Highly efficient one-pot synthesis of1-substituted-1,2,3,4-tetrahydropyrazino[1,2-a]indoles

Rakesh K. Tiwari, Jaspal Singh, Devender Singh, Akhilesh K. Verma* and Ramesh Chandra

Synthetic Organic Chemistry Research Laboratory, Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi,

Delhi 110007, India

Received 21 May 2005; revised 11 July 2005; accepted 28 July 2005

Available online 19 August 2005

Abstract—A practical and general one-pot synthesis of 1-substituted-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indoles is described. Theapproach uses 2-(3-methyl-1H-indol-1-yl) ethylamine, benzotriazole and aldehydes in the presence of catalytic amount of acid catalysts(AlCl3, ZnCl2, ZnBr2, p-TsOH, CH3SO3H) and proceeds in high yields via iminium cation intramolecular cyclization. The mechanism of theobserved intramolecular cyclization reaction has been investigated theoretically by means of PM3 semiempirical method and results wereconsistent with the experimental results.q 2005 Elsevier Ltd. All rights reserved.

1. Introduction

Pyrazino[1,2-a]indoles are biologically active, demonstra-ting serotonin antagonistic,1 thrombolytic,2 antidepressant,anxiolitics,3 central nervous system depressants,4 anti-convulsants,5 antihistaminic,6 protein kinase C inhibitors,7

5-HT2A, 5-HT2C agonistic,8–9 and selective imidazoline I2

receptor ligands activities.10 They are also found active invariety of cardiovascular diseases.11 Therefore, versatileand widely applicable method for the synthesis ofpyrazino[1,2-a]indoles are of considerable interest.

Many synthetic procedures exist for the synthesis of thepyrazino[1,2-a]indole nucleus,6,12–14 however, there is onlyone report by Hegedus et al., which describes the synthesisof 1-substituted 1,2,3,4-tetrahydropyrazino[1,2-a]indoles3a–c (three examples 37–58% yields) in two steps:(i) generation of palladium complex 2 by the reaction of

0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.doi:10.1016/j.tet.2005.07.088

Scheme 1. Reaction conditions (i) Pd(CH3CN)4$(BF4)2/RCN, rt; (ii) NaBH4.

Keywords: Intramolecular cyclization; Benzotriazole; Lewis acid; Frontier molec* Corresponding author. Tel.: C91 11 55782976; fax: C91 11 27666248; e-mai

1-allyl-3-methyl-1-H indole 1 and nitriles in the presenceof the strongly electrophilic complex Pd (CH3CN)4(BF4)2

(ii) reduction of palladium complex 2 with NaBH4 togenerate compounds 3a–c (Scheme 1).12 Reported method-ologies for the synthesis of 1,2,3,4-tetrahydropyrazino[1,2-a]indoles suffer from several practical disadvantages suchas the use of a costly catalyst, multi step synthesis, longreaction times, elevated temperatures, difficult to recoverthe solvent and moderate yields.

Recently, we described the synthesis of 2-substituted-1,2,3,4-tetrahydropyrazino[1,2-a]indoles in two steps by thecyclocondensation of 2-(3-methyl-1H-indol-1-1yl) ethyl-amine with benzotriazole and formaldehyde followed bynucleophilic substitution of the benzotriazolyl group toperform N-functionalization at 2-position.15 In light of therising interest in pyrazino[1,2-a]indole systems due to itsmedicinal importance,1–11 we now describe a more general

Tetrahedron 61 (2005) 9513–9518

ular orbital.l: akhilesh682000@yahoo.com

Scheme 2. BtHZBenzotriazole. Reaction conditions (i) 5b: RZMe, BtH, Lewis acids (AlCl3, ZnCl2, ZnBr2) or CH3SO3H, CH2Cl2, 25 8C, 0.5–6 h; (ii) 5b:RZMe, BtH, p-TsOH, benzene, reflux Dean–Stark trap, 6–8 h; (iii) 5a: RZH, BtH, Lewis acids (AlCl3, ZnCl2, ZnBr2) CH2Cl2, 25 8C to reflux, 0.5–12 h, orp-TsOH, benzene, reflux, Dean–Stark trap, 6–8 h; (iv) 5a (RZH), 5b (RZMe) Lewis acids (AlCl3, ZnCl2, ZnBr2) CH2Cl2, 25 8C to reflux, 0.5–18 h or p-TsOH, benzene, reflux, Dean–Stark trap, 6–8 h.

R. K. Tiwari et al. / Tetrahedron 61 (2005) 9513–95189514

and practical approach for the synthesis of novel 1-substi-tuted-1,2,3,4-tetrahydropyrazino[1,2-a]indoles 7a–i at rt inone-pot in good to excellent yields.

2. Results and discussion

2.1. Synthesis

1-(2-Aminoethyl) indoles 5a–b (5a, RZH; 5b, RZMe)were obtained by the reaction of indole 4a or 3-methylindole 4b with 2-chloroethylamine hydrochloride using thereported procedures.15 1-Substituted-1,2,3,4-tetrahydropyr-azino[1,2-a]indoles 7a–i were obtained as racemic mixturesin high yields by the reaction of 2-(3-methyl-1H-indol-1-yl)ethylamine 5b with benzotriazole and aldehydes 6a–i in thepresence of a catalytic amount of: (A) Lewis acid (AlCl3,ZnCl2, ZnBr2) or protic acid (CH3SO3H) at 25 8C indichloromethane; (B) p-toluenesulphonic acid in a Dean–

Table 1. Intramolecular cyclization of amine 5b with aldehydes catalyzed by dif

Entry Compound R1 C

1 7a C6H5 A2 7a C6H5 Z3 7a C6H5 C4 7a C6H5 p5 7b p-Me–C6H5 A6 7b p-Me–C6H5 Z7 7b p-Me–C6H5 C8 7b p-Me–C6H5 p9 7c p-MeO–C6H5 A10 7c p-MeO–C6H5 p11 7d p-NO2–C6H5 A12 7d p-NO2–C6H5 Z13 7d p-NO2–C6H5 C14 7e p-Cl–C6H5 A15 7e p-Cl–C6H5 p16 7e p-Cl–C6H5 C17 7e p-Cl–C6H5 Z18 7f p-Br–C6H5 A19 7f p-Br–C6H5 Z20 7f p-Br–C6H5 C21 7g p-F–C6H5 A22 7g p-F–C6H5 p23 7g p-F–C6H5 Z24 7h 2-Pyr A25 7h 2-Pyr Z26 7h 2-Pyr p27 7i 2-Thie A28 7i 2-Thie p29 7j iso-Propyl A30 7j iso-Propyl Z

a Reaction conditions for catalyst (i) AlCl3, ZnCl2, ZnBr2 or CH3SO3H: CH2Cl2/b Isolated yield.c Purified by column chromatography.d The compound was not obtained.

Stark trap (Scheme 2). A variety of Lewis acids (AlCl3,ZnCl2, ZnBr2) as well as protic acids (CH3SO3H, p-TsOH)under varied reaction conditions were screened and theresults are summarized in Table 1. The reactions were moreefficient in the presence of AlCl3 and ZnCl2 in dichloro-methane. It is noteworthy that compounds 7a–i isolated bymethod A and compounds 7a–g obtained by method B werepure and directly used for the spectral analysis, however,compounds 7h–i obtained by method B were purified bycolumn chromatography. The structures of compounds 7a–iare clearly supported by their 1H, 13C NMR spectra andmicroanalysis. The 1H NMR spectra showed NCH-pyrazinosinglet signal for 7a–i at w5.3 ppm and the presence ofexchangeable NH-pyrazino was confirmed by deuteriumexchange.

The reaction pathway is believed to involve the formation oftransient intermediate X and subsequent generation ofiminium cation Y, which undergoes intramolecular

ferent Lewis acids and protic acids

atalysta Time (h) Yields (%)b

lCl3 0.5 91nBr2 1.5 83H3SO3H 1.5 81-TsOH 7.5 79lCl3 1.0 84nCl2 1.5 77H3SO3H 1.5 80-TsOH 6.5 78lCl3 1.5 82-TsOH 6.5 77lCl3 0.5 88nBr2 3.5 78H3SO3H 1.8 77lCl3 2.0 93-TsOH 6.5 81H3SO3H 1.8 80nBr2 2.0 77lCl3 2.0 93nCl2 2.5 79H3SO3H 2.5 82lCl3 2.0 93-TsOH 6.5 80nCl2 3.5 78lCl3 1.2 87nBr2 3.5 65-TsOH 7.5 77c

lCl3 O4.0 88-TsOH 7.5 78c

lCl3 10 —d

nCl2 12 —d

25 8C; (ii) for p-TsOH, benzene/reflux using Dean–Stark trap.

Scheme 3. RZMe. R1CHO, BtH, Lewis acids (AlCl3, ZnCl2, ZnBr2) or CH3SO3H, CH2Cl2, 25 8C.

R. K. Tiwari et al. / Tetrahedron 61 (2005) 9513–9518 9515

cyclization to furnish 7a–i (Scheme 3). Lewis (AlCl3,ZnCl2, ZnBr2) or protic (CH3SO3H, p-TsOH) acid incatalytic amounts facilitate loss of benzotriazolyl anionfrom intermediate X to form iminium cation Y, whichfinally cyclizes with the loss of one proton to give cyclizedcompounds 7a–i. However, the 3-position methyl group in5b appears to be essential because, without it, we failed toobtained cyclization. The presence of the 3-position methylgroup activates the indole ring system, which facilitates theintramolecular cyclization via formation of tertiary carbo-cation whereas in case of non-substituted indole 5a,decompostion occurred, which might be due to the protonloss or dimerization or polymerization via cationicprocesses. It is also noteworthy that when the reaction wascarried out in the absence of benzotriazole, no cyclizationproduct was obtained (Scheme 2).

For showing generality in the reaction we had carried onereaction in 10 gm scale using 2-(3-methyl-1H-indol-1-yl)ethylamine 5b with benzotriazole and aldehydes 7e inpresence of catalytic amount of AlCl3. In addition,

Figure 1. Frontier molecular orbitals of amines 5a–b and aldehydes 6a–c and 6e

mechanism of the observed intramolecular cyclizationwith indolethylamine (with or without methyl at 3-position)with various aromatic aldehydes 6a–j containing electronreleasing or electron-withdrawing group is also discussed.

2.2. Frontier molecular orbital analysis

To demonstrate the results obtained in the work, we used asimple approach of frontier molecular orbital (FMO)16

based on the energy gap of HOMO and LUMO. Theineffective cyclization of 2-indol-1-yl-ethylamine 5a can beexplained through FMO analysis. It has been realized fromthe Figure 1 that the reactions are very much controlled byEHOMO(amine)KE LUMO(aldehyde) energy gap, if we observethe reaction of both the amines 5a and 5b with an aldehyde6a, we find that the energy gap for 5b and 6a DEZ4.76 eVis less than for 5a and 6a DEZ6.08 eV revealing that thereaction between 5b and 6a must proceed at higher ratecompared to 5a and 6a. Similarly, 5a and 6b DEZ6.13 eVO5b and 6b DEZ4.79 eV, 5a and 6i DEZ7.95 eVO5b and 6i DEZ6.61 eV, this reaction occurred

–j. (6d structure is far from equilibrium).

R. K. Tiwari et al. / Tetrahedron 61 (2005) 9513–95189516

with difficulty and took O4 h. Difference in the reactivity of5b and 5a is mainly due to: (i) formation of stable tertiarycarbocation; (ii) energy gap EHOMO(amine)KELUMO(aldehyde).In case of 5b(with methyl group at 3 position) cyclizationoccurs via formation of stable tertiary carbocation, however,in case of nonsubstituted amine 5a polymerization occursvia cationic processes. The data presented in the Table 1showed that the reaction of 5b with various aldehydescompleted in different time periods. This observation canalso be explained through same FMO model. The insertionof electron donating group such as –Me, –Cl, –F, –Br, and–OMe, at 4-phenyl ring of 6a–i increased the energy gapand subsequently retarded the rate of reaction (Fig. 2).In general observed reaction rate followed the pattern 7aO7bO7hO7cO7eO7gO7fO7i. However, cyclization wasnot achieved when the amine 5b is condensed with aliphaticaldehyde 6j and benzotriazole in the presence Lewis acidAlCl3 or ZnCl2, which is believed due to high-energy gap(Fig. 1).

Figure 2. Plot between the reaction time and energy difference of frontiermolecular orbitals for reaction of 5b and aldehydes 6a–i (DEZHOMOKLUMO).

3. Conclusion

The present studies have demonstrated the efficient one-potaccess to 1-substituted-10-methyl-1,2,3,4-tetrahydropyra-zino[1,2-a]indoles 7a–i from 5b using benzotriazole,aldehydes 6a–i and a catalytic amount of Lewis acids orprotic acid via intramolecular cyclization. Semi empiricalPM3 studies support the experimental results. The advan-tage of present work includes (i) use of cheap, easy to handleand commercially available material and catalyst; (ii) rtreaction conditions; (iii) short reaction time and high yields;(iv) no extra efforts for purification. Simple reactionconditions, high yields and high purity of the crude productmake this methodology applicable for large-scaleoperations.

4. Experimental

All reagents used were AR grade. Melting points weredetermined using a Thomas Hoover melting point appar-atus. 1H (300 MHz) and 13C NMR (75 MHz) spectra wererecorded on a Bruker 300 NMR spectrometer in CDCl3(with TMS for 1H and chloroform-d for 13C as internalreferences) unless otherwise stated. MS were recorded on

Agluent 1100 ES-MS Karlsrhue Germany. Infrared spectra(ymax) were recorded on Perkin Elmer FTIR spectrophoto-meter as thin films on KBr plates (for oils) or KBr discs (forsolids). Column chromatography was performed on silicagel (230–400 mesh). Microanalyses were obtained withan Elemental Analysensysteme GmbH VarioEL V3.00element analyser. The reactions were monitored by thin-layer chromatography (TLC) using aluminium sheets withsilica gel 60 F254 (Merck). All of the reactions were carriedout under nitrogen atmosphere.

4.1. Synthesis of 1-substituted-10-methyl-1,2,3,4-tetra-hydropyrazino[1,2-a]indoles 7a–j: general procedure

Method (A). To a mixture of 2-(3-methyl-1H-indol-1-yl)ethylamine (5b, 0.5 g, 2.9 mmol), an aldehyde (6a–j)(2.9 mmol), benzotriazole (0.342 g, 2.9 mmol), in thepresence of catalytic amount of Lewis acid (AlCl3 orZnCl2 or ZnBr2) or protic acid (CH3SO3H) in dichloro-methane (20 mL) was stirred at 25 8C for 0.5–8.0 h. (TLCmonitoring) The reaction mixture was quenched with waterand extracted with ethyl acetate (100 mL!3). Thecombined extract was washed with 1 N NaOH, brine anddried over anhydrous Na2SO4 and concentrated underreduced pressure to give solid compound 7a–j. Formicroanalysis, compounds were recrystallized from ethylacetate/hexanes.

Method (B). A mixture of 2-(3-methyl-1H-indol-1-yl)ethylamine (5b, 500 mg, 2.9 mmol), an aldehyde (6a–j)(2.9 mmol), benzotriazole (0.342 g, 2.9 mmol) in thepresence of catalytic amount of p-toluenesulfonic acid(p-TsOH) in benzene (30 mL), was heated under reflux forappropriate time (4–8 h). Water was azeotropically removedby using a Dean–Stark trap. The reaction was monitored byTLC. The solvent was removed under reduced pressure, andresidue was then dissolved in ethyl acetate (100 mL),washed with 1 N NaOH solution (100 mL!2), brinesolution and dried over anhydrous Na2SO4. Evaporationof solvent under reduced pressure gave a residue, which wascrystallized to give 7a–g and compounds 7h–j were purifiedusing column chromatography with hexanes/ethyl acetate6:1–2:1 as an eluent.

4.1.1. 10-Methyl-1-phenyl-1,2,3,4-tetrahydropyrazino-[1,2-a]indole 7a. (White needles from EtOAc/hexanes).Mp 122–124 8C; [Found: C, 82.38; H, 6.88; N, 10.59C18H18N2 requires C, 82.41; H, 6.92; N, 10.68%]; nmax

(KBr) 3315, 3055, 3043, 2956, 2920, 2880, 750, 677 cmK1;dH (300 MHz, CDCl3) 7.54–7.08 (9H, m, Ph, Ph), 5.37 (1H,s, H-1), 4.16–3.93 (2H, m, H-4), 3.34–3.14 (2H, m, H-3),1.93 (1H, s, NH), 1.86 (3H, s, CH3); dC (100 MHz, CDCl3)142.0, 135.8, 131.6, 130.5, 128.4, 127.5, 120.8, 119.2,118.2, 108.4, 106.0, 100.2, 56.6, 42.7, 40.0, 8.4; LCMS m/z263.5 (100, MC1).

4.1.2. 10-Methyl-1-(4-methylphenyl)-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole 7b. Yellow oil; [Found: C, 82.73; H,7.12; N, 10.24 C19H20N2 requires C, 82.57; H, 7.29; N,10.14%]; nmax (KBr) 3313, 3051, 3043, 2955, 2926, 2875,751, 676 cmK1; dH (300 MHz, CDCl3) 7.52–7.10 (8H, m,Ph, Ph), 5.30 (1H, s, H-1), 4.03–3.96 (2H, m, H-4), 3.24–3.13 (2H, m, H-3), 2.39 (1H, s, NH); 2.31 (3H, s, CH3), 1.85

R. K. Tiwari et al. / Tetrahedron 61 (2005) 9513–9518 9517

(3H, s, CH3); dC (100 MHz, CDCl3) 139.0, 137.0, 135.7,131.7, 129.0, 128.1, 124.3, 120.6, 119.5, 118.1, 108.3,105.8, 56.2, 42.5, 39.8, 21.0, 8.4; LCMS m/z 275 (100%,MK1), 276 (20%, M), 277 (8%, MC1).

4.1.3. (4-Methoxyphenyl)-10-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole 7c. (White needles from EtOAc/hexanes). Mp 126–128 8C; [Found: C, 77.72; H, 9.51; N,9.54 C19H20N2O requires C, 78.00; H, 9.58; N, 9.58%]; nmax

(KBr) 3320, 3049, 3044, 2955, 2920, 2877, 1041, 742,677 cmK1; dH (300 MHz, CDCl3) 7.52–6.84 (8H, m, Ph,Ph), 5.33 (1H, s, H-1), 4.16–3.99 (2H, m, H-4), 3.79 (3H, s,OMe), 3.36–3.15 (2H, m, H-3), 1.86 (3H, s, CH3), 1.66 (1H,s, NH); dC (100 MHz, CDCl3) 150.9, 145.7, 143.2, 131.5,130.9, 127.0, 119.6, 119.1, 118.6, 116.1, 108.3, 105.8, 58.2,56.2, 42.5, 39.8, 8.4; LCMS m/z 293 (5%, MC1); 292(30%, M); 291 (100%, MK1).

4.1.4. 1-(4-Nitrophenyl)-10-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole 7d. (Yellow crystals from EtOAc/hexanes). Mp 112–114 8C; [Found: C, 70.31; H, 5.56; N,13.45 C18H17N3O2 requires C, 70.34; H, 5.58; N, 13.67%];nmax (KBr) 3321, 3050, 3042, 2955, 2922, 2876, 1520, 1360,750, 680 cmK1; dH (300 MHz, CDCl3) 7.53–6.90 (8H, m,Ph, Ph); 5.31 (1H, s, H-1), 4.15–3.96 (2H, m, H-4), 3.30–3.15 (2H, m, H-3), 2.70 (3H, s, CH3), 1.60 (1H, s, NH); dC

(100 MHz, CDCl3) 135.9, 132.4, 130.0, 129.3, 127.3, 125.7,121.4, 119.5, 118.5, 117.0, 111.1, 109.0, 56.2, 42.7, 40.9,8.4; LCMS m/z 307 (80%, M), 308 (20%, MC1), 185.2(14%, MK122).

4.1.5. 1-(4-Chlorophenyl)-10-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole 7e. (White needles from EtOAc/hexanes). Mp 110–111 8C; [Found: C, 72.52; H, 5.40; N,9.21 C18H17N2Cl requires C, 72.80; H, 5.70; N, 9.40%];nmax (KBr) 3310, 3050, 3043, 2956, 2922, 2878, 1087, 760,689 cmK1; dH (300 MHz, CDCl3) 7.54–7.11 (8H, m, Ph, Ph)5.34 (1H, s, H-1), 4.15–3.96 (2H, m, H-4), 3.30–3.15 (2H,m, H-3), 1.88 (s, 4H, NH, CH3); dC (100 MHz, CDCl3)158.7, 140.6, 136.3, 133.5, 131.1, 129.7, 128.6, 125.1,121.0, 119.4, 118.3, 108.5, 55.7, 42.6, 39.8, 8.5; LCMS m/z297.1 (50%, MC1), 295 (100%, MK1), 280.1 (7%, MK15), 186.2 (12%, MK110).

4.1.6. 1-(4-Bromophenyl)-10-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole 7f. (White needles from EtOAc/hexanes). Mp 115–117 8C; [Found: C, 63.03; H, 5.25; N,8.27 C18H17N2Br requires C, 63.30; H, 5.03; N, 8.21%];nmax (KBr) 3311, 3050, 3043, 2957, 2922, 2879, 760,684 cmK1; dH (300 MHz, CDCl3) 7.54–7.11 (8H, m, Ph,Ph), 5.32 (1H, s, H-1), 4.10–3.90 (2H, m, H-4), 3.20–3.15(2H, m, H-3), 1.80 (3H, s, CH3), 1.26 (1H, s, NH); dC

(100 MHz, CDCl3) 141.0, 135.5, 133.1, 132.1, 131.6, 130.9,130.0, 121.0, 119.3, 118.2, 108.5, 106.1, 55.7, 42.6, 39.7,8.4; LCMS m/z 343.1 (45%, MC2), 341 (100%, M), 339(65%, MK2).

4.1.7. 1-(4-Fluorophenyl)-10-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole 7g. (White needles from EtOAc/hexanes). Mp 120–121 8C; [Found: C, 77.18; H, 5.86; N,9.62 C18H17N2F requires C, 77.12; H, 6.11; N, 9.99%]; nmax

(KBr) 3311, 3049, 3043, 2957, 2921, 2879, 1200, 761,683 cmK1; dH (300 MHz, CDCl3) 7.54–7.11 (8H, m, Ph,

Ph), 5.32 (1H, s, H-1), 4.10–3.91 (2H, m, H-4), 3.27–3.15(2H, m, H-3), 1.82 (4H, s, NH, CH3); dC (100 MHz, CDCl3)164.2, 139.8, 139.5, 139.1, 132.8, 129.9, 120.9, 119.3,118.2, 108.2, 102.4, 100.5, 55.8, 42.7, 39.9, 8.5; LCMS m/z281.16 (76%, MC1), 282.18 (14%, MC2), 279.14 (100%,MK2).

4.1.8. 10-Methyl-1-pyridin-2-yl-1,2,3,4-tetrahydropyra-zino[1,2-a]indole 7h. (White needles from EtOAc/hexanes). Mp 127–128 8C; [Found: C, 77.18; H, 6.34; N,15.69 C17H17N3 requires C, 77.54; H, 6.51; N, 15.96%];nmax (KBr) 3306, 3051, 3044, 2958, 2924, 2881, 1580, 1440,748, 704 cmK1; dH (300 MHz, CDCl3) 7.82–6.83 (8H, m,Ph, pyri), 5.19 (1H, s, H-1), 3.97–3.76 (2H, m, H-4), 3.15–3.03 (2H, m, H-3), 1.95 (3H, s, CH3), 1.80 (1H, s, NH); dC

(100 MHz, CDCl3) 154.2, 148.4, 138.8, 137.5, 134.9, 130.8,122.0, 120.7, 119.6, 119.1, 118.6, 111.1, 108.0, 54.2, 43.6,41.5, 8.6; LCMS m/z 364 (40%, MC1).

4.1.9. 10-Methyl-1-thien-2-yl-1,2,3,4-tetrahydropyra-zino[1,2-a]indole 7i. (Brown needles from EtOAc/hex-anes). Mp 130–131 8C; [Found: C, 71.54; H, 5.98; N, 10.38;S, 11.87 C16H16N2S requires C, 71.60; H, 6.01; N, 10.44; S,11.95%]; nmax (KBr) 3320, 3059, 3043, 2966, 2922, 2888,775, 650, 698 cmK1; dH (300 MHz, CDCl3) 7.43–6.33 (7H,m, Ph, thien), 5.19 (1H, s, H-1), 3.87 (2H, m, H-4), 2.90 (2H,m, H-3), 2.20 (3H, s, CH3), 1.90 (1H, s, NH); dC (100 MHz,CDCl3) 139.5, 139.1, 138.1, 132.0, 127.5, 124.5, 121.0,120.4, 119.5, 117.6, 108.1, 106.0, 54.2, 43.2, 40.5, 8.4;LCMS m/z 269 (25%, MC1).

Acknowledgements

We gratefully acknowledge financial support from Depart-ment of Science and Technology, New Delhi, for this work.We are thankful to Prof. V. K. Singh for valuablesuggestions and discussion. R. K. T. thank J. A. Gangulyfor JRF and J. S. are thankful to CSIR for JRF.

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