Indian Journal of Chemistry Vol. 38B, June 1999, pp. 648-656

Synthesis of thienospiran derivatives and studies of regioselectivity in Friedel­Crafts acylation reaction

P K Sen*, Uttam Kumar Saha & Tulika Das (nee Deb) Department of Chemistry, Presidency College, Calcutta 700 073, India

Received 10 February 1999; accepted 21 April 1999

Syntheses of several spiro[benzo(b ]thiophen-6(5H), I '-cycloaIkan]-4(7 H)-ones (Type A) and spiro[benzo[b ]lhiophen-5 , I '-cycloalkan]-4(5H)-ones (Type B) and their 2-alkyl derivatives are described. The regioselectivity in the Friedel-Crafts acylation of thiophenes with anhydride of various unsymmetrically substituted succinic acid having substituenl(s) at the same carbon atom in two different solvents namely dichloromethane and nitrobenzene is studied. A plausible explanation of such regioselective acylation of thiophenes has been incorporated.

In Friedel-Crafts type acylation of aromatic hydrocarbons by dicarboxylic acid anhydrides constitute an important step to build up six- or seven­membered ring onto an already existing aromatic systeml-5• Insertion of a monosubstituent in succinic acid anhydride leads to a mixture of isomers in the Friedel-Crafts acylation in most cases_ The ratio of the isomers depends on the reactants as well as on the reaction conditions6.

This paper deals with the synthesis of thienospiroketones of the types A and B and also with the regioselectivity in the Friedel-Crafts acylation of thiophenes with anhydrides of several unsymmetrically substituted succinic acid having substituent(s) at the same carbon atom in different solvents.

The procedure adopted for the synthesis of 4,5,6,7-tetrahydrobenzo[b ]thiophene derivatives including thienospiroketones of the types A and B is depicted in Scheme 1 . When 2-methylthiophene (1; R=Me) was acylated with methylsuccinic anhydride (2; RI=H and R2=Me) in the presence of anhydrous aluminium chloride, we might expect a mixture of isomeric keto acids (3a; R=Me and 4a; R=Me). We reported? the keto acid (4a; R=Me) as the major product when nitrobenzene was used as sol vent. Later when the same reaction was carried out in dichloromethane, 3a (R=Me) with alkyl substituent away from the carboxyl group was isolated as the major product. The structure of 3a was confirmed by spectral analyses and its conversion to the cyclic ketone (7a; R=Me) by Clemmensen reduction fol lowed by cyclisation with polyphosphoric acid. The appearance of a triplet at 0 4.75 (1=6 Hz) attributable to C4-H in the I H NMR

. 0

r-0 Rt

R�S�R2

(A) R = H or alcyl RIR2 - �(CH2)4- and -(CH2)5-

x:&0 RI

I I R2 R S

(B) R = I-l or alkyl R I R2 = -(CH2M- and -(CH2)5-

spectrum of the alcohol (9a), the sodium borohydride reduction product of the cyclic ketone (7a; R=Me), provides the necessary support for the position of the methyl substituent; 6-position in 7a and consequently 3-position in 3a. Therefore, 3a (R=Me) which is the precursor of 7a (R=Me) is discernible with 3-methyl-3-(5-methyl-2-thenoyl)propanoic acid.

The above regioselectivity in the acylation of 2-methylthiophene (1; R=Me) with methylsuccinic anhydride (2; RI=H and R2=Me) in two different solvents namely, nitrobenzene and dichloromethane, actually created much interest to study the reaction with similar other substituent(s) attached to the acylating agents. In order to test the generality of the above observation, Friedel-Crafts acylation of thiophenes with several unsymmetrically substituted succinic anhydride was studied.

When a,a-dimethylsuccinic anhydride (2b; RI=R2=Me) was treated with 2-methylthiophene

SEN et al.: SYNTHESIS OF THIENOSPIRAN DERIV ATIVES 649

o� �H o C n-'t-RI

IV "-s/y'-R2

3

0"" o/OH """ c

° n l �, RAS�2 5

1 (U)

'o � RI R�S�2 7

+

A(;I)

2

o� /OH o

C RI A(;i) •

on '[(R2 PhNOz R�� 0

o 0 4

0 1 (i)

6

I I�/:� R)QIJ

o 8

For 1 and 3-8 : R = H or alkyl and iJr 2-8 : (a) R I=H, R2=Mc

(b) R I=R2=Me (c) R IR2 = -(CHZ)4-(d) ){ IR2 = -(CHzh-

Reagerts : (i) Zn'H& HCI (iI) PPA

Sch�me I

(1 ; R=Me) n the presence of anhydrous aluminium chloride, the keto acid (4b; R=Me) was obtained in 58% yield in n itrobenzene solvent, whereas the isomeric keto acid (3b; R=Me) was obtained in 72% yield when the same reaction was arranged in dichloromethane. In order to confirm the structures of 3b (R=Me) and 4b (R=Me) both of them were separately converted to the cyclic ketones (7b and 8b) . The appeara!lce of two two-proton singlets at 8 2.35 and 2.80 in the ' H NMR spectrum was assignable to the hydrogens at the 5- and 7-positions of the cycl ic ketone (7b; R=Me); whereas its i somer 8b (R=Me) did not show any singlet in the above regions. Instead, two two-proton triplets appeared at 8 2.05 (1=7 Hz) and 3 .00 (1=7 Hz), which were assigned to the hydrogens at the 6- and 7-positions respectively.

When 2-methylthiophene (1 ; R=Me) was acylated under Friedel-Crafts reaction condition with cyclopentan- l -acetic- l -carboxyl ic anhydride [2c'

I 2 · '

R R = -(CH2)4-] In the presence of anhydrous

R)

� RI R�S�R:!

09 .J R-Mc. R I�I( R2-�1e and 1<.3-011 bJ R-Me, RIR2. ·(CH2J4· and RJ.on cJ R-Me, R IRZ_ -(C-H2.1;· and RhOl1

o

R'iIv::

o�S�l 10

a) R=Me. R 1R2= -(Clhk. R3 = Br2 aro R4=Br b) R=Mi:. RIR2= -(CH2)S-. R3=Dr2 and R4=Br

c) R=Dr, R IR2= -(CH2k. R3=Br2 and R4=H

d) R=R4=Br. R 1R2= -(CI-hk aro RhBr2 e) R=Br.R lR2= -(CH2)s-. R3=Br2 aro R4=H

f) R=H, R lR2= -(CH2k. Rh >CIlOH aoo R 4=H

g) R=Me. R lR2= -(CH2k. R3= >CHOH aro R 4=H

h) R=&' R lR2= -(CH2k. R3= >CHOH aoo R 4=H 0

Q R=Me, R 1 R2= -(CP2)s-, R3= >CHOH aro R 4=II j) R=H. R lR2= - (CH2k, Rh -CO:!Et and R 4=H

k) R=Me. R IR2= -(CII2k: R3= -COzEt and R 4=H

1 1 a) R=H, R lR2= -(CH2)4-. R3=OH b) R=Me. R 1 R2= -(CH2)4-, R3=OH

aluminium chloride in nitrobenzene solvent, the keto acid (4e; R=Me) was obtained as the major product in 69% yield. The same reactants gave 75% yield of the isomeric keto acid (3c; R=Me) as the major product in dichloromethane solvent.

It was difficult to distinguish between the two isomeric keto acids (3c and 4c) obtained from the Friedel-Crafts acylation in the two different solvents from their IR and IH NMR data. Neither of the proton signals could be unambiguously ascribed to either of the methylene protons of acetic acid moiety of the �­cycloalkylated isomer (3e) nor the ketomethylene group of a-cycloalkylated acid (4c). The structures of 3e and 4c were established through the 'H NMR spectra of the corresponding cyclic ketones (7c and 8e) derived from the keto acids (3c and 4c) through Clemmensen reduction followed by cycl isation with polyphosphoric acid. This was further substantiated by derivatisation of 7c. Reduction of the cyclic ketone (7c; R=Me) with sodium borohydride furnished the secondary alcohol (9b), which showed a one-proton

650 INDIAN 1. CHEM. SEC. B, JUNE 1 999

10.

triplet at � 4.7 (1=6 Hz) due to the hydrogen at the 4-position in the I H NMR spectrum.

Bromination8 of 7c (R=Me) in ethereal solution with excess bromine in carbon tetrachloride afforded the tribromo derivative (lOa) which showed no proton signal corresponding to C3-H and C5-H. The structure of lOa was further supported by the mass spectral " analysis which showed the appearance of peaks at rnIz 454, 456, 458 and 460 corresponding to M+ (molecular ion), M+2, M+4 and M+6 respectively in addition to a characteristic retro Diels-Alder fragment Fl (rnIz 2 1 6) .

Formylation of the cyclic ketone (7c; R=Me) with sodium hydride and ethyl formate in sodium-dried benzene under nitrogen atmosphere gave the product 109. The formyl derivative (lOg) showed no signal in the region due to hydrogen at 5-position. Instead, the appearance of a one-proton doublet at � 1 4.60 (J= l O Hz) proved the predominant existence of the hydroxymethylene form.

Carbethoxylation of 7c (R=Me) with sodium hydride and diethyl carbonate in sodium-dried benzene furnished 10k. The IH NMR spectrum of the �-oxoester (10k) showed a two-proton quartet at � 4. 1 6 (J=7 Hz) and another three-proton triplet at � 1 .26 (1=7 Hz). Al l these observations conclusively established the cyclic ketone as 7c (R=Me), which in tum confirmed the structure of the keto acid (3c; R=Me) as 1 -( 5-methy 1-2-thenoy l)-cyclopentanacetic acid. The same trend in regioselectivity was also observed in the acylation studies of thiophene and 2-ethylthiophene with cyclopentan- l -acetic- l ­carboxylic anhydride [2;RIR2= -(CH2)4-]'

When an ethereal solution of 7c (R=H) was treated with excess bromine in carbon tetrachloride a tribromo derivative (lOc) was formed though a tetrabromo derivative (lOd) with the fourth bromine atom at the 3-position was expected. The structure of the bromo derivative (lOc) was confirmed by spectral analysis.

Interestingly, when nitrobenzene was used in p lace of dichloromethane the other regioisomeric keto acid [4c; R=Me and R I R2= -(CH2h-] was obtained in a major amount in the Friedel-Crafts acylation reaction of 1 (R=Me) and 2 [RIR2= -(CH2)c]. The structure

of the keto acid (4c; R=Me) was confirmed by I H NMR spectrum of the corresponding cyclic ketone (8c; R=Me). A two-proton triplet at 8 3.00 (1=5 Hz) and another two-proton triplet at 8 2. 1 0 (1=5 Hz) were assigned to the hydrogens at the C-7 and C-6 positions of the " cyclic ketone (Sc; R=Me) respectively. Further, reduction of the cyclic ketone (Sc; R=Me) with sodium borohydride gave the corresponding secondary alcohol (llb) which showed a one-proton singlet at 8 4.00 due to the hydrogen at the 4-position. This singlet conclusively indicated the cyclopentyl ring at the 5-positiolJ in Sc (R=Me) . The same trend was also observed in the Friedel-Crafts acylation studies of thiophene and 2-ethylthiophene with cyclopentan- l -acetic- I -carboxylic anhydride where the cyclopentyl ring in the keto acid [4c; R=H Et and

I 2 '

R R = -(CH2)c] was towards the carboxyl group in each case when nitrobenzene was taken as solvent.

When cyclohexan- l -acetic- I -carboxyl ic anhydride and thiophene were allowed to react in the presence of anhydrous aluminium chloride in dichloromethane solvent, the keto acid (3d; R=H) was obtained in a major amount. The same reaction when arranged in n itrobenzene solvent (Scheme I) afforded the other regioisomer 4d (R=H) as the major product in 63% yield. This trend in two different solvents was observable in other sets of Friedel-Crafts acylation reaction i .e. , reaction between cyclohexan- I -acetic- I ­carboxyl ic anhydride and thiophenes ( 1 ; R=Me, Et). These structures were confirmed by spectral analyses and derivatisation of the corresponding cyclic ketones (7d; R=Me) (vide experimental).

A plausible explanation of the selectivity in the Friedel-Crafts acylation reaction of thiophenes in two different solvents (highly polar and less polar) gets support from the earlier observation6. When nitrobenzene is used as solvent, position that i s ordinari ly subject to steric inhibition is usually avoided. This may �e due to the formation of a bulky

- complex of nitrobenzene, aluminium chloride and the anhydride, which finds an easier reaction path at a lesser crowded position9• Our results on Friedel-Crafts acylation of thiophenes with substituted succinic anhydride in two solvents namely, nitrobenzene and dichloromethane also support the above explanation.

To the best of our knowledge, this trend in regioselectivity of acylation of thiophenes (1 ; R=H, Me, Et) with various substituted succinic anhydrides [2; RI-H R2_M . Rl_R2_M . RI 2 I 2 - , - e, - - e, R = -(CHz)c and R R = -(CH2)5-] in two different solvents has not yet been reported.

SEN et al. : SYNTHESIS OF THIENOSPIRAN DERIV ATIVES 65 1

Experimental Section Boiling points and melting points are uncorrected.

IR spectra (vrnax in cm' l ) were recorded on Pye­Unicam SP 200G, Perkin-Elmer 298 spectrometer in KBr or in liquid films, 'H NMR spectra on Varian 60 MHz, Jeol FX-90 90 ·MHz, Bruker AC-200, DPX­, 300, Gemini-300, Bruker AM 300L Supercon and Varian XL 400- l O33 spectrometers using TMS as internal reference (chemical shifts in 0, ppm) and mass spectra on HP-5995 spectrometer. Solvents were dried following the usual standard procedures. Pet. ether refers to light petroleum, b.p. 60-80°.

Alkylthiophenes and cycloalkyl- I -carboxy- l -acetic acids and their corresponding anhydrides were prepared following the standard literature method. Methylsuccinic acid and a,a-dimethylsuccinic acid of Aldrich Chemical Company were used.

General procedure for alkylation of thiophenes with ' substituted SUCCIDIC anhydride in dichloromethane solvent. To a well-stirred solution of substituted succinic anhydride (0.05 mole) in dry dichloromethane ( 1 25 mL) anhyd. aluminium chloride ( 1 6.6 g, 0. 1 25 mole) was added slowly during a period of 30 min while maintaining the temperature at 0-5°C. After complete addition, stirring was continued for another 1 5 min at the said temperature. Thiophene or 2-alkylthiophene (0.05 mole) diluted with dichloromethane (25 mL) was added dropwise at 0-5°C during 20 min. Stirring was continued for a further period of 30 min at O°C and another 30 min at room temperature. The coloured mass was then decomposed with ice (75 g) and concentrated HCI (30 mL) with vigorous stirring.

The organic layer was separated, washed with water and extracted with sodium hydroxide solution ( 1 0%, w/v). The precipitated solid obtained on acidification of the alkali extract was filtered under suction, dried and crystall ised from benzene solvent to give the corresponding keto acid. Yields, physical and spectral data of the keto acids thus prepared are as

' follows:

3-Methyl-3-(5-methyl-2-thenoyl)propanoic acid (3a; R=Me) , yield 74%, m.p. 1 35-36°C; IR (KBr) : 1 705, 1 650; 'H NMR (300 MHz, CDCh) : 0 1 .20 (3H, d, 1=6 Hz, COCHCH,), 2 .45 (3H, s, ArCH,), 2.90 (2H, t, 1=7 Hz, CH2COOH), 3 . 1 0 ( l H, m, COCHCH,), 6.90 ( I H, d, 1=4 Hz, ArH), 7.50 ( I H, d, 1=4 Hz, ArH).

3,3- Dimethyl-3-(S-methyl-2-thenoyl)propanoic acid (3b; R=Me) , yield 72%, m.p. l O8°C; IR (KBr) :

1 700, 1 650; 'H NMR (300 MHz, CDCI,) : 0 1 .55 (6H, s, COCCCH3)2), 2.50 (3H, s, ArCH) , 2.75 (2H, s, CH2COOH), 6.80 ( l H, d, 1=4 Hz, ArH), 7.60 ( I H, d, 1=4 Hz, ArH).

1-(2-Thenoyl)cyclopentanacetic acid (3c; R=H), yield 76%, m.p. 1 1 9°C; IR (KBr) : 1 700, 1 645 ; 'H NMR (300 MHz; CDCb) : 0 1 .70- 1 .90 (8H, m, cyclopentane ring), 2 .90 (2H, br s, CH2COOH), 7 .0 I ( l H, t, 1=4 Hz, ArH), 7 .60 ( l H, d, 1=4 Hz, ArH), 7.68 ( 1 H, d, 1=4 Hz, ArH) .

1-(5-Methyl-2-thenoyl)cyclopentanacetic acid (3c; R=Me), yield 75%, m.p. 1 22°C; IR (KBr): 1 700, 1 645 ; 'H NMR (300 MHz, CDCI) : 0 1 .60- 1 .95 (8H, m, cyclopentane ring), 2.50 (5H, S, CH2 and ArCH,), 6.78 ( l H, d, 1=4 Hz, ArH), 7.50 ( I H, d, 1=4 Hz, ArH).

1-(2-Ethyl-2-thenoyl)cyclopentanacetic acid (3c; R=Et), yield 7 1 %, m.p. 1 1 0°C; IR (KBr) : 1 700, 1 640; 'H NMR (60 MHz, CCI4) : 0 1 .40 (3H, t, 1=6 Hz, CH2CH3), 1 .60-2.00 (8H, m, cyclopentane ring), 2.78 (2H, s , CH2COOH), 2.90 (2H, q, 1=6 Hz, CH2CH3), 6.75 ( 1 H, d, 1=4 Hz, ArH), 7 .45 ( I H, d, 1=4 Hz, ArH), l O.80 ( t H, br s, COOH).

1-(2-Thenoyl)cyclohexanacetic acid (3d; R=H), yield 75%, m.p. 1 67°C; IR (KBr): 1 700, 1 640; IH NMR (400 MHz, CDCI,) : 0 1 .30- 1 .80 ( I OH, m, cyclohexane ring), 2 .94 (2H, br s, CH2COOH), 7. 1 0 ( t H, br s, ArH), 7.60 ( l H, br s, ArH), 7.78 ( I H, br s, ArH).

1-(5-Methyl-2-thenoyl)cyclohexanacetic acid (3d; R=Me), yield 75%, m.p. 1 23°C; IR(KBr): 1 7 1 0, 1 640; 'H NMR (300 MHz, CDCI) : 0 1 .40-2 .30 ( I OH, m, cyclohexane ring), 2 .50 (3H, s, ArCH,), 2.95 (2H, s , CH2COOH), 7 .28 ( 1 H, d, 1=4 Hz, ArH), 7.60 ( I H, d, 1=4 Hz, ArH).

1-(S-Ethyl-2-thenoyl)cyclohexanacetic acid (3d:

R=Et), yield 75%, m.p. t 29°C; IR (KBr) : 1 700, 1 640; 'H NMR (400 MHz, CDCI,) : 0 1 .28 (3H, t, 1=7 Hz, CH2CH,), 1 .40- 1 .80 ( I OH, m, cyclohexane ring), 2.20 (2H, m, CH2COOH), 2.85 (2H, q, 1=7 Hz, CH2CH,), 6.80 ( 1 H, d, 1=4 Hz, ArH), 7.62 ( I H, d, 1=4 Hz, ArH).

General procedure for acylation of thiophenes with substituted SUCCIDIC anhydrides in nitrobenzene solvent. To a vigorously stirred solution of thiophene or 2-alkylthiophene (0.05 mole) and substituted SUCCIniC anhydride in dry nitrobenzene ( 1 25 mL), anhyd. aluminium chloride was added slowly in parts at O°c. The mixture was stirred further for I hr, . decomposed with ice (75 g)

652 INDIAN 1. CHEM. SEC. B, JUNE 1 999

and concentrated HCI . (30 mL) and then steam distilled to remove the solvent. The crude product was dissolved in saturated sodium carbonate solution, charcoalised and finally acidified with conc. HCI while cooling. The solid keto acid obtained was filtered, washed with water and crystallised from benzene. Yields, physical and spectral data of the keto acids obtained are as follows:

2,2- Dimethyl-3- (S-methyl-2-thenoyl)propanoic

acid (4b; R=Me), yield 58%, m.p; 1 57-58°C; IR (Neat) : 1 695, 1 660; IH NMR (300 MHz, CDCh): 0 1 .40 (6H, s, C(CH3h), 2.55 (3H, s, ArCH3), 3 .20 (2H, s, COCH2) , 6.80 ( l H, d, J=4 Hz, ArH), 7.50 ( l H, d, J=4 Hz, ArH).

1- [(2-Thenoyl)- methyl]cyclopentanecarboxylic acid (4c; R=H), yield 68%, m.p. 148-49°C; IR (KBr) : 1 693, 1 665; IH NMR (200 MHz, CDCh) : 0 1 .40-1 .90 (8H, m, cyc10pentane ring), 3 .35 (2H, s, COCH2), 7.05 ( l H, m, ArH), 7 .70 (2H, m, 2xArH).

1- [(S-Methyl-2-thenoyl)-methyl]cyclopentanecar­boxylic acid (4c; R=Me) , yield 69%, m.p. 147°C; IR (KBr): 1 700, 1 600; IH NMR (300 MHz, CDCI3) : 0 1 .40-2.00 (8H, m, cyc10pentane ring), 2.58 (3H, d, J= 1 .5 Hz, ArCH3), 3 .35 (2H, s, COCH2), 6.68 ( l H, dd, J=5 and 1 .5 Hz, ArH), 7 .58 ( l H, d, J=5 Hz, ArH).

1-[ (s-Ethyl-2-thenoyl)-methyl]cyclopentanecarbo­xylic acid (4c; R=Et), yield 70%, m.p. 96°C; IR (KBr) : 1 700, 1 670; IH NMR (200 MHz, CDCh): 0 1 .3 1 (3H, t, J=8 Hz, CH2CH3), 1 .59- 1 .78 (8H, m, cyc10pentane ring), 2.86 (2H, q, J=S Hz, CH2CH3), 3 .29 (2H, s, COCH2), 6.90 ( l H, d, J=4 Hz, ArH), 7.55 ( I H, d, J=4 Hz, ArH).

1- [(2-Thenoyl)- methyl]cyclohexanecarboxylic acid (4d; R=H) , yield 63%; m.p. 1 38°C; IR (KBr): 1695, 1 655, IH NMR (400 MHz, CDCh): 0 1 .25- 1 .65 ( l OH, m, cyc10hexane ring), 2.00 (2H, d, J=7 Hz, COCH2), 7. 1 6 ( l H, d, J=4 Hz, ArH), 7.60 ( l H, d, J=4 Hz, ArH), 7.72 ( l H, d, J=4 Hz, ArH).

1-[(S-Methyl-2-thenoyl)-methyl]cyclohexanecar­boxylic acid (4d; R=Me), yield 66%, m.p. 1 04-5°C; IR (KBr): 1 700, 1 665 ; I H NMR (400 MHz, CDCh): 0 1 .30- 1 .80 ( l OH, m, cyc10hexane ring), 2.00 (2H, d, J=7 Hz, COCH2) , 2.52 (3H, s, ArCH3), 6.80 ( l H, d, J=4 Hz, ArH), 7.55 ( lH, d, J=4 Hz, ArH).

1- [(S-Ethyl -2- thenoyl)-methyl]cyclohexanecar­boxylic acid (4d; R=Et), yield 62%, m.p. 1 1 2°C; IR (KBr): 1 7 1 0, 1 670; IH NMR (400 MHz, CDCh): 0 1 .35 (3H, t, J=8 Hz, CH2CH3), 1 .20- 1 .70 ( l OH, m, cyc10hexane ring), 2.90 (2H, q, J=S Hz, CH2CH3), 3 .20 (2H, s, COCH.2), 6.80 ( l H, d, J=4 Hz, ArH), 7.60

( l H, d, J=4 Hz, ArH). General procedure for the Clemmensen

reduction of the keto acids (3 and 4) . The foregoing keto acid (0.0 1 mole) was gently boi led with amalgamated zinc ( 1 5 g) and conc. HCI ( 1 5 mL) with a small amount of toluene (2.5 mL) and acetic acid (2.5 mL) for 50-60 hr with occasional addition of conc. HCI (2 mL) after every 5 hr. Usual work-up afforded a liquid which was disti lled under reduced pressure. Yields, physical and spectral data of the corresponding reduced acids are listed below.

3-Methyl-4-(S-methyl-2-thienyl)butanoic acid (Sa; R=Me), yield 76%, b.p. 1 35-36°C/3 mm; IR (KBr): 1 700.

3,3- Dimethyl -4- (S-methyl-2-thienyl)butanoic acid (Sb; R=Me), yield 78%, IR (KBr): 1 700.

1-(2-Thenyl)cyclopentanacetic acid (Sc; R=H), yield 77%, b.p. 1 60-62°/3 mm; IR (KBr) : 1 700; I H NMR (60 MHz, CCI4) : 0 1 .30- 1 .90 (8H, m, cyc10pentane ring), 2.35 (2H, s, CH2COOH), 3 .00 (2H, s, ArCH2) , 6.70-7 .20 (3H, m, ArH), 1 1 .80 ( l H, s, COOH). -

1-(S-Methyl-2-thenyl)cyclopentanacetic acid (Sc; R=Me), yield 88%, b.p. I SO-82°C/3 mm; IR (KBr): 1 700; IH NMR (90 MHz, CDCI3) : 0 1 .80-2.00 (8H, br, s, cyc10pentane ring), 2.30 (5H, S, CH2COOH, ArCH3), 2 .90 (2H, s, ArCH2), 6.48 ( I H, d, J=4 Hz, ArH), 6.60 ( l H, d, J=4 Hz, ArH), 1 1 .20 ( I H, br s, COOH).

1-(S-Ethyl-2-thenyl)cyclopentanacetic acid (Sc; R=Et), yield 78%, b.p. 1 90°CI2.7 mm; IR (KBr) : 1 700; IH NMR (60 MHz, CCI4) : 0 ' 1 .25 (3H, t, J=6 Hz, CH2CH3), 1 .55 (SH, br s, cyc10pentane ring), 2 .30 (2H, s, CH2COOH), 2.70 (2H, q, J=6 Hz, CH2CH3), 2.85 (2H, s, ArCH2), 6 .45 ( I H, d, J=4 Hz, ArH), 6.55 (1 H, d, J=4 Hz, ArH), 1 1 .50 ( I H, br s, COOH).

1-(2-Thenyl)cyclohexanacetic acid (Sd; R=H), yield 7 1 %, b.p. 1 68.:. 1 70°CI l .5 mm; IR (KBr): 1 700; IH NMR (60 MHz, CCI4) : 0 1 .20- 1 .90 ( I OH, m, cyc10hexane ring), 2 .30 (2H, br s, CH2COOH), 3 .05 (2H, br s, ArCH2) , 6.70-7 .30 (3H, m, ArH) .

1-(S-Methyl-2-thenyl)cyclohexanacetic acid (5d; R=Me), yield 76%, b.p. 1 84-89°C/3 .5 mm; IR (KBr): 1 700; IH NMR (60 MHz, CCI4): 0 1 .30-2 .00 ( I OH, m, cyc10hexane ring), 2.40 (2H, s, CH2COOH), 2.50 (3H, s, ArCH3), 3 .00 (2H, br s, ArCH2), 6.55 ( I H, d, J=4 Hz, ArH), 6 .70 ( lH, d, J=4 Hz, ArR).

1-(5-Ethyl-2-thenYl)cyclohexan�cetic acid (5d; R=Et), yield 77%, b.p. 1 90-95°CI2-2. 1 mm; IR (KBr): 1 700; IH NMR (90 MHz, CDCI3) : 0 1 .35 (3H, t, J=8

SEN et al.: SYNTHESIS OF THIENOSPIRAN DERIY A TIYES 653

Hz, CH2CH3), 1 .40- 1 .80 (t OH, m, cyc\ohexane ring), 2.40 (2H, br, s, CH2COOH), 2.90 (2H, q, 1=8 Hz, CH2CH3), 3 .00 (2H, br s, ArCH2) , 6 .60 ( l H, d, 1=4 Hz, ArH), 6.75 ( l H, d, 1=5 Hz, ArH), 1 1 .90 ( I H, br s, COOH).

2,2-Dimethyl-4-(S-methyl-2-thienyl)butanoic acid (6b; R=Me), yield 73%, b.p. 1 1 5°ClO.6 mm; IR (KBr): 1 700.

1-[2-2-Thienyl)-etbyl]cyclopentanecarboxylic acid (6c; R=H), yield 72%, b.p. 1 70-75°C/3.5 mm; IR (KBr): 1 700; IH NMR (60 MHz, CCI4): 0 1 .60- 1 .90 (8H, m, cyc\opentane ring), 2.30 (2H, t, 1=7 Hz, ArCH2CH2), 3 .30 (2H, br s, ArCH2CH2), 7 . 1 5 ( l H, t, 1=5 Hz, ArH), 7 .60 ( l H, d, 1=5 Hz, ArH), 7.70 ( t H, d, 1=5 Hz, ArH).

1- [2-(S-Methyl-2- thienyl)-ethyl]cyclopentane­carboxylic acid (6c; R=Me), yield 82%, b.p. 1 94-97°C/3 mm; IR (KBr) : 1 700.

1- [2-(S-Ethyl-2-thienyl)- ethyl]cyclopentanecar­boxylic acid (6c; R=Et), yield 70%, b.p. 1 80-85°C/ 1 .2 mm; IR (KBr): 1 705; IH NMR (60 MHz, CC14) : 0 1 .20 (3H, t, 1=7 Hz, CH2CH3), 1 .59- 1 .78 (8H, m, cyc\opentane ring), 1 .90-2.40 (4H, m, ArCH2CH2), 2 .70 (2H, q, 1=7 Hz, CH2CH3), 6.33 ( lH, br s, ArH), 7 .40 ( l H, br s, ArH).

1-[2-(2-Thienyl)-etbyl]cyclohexanecarboxylic acid

(6d: R=H), yield 72%, b.p.·

1 60-62°CI5 mm; IR (KBr): 1 700.

1-[2-(S-Metbyl-2-thienyl)-ethyl]cyclohexanecarbo­xylic acid (6d: R=Me), yield 7 1 %, b.p. 1 80-85°C/ 1 . 1 mm; IR (KBr): 1 700.

1- [2-(S-Ethyl-2-thienyl)- ethyl]cyclohexanecar­boxylic acid (6d; R=Et), yield 67%, b.p. 1 65-70°Cl1 .5 mm; IR (KBr) : 1 700.

General procedure for polyphosphoric acid cyclisation of the reduced acids (5 and 6) to the cyclic ketones (7 and 8). The reduced acid (5 or 6, 0.025 mole) was heated with polyphosphoric acid [prepared from P20S (75 g) and phosphoric acid (40 mL, 89%)] on a steam bath for 1 5 min with vigorous stirring. The red-coloured complex was decomposed with crushed ice and kept overnight. Usual work-up afforded either an oil or a solid. The oil was purified by distillation under reduced pressure and the solid by crystallisation from pet-ether. Yields, characteristic physical and spectral data are as follows:

6,7 -Dihydro-2,6-dimetbylbenzo[b ]thiophen-4(SH)­one (7a; R=Me), yield 82%, b.p. 1 12- 1 5°C/ 1 .2 mm; IR (KBr): 1 670; IH NMR (60 MHz, CCI4) : 0 1 .20 (3H, d, 1=5 Hz, CHCH3), 1 .85-3 . 1 0 (2H, m,

COCH2CH), 2 .50 (3H, s, ArCH3), 2.80 (2H, m, ArCH2), 6 .90 ( l H, br s, ArH).

6,7- Dihydro- 2,6,6-trimethylbenzo[b ]thiophen-4(SH)-one (7b; .R=Me) , yield 73%, b.p. 85-90°C/ I -1 .2 mm; IR (KBr) : 1 670; IH NMR (300 MHz, CDCh): 0 1 . 10 (6H, s, C(CH3h), 2.35 (5H, S, COCH2 and ArCH3), 2.80 (2H, s, ArCH2) , 7.00 ( I H, s, ArH).

Spiro[benzo[b ]thiophen-6(SH),I' -cyclopentan]-4 (7H)-one (7c; R=H), yield 79%, b.p. 1 32-34°C/O.75 mm; IR (KBr) : 1 670; IH NMR (60 MHz, CCI4): 0 1 .40- 1 .85 (8H, m, cyc\opentane ring), 2.45 (2H, s, CH2COOH), 3 .00 (2H, s, ArCH2) , 7 .00 ( l H, s, ArH), 7.35 ( l H, s, ArH).

2-Methylspiro[benzo[b ]thiophen-6(SH),I' -cyclo­pentan]-4(7H)-one (7c; R=Me), yield 94%, m.p. 92-93°C; IR (KBr): 1 670; IH NMR (300 MHz, CDCI3): 0 1 .40- 1 .80 (8H, m, cyc\opentane ring), 2.34 (3H, s, ArCH3), 2.40 (2H, s, COCH2), 2 .80 (2H, s, ArCH2), 6.90 ( t H, s, ArH).

2- Ethylspiro[benzo[b ]thiophen-6(SH),I' -cyclo­pentan]-4(7H)-one (7c; R=Et), yield 84%, b.p. 1 45-50°C/6.5 mm; IR (KBr): 1 670; IH NMR (60 MHz, CCI4) : 0 1 .30 (3H, t, 1=8 Hz, CH2CH3), \ .50-2.00 (8H, m, cyc\opentane ring), 2 .4 (2H, s, COCH2), 2 .80 (2H, q, 1=8 Hz, CH2CH3), 2.85 (2H, s, ArCH2), 6.90 ( IH, d, 1= 1 .5 Hz, ArH).

Spiro[benzo[b ]thiophen- 6(SH),I' -cyclohexan]-4(7H)-one (7d; R=H), yield 74%, b.p. 1 92-94°CI7 mm; IR (KBr): 1 670; IH NMR (60 MHz, CCI4): 0 1 .50 ( l OH, br s, cyC\ohexane ring), 2 .55 (2H, s, COCH2), 3 .00 (2H, s, ArCH2), 7 . 10 ( I H, d, 1=4 Hz, ArH), 7.55 ( l H, d, 1=4 Hz, ArH).

2-Methylspiro[benzo[b ]thiophen"6( SH),I' -cyclo­hexan]-4(7H)-one (7d; R=Me), yield 9 1 %, m.p. 94-95°C; IR (KBr): 1 655; IH NMR (60 MHz, CCI4): 0 1 .20- 1 .40 ( l OH, m, cyc\ohexane ring), 2.50 (5H, br s, ArCH3 and COCH2), 2.95 (2H, br s, ArCH2), 7 .05 ( t H, d, 1=4 Hz, ArH).

2- Ethylspiro[benzo[b ]thiophen- 6(SH),I' -cyclo­hexan]-4(7H)-one (7d; R=Et), yield 90%, m.p. 79-80°C; IR (KBr): 1 670; IH NMR (200 MHz, CDCh): 0 1 .30 (3H, t, 1=8 Hz, CH2CH3), 1 .50 ( I OH, br s, cyC\ohexane ring), 2 .50 (2H, s, COCH2), 2.85 (2H, q, 1=8 Hz, CH2CH3), 2.95 (2H, br s, ArCH2), 7. 1 0 ( I H, s, ArH).

6,7- Dihydro-2,S,S-trimethyl-benzo[ b ]thiophen-4(SH)-one (8b; R=Me), yield 70%, b.p. 82°C/ 1 .2 mm; IR (KBr) : 1 670; IH NMR (200 MHz, CDCh): 0 1 .20 (6H, s, COC(CH3)2), 2.05 (2H, t, 1=6 Hz, ArCH2CH2), 2 .45 (2H, t, J=6 Hz, ArCH2CH2), 7 .05

654 INDIAN 1. CHEM. SEC. B, JUNE 1 999

( J H, d, J= 1 .5 Hz, ArH). 6,7- Dihydrospiro[benzo[b ]thiophen- 5,1' -cyclo­

pentan]-4(5H)-one (8c; R=H), yield 79%, b.p. 1 85-90°C/4-5 mm; IR (KBr) : 1 665; IH NMR (80 MHz, CDCb): 0 1 .30-2.00 (8H, m, cyclopentane ring), 2. 1 0 (2H, t, J=5 Hz, ArCH2CH2), 3 . 1 0 (2H, t, J=5 Hz, ArCH2CH2), 7 .08 ( l H, d, J=5 Hz, ArH), 7.30 ( J H, d, J=5 Hz, ArH) .

6,7- Dihydro-2-methyl- spiro[benzo[b ]thiophen-5,1'-cyclopentan]-4(5H)-one (8c; R=Me), yield 66%, b.p. 1 30-35°C/0.3 mm; IR (KBr): 1 668; IH NMR (80 MHz, CDCI}) : 0 1 .30- 1 .90 (8H, m, cyc10pentane ring), 2 . 1 0 (2H, t, J=5 Hz, ArCH2CH2), 2.50 (3H, br, s, ArCH}), 3 .00 (2H, t, J=5 Hz, ArCH2CH2), 7 .05 ( l H, d, J=2 Hz, ArH).

2-Ethyl-6,7 -dihydrospiro[benzo[b ]thiophen-5,1'­cyclopentan]-4(5H)-one (8c; R=Et), yield 73%, b.p. 140-42°CI2.5 mm; IR (KBr) : 1 670; IH NMR (60 MHz, CCI4) : 0 1 .33 (3H, t, J=6 Hz, CH2CH3), 1 .50-1 .90 (8H, m, cyc10pentane ring), 2. 1 0 (2H, t, J=6 Hz, ArCH2CH2), 2.60 (2H, q, J=6 Hz, ArCH2CH3), 3 .00 (2H, t, J=6 Hz, ArCH2CH2), 7.30 ( l H, s, ArH).

6,7- Dihydrospiro[benzo[b ]thiophen- 5,1' -cyclo­hexan]-4(5H)-one (8d; R=H), yield 73 %, b.p. 140-42°C/0.2 mm; IR (KBr) : 1 667; I H NMR (200 MHz, CDCI3): 0 1 .00- 1 .80 ( J OH, m, cyc10hexane ring), 2 . 1 0 (2H, t, J=7 Hz, ArCH2CH2), 3 .00 (2H, t , J=7 Hz, ArCH2CH2), 7.00 ( I H, d, J=4 Hz, ArH), 7.40 ( l H, d, J=4 Hz, ArH).

6,7- Dihydro-2-methyl- spiro[benzo[b ]thiophen-5,1'-cyclohexan]-4(5H)-one (8d; R=Me), yield 69%, b.p. 1 50-53°C/ 1 mm; IR (KBr) : 1 670; IH NMR (60 MHz, CCI4) : 0 1 .25- 1 .80 ( l OH, m, cyc10hexane ring), 2. 1 0 (2H, t, J=6 Hz, ArCH2CH2), 2.40 (3H, s, ArCH3), 2 .90 (2H, t, J=6 Hz, ArCH2), 6.90 ( J H, d, J=2 Hz, ArH).

2-Ethyl-6,7 -dihydrospiro[benzo[b ]thiophen-5,1'­cyclohexan]-4(5H)-one (8d; R=Et), yield 67%, b.p. 143°C/4.5 mm; IR (KBr): 1 670; IH NMR (300 MHz, CDCI3): 0 1 .30 (3H, t, J=6 Hz, ArCH2CH3), 1 .35- 1 .60 ( I OH, m, cyclohexane ring), 2 . 1 0 (2H, t, J= 7 Hz, ArCH2CH2), 2.80 (2H,q, J=6 Hz, ArCH2CH3), 2.90 (2H, t, J=7 Hz, ArCH2CH2), 7 .05 ( I H, s, ArH).

General procedure for bromination of cyclic ketones (7c and 7d R=H, Me). Bromine (0.01 8 mole for R=Me and 0.025 mole for R=H) in carbon tetrachloride (6 mL) was added dropwise during a period of 1 5 min to a magnetical ly stirred solution of the cyclic ketone (7; 0.005 mole) in ether (75 mL) while cooling in an ice-salt bath at a temperature of 0-

5°C. Stirring was continued for 2 hr after which the reaction mixture was washed with water, NaOH (5%, w/v), water and dried over anhyd. NazSO.j. The solvent was evaporated and the solid so obtained was crystallised from ethanol. Yields, physical and spectral data of the compounds obtained are as follows:

3,5,5- Tribromo -2- methyl-spiro[benzo[b ]thio­phen-6(5H),1'-cyclopentan]-4(7H)-one (lOa), yield 94%, m.p. 1 57-58°C; IR (KBr) : 1 680; I H NMR (300 MHz, CDCb): 0 1 .60-2.00 (8H, m, cyclopentane ring), 2.28 (3H, s, ArCH,,), 3 .00 ( I H, br s, ArCHz), 3 .28 ( l H, br s, ArCH2) ; MS: (mlz) 460 (M+6, 47%), 458 (M+4, 29), 456 (M+2, 30), 454 (M+, 20), 2 1 8 ( 1 00).

3,5,5- Tribromo- 2 -methyl-spiro[benzo[b ]thio­phen-6(5H), l'-cyclohexan]-4(7H)-one (lOb), yield 93%, m.p. 1 7 1 °C; IR (KBr): 1680; I H NMR (300 MHz, CDCb): 0 1 .60- 1 .90 ( I OH, m, cyclohexane ring), 2.40 (3H, s, ArCH,,), 3 . 1 0 ( I H, br s, ArCHz), 3 .40 ( l H, br s, ArCH2) ; MS (mlz) : 474 (M+6, 5%), 472 (M+4, 1 6) , 470 (M+2, 1 5), 468 (M+, 5), 252 (4), 2 1 8 ( 1 00), 2 1 6 (98).

2,5,5- Tribromo- spiro[benzo[b ]thiophen-6(5H), l'-cyclopentan]-4(7H)-one (lOc), yield 96%, m.p. 1 22-23°C: IR (KBr) : 1680; I H NMR (200 MHz, CDCb): 0 1 .70- 1 .95 (8H, m, cyclopentane ring), 3 .00 ( I H, d, J= I O Hz, ArCH2), 3 .35 ( l H, d, }= I O Hz, ArCH2), 7 .45 ( J H, s, ArH); MS: (mlz) 446 (M+6, 49%), 444 (M+4, 83), 442 (M+2, 86), 440 (M+, 49), 238 (8.3), 204 (75), 202 ( 1 00) .

2,5,5- Tribromo- spiro[benzo[b ]thiophen-6(5H), l'-cyclohexan]-4(7H)-one (toe), yield 94%, m.p. 1 64°C; IR (KBr) : 1 702; IH NMR (200 MHz, CDCb): o 1 .60- 1 .90 ( lOH, m, cyclohexane ring), 3 .00 ( I H, d, }= 1 O Hz, ArCH2), 3 .40 ( I H, d, J= I O Hz, ArCH2), 7 .40 ( l H, s, ArH).

General procedure for the sodium borohydride reduction of the cyclic ketones (7 and 8) to the corresponding alcohols. To the magnetically stirred methanolic solution (20 mL) of cycl ic ketone (7 or 8, 0.005 mole) sodium borohydride (0.5 g, 0.0 1 3 mole) was added portionwise during 20 min and kept overnight. Usual work-up of the reaction mixture afforded a solid or viscous liquid. The solid product was crystallised from pet-ether and the liquid product was distilled under reduced pressure. Yields, characteristic physical and spectral data are as follows:

4,5,6,7- Tetrahydro-2, 6-dimethylbenzo[b ]thio-

..

l'

SEN et al.: SYNTHESIS OF THIENOSPIRAN DERIV ATIVES 655

phen-4-o1 (9a), yield 93%, m.p. 1 24-25°C; IR (KBr) : 3620-3 140; IH NMR (300 MHz, CDCI) : 0 1 . 1 0 (3H, d, J=5 Hz, CHCH3), 2.00 ( l H, m, CHCH3), 2.20 ( l H, m, CHOHCH2), 2.35 ( l H, m, CHOHCH2), 2.40 (3H, s, ArCH3), 2 .75 (2H, dd, J=5 and 1 .5 Hz, ArCH2) , 4.75 ( l H, t , J=6 Hz, CHOH), 6.75 ( l H, s, ArH).

2- Methyl-4,S,6, 7-tetrahydro-spiro[benzo[b ]thio­phen-6,I'-cyclopentan]-4-ol (9b), yield 95%, m.p. 96°C; IR (KBr) : 3360-3300; I H NMR (300 MHz, CDCb) : 0 1 .40-2. 1 0 (8H, m, cyclopentane ring), 2.40 (3H, s, ArCH3), 4.70 ( l H, t, J=6 Hz, CHOH) , 6.75 ( l H, s, ArH).

2-Methyl-4,S,6, 7 -tetrahydro-spiro[benzo[ b ]thio­phen-6,I'-cyclohexan]-4-o1 (9c), yield 86%, b.p. 1 65-70°CI2.5 mm; IR (KBr): 3350-3000; IH NMR (80 MHz, CDCb): 0 1 .50 ( I OH, br s, cyclopentane ring), 2.50 (5H, br s, ArCH) and CHOHCH2), 2.95 (2H, s, ArCH2), 4.75 ( l H, t, i l l-defined, CHOH), 7 . 1 0 ( lH, s, ArH).

4,S,6, 7 -Tetrahydro-spiro[benzo[b ]thiophen-S,I'­cyclopentan]-4-o1 (l1a) , yield 67%, b.p. 1 24-28°CI l .3 mm; IR (KBr) : 3600-3200; IH NMR (60 MHz, CCI4) : 0 1 .00- 1 .50 (8H, m, cyclopentane ring), 1 .90 (2H, m, ArCH2CH2) , 2.60 (2H, m, ArCH2CH2), 4. 1 0 ( l H, br s , CHOH), 6.90 ( l H, d, J=4 Hz, ArH), 7 . 1 0 ( t H, d, J=4 Hz, ArH).

4,S,6,7 -Tetrahydro-2-methyl-spiro[benzo[b ]thio­phen-S,I'-cyclopentan]-4-o1 ( l1b), yield 82%, m.p. 1 69°C; IR (KBr) : 3640-3 1 00; IH NMR (300 MHz, CDCb): · o 1 .20- 1 .60 (8H, m, cyclopentane ring), 2.00 (2H, m, ArCH2CH2), 2.45 (3H, br s, ArCH) , 2.70 (2H, m, ArCH2CH2) , 4.00 ( 1 H, s, CHOH), 6.65 ( l H, s, ArH).

Formylation of the spiroketone (7). Ethyl formate (0.37 g, 0.005 mole) in sodium-dried benzene (5 mL) was added dropwise over a period of 1 0 min under nitrogen atmosphere to oil free sodium hydride (0.3 g, 0.0 1 mole) in dry benzene ( 1 0 mL) with continuous stirring at O°e. The foregoing cyclic ketone (0.005 mole) in dry benzene (5 !TIL) was then added over 1 0 min. After stirring for 5 h r at that temperature the reaction mixture was decomposed with ice-cold water. The organic layer was separated, washed with water and dilute sodium hydroxide solution. Acidification of the combined aqueous layer in the cold condition afforded a l iquid or solid . The solid product was crystall ised from ethanol . Yields, physical and spectral data of the formyl derivatives obtained are as follows:

S-Formyl-spiro[benzo[b ]thiophen- 6(5H), 1'­cyclopentan]-4(7H)-one (10f), yield 59% (crude), IR (KBr): 1 670, 1 625; IH NMR (60 MHz, CCI4) : 0 1 .80 (8H, br s, cyclopentane ring), 2.90 (2H, s, ArCH2), 7 . 1 0 ( t H, d, J=5 Hz, ArH), 7.35 ( t H, d, J=5 Hz, ArH), 7 .60 ( l H, br s, CHOH).

S- Formyl-2- methyl-spiro[benzo[b ]thiophen-6(5H), l' -cyclopentan]-4(7 H)-one (lOg), yield 55%, m.p. 1 2 1 °C; IR (KBr) : 3220-3060, 1 665 , 1 628; IH NMR (300 MHz, CDCb) : 0 1 .50- 1 .80 (8H, m, cyclopentane ring), 2.45 (3H, s, Ar-CH.,), 2.85 (2H, s , ArCH2), 7 .05 ( I H, s , ArH), 7 .50 ( t H, d, J= 1 0 Hz, CHOH), 1 4.60 ( t H, d, J= 1 0 Hz, CHOH).

2-Ethyl-5-formyl-spiro[benzo[b ]thiophen-6(5H), l'-cyclopentan]-4(7H)-one (lOh), yield 49%, m.p. 86°C; IR (KBr): 1 622; IH NMR (300 MHz, CDCl.,) : 0 1 .30 (3H, t, J=5 Hz, CH2CH) , 1 .60- 1 .80 (8H, m, cyclopentane ring), 2.80 (2H, q, J=5 Hz, CHzCHz), 2 .90 (2H, s, ArCH2), 7 . 1 0 ( t H, s, ArH), 7.60 ( t H, d, J= I O Hz, CHOH), 14.70 ( I H, d, J= I O Hz, CHOH).

5- Formyl-2-methyl- spiro[benzo[b ]thiophen-6(SH), 1'-cyclohexan]-4(7H)-one (lOi), yield 40%, m.p. 1 58-59°C; IH NMR (300 MHz, CDCb): 0 1 .50-1 .80 ( l OH, m, cyclohexane ring), 2.45 (3H, s, ArCH) , 2 .95 (2H, s, ArCH2), 7 .05 ( t H, s, ArH), 7 .58 ( 1 H, d, J= I O Hz, CHOH).

General Procedure for carbethoxylation of thienospiroketone (7) . Diethyl carbonate (2.36 g, 0.02 mole) was added dropwise to a stirred suspension of oil free sodium hydride (0.48 g, 0.02 mole) in sodium-dried benzene (25 mL). The mixture was heated under reflux and the cyclic ketone (7, 0.0 I mole) in benzene (5 mL) was added dropwise during 30 min. Reflux was continued for 8 hr. It was cooled and acidified with acetic acid. The organic phase was ·separated, washed and dried over anhydrous Na2S04. Removal of the solvent afforded a viscous residue which was purified by distil lation under reduced pressure. Yields, physical and spectral data of the compounds obtained are as follows :

S-Carbethoxy-spiro[benzo[b ]thiophen-6(5H), 1'­cyclopentan]-4(7H)-one (10j), yield 65%, b.p. 1 20-24°CI l .6 mm; IR (KBr): 3650-3340, 1 730, 1 670; IH NMR (60 MHz, CCI4) : 0 1 .30 (3H, t, J=7 Hz, OCH2CH) , 1 .50- 1 .90 (8H, m, cyclopentane ring), 2.80 ( l H, d, .1= 1 6 Hz, ArCH2) , 3 .25 ( I H, s, COCHCOOEt), 3 .40 ( l H, d, J= 1 6 Hz, ArCH2), 4. 1 0 (2H, q, J=7 Hz, OCH2CH3), 7.05 ( I H, d, 1=5 Hz, ArH), 7.35 ( l H, d, 1=4 Hz, ArH) .

656 INDIAN J. CHEM. SEC. B, JUNE 1 999

5-Carbethoxy-2-methyl-spiro[benzo[b ]thiophen-6(5H), 1'-cyclopentan]-4(7H)-one (10k), yield 67%, b.p. 1 30-32°C/2 mm; IR (KBr): 3660-3300, 1 730, 1 673; IH NMR (60 MHz, CCI4) : 8 1 .25 (3H, t, J=6 Hz, OCH2CH3), 1 .50- 1 .90 (8H, m, cyclopentane ring), 2.40 (3H, s, ArCH3), 2.90 (2H, s, ArCH2), 3 . 1 5 ( l H, s, COCHCOOEt), 4.20 (2H, q, J=6 Hz, OCH2CH3), 7.00 ( l H, d, J=2 Hz, ArH).

Acknowledgement Financial support to one of the authors (UKS) by

the Education Department, Govt. of West Bengal is gratefully acknowledged. Another author (TD) is thankful to CSIR, New Delhi for granting Research Associateship to her.

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