Indian Journal of Chemistry Vol. 40B, September 2001 , pp 834-836

Note

Synthesis of substituted 2-iminothiopyrans from aryl ethylidene malononitriles

Reichel Samuel & C V Asokan* School of Chemical Sciences, Mahatma Gandhi University,

Priyadarshini Hills, Kottayam 686 560, India

Received 11 February 2000; accepted (revised) 1 1 October 2000

The addition of arylethyl idene malononitriles 1 to dimethyl tri thiocarbonate in the presence of sodium hydride in benzene gives 4-aryl-2-imino-6-methylthio-2H-thiopyran-3-carbonitri les 5 in good yields.

Dicyanoalkenes and related compounds are useful in a variety of transformations leading to the formation of various heterocycles of potential biological activity. I Addition of electrophiles such as N,N-dimethylforma�ide, dimethyl acetal,2 trialkyl orthoformates, orthoacetates3 and chloromethylene ImInlUm salt

4 to alkylidene malononitriles and

subsequent transformations have been investigated. A variety of substituted pyridines are prepared efficiently by the cyclization of the initial adducts formed. The push-pull butadienes prepared by the reaction of aryl ethylidene malononitriles with carbon disulfide followed by alkylation were also found to undergo cyclization to afford pyridine derivatives5• The addition of dicyanoalkenes to heterocumulenes such as aryl or alkyl isothiocyanates or isocyanates results in cyclization leading to the formation of pyridine and thiopyran derivatives as wei \ .6 In our continued interest in the chemistry of functionalized dithiocarboxylates as useful intermediates in organic synthesis? we became interested in the conversion of dicyanoalkenes to the respective dithiocarboxylates. In this note we report the addition of arylethylidene malononitriles to dimethyl trithiocarbonate in the presence of base as a route to 4-aryl-2-imino-6-methylthio-2H-thiopyran-3-carbonitriles 5. Scheme I

The requisite arylethylidene malononitriles 1 were readily available from substituted acetophenones by Knovenagel condensation with malononitrile8• The addition of phenylethylidene malononitrile with

dimethyl trithiocarbonate was examined in the presence of sodium hydride. The reaction proceeded smoothly when the mixture in benzene was stirred at 50°C for 4 hr to give 3-cyano-2-imino-6-methylthio-4-phenylthiopyran Sa in 80% yield after an aqueous work-up. Similarly the other arylethylidene malononitriles Ib-d also gave clean additions to give the respective 2-iminothiopyrans 5b-d in 75 to 85% overall yields (Scheme I). The structures of 5a-d are fully supported by spectral data.

The Claisen condensation of the allylic anion generated by the deprotonation of arylethylidene malononitriles 1 with dimethyl trithiocarbonate leads to the formation of intermediate enethiolate anions 3 which on in situ cyclization yields the sodium salt of the imino substituted thiopyrans 4 which on protonation affords the substituted 2-iminothiopyrans 5. Alternatively, protonation of the intermediate enethiolates 3 could have afforded the functionalized dithiocarboxylates 6. However, we could not obtain 6 under these conditions. An attempt to extend the reactions to dicyanoalkenes derived from aliphatic and alicyclic ketones resulted in complex product mixtures.

In summary we have demonstrated that the substituted 2-iminothiopyrans 6 are prepared efficiently from the readily available arylethylidene malononitriles 1 in a one pot process.

Experimental Section General. Melting points were recorded on a Buchi-

530 melting point apparatus in open capillaries and are uncorrected. IR spectra were recorded on a Shimadzu IR-470 spectrometer, IH NMR spectra on a Bruker WM-300(300 MHz) or a Jeol EX-90(90 MHz) using CDCh as solvent and TMS as internal standard,. I 3C NMR spectra on a Bruker WM-300(75.5MHz) or a Jeol EX-90(22,4 MHz) using CDCl3 as solvent, and mass spectra on a Finnigan-Mat 3 12 model spectrometer.

Sodium hydride (50% dispersion in mineral oil) was obtained from Spectrochem, Bombay and was washed with dry petroleum ether before use. Dimethyl trithiocarbonate was prepared according to the reported procedure.9 Arylethylidene malononitriles

NOTES 835

if

N s �

� I CH 3 + CH3�SCH3 Benzene

X � X 2 3

I NNa

H2O SCH3 -

SCH3 X X 4 5

5 X

a H

b Cl SCH3

c CH30 X d CH3 6

Scheme I

were obtained by the Knovenagel condensation of substituted acetophenones with malononitrile8•

Reaction of arylethylidene malononitriles 1 with dimethyl trithiocarbonate 2: General procedure. To a well stirred suspension of sodium hydride (50% dispersion in mineral oil) (240 mg, 5 mmoles) in dry benzene, arylethylidene malononitrile 1 (5 mmoles) was added and stirred for 5 min. Dimethyl trithiocarbonate (700 mg, 5 mmoles) was then added and the reaction mixture was stirred at 50°C for 4 hr, cooled, poured into ice-cold water ( 1 00 mL) and neutralized with 3N HCI. The organic layer was separated and the aqueous layer was extracted with diethyl ether (50 mL x3). The combined extracts were washed with water, dried over anhydrous sodium sulfate and evaporated to a viscous residue. The residue was column chromatographed over silica gel (60- 120) using hexane/ethyl acetate (20:5) as eluent to give 5a-d, which were further purified by recrystallization from methanol.

2-Imino-6-methylthio-4-phenyl-2H-thiopyran-3-carbonitrile Sa: .Yield 1 g (80%), mp 1 02-03DC; IH NMR (300 MHz, CDCh): B 2.36 (s, 3H, SMe), 6.42 (s, 1 H, vinylic proton), 7.50 (m, 5H, Ar-H). IR (KBr):

2200(CN), 1 625, 1 540, 1 470 (C=C), 1430, 1 3 10 em-I ; ElMS: rn/z 258(M+, 25%), 234 ( 10 %), 232 ( 1 00 %), 2 1 7 ( 1 0.5%), 1 79 ( 1 2%) 172 ( 1 8%), 140 (22%), 97 ( 1 5.38%), 85 (23%), 7 1 (27%).

2-Imino- 6- methylthio -4- (4-chlorophenyl) -2Hthiopyran-3-carbonitrile 5b: Yield 1 . 1 g (75%), m.p. 1 55-56DC; IH NMR (300 MHz, CDCh): B 2.61 (s, 3H, SMe); 6.38 (s, 1 H, vinylic proton); 7.46-7.50 (m, 4H, Ar-H);. IR (KBr): 2200(CN), 1 620, 1580, 1560, 1530, 1 480 (C=C), 1430, 1 240, 1 1 60, 1 140, 1080 cm-I ; ElMS: rn/z 294 (M+ +2, 8%), 292(M+, 27%), 266 ( 100%), 238 ( 1 8%), 1 74 ( 1 2%).

2-Imino-4-( 4-methoxyphenyl)-6-methyIthio-2Hthiopyran-3-carbonitrile 5c: Yield 1 . 1 8 g (82%), m.p. 1 48-50DC ; IH NMR (CDCh, 300 MHz): B 2.56 (s, 3H, SMe), 3:85 (s, 3H, OMe), 6.43 (s, 1 H, vinylic proton); 6.98 (d, J = 9 Hz, 2H, Ar-H); 7.49 (d, J = 9 Hz, 2H, Ar-H), I3C NMR (75.47 MHz, CDCh): B 15 .90 (SCH3), 55.47 (OCH3), 1 0 1 . 19, 1 14.36, 1 1 5 .82(vinylic proton), 1 16.2(CN), 1 29.75, 129.66, 155 .9, 1 52.93 1 6 1 .55(arom and vinylic), 1 62.66 (C=NH); IR (KBr): 2200(CN), 1 600, 1580, 1 500, 1480 (C=C), 1 360, 1 240, 1 1 80, 1 120, 1 140, 1035,

836 INDIAN J CHEM, SEC B, SEPTEMBER 2001

820 cm- I . ElMS: rnJz 288 (M+, 3 1 %), 26 1 ( 1 00%), 226(39%), 208 (7%), 1 70 (8%), 1 27 (8% ), 89 (3%).

2-Imino-4-(4-methylphenyl)-6-methylthio-2Hthiopyran-3-carbonitrile 5d: Yield 1 . 1 6 g (85%), mp 1 l2- l 3°C; I H NMR (90 MHz, CDC13 : 0 1 .5 (s, 3H, CH3), 3.0 (s, 3H, SMe), 6.75 (s, I H, vinylic proton); 7.0-8 . 1 (m, 4H, Ar-H). I 3C NMR (75.46 MHz CDCI3): 0 15 .90 (SMe), 2 1 .4 1 (CH3), 1 0 1 .80, 1 1 5 .00, 1 1 6.00(CN), 1 27.72, 1 27, 1 28 .90, 1 29.55, 1 34.78, 140.86, 152.94, 156.05 (arom and vinylic), 1 62.29 (C=NH); IR (KBr): 2200(CN), 1 6 10, 1 580, 1 560, 1500, 1480 (C=C) cm- I ; ElMS: rnJz 272(M+, 23.2%), 246 ( 100%), 2 1 8 (36%), 174 (40.4%), 148 (43%), 140 (1 5%). Anal. Calcd for C 14H12N2S2: C, 6 1 .40; H, 4.42; N, 10.27. Found: C, 6 1 .76; H, 4.4 1 ; N, 10.29%.

Acknowledgement

We are indebted to CSIR, New Delhi for financial assistance (Research project 0 1 ( 1 324)/94). RS thanks the UGC, New Delhi for a Research Fellowship. We thank directors of Regional Sophisticated Instrumentation Centers at lIT Madras, NEHU,

Shillong and CDRI, Lucknow for providing spectral and analytical data.

References 1 a) Kasturi T R, Sharma V K, Srinivasan A & Subrahmanyam

G, Tetrahedron, 29, 1973, 4 103 b) Gewald K & Hain U, Synthesis, 1984, 62. c) Gewald K, Hain U & Gruner M, Z Chern, 27, 1987, 32

2 Baldwin J J, Raab A W & Ponticello G S, J Org Chern, 43, 1978, 2529.

3 Kilama J J, Iyengar B S, Remers W A & Mash E A, J Heterocyclic Chern, 27, 1990, 1437.

4 Ege G, Frey H 0 & Schuck E, Synthesis, 1979, 376. 5 a) Peseke K, Z Chern, 1 7, 1977, 288 .

b) Peseke K, Zahn K & Michalik M, J Prakt Chern, 336, 1994, 357. c) George M, Das S, Ashokan C V, Rath N P & George M V, Acta Cryst, C54, 1998, 1033. d) Peseke K, Heide G, Feist H & Michalik M, J Prakt Chern, 333, 1991, 1 19.

6 Peseke K, Aguila M & Bollin I, East Genllall Patent, 1982, DD154539, Chern Abstr, 98, 1983, 4475e_

7 Suma S & Asokan C V, Synth CornrnulI, 26, 1996, 847. 8 a) Mowry D T, J Arn Chern Soc, 65, 1943, 991 .

b) Jones G , Org React, 1 5, 1967, 204_ 9 Degani I, Fochi R, Gatti A & Regondi V, Synthesis, 1986,

894.