ad 6 - dtic.mil aminomethylation of ferrocene to form n,n-dimethyla-minomethylfer-roce aind itb...
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AD29 _6
ARMED SERVICES TECHNICAL iNFORMATION AGENCYARLINGTON HALL STATIONARLINGTON 12, VIRGINIA
UNCLASSIFIED
NOTICE: When government or other drawings, speci-fications or other data are used for any purposeother than in connection with a definitely relatedgovern-ent procurement operation the U. S.Govertment thereby incurs no responsibility nor anyobligation whatsoever; and the fact that the Govern-ment may have fomuated, furnished or in an y waysupplied the said drawings, specifications, or otherdata is not to be regarded by implication or other-wise as in any manner licensing the holder or anyother person or corporation, or conveying any rights,or permission to manufacture, use or sell anypatented invention that may in any way be relatedthereto.
NOT R ELEASABLE
T0 OISDepartmenit or chemistry
f Duke University
Cq Durham, North Carolina
c -in& R-port
CertAin Reactions of Organoietal1ic
C.) c:r: Compounds and Some Cy)clizat ions
Contract No. DA-36"O3d-O0D-2O11
forthepelod1 eptember I95 -31 ecember 1962
Submitted byCharles R. Haus erChief Investigator
NO OTS
The first Sectioft of this report lists the titles thereports issued during the period 1 JUl1Y 1955- i 311 Augut1959. The second section lists additional. repor-ts issuedduring the latter part of conitract along- with a dsuss3Inof work still ina progress.
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1. Acylatious of Nitriles with Esters by Sod-ium Amide in Liquid AuMonisato, Form:0-etonitrilles6 Consideration of Amide Formtion, by CharlesJ6 Eby, and Cf.R. Haner, in .1 An Chm So 79 (1957), p 723-725.AD-13 00A&
2. Cycijation of O-Ktoitviles or p-Ketoamides Vith Ketones byPolyphospoic Acid to I irfu gubtituted 2-Pyridontes, by C .R. Hauser
d Charles j,. 9by, in 3 Am 2o Chm oc 79 (1951),p~7871 AD"
~. The Conversion of 0.-Ktonitri'ltes to P46~toamid8 by Boo Fluo ridein Aq:ueous Aetic Acid by Polyphosphoric Acid, by C.R. Hauser andCharmlea 3. Eby, in 3' Am ChniSo 79 (19-57)) p 79&-797- ibse-7 006
4i* Aminomethylation of Ferrocene to Form N,N-Dimethyla-minomethylfer-roceaind Itb Conversion to the orreSPonding Alcohol and Aldehbyde byJacque K.- L-ndsay and C.R. Banner, in J_ ~ hi 2 (1957), "55-358.AD-137 002
5.Certain Acylat±±ons of Ferrocene and Some Condenasations Invol1vingthe a-Hyd ogen of Acetylferrocene, by C .R * Hauser and Jacque KLindsay, -in J 9M Chm- 22 (1957), p I482" 8. AD-137 007
6. Some Typical Aldehyde Addition -and Condensation Reactiow~of Forinyl-ferrocene, by C.R. Bauser and Jacque K. Lindsay,. in J hm22(1957), p 906-90. AD-137 008
7. N=-nd C-3enzoylation of p-minoacetophenone with Mthyl Benxioateby Sodlum Aide. Synthegis of P Diketones Waving p"Aqyl*;ino and
plyzOxy oupo, by C.R. Bagger and Chwles 3'. Eby, in J jChaan22 (957, p909"912. AD-l37 Oil
81. ANovo! Ring inr net Involving the ortho $mbtitution Rearoangepnent by Means of So ium Amid. in Li-quAANZonia, by Daniel L4iceiAn4 P.R. hauser, 1.n J Am Ce 422c 79 (1957 ), P 199"4-51. AD-137 012
9. 0-om eActious of the Xottiodlide of NNi-Diinetylainuoueth+.-ylerroone,by 0.R. Rawer ad Athera. ()s sub to hi)
1443-C
10. Certain Alklations vith the Methiodide of Nj,N-Detbyiaminomethyi-.ferrocene. Synthesis of an *.*Amino Acid Awing the FerroceneGroup, by C. &,user and Iacoze K, -Lindsay, in 0 Ce 22 (1957),p 12-46-1247. AD-137 013
U, . Rearrangemfenlt of 2, 4 ,o6 rfriioprpy-benytrimthyla.-moni-um on b-ySodium Amide to ForM an Mo-Methy~enecycohexadieneamine and ItsReactions- by Donald X. VaEnam and C .A. Blauser, in, J A mgaoc 79 (195-7), p5 -50-5524. AD-15 014
12.i Reaction, of 9-fromoethylofefluorenei with Potassium .Aside inivuid Ama-oni Z a O Dimeri ati--n- by- C.R. Hauser and Daniel Ledniaer,
in J 2M Chem 22 (1957),j p 12 .81Z50. AD -iS-3, 015
15. Conjuga&te Addition Condensations of Diphenylmethane Involving Mths-ylene Hydrogen, by Potassium Amide. Cyclizations of ProdUcts byPolyphospboric Acid, -by Ma.vin T. Tetenibaum and C.R, Hauser, inJ ~ hm2 158), p 229"255. AD.-137 067
14. Condesations of Benthy-dryl-Ithyl Ethe In volvinhg a-Hydrognb
Potassium Am-ide. CycJlizationi of Conjugate Addition Product byPolyphospboric Acid, by Cilt. ilauser and Ma-n .eebauam, inJ 2-: 2h~nj 23 (1958), P 253-235. AD-137 069
15. The ortho Substitution Rearrangemenlt and Certain Rel.ated Reactiornsin the Naplhthylene Series by Sodium Amide, by C.R. fauser,, Donald N.Van Eenam and PhiLlp L, Bayless, inJ9 Ciu 2 (1958), p 354w558. AD-137 070
16. Reaction of the Methiodide of NN-Dilethya noiethylfroane
with Potassium Cyande to Form Fer-rocylacetonitrile, by DanielLdicer, Jacque K. aids an C.R. BauseriJ Chm2(15)
p 653"655. __
17. Rearrangem~ent of the Methiodide of N.N-Diethyla noiethyferrocen,by Potassium Aznide in Liquid Ammonia, by C .R. Hauser Jacque K.Lindsa and Da)iel Lednacer., 1.n J Og C3rn 2(98,p 5-0.AM - 1 - 7 o-6 8_ __
18. Five-" vs. Six-Memnbered Ring Formaion in the Cyclization of 2,.,4-Triphen~1butyric Acid; the Relative Importance of Stereocemistry,by Daiel Ledncer and C.A. Hauser.. in J Am Ch Scem.198)p 34109"34l2. ,l) 401 e(9
19. a, O-DiPhentylbutyronitrile- (Eyh- Ioe), by C .R. Hauser ahd
20. ~,riphenyl rpontie, by C.R6 Hauser and W.R. DwmnaVaIt.(4s &Ub4 to gypSnthesis).
2-1. , -ihenylpropionic AcidI by C .R. Hauser and W.R. Dunnavant.(subto Synthess.
22. ac.gp-,Triphenylpropinic Acid, by C .R., Hauser and W .R * Dunnavant.(Ms sub to J Oraher)
25. Reductive Met-lation of Bentzophenione and Benztacetophfienonte byAlk&ai Met..ls in Liquid Atmonia and Somie Condenuations. of theResulting Dialkcali Salts, byPhllip J. H-anrick, r n ?R aasrin J AMCm So 81 (159), p 4934966
24. Alkylations of Certain Carbaniong with l-Chloro-l, 2-Dephenylethane6P-Eliminations with Other Bases, by C .R. iAusr Charles F. HUserand Phillip J. Hamrick, Jr., in J 23 Ce 2(1958), P 751I.jOi)/'
25. The Benzal Derivative of Fertocenylaetonitrile, by C.R. IH auser andCharles E. Cain, in .1 M Phe32 (1958), p 2006-2007.
26. The Methiodide of N-C if benzyloxy-2, 6-dimethylbenzy )-N, N-Dimethyl-amine. Attempted Rearrangement, by Daniel Lednicer and C .R. HAuser,in i 2M Chei 25 (1958), -p 2008-2009.
27. Rydroxymethyl- and FormyJ~ferrocene with OWcdizing AgentB. Bisfer-rocenyaxetby! Ether, by C . Hauser and Charles E. Cain, in jChem. 25 (1958), P 2007-20)8.
28. FTive- vs. Six-Memlbered Ring Formation in Acid Catayzed CyclIzations.n-. 5,J4-Diphelvalepric Acid and 2,5-Diphenyiglutaric Acid byD)aniel Leduicer and C.A. Hausr (n 958C1e.So6564".6367t- 19-) QiO 64 -, 80(158,
29. The Structure of the Product of the Aniomalou Leckart Reactionof 2-Ferrocylethyamno. A Boute to I,2D -sisiue ercnby Daniel Lednicer and C.R. Hauser, -in jg-rChern 21 (1959)1, p 4w6Al) /j/c5(/e?
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30. Addition Adetions of the Methiodide of Benzo-phenoznethyli-mite WidItts 4.Methyl Anaogue, with Nucleophilic Reageifta, by C.RA. Hauserand Daniel Lednicer, in J Chm 214 (1959), p 46"1496
51. N-ercl~h1NNNTintyam~ Iulodide (Mthiodide of~ byc C.H. Hauser. (Ma sub to ggs
13yntei.
52. Two-Fol1d Alkylationa of Sodium Diphenylmethide with Mthy1--h, M -*Halides to Form bis-BenIzhydr-ylinethvlene Hydroarbafns. Alkcylationisot Sodium Tripheftyl-ethide, by C.R Ilusr Char-lea F., Hauser andP5hillip J1. Hamrick, Jr, in 1 h~~ (1959),. p 397"40
Final Report for Contract with Army Research Office (Durham) for
period September 1, 1959 to December 31, 1962
By Charles R. Hauser
Duke Univevzi-y, Durhamj N. C.
"Certain Reactions of Organometallic Compounds and Some Cyclizations
(A) Publications.- The eighteen original articles listed below
were published or were accepted for publication during the three
year and four month period, September 1, 1959 to December 31, 1962.
Fifteen of the eighteen articles are papers, one is a communication
and two are notes, the communication and notes being indicated.
Ten of the articles were supported wholly by the Army Research
Office (Durham)), and five in part by this Office. Also, five
Preparations were published in Organic syntheses; these are listed
under titles 19-23.
1. "Condensation of Phenylacetic Acid with Certain Ketones
to Form aipha-Phenyl-beta-hydroxy Acids by Alkali *miles. Equili-
brium Factors' P. J. Hamrick, Jr. and C. R. Hauser, J. Am. Chem,
Soc., 82, 1957"1959 (April, 1960).
2. "Synthesis of beta-Hydroxy Esters from Ethyl Acetate and
Ketones or Aldehydes by Means of Lithium Amide. Some Results with
other Esters," W. R. Dunnavant and C. R. Hauser, Je Org. Chem., 25,
501-507 (April, 1960),
3. "2-Acetyl-6-methoxycoumaran-3-one. Benzylation at the
Terminal Methyl Groups," W. I. O'Sullivan and C. R. Hauser, J.
Org. Chem., g, 839 40 (1960)(A Note).
-2-
4&. "Certain Condensations at the Terminal Methyl Group of
3 -Phenylpentane-b2,4k-dionte through Its Dipotassio Derivative Cycli-
zations.." W. 1. O'Sullivan and C. A~. Hauser, j. Org. Chem,25
11l0-4114, (July, 19,60).
5. "Factors in Aldol Conde nat ions of Alkyl Acetates with
benzophenone arid -Reversals by Sodium Amide Versus Lithium, Amide.C. R. Hauser and W. R. Dunnavant,
Metallic Cation Effet,"x:63 Org. Chew., 2,5, 1296"1302 (August, 1960
6. "Condensation of' Alkcyl Acetates with Benzophenone by Lithiui
Aside to ForM: beta-Hydroxy Esters. Relative Ease of self-dondensa"
tion of Esters," W6 R. Dunnavant and C. R. H1auser, .1. Org. Chem.,
gj, 169341699 (October, 1960).
7. "Alkali Catalyzed Aldol Condensation of Bisacetylferrocene
with Benzaldehy-de to Form Mono- and Dibenzaldehyde Derivatives,"
T. A. Mashburn, Jr., C. E. Cain, and C. R. Hauser, :. Org. Chem.,
110 1982-4986 (November, 1960).
8. "Acylations of' Bisacetylferrocene with Esters by Potassium
Amide to Form Bis..beta-diketones. Consideration of Mechanism,*"
C. - . Cain, T.- A . Mashburn, Jr. , and C. R . Hauser, J. Org. Chem. , 26,9
l03o-lo34& (April, 1961).
9. "Influence of the Matellc Cation of Certain Organometallic
Compounds on the Courses of' Some Organic Reactions," W. 1. O'Sulliva
F. W.Sae:W .Hmphlett, and C. R. Hauser, J. Org. Ce. 6
2306-2310 (July, 1961).
10. "some Condensations at the Methylene and Terminal Methyl
Groups of Benzene sulronylace tone Through its Mono- and Dipotassio
Salts.." W. I. O'Sullivan, D, F. Tavares and C. R. Hauser, J. Am.
Chew. Soc., 9-I 3453"3457 (August, 1961).
-3-
11. "Reactions of Alkali Diphenylmethides with Certain Poly-
halides. Displacement on, Halogen or Hydrogen"' C. R. Hauser, W. 0.
Kofron,. W. ft. funnavant, and W. F. 0Owenz, J. Org. Chem., 293 2627-
2629 (August, !961).
12. "2 -w 3-, and 4-ithiobenzyldimethylamines. Grignard
!Reagent of -rmbnydmtyann, P6 N. Jones and C. R. Hauser
J. Org. Chem., 2 -7, 701 (October, 1961) (A Communic-ation) .
1.3. "Acetylation of Benzenesulfonylacetone with Acetic- An-
hydride by Means or Boron Fluoride to Form the Terminal Methyl
Derivative,"e D6 P. Tavares, W. I. O'Sullivan, and C. Ri Hauser,,
Jo Org. Chem., 27, 12,51-1254 (April, 1962).
14. "Ortho-Substitution Rearrangement vs. Elimination Reactic
of Certain Benzyl-Type quaternary Ammonium Ions with Sodium Amide,"
F. N. Jones and C. ft. Hauser, J. Org. Chem., 27, 1542-1547 (May,1962).
15. "Synthesis of 3-Substituted 3-Phenylphthalides," F. N.
Jones and C. R. Hauser, Jr. Org. Chew., 27, 3364 (April, 1962)
(A Note).
16 "rto ubsttto Reragement vs. Elimination Reactior
or Ring-osubstituted Benzyldimethylethylammonium, Ions," F. N. Jones,
and C. R. Hauser, j. Org. Chem., ~,k2O~I Nvme,16)
17. "Halogen-metal Interchan e of 2-, 3-", and 4-Bromobenzyl-w
dimethylamlnes with n-B$utyllithiumq Orignard Reagent of 2.-Bromo-s
benzyldimethylamine," F. N. Jones and C. R. Hauser, j. Org. Chem.,
(in Press).
i."Metalations of' Be nzyldimnethy lamne and Related Amines
with no-Butyllithium In Ether. Deuteration to Form, Ring and Side".
chain Derivatives,." P'. N. Jones,, M. P. Zinn, and C. R. Hauser,
J. Org. Chem., (In Press).
19. a, a ,0-TR IPHE NYLPR OPIONIMUMILEj C. R. Hauser and W. R.Dunnavant, Organic Syntheses, 39-, 73-7 15)
20. NNDMTftAMNEhLEROEEMBTHIODDE, D. Lednicer
and C. R. Hauser, Organic Synthetss 4f 0, 3-1--3- (-196)
21. aI$ DIPHENYLPROP IONT C ACID, C. R, Hauser and W. R,
Dunnavant,, Organic Syntheses, 4Q, 38-40 (1960).
22. FERROCENYLACETONITRILE, D. Lednicer and C. R. Hauser,
Organic Syntheses, 402 45-k6 (l960).
23. HYROXY14ETHYLFERROMEE, L. Lednicer, T. A. Mashburn.. Jr.,.
and C. H. Hauser, Organic Syntheses, 40, 52-53 (1960).
(B Work in Progress.- This work Is considered below under
appropriate titles (i-4). The completeness of' each of the problems
is indicated in the outline. We anticipate that these problems
will be completed under the new grant.
1. "Condensation of Aldehydes, Ketones and Other Compounds
at the Ortho Position of Benzyldimethylamine and Related Amines by
Means of' n-Butyllithbium."
BenzyldImethylamine was converted by n-butyllithium In ether
to the ortho lithio intermediate I, which was condensed with
benzaldehyde and certain substituted benzaldehydes to form II and
with benzophenone and acetone to give IMI The yields were good.
-5
CH~C~ CH2 N(C HS) MN s
O1H
Also, I was condensed with benzonitri-le to af'ford IV (%)and
with cyclohexene oxide to give the ortho derivative V (36%).
KNCH2N(CHC)2 cN(CH3) 9
TV V
Simiarl dibnzymetylamine was metalated with n-butyllithium
to form the ortho lithio intermediate VI, which was condensed with
benzaldehyde to give the Qrtho derivative VII (56%).
CH2 CH2CSHS CHSC
Li CH I
VI VII
jLikewise c,a-dimethylbenzyldimethylamine was metalated with
n-butyliithium to form3 the ortho lithio intermediate VIII" which
was condensed with benzophenone to give IX (57%).
"6
~~~C (ci3)2 g~H)N~H, L!
OH
ViII Ix
Certain other metalations and condensations have been effected
but the structures of the produets have not yet been established.
Some related reactions are contemplated,
2. "Condensations of Aldehydes and Ketohes at the Side-chain
of 2-Methylbenzyldimethylamine and Related Amines by Means of n-
Butyllithium."
2-Methylbenzyidimethylamine was metalated at the methyl side-
chain with n-butyllithium in ether to form the lithio intermediate
I, which was condensed with benzaldehyde, acetone and benzophenone
to give, fcr example, II. Mixtures of products were obtained with
the first two compounds but benzophenone afforded ii in 82% yield,
though the structure of this product has not yet been definitely
established.
-Hg OH
CHgC'(C8H8)2
CH2 1 OCHN(CHs) 2
Similarly 2,3-dimethylbenzyldimethylamine was metalated with
n-butyllithium to form III, which was condensed with benzophenone
and acetone to give IV where R 1s phenyl and methyl, respectively.
The yields were good.
-7-
CH3 H CH-3 OH.. ' w NG Z ,H 2COR2
-9(,C'CH(0 A3) 9H9
Also tertiary aMine V was Metalated with n-butyllithium: to
form apparently V! which reacted with benzophenone to give VII (35%)
though the structure of this produot has not yet been established.
Li
C'B5CHCH2CH9(C-3)9 C&H5CHCHtiC-H2N'(CHS5 CHCC 20H9N(HO
V VI VII
Purther studies are being made on such sideo-chain metalations
and condensations.
3. "Carbonyl Versus Conjugate Addition of Dipotassio-O-Di-
ketones with Cinnamic Esters."
It has recently been shown that dipotassiobenzoylacetone under-
goes carbonyI addition with chalcone but conjugate addition with
2,'&,6-trimethylehalcone (Re J. Light, T. MI Harris and C. R. Hauser,
J. Org. Chem., 26, 1344~ (1961)).
It has now been found that dipotassiqbenzoylacetone can be
made to undergo either carbonyl or conjugate addition with cinnamic
esters, the course of reaction depending on the R group in the
alkoxy or aryloxy portion of the ester I. Thus carbonyl addition
occurs with phenyl cinnamate to form II (550), whereas conjugate
addition takes place with t-butyl cinnamate to give III (70%).
Both courses of reaction occur with methyl cirmnamate.
CeH9CHCHCOOR CaHsCH&CHCO7CH2 C!OCH9COC6 HS CesSK-CH20C( CHs)sCH2 COCH2COC.5H6
The structures of the products are being established, and
certain related reactions are being studied.
4. "Reactions oD l,l-&Dichloro-2,2-diphenylethylene with
Nucleophilic Reagents. "
ljl-Dichloro-2,2 -diphentylethyleneiL (1) has been found to react
with potassium amnide in liquid a-mmicania to form diphenylacetonitrile
(1!, 90%) but with phanyllithiumn in ether to give tolante (i,67%)
and chlorobenzente (?1%).
(C.H5 )2C4Ccl2 (Can 5)gCHCN CeH 5C IS
The Dormer reaction appears to involve substitution at the
vinylic carbon to Dorm IV, which undergoes B-elimination to give V
and subsequently the anion or II. The reaction with phenyllithium
evidently involves displacement on halogen to Dorm chlorobenzene
and carbanion VI, which undergoes rearrangement to afford tolane.
(ces) 2C=c-Cl (cSH4I) 2C=C9NH (cOnS)2c=Z-ClNH2
IV V VI
The reactions of I with certain other nucleophilic reagents
are being studied. Also certain related reactions are contemplated,
(C.)Resah- Persone Iand, Dere wared The f ollowing
graduate s tudents were supported on the cont-r'2ct for a few months
to a year:e W. R. Dunnavant, F. N. Jones, T. A. Mashburn, and
Re. Li Vaulx. The first three of these men c~ompleted the research
for the Ph.D. thesis while on the contract. The last man is pre-
sently a third year graduate stude-it who has been on the contract
since last September.
The followirZ t c.: fc;.Jows were supported on the
contract for a y'~each: W. ii o~Fsullivan, D. F. Tavares,
P. N. Jones "crd F~. B. Kirby. DC. -i the acadernic year,
Drs. O'Sullivan and Jones were supported partly by Duke University,
since they were part-time instructors of chemistry. This made
contract funds available for securing Dr. Kirby, who started work
last January (1962).