 1^70 1610 3100
t1. B e -OH 1660 1600 3100 iz. CHgPb B 7 -OH 1610 1
3100
13. CHgFh OB, 7 -OH 1670 16^5 3150
14. CH H 7 -OH 1700 1630 3300
« -
Q
R Max* (m )
2«g4
1. ca^fe B B 4.29, 4.24
m^ H 246,291 4.36, 4.27
3. CHj h H 8 -OSRgPh 256,E9£ 4.43» 4.27
4. CHgfh GH 0 -OGHgPh 257,292 4.25
5. CH H § -QCKgPil 255,290 4.444»4.28
6. CffgS . H 7 -OCHgPh 317 4.35
7. CHgPli CH3 7 -CJCiyh 317 4.33
a. CKj H 7 -OCl^Pli 315 4.35 CBjgl'h K 8 -Oil 256,294 4.36, 4.22
to. CE Fh ®3 8 «0H S57,294 4.30, 4.24 11. CHj H 8 -OR 255,291 4.37, 4.23
12. Ci^Ph H 7 -OH 319 4.32 Cl^Ph 7 -OH 321 4.19
u . CB3 B 7 -OH 317 4.35
All th« a\)ov» spectra w»r« tsk«n in Mtb«nol mxo9pt JSo*1« wUieh w«s tek«n in «than<d.
hadt t^ b® i@mt%>«fi8fld as m lfit«ta»dlaft*
for Mrwjt liltrfttien ©f p^tmsol wssM
not l®ad tc dsalired proawct, baemiat of s t r o n g ©^p-dtrteting
infkamm ©f %fm fcgraroiQr eroup. This t*y<Srojgr rottp iia»«th«r»for«« to bo
iiiitiib}^ iSftaetiv«it»)S| r^ tbkt nitratioo plitco pxuf x lO^ tbo
poiition oribo to ths letthrl grmp* Coptse^v C S) detiefeiirattti tbia
tiij roscy tlbrott^ tlio jforsAtitsi of tbo carbomitof vhioli le oty&ttltMKi
hjr rmoislflg as aethitim of p-ertsol ^tfe plosgano. In nd^w &£ \ 1
tlw hiftatljr poisonms netur* of p)sx)§ifim, i t thought to t0vy
obh»ir ttoyl ipfoiips. Smiington et ml, Ol) oitrattd itio aeotyX
of VftBSlliR to etni^in IMs
rtaetion imolvmi tht 0ftl«ctiiF« dcaetivtttion of tho in ni
vii^iKi. ConM{|tt«»tljrj, p^rntol wao iioiriyli»t«d i t s nootyl doriimtiim
vm» n i t n t « i tmUtr tho •am* oonditiono. nitrittioii produet l» thie
o«M, hotiwr, w&a idontlfiedi 2«iS^din£tro*p»or*tolt iMob themgh
unittitablo for tho sjmthoalo of th« dtsifod pyi»idUio<l9ia"a)ii>doX«af
- § 4 -
« goe<S ii»fc®si8«!liat» for ^,6»digoiiie-p-<sr«aoa,, a ^^ ing «atwi»l
for leathmr O^) * ±9 unittabll^ in mir, tharoforft*
i t « i«rivmtiv»a mrsi isolatoi ,
Ritrati©ii of with fysalng ttitrie aeM
6 8 4 ftrodtaici. TM« %MI« A <disM«0T ITDIIFAYBTAI
owr tfm Urmt » i^ t ic»» (31), wfeloh l«ad« t o a tiitditii'® ©i* pm&wGtB
w etmberaoat niw&tim mM W ^ ^ nitfotis
gases (34).
SIhm txmesrl «tkar of m9 not i s
goodi yi®M % aoiaS- Bothode, tfcwi i i l w r aslt. of 2|,6-dlait3P0»p-«rei0l
vat boni^latetl with c h l o rMd *
^at iO^ie of 4iff«reiit
e«t«lyatii iit« «Kit U0ing me^it %h» tba
motion® and th# prosiueta IdaatiHad sjra in th® ^llowteg aeJaMW;
- 55 -
CVA-,
o ORc,
I. HNO3
2. KOH
CH-
o •NOi OH
P(r02.
vj/
0 6^
Hj ftcXMA^ N j
0 <
0^t HHAt
CU.
AcM H o oH
NHAc
• 56 •
CHEHICAL M m n m B m t * mOX^mAZIKOf 1. IHDQLBSt
I.^otmofelon ewir platiann oKMftt
Johnson ot (I t ) roportod the redact ion of iho 4fNSftrboii3rl
group la
to glim th» eon?«»|5oMij5® dll®r-iro coagjojud, Slueo ths datall® of
raduetion M«r» not
t»3rr«elno(1,^ft)ifulole mis 7«tueod ovar platiniiia oxMo imdor diff«r«nt
oonditions* unroaotsd mispotxnd m& roeovorod in n i l
— > u •N' .0
hO - k ^ N C H a ^ ^ i
I I . nmction with ^ k a ^ i
Mb«a 1#2f 3,4-t«tr«ti0Klro-2-beni|3rl-% indoU,
wae hMit«d with •qtiocus potasalua t tSroxido oolution^ ttko pymsitio ring
»t tho Vcarboivl gro«(p aiid th« op«n oiuiln «cld ms idontifiod.
o kOH •K
H NCH 'Pk
- § 5 7 -
p i . Rsdttetlon vrf-tb. lithiuKi elualaiing hydrides
(a) liS-Diozo-pj-rsztoolndoJ^es hava h9&n roducsd with lltteitun
aluffiinfest byifritis (13). To this reactloR with 1,4-dio5K»coinpound.
1 # 4-tetrahjdro-2-b-m2jl-i, l^^opyT&zin&i 1, C- a) indole was rdiluxed
with 21tMiMn eltiadniuw hQraridoCl.'S.gJ?), in p«rlfled tatraigrdroJtonac for
E4 hours. The asic^ss of liuliium a2ii«iijai«m wee dece^osad with
moist other, Ths «thcr estract vas dried OTsr magMaloiS
sulphate, concentrated to 50 ffll. cjid aatiirated with dry Igdrochloric
a£!id» A dark brown tar separated dat which eooM r«ot be eryiitalXisad.
(b) Oorieg « t e l . (35) raducad
phej3yl-IH-1,5-b<Hjaodiaaocii>.2»one to tb« corrtBpondiisg 1,2,3»4»5#5-h»3!a-
hydro-diaeocimusing r@zy large aisetrnt of lithinia altiminiua hydrld9(1i30)»
ci>
U AlH^
4000 3000 lOOF ' —
.80
2000 1500 CM-1 1000 900 800 700
60
z < a. ^20
3 4 5 6 7 8 9 10 II 12 13 14 15 wavelength (MICRONS)
to CH20H Hzi^NH-CHCHs
T T T T
^ 58 •
Slnea tbio involvej redbetion e£ om ftusido earboi^l (ia. »3ditl4»B to «
doablo hoi^),
uas «l30 roflussd vitt) a Xerge ftsaaoitiisi ef lithitis aluBliiliitt
in tetrat^^oflur&n. fh« of littiiuiai alumiRiua iDj^ridb was
with m i i m h^t&xMo aolutlm add tUvii th* raaotieea sdxtura m s
for another one hour ani eadraetad with Tha e^binod at bar wtraet
was driad ovar anlnirdrous stagGaaitm aolphata. Sha axiraet was thosi eimeantrat*
e i to SO sfL* anil dry hydlroc^orie aetd gaa uas paseod tht^ugh it* A brom
ta r aaparata^, which waa diaaolvad in abaoXuta etham}!. attdicg 4xf
ethar, eooline ani semtehii%» a UgM puirpla eoloarati potr;3ar aaparatad
out witb graat <Slflioulty* this powdar, altar two erystaXIlaatiofiaf gav*
a white iMmim eovpaaxA wbleh imlts at
IB apGotruB) of tha b^roehlorida of thie raduead prodaet waa takan
iA REr. Tha two oarbouyl banda at 1700 and 1650 eiT^ hava diaajq^arad
in thia apootrum anl thara ia a maw baM at 3180 eaT^ • fhia indleataa
that both tha oarboi^l groupa hava be«n raduead, o»a poaaitily to Cl^
and t\m otfatr ona to CliOH. Banda a t l6S5f U90 and 1450 and tha oaa at
1 / 1/
« / ' y /'
N^CHjOH
S, f'
220 230 240 260 2«0 t?0 MO 1*0 >00 J10 Wovtlinglh (m n )
m n r
f S 10
3 PPM S 4
tow* HW(C»6»H>
CHIOH nmt CM,C,H,
I • I 5 fl»f4 T 6
F I &
5 f -
30t50(iwiol« C4I) m'^ intlicat® that ixsdQlm ring U
th» ir? was tfiJsuR i a I t eteirs iisapfsftreasa
oC th« short wism te^ vitli 239 s>» «hioh i@
vitb a efefttneffc^r* iit^luiiifat ttae mrhot^l groapa. fh» long easS
»imuB & bypsoehnsnie sMffc with <l«ere)i9« in iil aofjptiaHa, (Hf.d)*
i m apectsuie of tiie l^dmsl^rido of tha tra«
in dautwraiM piriiUae a ffC iesfcrmsffiatt I t ahanta th t
f0l2««di^ fimtairost (Big. 9)«
Ci) f w iai«4tical tilpl«t8 at r6.74C2p) end ccmpll»g Ktfltli mm&h otiMr (4 B.5 c^s) •
( l i ) A iliiEltt a f T 5.59C%).
( m ) toother sharp Mnglat 5.29(2p).
{!•) Ao mirttaolirodi trlplot a t T 3.J?5(1p).
(•) lekiltipXoto betwowi T 2.90-g. .
(vi) A »lnfX«t « t r 0.36(2p)
(irll) A bmaii wwosolv^dl t r lplat fairly fielrt a tT
- 79 -
I'looaa featur^o o^i ha i f i t i a prosuffiod thali
ring opeaiiii^ at posltien-l h5.9 accoirpani^d ir@dbactlon, loading to tbo
foraattlon of aa opsn chain cor.potWKf,. Tfio ssquenoa of rsiRctiosis loadUng
to tb« formtion of tld.8 cos^jound my ba pcotulatsd aa folllowsi
a N
o N "^CHjOH C KzVW
L^NHoCHo^V^ a
Johneon et el.(l8) hav® reported the opening up of the amino alcohol in
their 4-l5niro3Qr ooipound under besio conditions to the intermediate open
chain aldebiyde which rtsoyclises in a different position to give the
pyridindole. (p.23).
- 80 -
Another ooneideratiQii in int«rpretting proton olgnnJUy la
tbat th« oKctonglng protons get 'AmmpXM ttm tttoifo m the
adjacent e«rl»m etona. Siltna^stein ot teira ttotu&ll^ obaervsdl
that In the efts» of loost of tfas ^Xiphetio maim ^ItSji i^ere tbo proton
maethmge ie mpldi^ lit! pn>ton(9) got decoupiod £roa tbo nitrogon atom
Mid ttom tbo protons on tho ad jec«»t oarlo^ atosso. fho IB poak ia,
a titrnxp gineiot end the «iJaoent CK protono ore mt opXlt lav
HP protons***
In view of the abo>ir«| the HI® oigttsia ean be inteo^retted aa
follovst
the tvo identical t r ip l e t s cen ti© to the protona on the
awthylene pt»ipe in the -IMSRgCH '-i ehain* fhe protons on i being
oeai^oteljr diKsoqpXod f r ^ the i^jaeent Bsdtfa lene pmtx>m ao that i t
beeoiBea a aiople eyates. The laett^lene neact to the indole
nlt^rogen can aeeoant for the v^fieM tripletf en«i the one mixt to $
Whioh i s 8»re deahliaied because of %ho positive charge on tha nitrogen
oan aoomnt for tbo oot^iarativelj^ downfleld t r i p l e t . SI»tiXarly the
einglet at ^ 5*59(S;p) say be due to the protona in the priearar aXcohoiio
group (-CKg-Oli) and the ainglet at T 5.S9(2p) my be accounted for ty the
• 63 -
protcfis flanked on m& t*
f t ^ 0ltigl«t oey bs duo to th» iMoIii prot<»i At
p08ltl(»a-3<i fbii «XtipJtMo<9p) obilQiitljr fioeountt for th« sroiiatlo
iprotofi0.
fhe e h ^ eiiigpl«t « tT 0*36(%) s»(sr ba eonsidorod to be duo
to the tvo protone on if tb« fi^id 03t0haJ»ge me^ng thn sigiaal into a
jj Mirp iiroad mresol're!! t r iplot a t T i s th«Q
ptotmW; 4ha« to th« |a*otai| oo iar ^oim JtioM duo to A
mim rossltsilo tofeeiwotion %dth Ibg . Botl; ttiose peaks dioappoarod in
ths qp^otsvA tfikon after oxftbango^ imieh eo»f3jm» this asolfiimsDt*
fh« onals^ttls f i b r e s tteigh not umci^ivoeaX in tliis oaoo aro
n«ar«r to tboas for tbt opoa ehtia ecajiotind.
fh« fcgrirogono of tbo jkeothgrleno crcop am ae t iva t^ <!tio to tbo
praaffnco of tbo 4-kotogroup, thttroforo^ alMylation vmy take placo a t thia
poaitioiu Shatt at al.(37} bava aXtt^latod attyelmind and tjomolna at a
aiailar position. 1, 4-3!atr«li Aro»2*lM»n6gKl«1» 4-dli0(X0pjnrftSl»0( t , 2-b} iMola
wa« Mitl^Iatad idth votl^l lodida in the of iodliu» aatboxMo.
4000 3000 lOOF '
2000 1500 CM~I 1000 900 800 700
3 4 5 6 7 8 9 10 II 12 13 14 15
WAVELENGTH (MICRONS)
Q-iYN-CHjCgHs CH3
FlGi.lO.
^ 63 •
t#?f 4-dio indole
M8 fti th<i isa^or wMeh was idtmtifieiS hf id«ntieaX
i r with th» i^^tbetie ceapsuna (Plf. tO)#
md the uneubstitutftd
ospen abiiiii ftei4 mm obtain^ as tli« jnimtr protluota* fhasci pr&^ets
aeparated on t ^ basis ef thdlr aoMbiliV and piirl£i«)d bf passing \
Qmt nmtr&l aluMna.
.0 NcxOr le
o HOO . N t h t P H
• 64 -
l i .
Bhatt «t ml (39) Hev atv^i&d the r«ai<i%idn of vith
Btr^QlsEdm &»<! hswaim in th» prMmxen of oodlua Ij^r^roadde in aXoobol.
fha r«aeti<»n took plftcs mt thtt Aetivo awth rlaK^ iKlJuoent to tfe*
earlTot^I and tti^jr war® abXe to i»olftto thd bdnnQrlidiRi derivaMims*
with btiisfiMftli^e tha imssanco sodlun ac«flftt« Ami noetic
plperidin* md «lso t r i«t l^l assdn * Chily ttnaal»tit>\it9(2 opo» ohais
«el<i coaia \m isolatoft* frem th» r®»t of tba raactiou wt*tur«, « t t r or
m i n defiiMia eoi poond oHidiidd iMoh oeiad not Im parili«di. Xt i«
poasibXe^ tbat in tulMtion to thw aotivo at |>ositlonp3^
th« s«aotl<m alao take* plsca at p08ltioa»tOf l^aKing a Biaetura ot
products. 2'*Sub«tltutoit iadolaa aira Jamm to oondaissa with aMal^yiaa
giving lo'odaets anaiogous to triph«ns^l iMthaiies (39)«
E X P E B I M E K f A I .
BXB BUXMBUt hh
g r o w u m m ^ m m p ^ ,
^zmmlmrn. mM§. »
Aiitii»> ftOid CO«t sol*) wat dittolvwl i s 50 of sddiuai
disUISjtd btiiimM*}^^* 10. f •a..C0»1 mM
utith i^iseHm* ntxiat*^ iil)«n sol t^im hmum
tsomgiman, 1*14 i* o t eeNlSisn Isorol^ariidA ifni ivldvd IB 8»ili |Hiitiim«»
flit wis \sm%m ^btting Aftw tfa*
«Kiditrioii» aolatimi w&« for «ix>t)iir half m hotst moA ttitm
tt)» tilbom p roo i^ f i hm ntpmtiA %wism th t ••»• ^ii)a((iiti«« of tMrnttH t SRi*
tttti aoaiua ATtsr two lioar* of stlnrins, weHnUm mm
tiiie« vitb vthtr And tnttitftilXiwKl vith h^^lfooblorie t o
pB uiidttr ir ifomit «ttrrii)i* ftui }mnjsj/!Umim uatiia^ C&t
pruoipltatid I t mn £ll.t«r«a •iietio% %ttth«d titU
with S«» ool4 wattr meA dt l id in th» fol3i>i«i»s laino
v r o i(^lMi«itifd tsar tM« mtliodit
B pg ehg • SH . ® • €<KJH
yieMC^
1* H WAt«r
e . 71 Iffttffltvotlianol.
70
,1.t ffllwai, f i l f r »
8,2 £.(0*05 a^*) WM talum tn IS5
•bsolutt •thanol In « lA. Ttui alatisr* was nttir«t«di with
(ix7 acid pi t Ibr tUtmt 10 hoar* rooa tmepwmtam* tbm
n»tk m» prot«ot«d m i i t a r t idLtli a ealeltia etOorld* tub* wM3L«
* f h i t miA iai iknaSgriWkA for G,H % A&fOraidi Sm i C, 75.27f % 6.71 j S, 5.49.
f OttoH C, 75»18| H, B, 5.11.
m * ^ i m pitssM* imftn th« foltitioii m t a m t ^
m» vmxt^H ttat«r retoed pnetiRir® m % m U r t i l l m e^mipy
t o i p t ^ y DS! ttiiai itnder r i i i i i t^ fiiriiaMr®* fh t
t ir^Mt^fi^^ 5«7 mil*)
Alas^iirad i a « i&iilJttm ^wMtit;^ of m t i r KoiatlQ^
Ira* mMrm nitfe Pi ®thcr, Jtt^^rirwut poinflate ©urtentl*
i» i^ertlona t l31 t\m m^mna Ij^r « m^ I to
Wft» W! t ^ mt*^ wm miiiii^ tritb itB»h lA.) i&m
iliBst. tt^Qf* mgtrmt mw mm m^^^semB peU^mlm
f i l U m ^ «%hm wMi tmemA m i m rMuc^d room tte^mtttr*^
k t h i c k 1i&» l i h u i m a , v m h u e i g m 1*1 i t m i t i e i » n t l ^
pir« tor IbrtlMf tis«,
17»$ g(0«l VM Uimn ixi 250 i t* of
«tlicttoI Alia Kith axgr r broetsderlo neid cm to c@st«rt
-
1% i t * «st«r th* l ^ f ^ b l o f ! ^ * mpmii-Wi
out tpm fitljimi im Mfiitioii df i f ^ •ttodri
yi«M g . O S ) .
ai t^i 6 f*^ vims
i m m ^ i ^ witb p>t«flai^ earlioQat* «a ^ e i o r i M abeint tn i t
i i ^ i t t ftti^i ttitsr, ^ f M 1*5 f •
Absolut* «t}iai}«il(1S0 la*) and mturattd vith mU
f h t •ytfO' l^riroQhlorid* tt|}«r*t<iii out tttdition of dxy m^m to th»
aypjpy U ^ i ^ ©Hmlima ul t t f i^noviog •tlwui^l, jfiwM 13 f*
AniljiifJ for C^^ggOj^l t
Foraais
dX-13-temigplptesarliAiKiR® ©tl;^ m%m B wit * fjoiASsima
ddKetlna 17.a teikmt in m§
iini witlt dx^ ^r^et i l i i r i i gm to ismmv% i t into
efl«r Aa s f i ^ w i i ^ M Cftltor mmmimg m
moA Oty ©tlKap wm m i ^ to f t . fii« wtileh
©o tamteMiig, - an $M mmim, yl«ld BB»3
( m ) [ M i . ISt-S^^'C^O)] .
S«rco»ia§ «tb}a ftstxsr i farochJLoild®, wm with
{Nitatste ttarlxmtt, iha tthvr «nt! tim 4ri*il
Aidiivet m9 eei«!»ijti«t«l to 150 A , tfeii ia tte© for» m9
usid oaloitUtdd m t»si« #f
1 « 1 , IMot* fenmS
on oonaaimtlon vltb intSole«>lS««arb(»^l ebloridt,
A aixttir* of g* of o-nitrolbmiiHiHftlQinl f 11-5 i* of
15*4 aodiuai ft§«t«t« «i»i ££0 of ftotit^
WHS b«it«)i for two and « tutlf botxrit en ft I& m
Brlmtm^W' flask, fb« r a t i o n aisEtur* Isio • solid
jallotf a»«a of er|p«t«ls m mdHag fit room te^petatirt tor mfr^ral hoiir«.
llw MoXiil smt» wtt v^, mtt&d vith ie» eold twtir af»! <Srittd la
vietia* GfT nodivm 11JS®, jpieM 110
Cmd(t ftilaetc^ of o»sitro-oC«&ett«i»£iioeii»3«^ aoid (48 «*)
imt f«fl»3ci(l for tuo • half bmre with 1^06 vil* of I ti|»!fool3lorio eelil*
Tha oolutlos wui t rwUd with 10 g. of eetlvrnted carbon mi. mitwA
whllo bot. Thf ClltrAto dtiposittd m oU wM^ orystftlXiatd m cooailog
«B«i aeimtolilBg. 7h« aolutioB wma Xefb a t for IS bottra to 0(« |a t t t th«
ei^atalliMiiciii. o-HltfwphKBjrlp^xtm^ct meU w&w filt<ix^ m^beA
icft mt^T* Alter df^ng i» intmui% pn^ltie^
£4 g. tzid 119- 20**. TIs® nether liqioor m mmnWet^^
gem m ftdditlei^i^t 16 g. of tho i8at«ri«3> eakleg « to ta l of 40
yield
(£0*9 f*) la ano»$«
(140 of a . ail^ttd tfitb ^ eH, mUr) m i » i^t mMUm of
orTatftlSiseA f«rmi8 aidphate (ISO in SW ad. m§ gmdaall^^
fibt raftetlo) alxtiitfNi f i rg t vt^md ms m mt»r ti«tli for Ifialf
ma {sour th«n boiled for m9 hour. Aitor UliMfix^ e f t f«rrie ojd<l<i
«nil iMtbinii i t idtb hot dilttt* tl)» eosd lnod ni tx^to w«s etfmm^
trttt«d* ttiMiflod in oold tmsr Is^olA-B-oariSXKt Iie
wbieta 0U,sltmA in m nmu^ torn m9 l i l t m ^ , vMti«d idtb ooldi
MAtor md ariad, ^.p. 802-4® U «. (750 .
I»d«il*-a-o«rtx»Qrlio Mid, (0«80 0.005 solo} in dry
tf*t trMtwl with 1.19 f.(0.6$ al .) of iTMhly distilXod thioegrX ehloriito.
• •
f h t reaction islxf^rn ms kapt nt roms t&s^mtum for txm limir*
Elb«r ttoo mmmm ^t thionjl nfctorid* umm rtnevttd tsi!l«r r«!!ttc«il
f^^fBtmr^ Mt t M r«»ida«l s^eii^Hd m t s 20 a l . of dty «th»r «
mi. thm tlils v«e as liMifta'*. fh i s ^^r^eetsi m»
t i l l ttit l.tt«fc traeea of t idoi^l cbltwia* hydrochloH«
•e i i gall ir»r« r»i8oy«d. f b t ««il<-ciy«t«llJlja« pifatutod indtelft-S*
osdPbciiyl vat taktta i a ^f^ vthir ma ui^d ica«d£tito3^ i&f
etaeild* (as avscrltitil igm
8 (0.05 ei i»lol»»S*earbc»sgrHc aeia i s o^e r ifus tr<MtM trith
* mlx^im of 10 weHit) of atlgrl sstar
10* t g.(0«1 m>3.«) ef tyiithifX isstlad In Alter k^sping thw iMNiotioxi
•laetuxv fcr ham At fooit twii t»>fttiir% tlis emtmtm of tbii fLaidc if«r«
r«fa.ti«id for & bcHirt. Tht iroiftotioii idxtui^ takes up in
iraeh«4 with diluta kj^ochlorle aeid (5$) mii iiat«r. Ths
fctiAntiitt larftr vaa dritd over anlijfdftma acidiiia ml^^hat*, aoliraiit wm
ratioirad and tha raiiditt iraa oryetaUiaad txm bi»0ai»»»lia]niit or ottiaaol
75*
m Uiixt y^leif nm&lm, ••p,, yteld 6 irCRSr)
I ^ S K H t w a M * 1 6 1 0 ^ 1 5 T O * I M S i l « f ) | ijflrCSfcOE)
X mm, m »A » 4 m!t(m% )T Cppia)
rnlUpm), iM'tp* iaBlMf^«t).
fmioli S, ?4#5«>| e, 5.05J 1,
mid, 1.6t gCO.fSI i^ln), ma emwrtt^ t»
I t i m M eiaorida i ^ n tM&ti^ witli m mlMt im
••lor, 2 . n t r m ^ f l m i m a.CP. g.CCJ#es a®!®)
i n othtr* tts* Mka mrk^d up miw tli« m&e mvAitim$ as
dBst^h^ h9ii(m* It ey^aUllMM iii'm mthmml, si.jp. j i ^
2 S mih M k b t ) Wt5(ii«$ol© C»0), 1580, 1440 ifUag)i A mm* m , mi log 4 4.36, 4.S7.
Iiad^tlM Cacd. for t C, fi, 5»30$ M, 9.21.
fam^ t C| 5.4S| llf
M anl^^fous of elAoi^d*
pt^pamd tmm 0.3 i;*C0»C!05 of inS&li»-£"6art»oigrlie «el4 mm
with an 93BB980 of either (ptapmi^ tr<m 6 0*04
of ataeottlcM fttlifl l ftibetieUlorliiQ) alxfKxrt u t t
tor 0 bimr«. uhioB tti^AiAd
•• B wbit« praeipltftt* during th» r etloa uai off* fl» vtbii^l
flltf&t* wm tilth mivi l^mHlwie fteM C5l) mt«r* Eiher
VMM thm •viipQf«t«i mad t\m tMok li^M ilibs tHAmtmi. m» es etalXiati
f5r<» is.p. ^OM®, [ l i t .
Z&dolo>»2*e«rlMS^ «hl<orl<l8 prci|>«rtd £ro» 0.8 g. (0.005 v»Xm)
Gt livloIt-a^ttrtKn^ifi eei4 trt»tei vltk CL*B«b«a9Qrl«ph«3grl4^jd9im
•Mi.vr, 0.41 i* (0.005 mU) e x A t M s»(O.Ot of tri«ttisa isiiM
ntlittr. AftMT kitpimg tbo rcaotioa aisetaim Ibr boiur at mm
tmspm%tixn, tb« oonttnta of th t iiiirt rwfliaxttsl Hoit B iteitrt. f
prodttot obttlnad (on itorki»c up as daacsrlbtd bafora) iraa i4a(8tl£Lad aa
ttui t^ ebaiti •stvr* I t ma ofirsiiaiiti^ ixm atliamly
f i m 1.43 c.CTODt ir(EBr) |SSO(iiKiol« m ) , 1720(««t*r 0«0)t
1506, mm rlog).
p<ni»ati e, moof a, 5.791 M,
h «tixr«d »ixtttf« g* of 150 aeid
ft»d ttOL. of 9alpli»ri« «eid ii»«i tr«Mit«d vi%h e aoltttion
of 35 g. Gf nitrliic W l i i t l * vAtor a t Aftwr » r«v
fiiimt«t, tlM »lj«tar« irat |tair«d in to ico eoM tmclsr and th*
iiitroao eei peiiiitd tms fiittr«dt mA pr»fi8»d out (m a f i l t e r pi^ier. Xt
liiui thtn iidtiAd in pcrttofift to a «tin>«a aixt^ir* of 50 a^. td i t ie aeid
(ep. cr< 1*4£) cn^ 150 iO.* of KUtw «t Stitrijng t«9 eeniiaifd
M long a i t r le 0*14* tm« Tb« rtaaltieg cmd» ait*o er«tQ3.
«»• isolttUd tor pMtrlKif inte v&tiar atM iirtasix^ e«t m • l i l t« r
I t w ciyrtnll i i td bdnavat, wup* 0 g.l90|S).
- 76 -
to m TOl«tloa of scdiuQ 3 g. In »beoIiit«
•t^nnolt ICO l a . ) , 20 g. ai«l fena^yi ebloildo
g. ¥er» adaed m^ t\m r«a«tlim alMteuro rtfluxifl m a Isitli
f©r S lioarf. Aleohol wto tfciia distiUwa of f , wiit aisioliraa
i s •th»r, with ailut® ««l4w» Mifcwddt mtm', fwm
tMs »q«eottt mluUm sfcttrtiag iwtoria t $ «*) m* r^vrnw^*
«thir«al »xferi!ct yt^MM 's ^ ich eff»tii31iee(S
t t m vUolmm «tto»r (tf>. IdlS-®)^, 70-71% j'AoM $ 4 9 0 ) •
to m iolatioH of 15.6 g. of potB»Bivm in 70 edl* of absel«U
•thtnol and MO afl.. of dry «fctey, g. aolvftim ef 4Bt6 g, o t £-aityo-
ftnd f , of d i t t t t ^ oxailwta in tOO aCL* of toltxwa«
««• add«a with ooolin^ in lea TimW^ th« x^Motion t«^p»mtiir« m s not
allowtd to go Sh» rmoUm adxtur* ma Z^fi evoftetsii^ at 10^
«nd thin nt roost t^^pffratam lor ttroi* tm^i^ mi^Atms o&Mitimm,
fho pot««i&tii9 salt which «qparat<i^ out was fiXt«ri4 md vaahed thoi uf bljr
with dty athar UKuiar aitctioii* I t imi than dltaodvad Sm TOO lA.* vaft^r mad
$£0 m ^ m mi otirrtd fisr nut hour with WO A*
ffthar. f k t cthtp l i ^ r vm mptacrn^ m^ itw toliitiim wui
with tiluHr flit aolDtioii tiMi ftsMifita
idth €»mi«iti!»t«l t^jrAroebiorie fh9 tit l^i eoi^imA vipidntttd
M a ^mm o i l vMdh s^diaified kei^is^g i t In eoXd emifwuii^.
This m s witb le* «eildl missx' «Bii diitf^i s«|)«
112-13® ^ X ^ S5 fi.
fli« i^metwSInf mM, g« (0«(I4 ttait 4i«soi¥«iS la ma t
AfSOteias seiistieii of MwoKd a w t mA9 ittim bO.*
A het toljijUefi «f isnrvoaa ialpluitii (72 la 60 wiL* watoir) iomi I
nod t ^ ulaetttm m» ^at« l m m mttr listli tm tiilf m INcur idtit aliiMbni*
thm tiM eoiit«nt« of tli« flaiile vitrt 9»ll»9GS<t for fiirtli»r m» tesiir m m
Mad tsKtti. Iron hydv&xii&m wm ifpmtvSi^ with li^t dilut*
«niO»l« and lintUjr vltli m&ixm l^ffozid* fbm eoabis^ mt»t*
ifM e(»ie«atrat««V eool.«l tnd ftQS4i£l«d with Igrdroeia^ie tiMi
light ytUoif prtoipitat* wsa UXtmrni, wa^ed ami dilad. Xt m»
ofyvtaUiMd flpoa diluta aoatic AOid txe «th«r, m,p,
5.8 c* ( 5 5 » ) . r u t . • .p . 190-I94®(85,g6)] .
m ^ m
miA, 0.66 g.<0.0025
wfts t o i t s fteld ehtocMd with g•
CCtCKSf ^ ^ fttsBilili^- fer tocii
tm^mmiMrtt, «th«r was tuBsdvr r«ltie«di pm&mafM fh«
tiftt tnwtttA Mith wsotbtr l o t of «lti«h wm aeaio tmdM'
pr««ft£r* t(B r«s0y«f t in l«tit truoM of el^rMv*
obli^dtt ii»a thfti %9km up in •tli«r sndi used iianNUjitsly^ ftxr
HiftbKr mmtimM*
a<t) of tlw eorrs^iondiiig teid In sthsr (SO s i . ) tens
trsfttsd Mith • solutiODi of 0.5 (0,005 «ol«) of t r i s t l ^ l sttiso m&
0*5 (O.OOSiS of K»tM»fgrlg!ljreln« s s t t r Cpr«|miwi tftm
H-bKiiylgljreiiw as dsserlbsti bs^srs) in dwy otbsr (SO ML*) in ooH.
Aitw kssping ieyr ons hour rooa Uaipmmimm, ths roftotion alatttart
i«s Mfliyovi gsnUy for 8 tjonrs trndw mBSs mx* oei»litions* tlis soHd
t^ieh sspsrstsd vaui f i l tsfodt iiashsd with l^^droohlorio aeid (5D« sodiuM
bietrbmiAttt {§$} wttr. It mm t ^ fttift
lM»iii»»-t»}(iiiift to gi'sn 0.5 £• i i # t jr^lov eirstilft^ m p*
An aSditi^s^ 0*11 ojT tlM auunfi ^^roitiiet 0tiitfiln«d tern tbd
fttlMrMl li|rer altor wasMag i t uith dUjutt ftoi4 tmA
wafttoe MeirlMmiit»i tnii dijirtitg m w Aftly^roue todlaav taApta^^
g462SJ)| SrCEar) I70e(ina«l«
I650(«idd« e«0)y 1S75« 1460Clid<»l# riMigh 1210 em'
(gtm» X mm, 292 is/Oc, log 4 4.41*
Fottods C, 75.46j H, 5.04i 7.14.
fta* lN»igpi03gr ec»ip)»ttd^O«39 f«C0«C^1 w S ) tms tHHu m idtti
100 «g. of l^«C(10l) in 25 a!L» oi «t»l«i»ol. 0!Di«r isn^gttA mt 45 Stal
for four boors, ftm ootaljrtt m§ fUtoroil off loid tho produot m*
cryB%»3Mni othiBOl. fhie oonpotma dark«o» ftt Mitt
«t 252-4® to « rod I m n oil , 0.84 « <70*)| lr(K8r) HSOCpfeoaolic 08),
I680(indolo IM^), I6l5 o '^msido C<<»)f isr(»iOII) X mm. £94 ,
log -f 4.36, 4.22.
iBol^oltt Cilcd. fbr C^^^^^O^g I C, 70.58| H, 4.61| M, 9.15.
foondi C, 70.43| 4.35| 9.01.
MM'-ut*
ebloftds itm g»
(d.<DQ25 of eorrttfoMliig mi^ wis eo^imftti ifitb 0*S4 i» dl-
mla) t t ! ^ ia tbt prosnie* o f
G«5 g* welt) of trictfj^l ttsin* in iitber t»iS«r
<$0ffilitiim8« ffe« ^ ( o d ^ taft iflGlfttdft tosl^* efjrat«lM«id Iktm
Btthanol, ibf* n f , yim I r d l r )
1600 1435(iiittol.$ rifig)^ liSIO cm^
(avoa. X mx. » log 4 4*^5.
AuOriitt C«X0d. Ibf O^fij^O^Bg I 76.0i| 5«40| K*
Fotm i C, 5.49| »»
0*41 (0«00l maUm) of tli* b«M9l.oaQr dorlirfttiiPtt «»«
dobts^liUd with Pa-C(tO]0» 100 in •coile aoli nnflor t^mgm
45 p»i for 4 ht«tr«* fb« preaueffc oryvtalliMd froit oiiiaBtil. I t
diukmx* At M^t* i t to • brown tdX, jdoXd 0.25 i4S0$)$
*>ii *
irCESr) 3100(tlieo<ai€ OH), l670(l»aol« S-CJ-O) 1610 C-05j
A 257$ M «A • ^ 4
Asaajrslat fm C ^H^ O Sg t H, »» B.75.
fmxdt e , 71.^S| K 5.091
C0«00i5 of tlw AcM) ia •tlwr m9 iritl» m •mma ot
te&m 3 of murooaliui
tts&ir . Aftcff* Umpimg itsat mm iKwr at vtK/m
maetioii ma r«llii3f»d Itor 0 l!0ur«t IBS vex^ed
up «9 l»*fiBro. I>3WuiiK>iisd«l« ei7»tamaeai •ttunoil m whit*
nMdlM. yi«l<l 0.51 g.C64$)| tfClBr) l69f(inael#
l645(ffiBi<l* C«0)t 1590, ring),
M^m) A 255, m m/i, log 4 4.88.
An^alat Caod. ter C^^^QjSg i 0, 7i.g4| g, 5.03f H,
Foa»d t C, 71.16| fl, 5.201
fh» btai^Io:^ 0.32 f . (0*001 eeil«) t»»
witis Fd*C(iO|{)| 90 vsB§»T t Q dregta at ^ etlnasoa. for i m t
fha pm^xt^ m * erj^nlUlMi S»t>w i t dftitens
t35®, Wi t t at 856-1^1 f i m 0.18 c.(78l>l iiKKar)^3t00 (pbtmUe OH),
I660(lntol« B-C-0), 1<S00 m ^ i m U * C«0)| iivC teOa) X m $ m
Itm 4 4.37t 4.S3.
toaJyiilit Oalcil. foj? C^ ^ O^Mg i 0, if
Feisttttt Q, m ^ ^ t H* 4.0d| % 12.00.
FlK>tg«M ga« ma pmama a. aoSxition ot pHitMeSL,
103 g.(0*1 »Qat*)» in ^ ot mdivm dlaaolvid Sa w t a r
(500 m.)^ Mlotstoing %\m t«i|)«r«tar« bttwMii Htm cts
m i no ioas*!* &li8orlMid« tUs p^oduet hm Il3.t«rad off «ni vatlitd with
colli soAitm l«rdn>xict« w«t»r aad b9lou 100^. thin {>»daot
wnt luffloitntly jsor* Ibr fkxrthnr rMeti«B% K«p. 113®, 11d.6
a-Nitro-]p-eir««»l{pp, e i t . ) s
A itiictsiir* of 15*3 nl. Mslphurlo iifild. (B f»ir SOJS <
75 «il* et A.!t. iQ];plsyirio neM) and 9*9 ml* <4* %•%%) of niirle
d !«• ii«attfilLl^ «Mttl to « ttirr«a tolnticm
eiupboo»t», 3B©l0) 4B 70 of i«il,pbttjrl# aeSd C|5y»piar«d
fta iilsov») «t fb» alacttii^t iNsiog atiJT«<l for two feKW^f®
«t ta^O®, w&ft pcurod oa omilioa ic« ywUow
•alidt nMob filtor«d md th i s thtm
tr«et»l witfe ja«Sltiiii MaatJuB (SO g* lu £00 Jsil. wntist) Iter
iMKira. 7hl« tointicasi mii tkijcm^ aeidifind wltl^ eomw^mttA
t^foehloirio afild ftt |»IIitro*|)«er«fel wt« hf tiUm diftilJUrtieB
•nd th« maidaiA. immeMP wm lectiwetadi Hgtm bmumm^ inifllQ«l itith
•odiiiB QlOoriila aatiarstod «Mtt*r aad drl§A ovsr ftia]isnlx«fU« nodlini
MiipbctM* fh t eoi|M»i»& wM trj^mttaMmA firos •thancily ii«p. 76*7^*
yiAA £1.1 §470$)
4 iiixbttr* of 10 f . (0.065 aoU)g btnigri
etaorid*^ 8.4 g«(0.066 •odlxui li rilYoxldio 2.75 SQ A* ii«t«r).
- § 4 -
//
in 60 ea. of mm h«itt«<l ind«i> rmtim l^r 10 ttomrt* MeoltCKl
IMS r«»Biv»d imdiffT rs^eadl ]>r«awr»» aiDa tfc* •xeasa of iKmioO. «t%(i(Mri<3»
m9 ttOKmA ^ ntdttst aistiMatloe* fh« selM w$m lum tip iUi atlssr
rniA iMtMl with aoiSl m i^roidd* (51 ) m t m l lUoror m»
dH§A emr Antrim* sodius mlj ip)^, Jki^r r«aovioi; ttui
vaut o s 7 8 t « l l i t * a ; £k> ib btne«tie-i»i^0jL«tiii «ith»r ( b .p * ^ a o P ) *
• .p . aneM t4 f . (83S6).
tc m solntiim of 7*8 g* of potfuMtoa im 35 »!• of iil»$oliit«
•tftiwca. mB& 16© ol, ©f « aolntion of 24»3 g» (Otl of
30 of dletbgrl oxttlftte in SO idL* of
toau«8« «fei «d!i«d with oooling i s k So i * ioAgrdbroaft eosditioatB, 7hi» m o t i o n m
ttus GtrvlAd m t ttui uay m a»»orjb«dl
pitxtaet otsfcttlaad Mlt* at yitW Ja!.71 g» (91%)*
hMmM^^Mf'iHtf^f^uU^, iff e
th» pxi^Mdiftff e, C0.04 mU), m» <lis9olir«S in
e w n l s soliitio»« dD ad. Cndt 56 lA. ftcptoaa ajMoalAf
0 . ^ ) «nl a hot aoltitieii of firvout fliOphBt* (72 «• In 80 i£li. wat«r)
• 85 -
warn Bdd«d to i t . Tht t^actien eArri0dl mt isfid«f mmetiy
th* tisa eeo^itiona tlcaoriM btlbr*. u»t
eth«r» inMm i l l 49iimd oryntftls vw^ obttiim^
133-5® 6 g,(36i)» [ l i t . 18S-S6® ( m )
eonviirt»a to mtil dhloridte vith ttileq^i eM-oHdCi 0*6 f •
CO,C05 » l e ) ill Sz^ 9tb*r. oos limir ftt meii
t«!)f)«rstiiri»f i t w e mrlmA loyp «• IMtiW* iistd inwdiat*]^*
ohSboria* pr«p«rtdl 0*66 g«
mitt) of tiMi HQitvmwffmMxis •eld in «tli«r ««« tr«ittd with
• «>lutio» of 0.5 i« (0«0D5 AOX*) of tri«tlQ4 aaim Mad 0«$0 g«
(0*0026 aol«) of ctl^rl •«t«r (ps-ipar^d «• daierilitd
^fOm) in dtf •th«r (80 la . ) in co34. fh t r4woti«ni •Ixtar* ktpt
tcct tm tmr «t rem tmpvtrntasem and tb«i iot B hoora isslar
eoaditioaa. tha pnOmt oHaiaad was ^ s t a U i t e d mm
- 4»
yi9U g« ir(Ear)
I7©0(i«slol® S-C-O), 1650(i»lil« H30(i8^i©i« «infi)t
1240 X m lisg 4
itoi lysias Cglea. for Cj^g^O^^ i C, 71.741 H, 5#09i
fhft tsonigr^^ eon^MfO*?? g, (0,001 aioX»)i was in /
25 ml. ©f mmi&l vlth 1CS0 i»g. «f i i ^ r Ig^regm ct ^ pal
£or tem eota ly t t itimi f l l t w e d ©ft t l » jprodwet t
ebtidnad m mrnptm^im of the fi l t jmt* *»»« esir^^^SliMa m » btssmt-^
btiwB* «tlt»ml* d«rk«n« ftt aiMt »»lts ftt
0.42 i* <80Jf)| iriKBt) mooiphrnmns mU lWine©l» S-C-0), 161C
(fUBldt C-0)| w(«iiOH) X sue. 319 » 4
AiuOysltt dOxMi. Ibr i C, ?0»58} fl, 4 .6t |
Fotsvlt C, B, 4*44| i * f«00»
obS/orMt Idmpiorad irom §•
CG.OOiS soil*) miA %nis eimdwastdi witliD.54
neat) of etl:^^ •ikI <0.005 «f
tfivthijrl «ilno «tfa9r i>nl«r taS^t^mB m^i^iotm, fhm v iqfMKrlaaatt
mn ixit iiiH$«r ssm eondiitio»« as b«D9ii>« f liui prcdotst
tMitt irm bvsttane-lwxsiwf cup* jrieH 0*67
1700(lj2de(l« JM>0)» I630{«idia« 1600 t$3l» t44e(iiil<»ia r i a ^ ,
IfiSO, %m tm^imm, CWM5)| uvCli^^X nwc. 317 i^a. , lof 4 433.
Attal^'ilif Ctled, for Cg^HggO^ i H, 5.40| B, 6,8?,
Foiandt il« Hf 7 •03*
b«n»yloay oo^pomi , 0*41 e*<0.00t soil*), hm wbjtettd to
lisnlrosiiiol^fait in «l)umol in tbn prtsme* of 100 i f , of PMiClOl)
li^rosian m% 45 pt i for fbtir hottrs* fho t l t l s eoapetmd wat a;3r«t«3.1lifl«d
fre» •tti»soX« i t darkana at SOO ami lealtt mt yloM 0*24
wmx* 321 m/^ , log 4 4.t9.
pir«|>sr«dL iron 0,66 f •
<0*00^5 M^l®) 0f th« eomMiip«ii4ing miA in ^wy ttihef met tdth an
of ^Vdfl estcir (pir«paf«i tmm 3 ef Sftmoiim
Ktljyl tiittr ISylitjeKlofiat). Affctr Jiatpiag i t fer o»t hesjir mt r«o«
riHiotion attxture w* reHaxed fer 8 bG»il>s. fii* p rJ atstoo*
MIS ittolfltwd «• btfotii mni l^oii htnmm, «.p«
yitld f.{6S$)i ir(KBr^ m5(ial©l» S-C-0), l670(B»id» C-O), l^fiO,
1590, 144D{lndol« ritjg), t£40 C-O-C)} «««•
lof 4
Amayalij C«lc<l. for *
FooisSt H, 5.Mf li,
with 90 ««. of f^CClOJO uaSor fcgrd*®^ iml in bi^ttnfMitfetaeil
for fear bi^srt. t i t i * {sfetot w«t ef:y8t«31i«id AtlMimi. Xt
dKtimm mt ei^ts ftt 276-77®, j r i t ia O.ft «(80SOl iriSQt) 1300
CpbeBoHc OH), t700(4eaiSl» li-C-©) 1630 C«0)| *w(HiOH)
517 »//- , log 4 4.55.
AniOysisi Calcd. ior O gH O Kg i C, H 4.3«|
retoidit €» 4.£tf 12.09*
mmmm w ^.uQim^
it^ydsol (20 fi.) in portitms to Itmifig maljilsiric
«eid (74 ol«a% 35 lO.. And •olphuorie aeid, ia*) vitli food
cooling in iee* k adxtur* of 8.6 nitHo aeld and 20 iiX« «a!l|il»ifle V
«cid of' thd ftbovt «02^8ltion, itt« uddod, t^aperatttr* ma »(iiot«lia»d
bttiwtn 4 to 6^* Aflar kMS>iug tht rmot im aixtuTA ftt roojt tMi|«ratiirt
for 24 houra, 30 lil. of mtmt vat «dd«d mi iii« eoHfceatt of tbt fUide
-
mtm stefto disUil*^ tsr suptr-lt«at«d itttidti ni •
e«s!« ss • Ixrtitar Ul(e «ml«tim with eilwr
tsowstrs. fh« dl0tlU.*t« mB with •th«rj| tlt« vthwraaX
VM» '^zittd mar iKMm iiiil,phat», wftc f«K0V8d
•jad « thiek U ^ d m» 25 f«(d8|)*
fh9 proittflft Ct2*5 i*) i9£tiix»a wttiai aSU
aeetie ftntig^Ha* for tV9 imr», mH^dHd^ im» m^w
reduo^ pr«si«r«, imd t ta r t a l^ t t «»• dis t iUei at $ « »
prdsmr* to tlui aectjrl derlvAtivo of a.|>» 5^}
yi«l<i» 15 g487i5).
fhd flteetyl d«rlT3tlve of (eg.) uas roftossd
vith »1* of iK|ii«oaf etoAiun fosdde aottition for tieiiar*
«lk«lin» 8oIixtio» vfttt tisatraliiMd with sulpbarie aeld
•xtrftcied with tttlisr. fhs othsroel laycer m» RgMin wshed with aodluBt
ohlorldi* tttttrttodi witt*r to nmtml pH. tha «xtr»et was dridd oiiw
•ahs^droiift todtuiB aalphut^^ Aftor remotdet etlieir^ coiaitcuaA iitt
eryiit«lli«M!, •.!>. 41®, yield 4t . (94*). l i t . a.p. 41®C30) •
• *
S-Kitro-n-ereaol (14 g.) ««• mfXm^i vttb Iwacyl e^loxld*
(t t .76 g, in tS*4 i^* ettumol) in moAhsm l ^ d f ^ d t C3«@ g, in 2$
v&ior) Ibr 10 Ixsors. was imtiiir rej^ue^ i^x^aMa*^^ h^I
the ioceftsa of bmsi^l et^oi>Me ««» f«s<<9v*d hy atmm distlUatioa. Thwi
t ^ omtatAn ei t l» llti«k m m taktu up tn snd vaids^d ^ i b tt^uii
sDd mtme* Itluir w off ai WBMiSm tnit
distilXiKl ftt at >>4 sn. presmrsf 10 g.
teeaysiai 0al««l# §i>r G jM j ^^ t 0, % H.lff H,
Fottoai C, K,
Potftssltis M t ^ 1.9 g. (0*1 mlM)^ mu dlsaeXvisi in 17 lO.* af
Absolut ethaneX* aisdl 80 ad., dxy adisd to i t . Jk ida^xtt e£
diatfea?-! oxftXat* 15 fi. C0»1 i»l«) «M
to tlw fttsomi solnitect. fteiithn ronetlcm irts c»iTi«d mit m
* 9 2 " ^
f o r mM* fim rmetim mt
«• « lifGim t ^ , tfbleh eotlit ^ di^tniaiMfii. fli* ttiof* /
reftetion wni ttsnai tittOA th» ^wtiTwA i ^ o ^ t net
ifioii^fti,
mmmmm m^ mAmiQ mmmmnon m
ft «0ltitiffla of £1*6 g, ©f pHsres&l SM im ©f
3M iodiiaa g. of erttsbo!! ioo 6a<t 30 la* of ao^feie
eiitt poftiofit m^ tlum the eontoixitt of tli* Hatk twro iluikon
Tho ofljr a^ermioai out <ma &iek,vmtM uitli ottMirt
waih«d ftnd or«r sodioei ^hor intf wmt!m&
rodboea pfMaiifo th« tldeie oil tmt dlstiUM at yUM, M6
Cc£Ld Aoobjrl-p-erotol^ g,, was «dd*d dropwifta to «oid ftirrod
Aftor ill* iddltioc, ih» rcN^otion tab^ore atlrrod for a m t ^ biif MI
boitr and thou poiarod on erushod too, tbo mhstmcB wVdob siporatod out
- 93
if&B coitmr&d^ idtb 0tb«r» fnet^efe vii8 weahM witli ioditts
emoifid* «8twatca i»ttir to is«atwa pS. t t i m inl« mmm^, cnl tli»
jfsst. k® tmtk3tm& with lif ibpcediia® ad-
tfwS wemmlt 90.450^)0 for 0 sdmUM, liatteiBjea, mmimi mi.
ttm resi<hit ma in ooM idltti to pE
Xb« tjTowfi t i r ifeuis obtaiiwiai m* tmlxmtmi with Wft8li«« with
ti»9 was i rm ^^mreX f»]|>«it
^ l i t . §4^(345 .
Aimlyslti Galet. for *
s.) was (iissoXv«d in atsr^niitii l^roxidt /
iM>liiti.<m» of Mi«K»ii« mm r«w>y<»d iiadi«r and m
ftAtmwtwi mlxibim of wUmst nitx«t« (4*2 f . ) tu t aidAd* A «oloiirtd
Mlt i)rtoisdt«t»a ottt« tihi^ m» wAtlMd wltti IntuHnM^
fhta tairmt mXt (2»3 g») ^ihxmi irltti btni^
f . ) in Absoluts •thanci itor 8 licmrf. SthamX wam tbsii
tmiffr r«iae«ai pmtmm «ni tb« imt dioaaivwl in ami «thtt««i
lagrar m* waalhttl with mMm Igrdrexid* soSiitioii va^ ii»t«r* SblMr
th«a <!iatSll»i off ami tbo i m t ^ eUtoildl* wk§ rtMsemil
«t«flue tls* f«siiila« im« oi^ctaSJlied £ tm bimf«ii»»|Mit.*
• ^ • r tl<V111®, yim, 1.29 g45M)» 0.S f . ©f tti»
VMI yWiOWSlTlldt jCiPC i lmUilMI 803Uxt>ill3KI liR
rnUimmrni. 110-lt1®(33)] ,
S,6-Dliiitro»p-crii9<3il <0.4 g) wm r«i»ui08<l witfe ©wr
j^tinspei oxliSt (50«(g.) i a afi«tie nidxfilri^t {Z
pr«»!9ur«. eitt«l/«t was fiXtorad o f t tkoetlo ii«*
mrncmd tm^tr reiaofld protntitw* fli t rosldti* m» er j f t ta l l i t f t i £rm
©tfewsea, S27-S®, 0.4S [ l i t . .
MsK^Uwi ftl' J^iHltiA^rffirBfTffirit^l tetaiyX f^few .Oft^tea
2r<^Sinitro-pN«r«aoI eth^r, 0.6K f . acl©),
•)}»i(«n with pHatinua oadtt« undmr }<^roe«8 «t tttaoflf^harle pr«star*.
Ubflo Mat 00 fiarfchtr •b^orptioB of (100 IssrdToe o m9
ftboorWl)^ thft e&taJ irirt fiXtered th« p t o ^ t obtNiiiMNl
imm ths lil&ffattt aa the triasolyl of
z&tf m ^ d g.C^sO*
AaaSytiii {^leil* iitr 8 i , 10.60.
feasSf K, 10.5!.
Itn ei«oholie eolutlen of 1,51 g.(0.004 ffioS.*} of
ertsol btfiagpl mth^v wss unler bQrdrogm «t i 50 p«l in t t e
of about the aasi ^uuuatit^ of Bae*^ ajek»3.. After ihakii^ th» ml ffyxptt
for fottr honxpB, ttie csmtmifc* of th® bottl.« q[uiekly flliert!l Into
«n excess of «ootic The ftltmfc» fdoae with aoeiie anlisniriat
was «va|iox«t«d off imder rMtiood ptmmiafm, iolid r«0idu9 wawM
idth mtwg <lrl«d end ciyitallitedl t t m teauntne-biaan® or ©tbanolp lAlte
medlot, 135-186®, y i m , 1 g.(80jl).
An»ljrfiai Caiea. for C^g^^O/^ '
Feandf ti9.10| % e.80.
flw dinewtTi <l«rivatiini of benm^
OM (C.Of mw otrnkflii vith 100 In laeob^l
un ler l^ogoi i cfc ^ f i l fbr f ^ I x r ^ f w m m ^ t S . of tbK ostal^st*
•nd tt?t e^lroaiti, ttttt djjusAtff dtriiratlv* of aj6»<liaidis&-p-er«aoX
cryttallieidi flros alcohol er hmmm, ».p. yt«M, 0.4
Jln«ly«i®j for «
Fottuas t2.47.
Thl« ainostyi fflR 3li«ldiiis wltli ttootie afilignli'ido t» alcolioX
fRW tii« triteaigrl dwlmUm, la.p. adsrtd B.p.
- § 9 7 -
O m i C A L a E f t C T I C ^ S O f
If is aol®
was elmkan with pletiams oxl4e cataJ^st laidfty Aft«r eofi^lstioo
©f tli0 rsaetion, tha Cfttalyst was filterod off and fjro» tb« ru t ra t^ ,
solvent was rmrnvaA end ttee rtoidiw was ory»t»llis»!| fSroo ©thanol.
In cmm, iiisreact©jl starting raatarial was r ovffir<a«l# Tb® exporin^tftl I
conditions are @aii:!aariised bolow:
Cos jeand GataJyst prassaro
Tim (fero,) Solvmt
1. 0,2 g. 0.04D g. Atu»sj5h«rl® 20 Kethasol
S. 0.2 0.05 g. 45 psi 8 3. 0.2 g. 0,05 g. 63 psi 10 iie^ie acid
4* 0.2 g. 0.05 g. TO pei 24 Ac«tic acid
5. 0.2 g. 0.05 g. 70 p»i 50 Acatic aeid . • Ill iiimiiiimi II
fetrah^rojEUran waa f i r s t rafluxcBS o*wr potaaatoia tj ^dit xide for
six hours and than dlatllX«i* I t was again r9nm:<!!d over stdiua wirs for
•i* boors and distlllodi. I t was finally raflASxad mw a eeall qumtitjr
o f l l t h i a i s alaatiniuD l ^ d r M t end <3ist i l l«4*
1 i 4-T«trah3rclro-2«i»njigrl-1»4h^ioxopyr«eiao( 1 i » d o l o *
sold)* was talraii 200 nl . of t»tr*l3griSi>efUran iiM thia
ftolutlon waa addad dropwisa to a suspafision of 45*6 g* <t*£: iaoI«) of
liihluts alueiniois Is^drida in S80 lal* of iatrabirdro£^an. 7ha raaetim
sAxtam raflux^d for Itours Kith atirring. fb« axeaas of lithiiam
a^Msdeivw hydrida was daooepoaad »ith 73 inl. of lOJhl aodlos l!^ro3d4a
90 a l . of wet or vfith ipao ccolisg. ffem th i s siteturo was «!fiiS.n
rofliijsad for or® hour. The issorgfinie proeipltato vas filterod off and
^mltml with ^ihsr tim»* fhm ooalxiiMid f i l t rnto and iiaahiet|«
vara 'mpt ©var aal^droua laa^iaeiuia miXphata ©viar n i^ t* Ethar end
tatrfthjrdro^ran vara resoirod imdor low praesarii and thm tho rasldua
W&8 tali»a up in di7 ethar eaiiS Hvy iiiydrochlorlc acid gaa waa paatad
thrcmfh i t . A Xight brown coloured ta r aaparatad* wMob on ooolinK and
ftoratohing geva m smtpbmsi pow^^r. Ifhia jpowdar af ter two cr^etalliaationa
gave wbita shining oiyot^a 154®, yield, 6 g. (6l$)| ir(SSf)
3l80(Mro*yl), 3C500(3aiol9 C«H), m s , Um, t450 etT^Cindole rln«)}
uv(BteH) A mm. 274, & 292 4 3.955, 3*U & 3,845? ntrCC^D^M)
r (ppa) 6.74(2p, t r ip la t , i opt), 5.35(£p, t r ip le t , Jf £.5 ^ ps)*
- § 9 9 -
iiingl0b), 3.25Clp, wxtomlvii mpXet),
2.90-E»16(9p, aromtiet imltiplefc), sifigl«t), broad
i3Bap#«©lv®!l t r i p l e t ) . Tha las t tw© peaks fttT" •2,34 4i®app®ariid
in tfaa ^eetrusi tAk«fi a l t ^
Analyalsi Ca'i«d. for C gHg C J-gCI s C, 68.27} 0, 6,63} »»
Foai»a« C, 68.44; % N, S . ^ .
1 » 4 - f ©trabjfdro-g-l^n^yl-l, s i m d $ S-a) Itidola,
(0.5 g.) was tr«at0!l with 10 Ml. of 0.5N potasalw l^droKida, and tha
raaction mixttira was heatad m a water batii for aiiaitaa* Tba eca.d
alicalina solution waa aoi4ifledl with dilute hydJwWlorie acid, Xha
wMt® praeipitat® thua ofetainad waa waefead, dr i s i a»dl crystallised froia
•tfeaiiol, o.p. 213®dac., yiald 0.47 g. (90lS)j ir(K8r) 3230(carb©3grl OH),
3000(iBdol© C-H), 1700(carbojiyl I630(awi^» C*«0), 1530, 1500,
1465 effl"^(li«lol® ring),
Analyaiai Calcd. for O^^^^O^Jig t C, 70.11| H, 5.23| J5, 9.09.
Foandi C, 69.86j H, 5.16? K, S.71.
IV. Mefeterlatliaa o£
A oolutloii of
(0.01 mli&). In tC of dr^ bAnsone amd 5.6S g.
(0«C4 noOLe) of oatl^srl iodide was to a solution &t ttodium
(300 t!^.) iu 50 xb1« of ft^solutf) m^lMeml, The r«aetion edxtuiw mB
etirrod for four and & Mlf hours et §0*60^. flacnt Atlfxljntg was AtoppM
and th® solvemt audi oscos® of etathiyl iodide war® rewoved wilder razeed
pm»mv9* Tiio rosMua m& ihOKi »ltb li^drooliloric aoid, 100 nl*
(10;^), in orusbad is®. 4 solid product obtalnadt which was filtor«i»
tfashdd find <iri@d« Thia iioXi<l proiSuet was ostn^ctM with bons mo in *
iioxhlat. ?bia white powder l e f t in tta* thittbX* mB fsrystallited Droffi
tfthaooX as whit« oryataXs* I t tf«e id«ntifi«di as open obsin fteid^a.p*
o,p, Mltb th» hjfdrol^reis prwdaot yield, 0.2 ^ ^ ^
coapoaM «Mi8 also found idamtical with that of the hydrolysis produot*
fho bsnsano AICTRECT OB j^tirthar oom>«ntxnti<m IGAIM a inAilta
erystaXlifie oonftound^ wbioh was filtarod and driad. I t was paastd m«t
neutral aluaina using a liixtura of hmt&nw^h&mtm (60t40) aa a aoXvmt.
- 101 -
A Mhit« ei^stallino eoa tooM lias.olKtatnddiy la.p* yltM 150 tsg*
Tbl® was idoiitlfied as
10-dl»®t»grl®yr«Bjji©(l,£-a)l»dol«| Ir(Rar) 17O5(in!i<ii«*K0«O), I645{«»ia« C«©), 1600, 1590» 1500 CBT^Ciudolft wimg)t X »w*.
Asalirelst Caled, f w ' 5#70| K,. 8,8,
FouukSI a, 75*48} H, 5,75$ K, 6.63.
fha be)ne«B« »&th»r iiiiuor <m eo»&«!!itr«ti(m g«v« m y«31oii eryetallino
product, ffl.p. 1£3t®i eiJ!»a ffl»pt with
iir traa also fotuid
to b« itSonticaX* '
the rasetlon of bensaXdahyda with
1,4-(lioxc^yr«sino(1,^8)iistlol« in th« ptmmm of « aiitatsiii basa vaa
• j ^ t a d to glva t,£,3,4<»tatra)Qr;lro*2»bani^l*>»filitiQrlAathyl«ii»^
pyra«iiJ0<1,2-a)lni0la. This raaction was cnrriati out imdor tfea JbHoidng
diffarant axpariisantal oozatitlonat
- 102 -
Ooipoimd CNinsaMeliQrde Base Solvent & t ine
1. 0#87 g. (O.OOJaole)
0.318 g. (0.003 nels)
Na0Ac«0.4>9 B* (0.006 iwae) & ACgO, 0.3 g. (0.015 nele)
2 hrs.
(O.OOSnoilt) 1.06 g. {0.01 aele)
H p e r i d ^ d i a l . ) EtOfi, 6 hrs.
3. 1.45 g. CQ«00$Bole)
1.06 g. (0«01 jsole)
E t ^ C n 5 la.) StOH* hrs.
K3X th« «bmr6 -mtm enxrinA out et thft stesa hath to^arat»r«*
Alter eof9:a«tio» of tbs i<etietl0% tlito r«KietioB aixtvrt was
pound into a alxtur* of lnydrocWorle 50 oCL. (10^) crushed
solid autsrial wao fil tered and iMshod thoftni^Osr with petrolena ether
to r<Keove the escoese of bensaldehyde andi beneoie acid, fhia solid |irodttct
was then esttraoted with heneene* A bmsme insoluble li^ite {jowder was
l e f t which on crystallisation fron etha&ol $e;v& tMte needles » dee.
Qixed «.p. with the open chain acid, dee*
The benwrne extract affcer reiaoval of hsnssene gave a brown ta r ,
Ciyotallisfition btA colutn ohrosiatograpl^ over elosdna in different solvents
failed to give any pure product. Sa»e results were obtained in a l l ttM
above ea wtiiMNxts*
112, 1602 Ct92l).
Z, Piitaier, Jotaaoii* aM
3. Jolmeon, hmmi, BolHir* I.f jr*ila.CltiB« Soo.« 2364 (194?).
5, S285
7. m , H.3., Stmmcm, ^•tSUm.Sodu ^ 4 4 (1968).
d* itoraMtk* U«0.f Ftfkin, St,, Bof^immmt | g t # 1378 c m s ) .
^ S370 (1947)»
10* JolmaoB, a.R.^ Tlw stmetnrd ^f in *th» Bogcr M«m JSIy^potlW Jolm & Simsji Iiio* foity 1955« pp»
11. JobnMQ, and tipibaJLiAisd obatinr«tioos {QmUof^ thtsis, OonoMO.! OBivtraitj, (19$3)»
12. Hodi, H.f., S.E., Kidind* A.il*. and Jotmson, J.Org.CbMkt (1970) •
13. tr.S. 3, 317,524 Uwy iWtp Fab. 4» 196f« pp. 7 (C.A.,68i21956k).
14. SiiGkM*, C.I., andi Robarfea, Anal.Cbaii., £b 1331 (1949).
<li>
%§* Slireiov, Altakte^, UB., Qyiaar^ Alikmm,
(C.A., ma^im vh
(Ci* Fxt». trnht&^^m Pmm O^e&iDr
1?* Shvwtot, f a*^ Al^aMftt Oxititnrt Shlji.Fft3m.2h* 8(12), 3(Bwi»4 2(12) J-?. (C.A.t 70j87750iO»
19. ttsd Unpabliabftd 4»1>tg«iflf«ti<^
19* l^tel!^! Johaaon. mH Bruet, U^f^,, a.fts.Otuie*^*^ ^ 419 (1944).
£0* foKtngi 3493 (1950)} uraS HOMVFI.* ^ 094 (1959); J ^ A* aad Mitko|$t 3.i
(19^)» SoMfiai«r« H.S, J ^ i l 21,1959 (e.A., 54iJ?35W»
jSI. Harel»lli» lNMBt»g«ir» H«acoeliy fi.H.* •Chwsi.^ 4375(1^)«
S3* 30lmmmt fiatldroiielcr Dutoli«r« SJHm, mA J.Aii.Ch«*.3o6*« 463 (1945K
24* XctlMh, » £019 (1944>«
r . , wad ICorrltQ% 4»Gliiii»Soe*^ (l^i^)*
26, Stoli, k ; tmiCLXw, aM Boftetniv A** H9lv« CliiMi Afit* » ^ 1452 (1955).
27. SehiBai«r* W,, R«ly«Chi».AoU gU 1^30 (1957).
( t l i )
Bttrtoai Stoif«o, J.U, (1937).
(1943).
Maciii, mi t*C« ^.Or^tChiiii.^ , 917(19^).
f., B»il«i«t»s HsMlKieti Orgenlebtts Vol. 13 ( I MippiifMitt), m *
33*mmh9, f., AiiA.C}tw.» lis ciaaOi ibi^ 143
B.l». ttoi f m m , 2C41 (1919)•
M.E;., Sobirttaidn«ert B.M., f t ^ , 179(19^)<
M.R., «iil H^ HI? (1965).
rr.Bb&tt, ?ti«kdf, K.A., ^ 1049 (1969).
a.ll., K.i., ^ 10S3 (1969)*
39.nisMOt, 9tin.3oo.ChM.(4) 736 (1909).
H.p S.Fta^oH.Clun., m ( m s ) .
-P -R T - I I
1 1 3 1 a 0 & i e t X 0 B
- 103 -
I J j f R O D f i G t l O K
(l-b0aKo(b)y;ywrolo, l-aaftSisdone, ketole)
Is a nc«tib«eic nitr<»|pnous compam^ in whieh & bsnKono m d n pyrrolo ring
«r« fu»0i tofsthor in positions of th® pyirol-a ring;. TH«t forsiils mv
aeeoptodt for itidolo w s propoeed tjf Bae^^r and feaerling (1). Th» carrmt
praotlce in noesncietur© ia eteown below <R.I. 881).
H'
Tho original systeo of uoHmtclaturG diavifiedi by Sseyar nnd lotor b^
Fiselisr (3) was too assste reos© eiise® i t ©ffifslojoS tiii»bari«g
for each rluu,
Iniolo nucleus i t presoot in isany natural producte. fh« «arV
uorls: on indole dorivativ is was dons ^ ^ j n ^ r i» coimootion vith his
r«3oareh«s on tha stmcturo of in jJtiO (4).
- 1 0 4 *
SniSeog if 3-h^ro^RloXe or ia m
i i ^ r t a n t l&tomediattt in tti«i s^mtliddls of indli^e* XnoaiaKL of
bioelitsfflioeA. ifeporictnos «« wftil^ i t s giuoosido occurs in oortftin
piKn(t« mi i t s sal^lnirio acid etitsr «xoret«Ki l>jr atiifittis*
3 - % d [ r o i Q r i n d o l & - 2 - c « r b c M s y l i o a l s o e a U w l i n ^ o j ^ l A c n e i a
i s « s m o f t b « 8 s e s t i i q ^ x t a n t i ! « r i V 8 t i w « o f i n d i o a q r l . I t v a t s U r t H i
^feparwA trm o->»itropb«n|a.prppio3.io aeid
H C C O O B ColdL H2SO4
D OH
H
( ^ ^ C O O E t
- -
I t hftO also boen } re f^ed by the ftision of l.'-phiBiyl^jrCina-o-ciif'bosfylic
acid with iiBlten alkali <6) or better s t t l l with (7). Xn the
lat i«r ease, tho raactlon i s c«nl®4 m t at a Ijswar t«nf!erat«ra ami
ther^fera the yiolrl© are teflittar.
•IMH CH2COOH o •OH
H
Anothar ayntbasia of irtSoxyHc acid bas baen aeeoi^llahad ^ heating
aniliao atalonic oater (B),
Q / COOEt
\COOEt "O^N-^COOEt
Itidoxylic acid undergoea r«ady <3aeartM»^XatioR to indoxyl, a
fact that Bakas i t an important intwmii&to io tha aynthasia of indigo.
- 106 -
md it® clflrJvativet «xp©ot®<i to ahow k®t©-eaaol tmtm@vtm»
Q H
'OH Q 0
H
the infirared opBetmm of t-«eetyl e»d l-aet^f^l inaoxsrl neesured in
cl3lorofor» indiea t^ thst oxofwm proeHosdmtea* Howdvevi the ipi^aftnco \
of an seetjrl groap in t]:» smmn to stftbliae the cmol fore due
to byiSr©|r«9 boniina (9^10).
0 -N R
Q H
0
CH-
H « Mo, CCCH .
Similar observations bad earlier been mdie for oxindole or
The phenolic oheraeter of Indoxyl ie ehown h r i t s solubility in
aqueciuo alkali as well as tyr the developioent of a dark red eolour wil^
ferric chloride. The ketonic character ia ahovn in the reaotiona involving
the condeneaticm of active netbylens group with the carfeociyl groura of
- w -
arDBatie ttld«hyd«8 or of koto aeido i^lvln® iRiog«aid«a. IMojcia
ooitdeiiifies with iamtixk to eni uith idatin ehlorMtt
i t givws iadig©, Metbyljtioii ©f ledos^l with Eotkarl sulptetfi givea
while mth^ Iodide j^^Ma .?,«-.tl4Bs0tiKylin«io}?yI ( t2 ) .
l»a©la<-2-©«rb©»&i8idi08 liav® bom ltett»3 to b© vm^ ti8«l^l ooRjjoimias
as iut«i?i!^ifit®8 in th@ fl^ttsosia ©f loott^rp^ophaw (13)» fi-wetfeoxyisotrypto-
phsn (14) fflw9 ©f iaoiaretonlJi (15). Thoy poseioes v«ry wseto
Fbiijn»se©l©|;icai properties.
Ki»risaok ot (16) tiavo iQmthooi@9d e^-sabstittttei
cnrboxftoidos mo int«r«Qaieto« in tl3»ir assmtteais of feaMtoe aiid harisalirto.
Olaikio aiKi Forkin (17) have syKthoaiaai 4,5»6-s»batitttt%J Indola-?-
carboxeoidtos ea intorB!oaiat»» in tboir ayntbosls of pyraaifio- arul
pyridlRtioloB. Johnsoc ot «1. (18) haw also uaodi ir^ols-^g-certoosfcaffiidea
ae i»t«rno:3iatea In tlteiz* aynthaais of pyrasdnoiniolot* /a i tbase t^orkara
start<5d with iiKlola-^-eorboxylic acid, comrarting i t to tba acid oblorld®
«al than to the aroida. Jacob and Keaser (19) had earlior wsoi tho aaida
aathoiS. A mm reaction vm oarriod m% iQf ShlrXay aaid Ecmaaal (20)
- 108 -
fcr thi» ty&theais of iudoXck-Svearboxastides*
Q ^ NCO Q ^CoNHft^ CH, CHs
iSHibstitutdd ir^olo-S-carboKasslded alao b»«a »ynt)i€ioie«Ki hy a n&v
roaie by 2€W»h {^1).
PK COTK i - M ^ 3 c n c . SF^ Q Th
- CONH C Mcj CMe.
CO eUj -V Me3CNC D N'' H
•CoNH CMe
- 109 -
Fbtarffiseologieal ftetivlty of « nxsmh&r of IMolo-S-earboxeiai'iae
baa b0en atvidiled. Th® work suemriacNSt in t&bhs I*
l A J L k J I -
H • '
tisarnacological aetlvlty Bsferoncc
1.
n-H^tyl, But.i
OSti
4. if 0}
-Wv 0 J
AntieoR'vuIssnt
IJjipotiMsalv® ftctltrit^?, taofeefl orally ewJ intra-poritoneally on rata
AntioiMtie
lurittiieproseent
CNS Depresseci
19
22
23
25
• 110 •
0 1 S 0 { r 3 5 1OK
^tlb^m^h it)do3eylits A€!ld hoe hsm tmom to be m Sm^ ortant
IntorsMjiliato In th« »ynth«aie of indigo, v«r j few of it® derivatiims i.®.
tho Betl jrl aand ethj l esters (26) «o<l the itnllido (27) haira betn syntheaised.
i t i s wall-knoMK that th© carbojtaajldo grotip i s respimalblo for the isioXogical
activity of ft fwiBlier of o r ^ i e coH5;oiai<la (20). JJ-Alko3!yindol6«2-"Carbo*«)niide«
heve bean 8hoi«ti to poasess useful pharssacologlcal jpiropertieo (Table 1). jit
ma, therefore, fe l t t!mt tbo iKttjnoiluotion of osrboKataido &N>itp at the
^-position of l-hydroxyln^ole miety giw coa iountis of phar«aeologic&l
interest, fhey can also t^ osed ea intonsedii&tee in ame iBportant
fQnnthosea* 3n the present work; a nuEber of K-«ubstit«t«i J-ity4roxyiaiolo-2-
oarboxotti I00 end befityl 3-hyir©j(3'i«dole-X-eiirb03^1«t8 have teseB es^theaieed,
Sooe 3*iBethoX7i»d[oIe- and in<$ole»2*oorboxanMea haw aleo bowa prepared.
Since diin»ot condensation of Indoagirlic acid trith wBinoa or
alcobole in the praaence of dicyclOheaylcerbaJilaiie, %fithout the prcteetlon
of 3-hydro*y g^mp, was not posalble duo to the phsnolie nature of 3-hydroxy
group, i t was proposed to prepare Batlyl 3-hydro^ln4<^«H£-oerboxylate and
« 1t1 -
trjr i ta asmnolysia accordSing to the following echett® :
o UJ
Q H
'OH
^CONHR
o-Cas?b0BK3th0»yphenylglycin» ffietligrl «st«r ma pr®por«J by heating
Bsothyl anthranilato (2 ml&a} and meth 'l chlo:^®tate < 1 ©ol«) in iBethamol
for 13 ^BfB (144 hours) on a stoan bsth. Methanol was dlai i l l i^ th«
r<9«ction Bslxtura was taken in chlcarofor», waahad with aodims carbonate
solution and then vitb vator and finallj ' dried over antisydrous sodiua
ewlphata. Chloroforo wa« distilled off . Wnraacted enthmnilata
and ssethjrl chloroaeotate were r^soved fcgr distillation under tmeaua and the
residue was crystelllea^ Iroct ffi@ti^ol*
- 112 -
Q .C0DCV\3 -V Q • COOCH^ Q COOCH^
NHvl-'d
Metfce'l |jh®iitylflyciiw8-o-carteo3Qr3dat(8 am cyeULsed in the presoiice
of a^iim In drjr m a atoa® Isatli* l ba sodium Bait
was filt«r«d» dlissolved in iet eold mMer m i f^ adding ^ihito
«eetie acid. The todoxylic eeld tsatfc^l estor waa esysiailised fpom i2«9thanol«
tOOCH^ '^S^ NHCH I OOCH^
0 \ i
COOCH3 H
U) Aaaonolyalg of 3*hydroxylodole»2>^«rbo3cylat«i
Amonolyals of wttayl 3»togrdro9grijr«telQ«-?'-earl303ylRto with unllitte
was carried out fcQr bMtinfi' tha ester and anilina directly; and also in the
pr«»9no« of e«tal}^io aaount of Asnoniuss chlorido sni eijiiivalont ssiount
- 113 -
©f seditj» ethoxa^e. fhest ©xj eriuients er« aimairiead In th© following table *
Catalyst Tiiat Belveat
1. ag.(o.oiffloi®) i©iiaL.(.to9 ®oio)
2, toi©)
bTB,
bra.
Benzene
Dipbanyl-athflsr
3. «.1oa40.f«ol9) fJtt Gl hrs.
4. -4g.(0.02isolo) 18.euil.(0.2 mole) NaOSt 78®, 4 to-a.
In th« f i r s t tbx^ •jcporiffisnfea, unreactei irdoajylic wsM ©stor was reooverei.'
In tbe iBot expdrimsmt, « feOsek mM^ product was otitainad, from which oothlng
coaM bs iooXatdd.
Q -OH
fvi'^ COOCHo H
HHx f o M • H
.OH
- tl4 -
Kfttfcarl 3-hydbro3qri«4ol8-2'KsarbM( i'lato i s m -Koto and
abould be fairly raftotive io this torn, rJut i t s ©ncaic fore i s capeblo
of vtMergolng fc(jrdrog«n bonding as sfeown fcjy i t s infrared speotniB (3t).
Aa a rdtttlt ths »mlie f&rm i s stalb3.i8«dl etttd oon^qitentlj the estor group
daactivatod. Thie my sccmmt for f&i1Uir» in tlie abew aspeilei^flts.
Q , .0
H ^ Q IM-
H
4 6 OCH^
>^Metboxy3jnilol0-£-'Cerbo3»ttl<3«» irtire propar»a witb a view to
datsethylste tli«« at tbo laat ondw ®il<i carrilitiona. Xho progosoS
acheoe ia as follows;
D • OH
H •Coocw, a
H COOCH3 Q
H COOH
^OCH^
^ ^ - c o n H - R H
o N' H
OH
COT H'R
« 115 -
Im) M«thyl S-TOtboKvin^ole-g^arboxylBto (32) t
Hethyl 3-hy»3r0»yini0l®-2»c«rfe05?yl»t« mo« ffistt®'! at<)i with dlcjaftnyl
sulphate in dry acetots® in tfie prdssnee of an^drous {;^tas»iusi carbonato.
OH ( ) I
Mo 0CH3 D H H
OCH^
C O O C H 3
>a»eth©jQ? iKdole-2-cwrbO3tylat0 was hydrolya®! witb IN
aatlianollc fotaosiuia t^ytiro*!!®. aol'i was cnystaUisoi l om benzena.
Q -OCH-KQH/cVi^oH
. j S ^ C O O C H n HCl H
a OCH3
H
(e) 3.S40thoyginiolo-g»Cflrbonyl cfetor^de floe. c t t , ) t
>.M0tho»3rJniol0«»2«-carbox^ic acid was troat^sd with Oashly distilled
tMonyl chlorido (IjS) Irs dry othor at room tOEporaturs for on© hour, th®
esreens of thionyl chloride and hydrochloric ecid gas wor« reisovrjdl under
- 116 -
reduced Th« aenisoliii csbss X ift was Cftkon iisto ether and
was uaod as such, slnc*^ i t readily.
o w
.0CH3
• C O O H
s o d , o H
,0CH3
coct
>.M«tbo3^indiol«-g-.c«rbo»jl cfelorid*, propurM froia th® eorfeapontilinj
&ei4 (O.CO$ Mm treatod viib vaHoos ansinda (0*012 sole) in dry ether»
Aft«r k^epinn; tti9 raootion fixture At roo» t«siparatura lor om mni a twXf
V»iir«, othsr ima removed and tto roai^u® tmts washed with diJiito bydrocKLorSjc
acid, aodium Mesrbomta aoXutlon and linaUly with water* Tha dried product
was oiT^aialXlfiei froa athtmol.
o 0CH3
H
-RNH: Q H
OCH3
CoHHR
- *
fti» baa btfortt tli« m^x^fl^
«a9 aietlwtfti of ^lijfdiroagr
Aetitjrljitliiii mi <m3^ to thm
formtim of O) Ixil miM «lm a«ii6«t|'li«tifm
im t&tt m&»r ^ l e h nffeet th«
eartoojsaHidA giemp idio, Bm^t &t<mt thcsigfe raaowd Igr
too Ms MBi 60 in»Qf%if>ftt«t tlw st^rie
Mfii«reno« OiS).
JolliAii fiBd PilO. Cll) Afl peU^ ^ of ^ etiQrl
of ••oroliut r«l3xucliig I t with iiuelnttni oblorM® I s etli«f*
3*ll«itbo9iariiidol«*&««arboia«iili<itf txniflni^i f i l led t^ m d w ^ dtfuftl^letiofi
tlMiMi 4M>naitl6iui.
OCH
IS-H
3
CONHPK ra H X COHHPw
• m -
3--!fivdrexyln.1ol ftyboKfisd^oiii
fho following etsbaas wss thsm ptopos®! to 3jnnth«0i@e th«
Q C00CH3 -V o
C00CVA3
u a OH
H
A bonzeip® solution of chloroacoty.l chloriie wao treatad with
various aminos dlasolvod In tsansano in th© frasenc© of sodium hydreailcl©
solution. chloroacflftyl aeddoa ware filiorod, wftshod and rlrtod.
ClCIlgC^Cl • n-NHg No- OH ^ ClCHgCKKm
- 119 -
(bV o- SarboaethQXTOheavXfflvctm maiUm..
Chloro&catjlaffiidioa wore eandenaed with enthranilato (1s4)
on a fltean bath without asiy solvdnt for S tours. H«thQrl enthmniXatQ
h^tlroeiaoridl® was rotsoved tj/ ahaktog th© raaetion »i3stwo in dry benzona
eni fl3.tsring off tha insolubla bydrochlofldo. Baaffl»«e wfts ranjoved
th© f i l t ro ta un4®r vacwttis awi the reaidua was again heetad for 6 hours.
The excsea ©f isethjrl antferanllatD wao remmi by washing th® reaction
miyturo with iwlplniric acid (10^) an4 finally with wator. tto® reaidu®
w»o crystallised ftcw ttlcoi»l.
U NHo ^ dcVAlCO^AH'R o COOCH-i
u Q . O O C H < ^
N HjHqSL
-
o«CarbGS!5tbox7pb9f iigXyoin* aisido (0*01 ml&) was eddod to a
me^maien of aodiius (O.OtI ^.tttoe) in diy Innssne alont « fev
of matbanol ixrdfiii' anhydrous flie reaction edxturo t^as
hdettjd on a %rat«ir bath. Tha soSiuiu aalt^ i<rfoloh saporatad, ma i l l terad,
dried and disaolmad In a sainiaum quantity of wBter enfl acidiflod with
cold aeatie ©fftd. Ilia wfeita |a?«ci|>itat« tims oM.als»w3 was vaslwwi, drioi
awi crystaXllsad*
u COOCLV\-i, i Na OMe
N h C H ^ C O N H R l^-OH H
,0H
CONHR
KHU • - NHI'h, -hm^il^n^p, -NHC^H^Oat-p,
All tfea abovo con|;ounda «}»v tha fraaance of cl^latad hydroxy group in
tliair Infrarodl spaetra.
- 12! -
Banssyl alcohol was treated with obIoroac£ityX ebioride to give %
bsTiayl cblcroeeotate (35)* whieh wae condonaed with aatbyl enthranilate,
cHSerboiasfttwi ypfeQnylgl iR® bawwyl est»r thus obtaiwail we eycliiwid with
sofiixus in bawzgrl alcohol to give bensyl S-by^roxyinlcrl^-S-carbosiyXats.
d C H o c o d PVyCVAiOH V dCrtiCOOCHaPk
u COOCH 3 -v
HH2_ cJCHiCOOCH^PV) D COOCH-
o . O H
M - ^ C O O C H x ? ! ^
H
A series of H-auhstitutodi irxlele-C-Cijrboxnffiides were alao j^repered.
Ch-MtropMnylpyravlc m i i was prepared the reaction of othyl oxalete
with o-nitrotolu«s0 in the presence of potassdu® otboaride (36) in B5% yield
* In the Fart 1, the preparation of thie conf ound l5|y the "azlactone jnethod has bean doacribed.
m -
Carlo (37) has reported a ^deid of 75% i»alng sojJiu® athoxide.
0^ C H 3 COO'iJr yx^oiy • c h ^ c o c O O H
N02.
o-Mtropliectf'lpyruvic bcM reducai with ferrous mi eEBonin
to give iii'iole-2-oarboxj'llc acid, wbieh was contntrfeed to i ta aeM ctfloride
with tMoiJyl chloride, and this was reacted with various afiiiB®8 to give
the correapoiidinK ealdes.
o H
c o d 'RNH^ Q CONHK
h
i%HR • - ^mh
- li .0
« 123 -
IR eoQotm. of oni.eafcgr
Ko0t of the indolo-2«earboxaiaid©o jjr«par»d give their ch&racterw
is t ic iiidolo m band botwen 3325-3355 ct f^ . l bo carbonyl band
in both iji{lol«-g-c»rboxfi«s}id«o >Hjattoa(yindol«-2-cerboxaudd0a i s
sharp ana cot©» in tb© range, 1630-1650 ceT . In th@ caee of 3-fe^roaQr-
inrtole-£-carb03tiHaid9s, this bairf is bread ai^ ia sJjdfted to
a lowor trftqu&mj du® to ^drogen bondtee with grouj^. She
3-b3rdroxyiii3ole-2-carboxa»ddiee okow a br©a4 band bafcwsan 3100-3150 csT^
for the chelated bydroxy group. Tim 3-.s®ttoxy show two bsanda
betwaan 12:35-1^5 euT for • C-OG. In the jMinaubatituted carboxasAdas,
a band dua to ii)doIa CH jgtretohin^; %irhich waa abaant in tba 3-subatitutac3.
cottf-ounde ia aaan betwean 2915-2970 . Tba inorptolidaa abo« a sotca-.
What fiiffararst bahavlour, in that the fiH ia tsroad eni i s shifta-i to
a Lowar fraqiuency (3260 chT'),
In thij caao of banzjl 3-hsytHr«»5ylndolo-2-C'»rbo3rylate, in addition
to tha othar characteristic bantia, the eatar carbonyl ba?ii ia obaarvea
at 1720
l A J L k l - n IR SoftctTO of lKrlole-g*c«rhc»comlde» ftM mUr
« -
E KII (indole)
era ' Ctrl (lutdde) Cffl"'
(indole ring) era"'
3335 1260,1^40 1650 1610,1595,1455
WIC^H^OCgHj-p 3335 1630 1610,1590,1450
0 (taroad)
1265,1^50 1605 1505,1430.
H hU {iniol|)
OH cbelntstl (broad)
eirf-i CcO
ciT^
(indole ring) Oft"''
..UC^H^XHj-p
i HC R OCgTyp
3340
3325
3355
33S5
3100
3130
3150
31C0
1620
1615
1660 (broad)
1720 (©jrtftr)
1590, U95.
1595,1510,1455.
1570,1505, H50.
1600,1575,1500.
f-.A .S I. B « I I (C<^t.)
- igj; -
• ts l^COR H
n fJH CIndole)
earl
eO-Jf (IndGlo)
ClT^ (aside)
ear^
Untele ring) ca"''
hKC Hj 3335 2915 1640 1600,1590,1445.
KRG H OCgHg-p 3335 mo 1640 1595,1515.
U 0 3260 2960 1605 1570,1450. (broad)
1570,1450.
S X F E f i l H H H f A t
« 126 -
S X F S R I H S N f A t
A sol'dtton of 500 g. (3.5 ®ole«) of ia«thyl atithmBllet© ftisd 180 g.
(1.6 ef ®«thyl ehXoioseofcat® in «S0 a l . of astbanoX was TBtlnmA
for 1M hoiurs on s staasa bath, hft&r dlafcilling off BobUanel, tb© roactlon
Kixturo wao afeakew with eWLoroforra on-i wat@r. Tha ebloroforir. leysr was
waahed with spdlam cafbensto aolMtlon, mt&r anl drisd m&t ijjshydrais
soditiis Ewlphate, Aftor distil l ing off ehloroforiB, the wnroaeteS metliiyl
chloroac«tftt« antl aattig^ ai3tlsraBilttt» w«ro rtrowed by distillaticsn at low
prestturo (up to 105® at 2 Eas.). Tho rosiciual llquM, while s t i l l wisra
was poared into 600 ml. of 95% ^tfeanol. Affcar staniine for acnrernl houra
at SO®, th® cryatela of dicwtrisyl phof^lglycino^o-carbOTiylato were coll<set®d
and W88hi»3 with coM ©thanol. Xtio product fornwd colcurXoss needles, a.p.
96®} ylold £65 g.
To ft sjixturo of pulvorisod eodiua, ?,7 g. (0.11 sole) •nd diEotbyl
ph«nylfi3ycino-o-Cftrboxylat®, 25 g . (0.11 nolo) i n djty b0»B0tta (TOO ffil.),£ ol.
« 127 -
of absolute raatlmnol wof© a^ded m4 tha ©Ixtura was gontly warwod on a
atwim bath until a vigorous reaefciCBa set In, The sodius oalt of osth^yl
>-h3rJroa5yindol®-2-oarbO3!ylat0 started separating out. Whan tba reaction
hiadi aluioat ceassji, tha raaetion rAstara was haat®! under reflux for
30 eijfaitea aiM than eoolad* fho aodiuQ aalt was collected on a
washod with dry banaaue, dried ani disaolvod in 250 liil. of ic© water.
Thia aqfiiaenis solution m» f i l tarad tmi acidified with acotio acid
Tha indoso'lic acid aotar tteu® |r.r®cli;itotad was cryataUiaodl fro® diluta
natbsnol {10%) in aiongstei gliataMng naadlao^ 157-8®, yi®M n g . i J ^ )
(c) AttaroiAa for atr-aonolvals of mthvl 3«hvdro3cyindole*g»carbexylat9i
1. ^tethyl 3-hydrojgfindola-?-eartooxylRte £ g.CO.OI oola) was
roHusrad with 10 isl. of anilina in SiO of bsnssana for SB houra. Thmt
the reaction edxtura wao waahod with hy^oohloric acid (536) # sodiua
bioarbocata solution (SJS) and firjally with wat®r« fh© aolvont l«yar waa
dried ovnr ahfeydroua BOdiuE eulphata, ooXvant waa ratsovad and the rosldua
was cryatallisod firoo mothanol, E.p. 157®, mixed m.p, with the atarting
con joundy 157-^®.
» m "
Xiidoii^lic icid (0*02 was heated with
emiiino^lrl.S s i . (0.2 sol«) for 3 boixrs. Stesrtlng cov^omd was o)3taia@d
aft«>ir working tip ttei reaction as above.
3. Indosiyllc aei4 eister^ Z g. (0.01 »ol®) was te&tad with aniline
9.1 (0.1 ffiole) at 170** in tba rrsseioo of catalytic aruount of
oRBoniua cMoride for 3 bouro on m oil bath, f ha r^e t ion Mxturo waa
takan in \mns»m and vorkad aa daooribad abova, atarting ooispound ims
ieolatod, ffl.p. IS*/*.
4* lz»ioxyXia ostar, A g. (0.0^ siaola) wao tr<^tad with aodiutc
atboxi^a praparad firom 0.02 g. atoia of ifodiuia in ©thasol a««J issl.
i0,2 taola). fha raaetion sdxtura waa ralluxed for 4 teura. After tba
rosction, atbanol was ram^vad^ a black ouddy prodoot waa obtained, fron
w iich rothins could be i a o l a t ^ .
A Bijctttr® of 16 e . (0.083 iS0il») of awt^yl >i^ro«3rinaolo-2-
earbQ3q^at0« 10.6 g* (0.08 i»l«) of diiMitlisrl sulpluitA and 30 g* of
poteseiust earbomto in 300 ad. ao^tom iifts rsfloxoiJi tiitior
anh;rdroa« oonditioss t i l l i t gava ft nogatiim test with aleoholie ferric
cblorido. Fotaseiv» earbozMite ims filter<^ off m i aeetcmci uks evftporated.
The time obtained waa or^ta l l i s t i l froo etliyX acatate - petit^Xmis
ether (b.p. ilO^&f), yield 13.7 g. iBO%)*
(^V aeid (loc. eit .>i
K«tl^ 3»»3thoi^tidio3«->£-earbe9(3rXate, 10 g* <0.G4S iw^e) m.»
di8«^3.ved in 100 ai,. of B ð«Eaca.ie potaaMdun tsu^roilde ixnd refluied
for tlame hotars rni a water laatb. INfettuisu^ vaa dietiUed off ami tbe
potaeelxn salt of ^aitfiojQriBdoXe-^'OarlxtJi^lio aeeid waa disiolved in m
idniniai quantity of nater. the t i t le acid waa precipitated adding
dilute tiQfdroehlorio aeid in eold. This aoid waa f i l t e r ^ * dried asd
crystamaed from dry bencene, «.p. 135^ dee . , yield 8 g. (86$).
- 130 -
le) 3>M>thoxvipaol».£»cagtenyl ehleri^g
fh« mham aoid ehloxidt was pfpm«& ^ tb« r M e t i m of thionjfl
eWiorMe dtisUUsd) on 3-»itbo^inaol®»2-eftrboa^Ue «cid I n
atber. Tha rouetioii nwi earri«d out tmiar extetly th« «tum eondltlon*
s8 asseribod eljiorid*. )
to ft solution of ehlojrido in othtr
(pnpered trom ig,, 0.<K35 im^ of tti* eorr9i|ioniing csld), a solution
of 0.96 g. (0*0t i»l«) of iinllifia in ethsr was addsd* Xfae roaetlon
aSsdtors was kspt at rooa ts i^i%ts irs for osos siid a ti«a.f i^nurs* Bthsr
was raiBQwid and ths rtsidus was uashiKt with fe^oeUXorio aeld {$$)» sodiitiai
biosrbosats (5^) sM f i n a l l y with wat«r. f h s dxlsd p rodmi was erirstaSlissa
f^oii ethanol, s.p. 176% y l s M 0.66 g. (50^); ir(K3r> 3B5(i»doJji M ) ,
I650(ssdds C * 0), 1610» m S , riii£)f 1£60, 1240
Analysist Calcd. for C^^Ej^O^^^ t 7£.l6| B^ 5.30| ly 10.52.
Fottod: C, 71.76} H, 5.19| 10.4^.
3-»fetbo}grindols-2-esrboQ]a ehlorids prapsrsd C.5 g. (0.0026 mXm)
of ths oorrsfltpoBdlng acid iras oonisnssd with 0.710 g. (0.005S aola) of
- 131 -
p-pliwMitMitift In f he retttXtitif «i>ld# was iael^Ad «e dlaiKtribed
bdfoxn^ or^mtalXlsoit ito'm »«p. g*
lT(K8r) 3335(indol® SB), t630(iuaid« e • 0) 1610, 1590, 1450(indol« ring),
1255» 1835 •C-O-C).
AnilyaiBi Gelcd. for t C, 69 .% H, H» 9.03.
Fotaidi e, 69.39} H, 5,87| 8.96.
f htt alxivt ooaiiettBi isGCLisdtoA aa ttio ooni3«ii8i,tlf)n jproduet of
(prtpotiradi i ^ a 0.5 g. ol* tlM ootT«ep<»iil-
ing «ei(l) mrpholift9j0.44 mde). I t vtm er^stalMsad £ro&
«th«aol, ».p. 150®, yield 0.37 g.CSSJJ)} ir(Kgr) Iti),
1«05(«ii<i» C « 0) 1505, U30(l!Kiole ring), t£65, 1250 ciT^C • WW;).
AM l y sda i Calod. for ' i , 10.76.
FouRdt €, 64.58| E, 6.03; B, 10.^9.
1*5 g. (0.0056 mU)
mf reawwd with S.S g (0.05 ml») of ms^rous alnaiBliie staorid* ia
SO a l . dry hmmm for 12 boors. Aluainitui oblorldo m& than filtorad
* m -
off and b«Bfsdn«» ligrir vas wanlMd with tniiM* wxl dri«(S
Anhydroae eiilpltMit*. dtnamoi m» ditttiHed off and tb»
r«8Mu« was erytsHl^a^sed £rm ottuyndlt sdmSi m,p» idtb tht
fltftrting aater i t l 174®.
i f ) . »
fc fi eoM aoluti<m of 20 g. (0*E15 nole) of ea^lim in 3G ail.
btnstn* over tOO aH, of ^ ao^ua t jriArdsdd*, wart udded $0,28 g.(0.26 8o3l«)
of ottloroftC^tjrl in 40 of bma«m with eoolietg md otirring*
Obloroaootyl anilins aiartod mperMtiag out aa a i^ittt praeipitata. Aftar
the addition, tha fisaotion slxtura was atlrrad ftMr anotbsr 30 idmtaa.
PetrelMum ather ita« addai for cos^ilato praoipitation, K-etiiloroacatyl
anlliiM waa fil tarwl actd driad. I t waa aiifHoia&tljr pura Ibr l^rthar
raaetioa, ».p. 136®, 28 g (77J)| f u t . m,p. !35®(34af — « ^
In a 500 sa. ground #aad round botto»ad f l a ^ Uttad with a
raflux condansar, 5.0B g, (0.03 »ctla) of cbloroaoetyl aailina and 18.12 g.
(0.12 sola) of Battel anthraniXata wara tcOian. tbia Mixtura waa baatad on
a ataaa bath for $ houra undar anl\ydroaa eonditiona. Than about 100 aO..
- 133 -
of b«mioii« t^doA, tint alxturft was for SO ladnittts
rod timi eoo3.<»dl. «iilihrBiiiliit9 t^tlroohlorJudi* fortaed daring tlw
condenwition was flXt<ir«d off «iu3 with tiio 50 |>drtiims of
dry hmwmm, 4*1 g« of liindroetilorido vttm olsttblnad* 0tiis<»ii« mti ooe-
rmo90A vMmr redbit09d prtatiai* on « stoAffi Iteth uB^mp
ef^Mliticms. f r « » i d t t { i m» etttis imin i on m stmm for Aarth«r
six bours. fhft |]$droe%ilorldo m» roeoved b»£&t», cwOy 0*9 g« of
l^rccbXoridft elybAinisd this t l s» . In 5 g* ttg^drooKLorids vios
oMaitisd as sfs last g» of t t e thooretj^sX ii.«i about 90$ of ths
r«M3ti<m WAS eos^lstod* flis fl3.trat« a»4 imsMngs wsra etxsd ei^ baovan*
tiaa rtsoved imder raduead prassara. fha ajsoaas of nattisrl anttiraniiata I
vaa tmawtA ^ diaaoXirix^ ttoa rasidoa in banMna and washing i t i«itb %0%
suXphurio ae i^ sodiusi eafbenata (10^) and finally with watar* Bweana
ii^ar ma driad mvr anhgrdroos sodltM solphata, avaporatad and tha rasolt*
ing aollida waa cryataaXisod flro» athanol, 146% iriald 5*9 g. (70J().
Analysiai Calcd. for C^^B^^O^g i C, 67.591 H, 5.67| M, 9.85.
Foandi C, 67.19| H, 5.54f % 9.77-
- m -
Xo a tua^enaien ef 0.32 g* {0.014 of pnlif^rited sodium
Sj> UQ ml, banMne, & sol^tioa ©f 2 g* (0.007 fflol«) of o-eferbOBftthojqr*
phfonirXgl^in* iflsilitle in 10 dI* of Imseiia ims ttMvA %Ath a f«i« drops of
eba^l^t* svtlsemX. roaetion aix^um ms than hwit«d on * «tmm both
AsH^f^mn e d i t i o n s for 30 aimites idth gbaktng* I t vm ttsMi
r«flisxat! for ^rttovr ^ almtes, oa^M and ^thtar was Added to i t .
the sodiiXD aaltf which septreted oiat» vas (Sriod by filtimtion under saetien
m a IkioHiior, i t vas them dissoliro£ ia a iBiniinim ({aantitjr of mtmv and
fiXtarad* elaar f i l t r a te was atsidifial «dth acotic aeid in ooXd.
fh» t i t l a oospound jM9i:>aratad as a whita prsoipitata, whioh waa uafibtd^
driad mtd orystiaiioed f^os matluBnol, B.p. t yitild 1 g. Xt
gives a gra«a toXoar with aXofihoXie farrio ehXcarida eoXistion} ir(SSr)
3340(iniloXa KU), 31OO(ehalat0d CB), 1«E0(i»iiio C»0) 1590, 1495 em^
(ii^oXa ring).
Analyaio t Caled. for C^^U^^Q^^ t C, 71.41t H, 4.80| N, 11.11.
Found: C, 71.75| a, S.IOj 11.29.
- 135 -
fh» abovt product was prepared ©hl©roiie«tyliition of p<-«&i0i<lln««
€ g. (0.04B 390io) vi tb ehlKKToaeetyl e b l o r l ^ , solo) ID 20
of aoiius t^irojddo il«8erlb9a Ixiforo* m.}>* 9*4 g*
CKLoroaootyl^l>eni«ldint« it g. (0.03 wfti eoadttnsod with
18.1 g« (0.12 of m t ^ l «nthr«nlliit« to g tw abova aidddj^ whieh
wae ef7tte2.Xi8«d t r m «thji»ol| ».p*150% yiel^ 6.3 (66^)*
Aniasrtlet Caled. for '^ iT^tsVs *
Fotmilt 64.68; 5*79| 0*9^.
iaa {H-|>-B»t1ioi!3rpheD3d) aii'boxAtBid*
3.14 g* (0.01 iBoXa) iras cgrolisaii In tt tt pratvRca of aodlua atthoxida
praparad l!rci 0.416 g. (0.02 cola) of sodium iaspandiad in 20 aX. of df^r
bsnsana to glira tba titXa product. St was isolatad as dascribad bslbra
•nd etTstaUlssd ito* aathanol. I t darkens at and nsXts a t S38%
y i m 1.63 g. iiiKBs) ,
I6l5(as»id« C-0){ 1595, 1510, 1455 csT^diolol® ring),
Analyaiat Calca. for C M O Ug i C, 68.07} H, 5»00j H,
Vaem&i C, 67,73$ H, 5.04| 9.61.
ifil .^t^ffy^^cff^yl-p-B^l^ffltf ffs
, fMa Gorni ami m9 pr(apmted tijr tli« ehloroeft^yla^lisi of 50.3 g.
(0.4S i9oX«) of idtta £3.7 g. (Q.Sl tsoitt) ef Gtilorono«tyl
ciStorlde an b»for«, «.p. 145®, 35 g. (8156)| llt.ia»p.14i6®
(34b) .
Tha t i t l » eoafwimtS mtt ligr the esond»mfttiott of 6.3 g*
(0.03 w)!®) of ehloroiic«tyl-|s*pli9n»ti<iia0 with 18.1 g. (0.12 Bola) of
n«thyX anthranllata* I t traa ersratallised flt>!B attwnol, ».|>. 155^,
yimU 6 g. (65?i).
jbfuojraiai CaXed. for C^gfi O^Kg t C, 65.84) B, 6.14i K, fi.53.
Potuidi C, 65.86} H, 6.21} 8, d.52.
- 137 -
o- Carbomattooxysphenylfljreifidi;
3.2a (0.01 B»l®) was cjneXiaed la presano® of 0#4i6 g* »ol«)
of aM a fmr drops of nathar^l. Tha ear^xaeida oryatallieod
l oia Bsatbanol. I t ^arltona at mo^ aM laalta at g. i&0%)i
ir(KSr) 3355(laaola KH), 3150(chalftt««l OB), l660{aBido 1570,1505,
1450 ciT^Cinaolo ring).
Anaa^aiat Calod. for ^ ^.90} i , 5*44; H, $.45*
Fottwd: G, 68.95J H, 5.59| H,
11' ^ r^a^M^Mfefe l f r - fTFl i f f i l t i ^ lP t^
Chloroaeetyl etHorida, SO g, (C .031 ooXa) in 60 n l . 0tbar ima
addadt to 27.6 (0.17 mole) of ffiorfbolina in 50 ol» of atber with oooUng
and stirring. A whita |>racipitata of aorphoXina tifydroohlorida atartad
aaparating out* After tl»» addition, tha Mxtura waa atirrad for anothar
30 Mnutaa. 7ba praeipitatad tti»rpl»>Xina l^frdrochlorida waa fLXt«r«d off
and washed with athor. Tha ooabinad atharoal axtraot waa eoncantrat«l
to a thiok liquid, tdiieh waa diatiUad undar raduead praaaura. b.p. 130-135**
at 3 praaaura, yiald 22.7 g. (80$).
• 133 «
fbo above eoaspouodl was •pmptoped b j th«f cora WQafttion of IS.36 g,
(0.07B ml&) of chloroscotyl »rphol4na and 45.3 g. (0.31 i»l«) of
mthgl «nthr«j341ot« with other corboaaHBtditta oxcopt that I t was
f iml ly taken in eKlorofom mrA waohod fro* of unreiiot«4
i»tlirAnilato ^ith nilpimrlje aeid (51) andi with ao^iuia oartionftto 0%)
to ronoird ttorphoMsio* this ssxpholido waa oryataXHaad
yield 14.5
AiwOysist Geled. for * 10.07.
fottinti C, 60.0£| K, 6,495
Xfao op«n oltfiin aaddo, 2,7B g, (6.01 weH*), wa« oyoHsod in tho
proaonea of soiiuM vathoxida praparad frois 0.33 g. (0*614 nolo} of
aodiiaai in banssana to giva tha t i t l o prcduct. I t iraa oryatelliaad froa
athanod a.p. . 169-70®, yiaH I . U (60%).
An^aia i Caled. for t C, 68.40f M* 5.73| 11.38.
founii C, H, 6,20f K, 11.30.
« 139 -
i f ) aonayl €hloro>eet«tft( 35) t
A isisetur* of g. iB&l«) of cMloroseet^ oldorM*
«nd 24 g. of ftlieolsol wm vxm^A get^ljr g» • steasi
bath for mixiutes. tiar<Mict«ii etaoroaeotyl oIsIoHjI* w&« dostroyed
W a^din^ 2 nl. of siAthano}.* th» thiek liquM <iistm«i a t
under 7 preaturt, yi«M e* •
g. (0.28 laole) vm c<»idi9»8«d with
13.1 G. (0.07 sole) of banisfl ohXorcN)0»tfit« AS dasorilM»d bofoFO.
Ctaomfora vm iiidd instead of iMnsano «o th» iK>Xvitnt« fh t «st«r
ex78talXi«ed fre» bengono-pot.cihftr (b.p. ii#|i. TIT®,
yl«M 12 f . (55J0.
Analysiit C«Xed. for C yi ^O^M i C, 68.21 j B, 5.73| K, 4.68.
FoaMt C, 69.10} 5.66{ 4.80.
- 140 -
3c41uoi flHitalt jg* (0*01 8iol»)« ma addad In portien*
to t}o»syX aleobol^ 1*51 e* uele). iilh^ aH 8odii;Ai had r-
reacted with totn®^ etXeoholf m solution of g. (0.01
oH^erboiasthoj^hasylgl^lnd hmzyl «star in 25 as * ot bmteeoe
was ftddfld. fbt reei^ion miMnWi^ Ufts h@at«d <m m steass batli for
15 idnutea snd then r«fXux«d for another idiaatee tmdtr eidisfdmis
eoniSiti^ns. I t i«»m» then eooled^ ilry fttwr u&b added to i t eiid tl^e
sodiUiK ts l t forsed wee fiXti^ad *nd dried, fide eodism ealt vam
dissolved in a lainisun (pantity^ of weter and e«idi£iea in oold with
ecatis aoid. i^ i t s preoipitste vbieh seii&rated out was filtered^
d r i ^ , enil esystalUsed ftoas beaseae-petroletts etbcar (b.p. €0-S0®)»
B.p. 158-3®, yield 1.5 g. ir(KBr) 3525Cin«ole Bg), 3100(eholtted
1720(e«t«r C*0), 1600, 1575, 1500 ©•"''(indole ring).
Aftnlyeiei Calod. for C^ H^ Oyi » C, 71.90| K, 4.90| 5.24*
F«»wllt C, 71.65} H, 4.83| 5.20.
- H % -
fo a adititlon of 3.t g* of l>otiii8iuis in 14 s3l« of absolute
etfeauol «f»3 14 of a t^titlon of 5#5 g. of ©•nitrofeoluen®
iB g. of l ^ s ^ y dii9tm#i dlottgO. oxsnlat* «nd 20 of tolufiw
wm iiMod ttlth eofiaifSf «th«king. toi^emivr* m9
baaotf Murine tlw lutMtiim* f h« mmtt&n tBixturs kept o<r«might
at aiKi tbma at room tt£i§j«nitur« for undtor anbs^reui
coiiiitioiMi* Tiie.pot««»ttti5 salt which ®aparait.«d w t m» 4i«a»lir»(l in
40 lal. of vstsr . f]m ottwrMdl soliatioQ alao «xtr«ot«i tuith 100
of water* fhn aqitiooue aolution vftsbed agftiE with
t h ^ eov»r«di wittt 60 ml. of «th«r and itirr«di with 25 of iSNf aoaitm
lyritrojddo. I t was wathod t h o m i i ^ with «th«r lucti «eldiifi«t with oce*
e«ntr»t«i t^roohlorie eeidi to pB with good cooSli]^. Tho Isrown t i ^
wbieh taparatod cat was «attx«otod with bamsmt md washed with ool4 water,
the bensena extract wae dried ever anbydroiis aMitus eulphate. Seaseae
was distilled off muter reduced {jfeaaare. flMi thick liqpid l e f t wae
eryetalliaed flron bM»Mine-petrol«u» ether (b.p. m p*
y i ^ d 7.1 «. (85?^).
- 14S -
A flolx2tlo& of 0.93 g* (0*01 of aniliio® ia dry vtHwt
ma AMtfd t& A solution of IMolt-So-oarbonr^^ el^orM* in «thtr (pmpared
fiTOB O.S g,, 0*005 iK^a of itei^)* fh« j-ototion
Bdxlura ms lespt for on» esdi & half hours at room i t s^ ra tu ro , fhm
etboF vats rwnoved niiior ttclhioedl pressuro and ttot r«si(tti« nan washed
with iQrtslroehloxie acid sodi no bioarboueto mi vitb
vator* Tim solid nasa uaa driad and ex^irstalXisad ieom 9tkme^p m,p*
yield 0.9 e. lr(K8»') 3335(iiidcao SH), £9t5(ii>do3.e l640(aiaida-
1600, 1590, 1445 oiT^Ciodolo riag).
Aaalyaiat Calcd. for C^ H gOJ t C, H, 5.12| 11.86.
Fourod* C, 76,13} H, 4.96f H, 11.79.
XndoXa»S*earlx)nyl. ehlorida prfl|:ifirad UTobi 0*8 g* (0*005 isola)
of tha oovraaponiing acid was oondenaad with 1*37 i* (0.01 oola) of
p>phfm«tidiaa. tha rasultif^ piroduat was iao3.«t4iKl aa dasoribad abova.
I t was oiyatallisad from athanol, ii,p, 219®, yield 1* g, ir(ttar)
-
3335{ Indole liH)» 2970<iiHtoU CH), 1640{«sld« C-O), 1595, 15t5 ciT^
(ixySola ring).
m a y i a t Cae«. for C^^^^O^g i C, 7S.04| H, 5.75j 9.99.
FouMi C, 72.91 J M, 5.?0j H, 9.72.
wis ps^ared ^ th« ocoidensation of
elOoriao (prtptir^d itom 0*8 g*, 0.005 of
eoiT«ap«milii3ig with laorphoHn®,©.'^ g. (0.01 resulting
loi^e vas Isolftted in ttae usual wm or^arfeeOlieei from etliacol, a.]^. 179 »
3rl«M 0.85 fi. (73i)i ir itW} indole »»># 2960Cii»!lole CH)»
I605{««l<io C-0), 1570, 1450 e»r'{iii<4ol» ring).
Aoiilyalit COcd. for » ^ .81 j H, B, 12.17.
fottodi C, 68.001 B, 6.50J ii, 11.93.
R B F S R g M C B S
t . mwor, tmd Etaeeraiiig, A*» Bar., g 679(13^)$iM<l*«l» 5t7Cl370).
t . 8efl!}rar» A., (1684).
riaeh»r» jl^m., 1t6 (1386)*
4* Eafti'dr A*« Bqt,, 2^54 (13^) •
5. aasyor, 2260 (1880).
6. Hoanuni, itxid.^ ^ M34 (1890).
7. Oansaii pattnt 137,955| 1903, If 116. ^Tsm pat«nt 141>749| 1903 ^ m (1914)1 Abitr., S, 3780 (1914).
a. mjttik,, E,, Bw., 1814 (1098).
9. Holt, S.J, , Kallla, A.S,, O'SiiUliraii, tsa f.W., J.CheiB. Soe*, 1217 (1958}«
10.K«Itn, C.F.Su.f md facrn, K«C«, Soe., ^ 11^ (19^) .
11.0*aulUv«a, S.G., and BaAlw, P.W., Soe,, 876 (1959).
12.Stl«emHi, A., CeitiTt. r«n<i.|» 1£4 (1947)j Bull* Boo. CIhks. FWno*, 651, (1948).
13.Kor»ftld, g.C,, J.Org. Cham., Ife, 806 (1957).
14.Snydor, H.R., •nd Codt, L.P., J.te»,Cht«. Soe., m 96? (1956)| Sehlndl«r, M,, Holv. Ohin. Acta , 2156 (1957)} 0«»igy, Brltt 8C4,237,Hov., 12, 1958 (C.A.,53»7197c).
d 15.3ehi»ax»r, W., Malv.Chia. AoU 1130 (1957)| Sohlirilor, W.,
U.S., 288,3394, April 21, .1959 (C.A., 54i2357r; i
- ( i l ) -
16. PtrklHi Kolainvon il^Oben. Baa*, m* dm).
17* ai«ikl»# K.O., and ibid., (1924).
18. Johnion* lloll«r» «nii iinrmn, J.Aia.Cii«s. Bee., £364 (1947).
19. iTafiot) and ««s«8r, IT.M,, U.S., £a4f|590, 1950(C.A.,53J43O1d).
20. 0.4.« Eoutml* A.P., a .As. Ch«s>. Soe», 37S (1953)*
B., TiHftrahaiw© Jg, 3881 (1967).
0.1., MiUiiua, H.irf.H., gr i t . , Aag., 31, 1960 55i9429»).
S3, f m e h patwit H.15S7, Kov. 1962, (C.A., 58i78l1*)i Freneh potent 1313759, Sm,, 1963, 59i2776h).
U . Wright, U.S., 3503968, 7 S«pt.i967, (C.I., 7J i 132754^).
25. 8«ti«b«t, A.H., K.V.S., Sasiiadri, S., moi^tw, A.*. an<l Mo, M.B.a., Ind. J.Ch««., g, 704 (t970)«
26. Vorlaader, 0. , rniA Shilling, R., Aaa., 301, 351 (1898)j i m , m499(lS98)
27. Vorltndttr, D., and ytti««hr«»n«r, K., S«r., 555 (1900).
28. Sogimi, S.K., ced Osndlj^ft, P.O., €h«at», 139 <1965)| Daniflisr*, F.C., Shamn, and Mttaon, H.K*, X»i«
750 (1962)} F^tigsrft, E.B., Ooliwalu, C.V., B.S., tm^ S«th, 0.x,, J,M«d. Ch«a., I I , 332 (1968)j 0«iri», H.A., Wlntlsrop, S.O., fho»aX, R.A., fi«fT, F., Ch«r«t, U.P,, und Qtadry, fi., ibid 2» (1964).
29. O .ft., and Ai»lr««, J.H., ^•An.Cbttt* Soe,, 286JS (1950).
3D. nob»rt»en, A., J«Ch«m. $oe.« p. 1937 (1927).
31. Chong R., mi Cl»ty, ^.Cheia., 935 (196 7)»
32* Modli 13.7.* AlttMKi, S.E., Kidwui, and ^otmsot), J.Orf. Chfjs., 2228 (IfW).
33. Jiilliwt, m i Pikl, J . , aoc., ^ ?55 (1931).
34. (ft) Seil8fe«laa Biind^h dor l^mieliva Ghmlm 22,463.
(b) Jacobs, «nd Heid«lbarfidr, ft., J . Biel.ClMB*^ gjU t03(19t5).
(o) wad Ki^iftcitao* Fttesaseo, M» Sei., 2X> ""l^t (1956)1 (C.A., 50i13f33«).
35* mi Ehuraeov Sorli^v* Obstioh. KlbiJUs*! ^ I47t (1956)I (C.A., 50t14765«).
36. Bto}J» Ik*, F.^ Vymr, e»l fhitmm, H«lir. Ghiis. Acta , 28, 1452 (1955).
37. Cta%o P.J., Ct»». Soe», ^ 1420 (1944).
[Reprinted from the Journal of Medicinal Chemistry, 12, 1120 (1969).] Copyright 1969 by the American Chemical Society and reprinted by permission of the copyright owner.
Synthes i s of 3-Hydroxy- and 3-Methoxyindole-2-carboxamides and Esters
M.-vhi0N1)r.\ p. 8.\x1':na and Shakt i R,. Ahmed
J)epnnm,ent of Chemistry, Aligarh Mvslim University, A ligarh, India
Receiiied April 14, WnO
8-Alkoxyindo]e-2-carboxylates and -2-carboxamide.s have been shown to possess antienaetic properties.' Most of the compounds studied have alky] or dialkyl-aminoalkyl side chains. In this communication 1hc preparation of some 3-hydroxyiudole-2-caxboxamideR with aromatic side chains is reported (Table I).
T^iu.k I I
•COOCH,
NHCH^COY
Re-M p , crystn" Yield,
No. y ° c solvent % I'orinnla' '
1 N l l P h 146 A 70 2 N i i c , n 4 0 c i i , , - p 1.58 A 66 C„H,8N.,()4 3 NHC6H40C2H,-P 1.55 A 65 C,sH2ON204
4 N p 1.52 A 60 CuH.sNjOl
."3 O C H j P h 77 C 55 C , - H „ N 0 4 " A = Kt.OH, B = M e O H , C = CcHc-petroleum eUier (bp
00-80°) . '' All o o T n p o u i i d s analyzed correct ly for C, H, N .
(b) 3-Hydroxyindole-2-(N-p-methoxyphenyl)carboxamide.— T o a suspension of N a (0.26 g, O.OJl g -a (om) in 20 ml of d r y
T \B]>E I
P C - X
n - ^ c o y Mp, °c 220 2,38 206
169-3 70
176 211 ].-)0
200 21i)
« A = E f O H , B = M e O H , C = CsHs-peti-oleum ef,her (bp 60-80° ) . All t h e analyses wei'e pe r fo rmed for C, H, and N and results were in the range ± 0 . 4 % . ' These cornpounds first darken and then melt..
No. X Y
1 OH'- NHPh 2 OH' NHC6H40CH.,-P 3 OH' NHC6H40C2H-,-?) 4 OH' 0 .") OH OCHiPh 6 OMe NHPh 7 OMe NHCr,H40C,H,--p
s OMe N 0
9 H NHPh 10 H NH(;jt40C2H.,-?, 1 1 I I N 0
Recrystn'* Yield, solvent % Formula ' '
A 58 C,6H,2N202 B 58 C,eH,4N203 B 60 CivH.eNjO;, A 60 C,.,HJ4N20;, C 51 C,6H,3N0., A 52 CieHnNjO, A 54 C,8H„N20. A CMH.eNO,, A 76 C,.,H,2N20 A 71 C. iH.eNjO,
A 73 CK,H,4N202
Experimental Section®
3-MethoxyindoIe-2-carboxamides (Table I).—Indoxylic es ter was p repared by cyolization of o-oarbomefhoxyphein- lglycine methy l es ter in the presence of NaOMe.^ T h e eslei- was met,hyl-a ted and hydrolyzed wit.h elhanolic. K O H . ' 3 -Methoxyindole-2-carboxyli(! acid (J g, 0.00.') mole) wa.s conver ted to it.s acid chloride wit,h SOCI2 (1.42 g, 0.012 mole) in d r y EtaO. Af t e r s tand ing for 1 hr a t rocmi t empera tu re , EtizO wa.s removed under reduced pre.ssui-e and t h e residual acid chloride was flu.shed wi th d r y EtrjO to remove t h e last t races of SOCU. T h e acid chloride wa.s t,hon taken up in 1512O and treat.ed with ethej-eal P l i N H j (0.96 g, 0.01 mole) . T h e reactio\i mixlm-e was l e f t fo r 1 ..5 hr a t 30°, PJt.jO was removed, and t h e solid residue was washed ( 5 % HCl, 5 % N a H C O s , HjO) , dried, and crystalHzed ( E t O H ) , m p 376°, 0.66 g (52%) . Anal (CicHhN.^Oj) C, IT, N.
3-Hydroxyindole-2-carboxamides (Table I ) .—Chloroacety l der iva t ives of aniines aud benzj ' l alcohol were p repa red by t h e usual methods. ' '
(a) o-Carbomethoxyphenylglycine-yj-methoxyanilide (Table 11).—Chloroacetyl-p-anisidine (6.0 g, O.OH mole) and met.hyl an th ran i l a t e (18.12 g, 0.12 mole) were hea ted on a s team b a t h fo r 8 h r under anhydrous conditions. D r y CcHc (100 ml) was added, and methy l an1,hranilate hydrochlor ide was filtered off. C(,Hc, was then removed imder reduced pi-essui-e and the residue was hea ted again for another 6 hr and t.heii t.he hydrochlor ide was removed as before. T h e hydrochloi ide which separa ted weighed 6 g, i i idicatiug a 90%, completion of t h e rcact^iou. Excess methy l an th ran i l a t e was I'emoved by washing the Cr,llr, layei- wit.h 10%, 11-.SO,, 10';;. Miiil i l / ) . T h e Cr,ll,, was dried, solvent
I'eniovpd, and the resulting auilide was crystallized ( E t O H ) , m p 1.58°, yield 6.3 g (66%). Ann!. (C.jH.sNJOi) O-, H, N .
CsHo, a solut.ion of o-car l jomethoxj 'phenylglyc ine-p-methoxy-anilide (3.14 g, O.OI mole) in l.i ml of d i y CcHc and a few drops of absolute M e O H wei-e added . T h e I'eaction mix tu re was warmed on a wa te r b a t h wit.h shaking for 30 min and then refluxed for 40 min under anhydrous condit ions. Af t e r cooling, dry E t 2 0 was added, t h e N a salt was filtered a n d dissolved in a l i t t le cold H2O, and t h e solution was acidfied wi th cold AcOH. T h e car-boxamide which sepai-ated as a wh i t e p rec ip i ta te was filt.ered, dried, and crystallized ( M e O H ) , m p 238° (darkens a t 225-236°) , yield 1.63 g (58%) . Anal. (C,cHi4N203) C, H, N .
T h e compounds listed in T a b l e I were prepai 'ed b y convei'sion of indole-2-carboxj-lic acid to t,he amides via t h e acid chlorides.
Acknowledgments.—The authors wish to thank the Head of the Chemistry Department for providing the necessary facilities for this work and the C.S.I.11., j\e\v Delhi (India), for a Junior Research Fellowship (held by .AT. P. S.).
(1) Soci^tlS d 'Etudes scientifiqiies et, indu.strietles de ITle-de-France, French Pa ten t 1527 (Nov 12, 1962); Cliem. Abstr., 68, 7911a (1963).
(2) Melting points are uncorrected. (3) A. Robertson, J. Chem. Soc., 1937 (1927). (4) N. T. Modi, Ph.D. Thesis, Aligarh Muslim University, 1966.
(a) W. A. Jacobs and M. Heidelberger, . / . Biol. Chem., 21, 103 (1915); (b) P. Malatestn and G. Migliaceso, Pnrmaco, lid. Sci., 11, 113 (1956); (c) A. L. Remizov and N. V. Khromov Borizov, Zh. Obnhch. Khim., 26, M71 (19,56).
Reprinted from the Indian Journal of Technology, 1971, Vol. 9, No 1, pp. 37-38
Catalytic Hydrogenation of 2,6-Dinitro-/>-cresol
MAHENDRA P SAXENA & SHAKTI , R . AHMED
D e p a r t m e n t of Chemistry, Aligarh Muslim Universi ty Aligarh
Manuscript received 1 April 1970
The preparation of the derivatives of 2,6-diamino-p-cresol from 2,6-dinitro-p-cresol prepared by the nitra-tion of the acetyl derivative of p-cresol followed by alka-line hydrolysis is reported.
' ^ H E compound 2,6-diamino-^-cresol, an important dyeing material for leatheri is prepared by the
reduction of 2,6-dinitro-/>-cresol with tin and HCP. In this communication, its preparation from 2,6-di-nitro-^-cresol by catalytic hydrogenation under dif-ferent conditions is reported.
Nitration of the acetyl derivative of ^-cresol with fuming nitric acid (2-6°) yielded 2,6-dinitro-^-cresol as the single product. This was a distinct advantage over direct nitration^, which leads to a mixture of products or the cumbersome nitration of ^-cresol-3-sulphonic acid« by nitrous gases. Catalytic reduc-tion of 2,6-dinitro-^-cresol and its derivatives was carried out as shown in Scheme 1. In all these cases, 2,6-diamino-^-cresolwas isolated as its acetyl deriva-tive in view of the ready oxidation of the free base.
2,(i-Dinitro-p-cresol (I) —Cold acetyl-^-cresoP (26 g) was added dropwise to cold stirred HNOj (density 1-5; 86-6 ml) keeping the temperature in the range 2-6°C. After the addition, the reaction mixture was stirred for another 30 min and then poured on crushed ice. The substance which separated out was washed with NaCl-saturated water to neutral pR, ether was removed, and the residue was reiiuxed with KOH (5%, 25 ml) and aqueous MeOH (50%,
CH3
id) Fuming HNO3 f'^ (I) Ag-Salt '(IDAIc OAC OH ACHJCsHJ,
^ PIDJ/Hj „VO'
A C H N
AcHN-Vf^NHAc OH Scheme 1 — Catalytic reduction of 2,6-dinitro-jf-cresol
I N D I A N J . X E C H N O L . , V O L . 9 , J A N U A R Y 1971
50 ml) for 45 min. Methanol was removed and the residue was acidified in cold with HCl to pH 2-3. The brown tar was again extracted with ether, washed with water, dried (NagSO^) and after removing ether, the residue was crystallized from benzenc-hexane or alcohol as yellow needles (20 g, 65%); m.p. 83°C (literature* m.p. 84°C) (Found: N, 14-20. CvHeNaOs requires N, 14-14%).
2,6-Dinitro-p-cresol benzyl ether (II) — Dinitro-p-cresol (I) (3-69 g) was dissolved in ammonium hydroxide. After removing excess of ammonia, a saturated solution of silver nitrate (4-2 g) was added. The red coloured silver salt (2-5 g) precipitated out, which was filtered, washed with benzene and dried. The silver salt was refluxed with benzyl chloride (1-26 g) in absolute ethanol for 8 hr. Then alcohol was removed under reduced pressure, the residue dissolved in ether and washed with NaOH (5%) and water. After removing ether, excess of benzyl chloride was removed by steam distillation. The residue was crystallized from benzene-petroleum ether (60-80°C) (1-2 g, 53%); m.p. 110-11°C (lite-ratures m.p. 109°C) (Found: N, 9-69. Ci4Hi2N206 requires N, 9-72%). Dinitro-^-cresol (0-2 g) was recovered from NaOH solution on acidification.
Reduction of 2,(i-dinitro-p-cresol with PtO^ in acetic anhydride — Dinitrocresol (0-4 g) was taken in acetic anhydride (2 ml) and reduced with hydrogen at atmospheric pressure in the presence of PtOg (0-05 g). In all 140 ml of hydrogen was absorbed. The catalyst was filtered off, acetic anhydride removed under reduced pressure, and the residue crystallized from alcohol to give compound I I I (0-45 g, 85%); m.p. 227-8°C (literature^ m.p. 227-8°C).
Reduction of 2,6-dinitro-p-cresol benzyl ether with PtO^ in acetic anhydride — Compound II (0-62 g) was shaken in acetic anhydride with PtOg (0-05 g) under hydrogen at atmospheric pressure. When there was no further absorption of hydrogen (160 ml Ha was absorbed), the catalyst was filtered off and the product crystallized from ethanol as white needles (0-42 g, 80%); m.p. 228°, m.m.p. with III
227-8°C (Found: N, 10-51. CioHieNaO^ requires N, 10-60%).
Reduction of Ifi-dinitro-p-cresol benzyl ether with Raney nickel — Alcoholic solution of compound II (1-15 g) was reduced with hydrogen at 50 Ib/sq in. in the presence of approximately the same quantity of Raney nickel. After shaking for 4 hr the contents-of the bottle were quickly filtered into excess of acetic anhydride. The filtrate along with acetic anhydride was evaporated off under reduced pressure,, the sohd residue washed with water, dried and crystallized from benzene-hexane or alcohol as white needles (1 g, 80%); m.p. 185-6°C (Found: C, 69-10; H, 6-40; N, 8-88. CigHjoNA requires C, 69-21; H, 6-45; N, 8-97%).
Hydrogenolysis of diacetyl derivative of 2,6-diamino-p-cresol benzyl ether (IV) — Compound IV (0-625 g) was shaken with palladium charcoal (10%, 0-1 g) in alcohol under hydrogen at 40 Ib/sq in. for 4 hr. After removal of the catalyst the diacetyl derivative of 2,6-diamino-^-cresol was crystallized from ethanol-benzene (0-4 g, 90%); m.p. 225°C (literature^ m.p. 22$°C) (Found: N, 12-47. C11H14N2O3 requires N, 12'60%). This diacetyl derivative on shaking with acetic anhydride in ethanol gave compound I I I ; m.p. 227-8°C. Hydrogenolysis of compound IV with • Pd/C in acetic anhydride gave directly the triacetyl derivative (III).
The authors are thankful to the Head of the Chem-istry Department for providing the facihties and the Council of Scientific & Industrial Research, New Delhi, for the award of a fellowship to one of them (M.P.S.). References I. HOCHSTER, F., Beilsteins Handbuch der Organichen Chemie,
Vol. 13 (t supplement) , 230. 2. PROMM, E . & EBERT, R . , J . prakt. Chem., 1 0 8 (1924 ) , 8 3 . 3. p R i s c H E , P., Justus Liebigs Annln Chem., 224 (1884), 138. 4 . DATTA, R . L . & VARMA, P . S . , / . Am. chem. Soc., 4 1 (1919 ) ,
2041. 5. VoGEL, A. I., A textbook of practical organic chemistry
(Longmans, Green & Co., London), 1956, 682. 6. FRISCHE, P., Justus Liebigs Annln Chem., Hi-