30001, Murcia, Spain

Received July 14, 1986

YAlIy1thio)quinazolines 2 and 4-@ropargylthio)quinazolines 8 undergo cyclization by action of bromine to give 3+romome- thyl)-2klihydrothiazolo[3,~~]quinazolini~ and 3-@romome- thyl)thiazolo[3~-e]quinazolinium salts 3 or 9, respectively. Bro- mination of 3-allyl-4(3H)-quinazolinethiones 6 leads to 24bro- momethyl~2,3dihydrothiazolo[3,2-~]quinazoIinium bromides 7. Rcaction of 4H-1.3-benzothiazine4thiona 5 with propargyl- amine yields imidazoie derivativa 10 instead of the expected 3-propargyl-4(3H)-quinazolinethiones.

The reaction of primary amino groups with 4H-1,3-benzothia- zine-4-thiones to give the corresponding 3-substituted 4-thioxo-3,4- dihydroquinazolines has been reported ',*I. Recently we have studied the reaction with thiocarbohydrazide 3, and with unsubstituted amidrazones4) giving 1,2,4-triazolo[1,5-c]quinazoline derivatives.

In connection with our studies on the preparation of fused het- erocycles we have reported the synthesis of bridgehead nitrogen heterocycles which contain the quinazoline moiety, e. g. 1,2,4- triazolo[I ,5-c]quinazoIine 3,4,5), pyrazolo[1,5-~]quinazoline '1.

We now describe new methods for the synthesis of oth- erwise not available cationic derivatives of the thiazolo[3,2- clquinazoline ring system which contain the thiazole and the quinazoline moieties. No general useful procedures for the preparation of thiazolo[3,2-c]quinazolinium cations have been reported, it has only been briefly mentioned7), that thiazolo[3,2-c]quinazolinium cations are intermediates in the preparation of 2-(o-aminophenyl)thiazoles from 2-(4- quinazoliny1thio)acetophenones and perchloric acid or phosphoryl chloride. On the other hand, the chemistry of mesoionic derivatives of the thiazolo[3,2-c]quinazoline ring system has been studied in detail').

Our approach to the preparation of thiazolo[3,2-c]quin- azolinium cations is based on the cyclization of S- and N- allyl derivatives 2 and 6 of 4-quinazolinethiones. In this type of compounds the allylic side-chain can provide a secondary carbonium ion at the carbon appropriately placed for attack of N-3 or exocyclic S to form the thiazole ring.

As alkylation in heterocyclic thioureas with an exocyclic thio function proceeds at the sulfur atom, 2-aryl-4-(allyl- thio)quinazolines 2 are obtained in excellent yields from 2- aryl-4(3H)-quinazolinethiones 1 and allyl bromide in the presence of triethylamine. Compounds 2 undergo ring clo- sure by action of bromine in glacial acetic acid at room temperature to give the corresponding 5-aryl-3-(bromome- thyl)-2,3-dihydrothiazolo[3,2-c]quinazolin-4-ium bromides 3 in good yields. Bromides 3 can be converted with tetra-

P. Molina, A. Arques, M. V. Vinader

Preparation of 2,3-Dihydrothiazolo[3,2-c]quinazolinium Salts from 4(3H)-Quinazolinethiones or 4H-1,3-Benzothiazine-4-thiones Pedro Molina", Antonio Arques, and Maria Victoria Vinader

Departamento de Quimicd Organica, Facultad de Ciencias, Universidad de Murcia,

103

Syatbese von 2,3-Dihydrothilzolo[3,2-c]~ninmSalz pus

4-(AUylthio)chinazole 2 und 4-(Propargylthio)chinazolinc 8 lassen sich mit Brom m 3-(Brommethyl)-2,3dihydrothiazolo- [3,2-cJchinazolimium- und 3-(Brornmethyl)thiazolo[3,2-~]china- zolinium-Salzen 3 bzw. 9 cyclisieren. Bromierung der 3-Allyl- 4(3H)chinazolinthione 6 tiefert 2-(Brommethyl)-2,3dihydrothi- azolo[3,2-c]chmazolinium-bromide 7. Umsetzung von 4H-1.3- Benzothiazin4thionen 5 mit Propargylamin ergibt die Imidazole 10 anstelle der erwarteten 3-Propargyl-4(3H~hinazolin1hionc.

4(3H)-Chili0taiowlr oder 4 H - I , 3 ~ t ~ ~

fluoroboric acid into the corresponding tetrafluoroborates. Compounds 3 undergo ring opening of the thiazole moiety by action of water under acid catalysis to give the corre- sponding dibromide derivative 4 in moderate yields.

+ Br-CH2-CH=CH2

\ NH

s 1

w s 2

3 4 - 1 Br

Presumably, the conversion 2 + 3, involving initial for- mation of the bromonium ion and subsequent cyclization by intramolecular nucleophilic attack of the N-3 of the quin- azoline ring, would give the corresponding 2,3-dihydrothia- zolo[3,2-c]quinazolinium bromide 3. We believe that the conversion 3 + 4 involves initial nucleophilic attack of water at position 3 of the 2,3-dihydrothiazole ring followed by nucleophilic attack of the bromide anion on the open- chain bromohydrine to give 4.

As it has been pointed out preparation of N-ally1 deriv- atives 6 by direct allylation of 2-aryl-4-quinazolinethiones 1 is hampered by the preferencial reactivity of the sulfur atom

Liebigs Ann. Chem. 1987, 103 - 109 0 VCH Verlagsgesellschaft mbH, D-6940 Weinheim, 1987 0170-2041/87/0202-0103 $ 02.50/0

104 P. Molina, A. Arques, M. V. Vinader

with the alkylating reagent. For this reason, compounds 6 have been prepared in good yields by the reaction of 2-aryl- 4H-1,3-benzothiazine-4-thiones 5 with allylamine. Bromi- nation of 6 in acetic acid solution at room temperature di- rectly leads to 5-aryl-2-(bromomethyl)-2,3-dihydrothiazol- 0[3,2-c]quinazolin-4-ium bromides 7 in good yields. A con- ceptually similar reaction has been reported" for the prep- aration of 2,3-dihydrothiazolo[3,2-u]pyridinium bromides by bromination of I-allyl-2( 1 H)-pyridinethiones.

5 6

CH2Br 7

On the other hand 2-aryl-4-quinazolinethiones 1 react with propargyl bromide in benzene in the presence of tri- ethylamine to give the corresponding 2-aryl-4-(propargyl- thi0)quinazolines 8 in good yields. Bromination of com- pounds 8 leads to the corresponding 5-aryl-3-(bromome- thyl)thiazolo[3,2-c~]quinazolin-4-ium bromides 9 in good yields.

1

3 q y r CH

8

+ Br-CH,-ECH

s-cg

In this context, we tried to prepare the regioisomer of 9, 5-aryl-2-(bromomethyI)thiazolo[3,2-~]quinazolinium ca- tion, by bromination of 2-aryl-3-propargylquinazoline- 4(3H)-thiones. However, attempts to prepare these com- pounds from 2-aryl-4H-1,3-benzothiazine-4-thiones 5 and propargylamine were unsuccessful. The reactions between 5 and propargylamine take place by a different way and the

reaction products are found to be the unexpected imidazoles 10. Compounds 10 react with methyl iodide in ethanol in the presence of potassium hydroxide to give the correspond- ing S-methyl derivatives 11 in excellent yields.

We believe that this transformation involves initial nu- cleophilic attack of the amino group at position 2 of the 4H-1,3-benzothiazine-4-thione to give an open product, which undergoes ring closure by nucleophilic attack of the amino group on the carbon-carbon triple bond. Subsequent carbon-carbon double-bond migration leads to 10.

H,

cBc,l > + HZN-CHz-CECH

5

10 (R = H); 1 1 ( R = CH,)

4-H,C-C6H4

To discuss the 'H- and "C-NMR results it is useful to divide the compounds into two classes: quinazoline deriv- atives 2, 4, 6, and 8 and the bicyclic compounds 3, 7, and 9. In the 'H-NMR spectra of compounds 2, 4, and 8, the chemical shifts of the SCHl group are characteristic (6 = 4.2), while the signals of the NCHz groups in compounds 6 appears at 6 = 5.1. The SCH2 carbon signals in compounds 2, 4, and 8 show up characteristically in the I3C-NMR spec- tra at 6 = 32, 35, and 18, respectively, as do the NCHz carbon signals in compounds 6 at 6 = 53; the quaternary carbon signal (C-4) in the quinazoline ring in compounds 2, 4, and 8 appears at 6 = 158 and in compounds 6 occurs at 6 = 189.

The 'H- and 13C-NMR spectra of the bicyclic isomers 3 and 7 show striking differences. Thus, in the 'H-NMR spec- tra of compounds 3 the signals of the diastereotopic protons at position 2 appear as two double-doublets at 6 = 4.02 and 4.53, similarly the two diastereotopic protons of the group C3-CH2Br cause two double-doublets at 6 = 3.41 and 3.45, and the methine proton at C-3 gives a multiplet at 6 = 6.18-6.32. In the 13C-NMR spectra, C-2 and C-3 signals appear at 6 = 34.9 and 71.36, respectively, while the signal of CH2Br attached at position 3 occurs at 6 = 32.04.

In the 'H-NMR spectra of compounds 7, the signals of the diastereotopic protons at position 3 appear as two dou-

Liebigs Ann. Chem. 1987, 103-109

2,3-Dihydrothiazolo[3,2-c]quinazolinium Salts 105

ble-doublets at 6 = 5.12 and 5.55, the signals of the two diastereotopic protons of the CH2Br group attached at po- sition 2 appear as two double-doublets at 6 = 3.85 and 3.94, and the methine protons in position 2 cause a multiplet at 6 = 5.22-5.37. The signals of the carbons C-2 and C-3 occur in the 13C-NMR spectra at 6 = 48.6 and 64.5, re- spectively, while the CHzBr carbon peak appears at 6 =

34.26. The assignments have been done by two-dimensional NMR HCCOR and COSY experiments.

We thank Dr. M. Grande (University of Salamanca) for recording 2D-NMR spectra, the Comisidn Asesora de Investigacidn Cientijka y Tkcnica for financial support (project number 2019/83), and one of us (M. V. V.) thanks the iNAPE for a grant.

Experimental Microanalyses: Perkin-Elmer 240C instrument. - 'H- and I3C-

NMR spectra: The 1D- and 2D-NMR spectra were obtained with a Bruker WP 200 SY instrument (200 MHz for 'H; 50.3 MHz for 13C). The COSY and HCCOR programs were supplied by Bruker. Data points: 1024 x 1024. COSY, 4 scans per accumulation; ex- periment delay D, = 1 s; D2 = 5 ps; Do = 5 ps. HCCOR: 64 scans per accumulation; experiment delay D1 = 1.6 s; D2 = 0.0037 s (one bond) or 0.04 s (long range). - IR spectra: Nicolet-5DX, Nujol used in all cases. - Mass spectra: Hewlett-Packard 5993C. - Melting points (uncorrected): Kofler hot-stage apparatus.

4- (Allylthio)-2-urylquinazolines 2. - General Procedure: To a so- lution of the appropriate thione l ( 5 mmol) in benzene (50 ml), triethylamine (5 mmol) and ally1 bromide ( 5 mmol) were added; after 3 h of heating under reflux, triethylammonium bromide was deposited. After cooling, the salt was separated by filtration and the filtrate concentrated to dryness to afford a crude product which recrystallized from ethanol to give 2.

4-(Allylthio)-2-phenylquinazoline (2a): Yield 91 %; m.p. 6 9 T , yellow needles. - IR: 1558 cm-', 1536,1483,1444,1343,1310,993,

J = 7Hz, CH2-CH=CH2), 5.10-5.65 (m, 2H, CH=CH2), 5.80-6.50 (m, l H , CH=CH2), 7.40-8.10 (m, 7H, aryl H), 8.5-8.80 (m, 2H, aryl H). - 13C NMR (CDCIJ: 6 = 32.29 (C-a), 118.25 (C-y), 122.6 (C-44, 123.66 (C-5), 126.53 (C-6), 128.39 (C-3'),

138.03 (C-I,), 148.94 (C-8a), 158.7 (C-4), 170.3 (C-2). - MS (70 eV): m/z (%) = 279 (M+ + 1) (lo), 278 (M+) (35), 277 (loo), 263 (24), 251 (5) , 245 (21), 244 (lo), 205 (11).

Calcd. C 73.35 H 5.07 N 10.06 Found C 73.54 H 5.14 N 9.87

924, 865, 774, 761, 705, 659. - 'H NMR (CDC13): 6 = 4.15 (d, 2H,

128.47 (C-2'), 128.98 (C-8), 130.43 (C-4), 133.33 (C-p), 133.46 (C-7),

Ct7Ht4N2S (278.4)

4- ( A Ilylthiol-2- (4-ch2orophenyl)quinazoline (2 b): Yield 87%; m.p. 130°C, yellow needles. - IR: 1598 cm-', 1582, 1557, 1471, 1365, 1345, 1206, 1088, 1014, 961, 822, 769, 720. - 'H NMR

(m, 2H, CH2-CH=CH2), 5.85-6.55 (m, IH, CH=CH2), 7.50-8.25 (m, 8H, aryl H). - 13C NMR (CDCIJ: 6 = 32.35 (C-a), 11 8.23 (C-y), 122.52 (C-44, 123.71 (C-5), 126.66 (C-6), 128.56 (C-3'),

148.98 (C-8a), 157.84 (C-4), 170.44 (C-2). - MS (70 eV): m/z (%) =

314 (M+ + 2) (14), 313 (45), 312 (M+) (33), 311 (loo), 299 (lo), 297 (30), 281 (9), 279 (28), 278 (12), 241 (6), 239 (17), 111 (7), 102 (18), 76 (ll), 41 (11).

Calcd. C 65.27 H 4.18 N 8.96 Found C 65.37 H 4.09 N 9.11

(CDCI3): 6 = 4.25 (d, 2H, J = 7 Hz, CH2-CH=CH2), 5.15-5.60

129.06 (C-8), 129.81 (C-2'), 133.03 (C-p), 133.50 (C-7), 136.69 (C-4'),

C I ~ H I ~ C ~ N ~ S (312.8)

4-(Allylthio)-2-(4-methylphenyl~quinazoline (2c): Yield 81%; m.p. 73-75"C, yellow needles. - IR: 1608 cm-', 1562,1540,1489, 1449, 1381, 1342, 1308, 1251, 1117, 996, 917, 832, 798, 764, 780. - 'H NMR (CDC13): 6 = 2.40 (s, 3H, CH?), 4.2 (d, 2H, J = 7 Hz, CH2-CH=CH2), 5.15-5.70 (m, 2H, CH=CH2), 5.90-6.50 (m, 1H, CH=CH2), 7.35 (d, 2H, J = 9 Hz, 3'-H, 5'-H), 7.60-8.25 (m, 4H, aryl H), 8.15 (d, 2H, J = 9 Hz, 2'-H, 6'-H). - '3C NMR (CDCI,): F = 21.29 (CH,), 32.31 (C-a), 118.08 (C-y), 122.39 (C-44,

133.40 (C-7), 135.28 (C-l'), 140.71 (C-4'), 147.80 (C-84, 158.60 (C- 4), 170.04 (C-2). - MS (70 eV): m/z (YO) = 293 (M+ + 1) (9), 292 (M+) (34), 291 (loo), 277 (25), 259 (28), 258 (12), 220 (9), 219 (29), 102 (13), 91 (18), 76 (9), 41 (10).

CI8HlhN2S (292.4)

126.30 (C-6), 128.59 (C-2'), 128.75 (C-8), 129.12 (C-3'), 133.18 (C-p),

Calcd. C 73.94 H 5.52 N 9.58 Found C 73.87 H 5.46 N 9.72

4-(A11ylthio)-2-(4-methoxyphenyl)quinazo/ine (2d): Yield 85%; m.p. 80"C, yellow needles. - IR: 1606 cm-', 1556, 1538, 1516,

'H NMR (CDCI,): 6 = 4.05 (s, 3H, OCH3), 4.30 (d, 2H, J = 7 Hz, CH2 - CH = CH2), 5.30 - 5.85 (m, 2H, CH = CH,), 6.05 - 6.70 (m, 1 H, CH = CH2), 7.30 (d, 2 H, J = 9 Hz, 3'-H, 5'-H), 7.55 - 8.50 (m, 4H, aryl H), 9.00 (d, 2H, J = 9 Hz, 2'-H, 6'-H). - MS (70 eV):

275 (17), 235 (lo), 107 (6), 41 (5) . CI8Hl6N20S (308.4)

1454, 1348, 1319, 1247, 1167, 1032, 988, 792, 759, 745, 719, 625. -

rn/z (Yo) = 309 (M+ + 1) (ll), 308 (M+) (41), 307 (IOO), 293 (20),

Calcd. C 70.10 H 5.23 N 9.08 Found C 69.93 H 4.99 N 9.18

5-Aryl-3- (bromomethyl) -2,3-dihydrothiazolo[3,2-c/quinazolin-4- iurn Bromides 3. - General Procedure: A solution of bromine (0.48 g, 3 mmol) in acetic acid (20 ml) was added dropwise to a well-stirred solution of the appropriate quinazoline 2 (3 mmol) in the same solvent (15 ml) at room temperature. When the addition was completed, the yellow precipitate which gradually separated during the reaction, was filtered off, washed several times with die- thy1 ether and crystallized from ethanol to give 3.

3- (Bromomethyl)-2,3-dihydro-5-phenylthiazolo[3,2-c]quinazolin- 4-ium Bromide (3a): Yield 60%; m.p. 207"C, colorless needles. - IR: 1608 cm-', 1602,1591,1574,1557,1489,1421,1404,1347,1296, 1251, 1177, 1064, 962, 888, 854, 781, 752, 718, 662. - 'H NMR (CD3OD): 6 = 3.41 (s, l H , CH,Br), 3.45 (d, IH, J = 3.1 Hz, CH2Br), 4.02 (dd, 1 H, JAX = 2.1 Hz, JMx = 12.6, S-CH2-CH),

6.32-6.18 (m, l H , CH-CH2Br), 7.66-7.80 (m, 3H, aryl H), 7.93-8.01 (m, 2H, aryl H), 8.03-8.08 (m, l H , aryl H), 8.20-8.26 (m, l H , aryl H), 8.35-8.44 (m, 2H, aryl H). - I3C NMR (CDCI3 + CF3C02H): 6 = 32.04 (CH2Br), 34.90 (C-2), 71.36 (C-3), 118.64 (C-IOa), 128.31 (C-lo), 128.80 (C-2'), 129.55 (C-7), 129.90 (C-

(C-64, 177.82 (C-5). - MS (70 eV): m/z (YO) = 359 (M+ + 2) (7), 358 (ll), 357 ( M f ) (7), 356 (lo), 277 (52), 263 (9, 238 (23), 206 (21), 205 (loo), 82 (19), 80 (20), 77 (11).

CI7Hl4Br2N2S (438.2) Calcd. C 46.60 H 3.22 N 6.39 Found C 46.40 H 3.40 N 6.22

4.53 (dd, l H , JAM = 8.8 Hz, JMx = 12.6 Hz, S-CH2-CH),

3'), 131.85 (C-9), 132.69 (C-4), 141.25 (C-8), 147.22 (C-lob), 152.52

3- (Bromornethyl) -5- (4-chlorophenyl)-2,3-dihydrothiazolo[3,2-c]- quinazolin-4-ium Bromide (3 b): Yield 63%; m.p. 150"C, yellow prisms. - IR: 1602 cm-', 1585,1568,1557,1500,1404,1308,1296, 1143, 1092, 1013, 956, 883, 764, 730, 684. - 'H NMR (CDC13 + CFjC02H): 6 = 3.35-3.60 (m, 2H, CH2Br), 3.80-4.05 (m, l H , S-CHZ-CH), 4.90-5.15 (m, l H , S-CH2-CH), 6.70-6.85 (m, l H , CH-CH,Br), 7.40-8.80 (m, 8H, aryl H). - l3C NMR (CDCh + CF~COZH): 6 = 32.85 (CH,Br), 35.59 (C-2), 71.50 (C-3), 118.69 (C-lOa), 128.41 (C-lo), 129.74 (C-7), 129.80 (C-l'), 130.25

Liebigs Ann. Chem. 1987, 103-109

106 P. Molina, A. Arques, M. V. Vinader

(C-2'), 130.70 (C-3'), 131.77 (C-9), 139.33 (C-4), 141.00 (C-8), 147.24 (C-lob), 151.56 (C-6a), 178.11 (C-5).

Cl7H13Br2C1N2S (472.6) Calcd. C 43.20 H 2.77 N 5.93 Found C 43.01 H 2.90 N 6.04

3- (Bromomethyl) -2,3-dihydro-5- (4-methylphenyl) thiazolo- [3,2-c]quinazolin-4-ium Bromide (3c): Yield .59%; m.p. 135 - 138 "C, colorless needles. - IR: 1608 cm-', 1562, 1545, 1489, 1421, 1347,

'H NMR (CDCI; + CF3C02H): 6 = 2.45 (s, 3H, aryl CH;), 3.30-3.60 (m, 2H, CH2Br), 3.90-4.70 (m, 2H, S-CH2-CH), 6.50-6.85 (m, l H , CH-CH,Br), 7.45-8.90 (m, 8H, aryl H). - MS (70 eV): m/z (YO) = 373 (M+ + 2) (4), 371 (M+) (4), 291 (35), 277 (9), 252 (41), 220 (12), 219 (loo), 116 (ll), 91 (77), 82 (73), 81 (37), 80 (71), 79 (35).

1338, 1308, 1245, 1172, 1073, 1041,990, 837, 792, 730, 713, 622. -

CIRH16Br2N2S (452.2) Calcd. C 47.81 H 3.57 N 6.19 Found C 47.59 H 3.44 N 6.03

3- (Brotiiornethyl) -2,3-dihydro-5- (4-rnethoxyphenyl) thiazolo- (3,2-c/quinazolin-4-ium Bromide (3d): Yield 64%; m. p. 246 - 248 "C, yellow needles. - I R 1608 cm-', 1591, 1568, 1517, 1483, 1353, 1245, 1183, 1024, 843, 775, 741, 724, 628. - 'H NMR (CDC13 + CF3C02H): 6 = 3.25-3.70 (m, 2H, CH2Br), 3.90 (s, 3H, OCH3), 3.95-5.05 (m, 2H, S-CH2-CH), 6.40-6.90 (m, IH, CH-CH2Br), 7.35-7.90 (m, 8H, aryl H). - MS (70 eV): m/z (YO) = 389 (M+ + 2) (12), 387 (M+) (12), 307 (53), 293 (9), 268 (42), 236 (16), 235 (IOO), 132 (II), 82 (41), 81 (32), 80 (42), 79 (30).

C18HlbBr2N20S (468.2) Calcd. C 46.18 H 3.44 N 5.98 Found C 46.23 H 3.47 N 6.07

2-Ary1-4-[ (2,3-dibromopropyl) thio]quinazolines 4. - General Procedure: A solution of the appropriate bromide 3 (1 mmol) in acetic acid/water (60 ml, 2: 1, v/v) was stirred at room temperature for 5 h. The solution was poured into ice and the resultant precip- itated solid was filtered, washed with water, and recrystallized from acetone to give 4.

4-[(2,3-Dibrornopropyl)thio]-2-phenylquinazoEine (4a): Yield 40%, m.p. 107-108"C, colorless needles. - IR: 1614 cm-', 1559, 1540, 1484, 1455, 1342, 1312, 1251, 1196, 1027, 992, 869, 849, 775,

11.1 Hz, J A X = 4.45 Hz, CHBr-CH2Br), 4.07 (dd, 1 H, J A M =

11.1 Hz, JMx = 6.2 Hz, CHBr-CH2Br), 4.17 (d, 2H, J = 7.6 Hz, S-CH,-CHBr), 4.42-4.83 (m, IH, CHBr), 7.50-7.58 (m, 4H, 6- H, 3'-H, 5'-H, 4 - H ) , 7.86-7.91 (m, l H , 7-H), 8.04 (d, l H , J5,6 =

8.33 Hz, 5-H), 8.11 (d, l H , J8,7 = 8.45 Hz, 8-H), 8.64-8.69 (m, 2H,

49.45 (C-p), 122.22 (C-4a), 123.49 (C-5), 126.89 (C-6), 128.47 (C-3'),

148.96 (C-8a), 158.72 (C-4), 169.00 (C-2). - MS (70 eV): m/z (YO) = 440 (M+ + 4) (3), 438 (M+ + 2) (6), 436 (M+) (3), 360 (18), 359 (88), 358 (18), 357 (87), 277 (46), 263 (22), 245 (20), 238 (73), 206 (20), 205 (loo), 103 (21), 102 (32), 77 (37).

Calcd. C 46.60 H 3.22 N 6.39 Found C 46.58 H 3.46 N 6.22

759, 704, 658. - 'H NMR (CDC13): 6 = 3.88 (dd, IH, JAM =

2'-H, 6'-H). - I3C NMR (CDCl;): 6 = 35.64 (C-a), 36.29 (C-y),

128.63 (C-2'), 129.04 (C-8), 130.71 (C-4), 133.88 (C-7), 137.41 (C-l'),

C17H14Br2N2S (438.1)

2- (I-Chlorophenyl)-l-[ (2,3-dibromopropyl) thio]quinazoline (4 b): Yield 42%; m.p. 126"C, colorless needles. - 1R: 1613 cm-', 1585, 1568, 1540, 1528, 1450, 1404, 1342, 1314, 1251, 1172, 1092, 1013, 871, 843, 792, 758, 736, 701. - 'H NMR (CDCl,): 6 = 3.80-4.25 (m, 4H, CH2 - CHBr - CH2Br), 4.50 - 4.90 (m, 1 H, CHBr), 7.60-8.90 (m, 8H, aryl H). - MS (70 eV): m/z (YO) = 476 (1), 474 (M+ + 4) (5), 472 (M+ + 2) (7), 470 (M+) (3), 395 (26), 393 (loo), 391 (76), 313 (20), 311 (51), 299 (13), 297 (36), 274 (24), 272 (60), 241 (33), 239 (97), 113 (9, 111 (14), 102 (43).

Cl7HI3C1Br2N2S (472.6) Calcd. C 43.20 H 2.77 N 5.93 Found C 43.43 H 2.80 N 6.05

4-[ (2,3-Dibromopropyl) thiol-2- (4-methylphenyl) quinazoline (4c): Yield 47%; m.p. 103-104"C, colorless needles. - IR: 1608 cm-', 1568,1545,1483,1381,1336,1308,1251,1177,996,782,

aryl CHI), 3.75-4.45 (m, 4H, CH2-CHBr-CH2Br), 4.50-4.85 (m, l H , CHBr) 7.30-8.60 (m, 8H, aryl H). - MS (70 eV): m/z (%) = 454 (M+ + 4)(3), 452 (MC + 2)(6), 450 (M+)(3), 373 (78), 371 (75), 292 (Il), 291 (42), 277 (30), 259 (16), 252 (57), 220 (18), 219 (IOO), 102 (22), 91 (29), 76 (10).

C18H16Br2N2S (452.2) Calcd. C 47.81 H 3.57 N 6.19 Found C 47.87 H 3.64 N 6.13

758, 735, 628. - 'H NMR (CDCl, + CF3COZH): 6 = 2.5 (s , 3H,

4-[ (2,3-Dibromopropyl) thiol-2- (4-methoxypheny1Jquinazoline (4d): Yield 40%; m.p. 146-147"C, colorless prisms. - IR: 1602 cm-', 1562, 1541,1514,1457,1348,1254,1166,1027,841,790, 763, 743, 719, 695. - 'H NMR (CDCI,): 6 = 3.70-4.40 (m, 4H, CH2-CHBr-CH2Br), 4.02 (s, 3H, OCH3), 4.55-4.90 (m, 1 H, CHBr), 7.35 - 8.65 (m, 8 H, aryl H). - MS (70 eV): m/z (Yo) = 470 (M+ + 4) (6), 468 (M+ + 2) (ll), 466 (M+) (6), 389 (42), 387 (42), 307 (49), 294 (13), 293 (63), 268 (43), 236 (19), 235 (loo), 133 (8).

C18H16Br2N20S (468.2) Calcd. C 46.18 H 3.44 N 5.98 Found C 45.99 H 3.50 N 6.07

3-Allyl-2-aryl-4(3H)-quinazolinethiones 6. - General Procedure: To a suspension of the appropriate 1,3-benzothiazine 5 (4 nimol) in ethanol (50 ml), allylamine ( 5 mmol) was added. The reaction mixture was refluxed for 1 h. After cooling at 0°C the yellow pre- cipitated solid was collected by filtration and the crude product recrystallized from ethanol to give 6.

3-Allyl-2-phenyl-4(3~)-~uinuzolinethione (6a): Yield 81 YO; m.p. 9 0 T , yellow needles. - IR: 1583 cm-', 1559, 2473, 1359, 1340, 1206, 949, 916, 859, 768, 701, 658. - 'H NMR (CDC13): 6 = 4.85 (dd, 1 H, JAX = 17 Hz, J M x = 1.6 Hz, CH =CH2, trans), 5.18 (dd, l H , JAM = 11 Hz, JMx = 1.6 Hz, CH=CHZ, cis), 5.23-5.27 (m, 2H, CH2-CH=CH2), 5.82-6.01 (m, 2 H, CH2-CH=CH2), 7.52 (s, 5H,aryl H),7.54-7.84(m, 3H, aryl H), 8.85(d, 1 H , / = 7.8 Hz, aryl H). - 13C NMR (CDCI,): 6 = 54.60 (C-a), 11 8.2 (C-y), 127.97 (C-3'), 128.53 (C-2'), 129.06 (C-4a), 129.89 (C-X), 130.99 (C-4), 131.35 (C-7), 134.45 (C-p), 135.72 (C-l'), 141.97 (C-Sa), 155.24 (C-2), 188.73 (C-4), others: 128.16, 128.35 (C-5 and C-6). - MS (70 eV): m/z (%) = 278 (M+) (34), 277 (47), 264 (19), 263 (M+ - 15) (loo), 245 (20), 205 (28) 102 (22), 77 (49).

C1,HI4N2S (278.4) Calcd. C 73.35 H 5.07 N 10.06 Found C 73.22 H 5.14 N 9.87

3-Allyl-2-(4-chlorophenyl)-4(3H)-quinazolinethione (6b): Yield 82%; m.p. 130°C, yellow needles. - IR: 1590 cm-', 1560, 1540,

'H NMR (CDC13): 6 = 4.80-5.50 (m, 4H, CH2-CH=CHz), 5.90-6.55 (m, l H , CH=CH2), 7.25-8.10 (m, 7H, aryl H), 9.00 (d, IH, aryl H). - MS (70 eV): m/z (%) = 314 (M+ + 2) (16), 313

15) (IOO), 281 (6), 279 (15), 241 (4), 239 (10).

1494, 1451, 1335, 1308, 1087, 1009, 994, 850, 792, 761, 734, 691. -

(25), 312 (M+) (47), 311 (70), 300 (7), 299 (38), 298 (20), 297 (M+ -

C17H13C1N2S (312.8) Calcd. C 65.27 H 4.19 N 8.96 Found C 65.07 H 4.1 1 N 9.12

3-AlEyl-2-(4-methylphenyl)-4(3H)-quinazolinethione (6c): Yield 77%; m.p. 117"C, yellow needles. - IR: 1583 cm-', 1557, 1470,

'H NMR (CDCIJ: 6 = 2.45 (s, 3H, aryl CH,), 4.75-5.50 (m, 4H, CHz-CH=CHZ), 5.70-6.60 (m, l H , CH=CH2), 7.30-8.00 (m, 7H, aryl H), 9.05 (d, 1 H, aryl H). - MS (70 eV): m/z (%) = 292

(31), 91 (43).

1360, 1343, 1207, 1111, 1023, 953, 914, 813, 770, 722, 625. -

(M') (32), 291 (50), 278 (21), 277 (M' - 15) (loo), 259 (23), 219

C18H16N2S (292.4) Calcd. C 73.94 H 5.52 N 9.58 Found C 74.07 H 5.61 N 9.40

Liebigs Ann. Chem. 1987, 103 - 109

2,3-Dihydrothiazolo[3,2-c]quinazolinium Salts 107

3-Allyl-2- (4-methoxyphenyl)-4(3H) -quinazolinethione (6 d): Yield 77%; m.p. 156"C, yellow needles. - IR: 1609 cm-', 1583, 1511, 1471, 1363, 1341, 1251, 1204, 1179, 1027, 951, 832, 774, 626. - 'H NMR (CDClJ: 6 = 4.00 (s, 3H, OCH,), 4.85-5.55 (m, 4H, CH2-CH=CH2), 5.85-6.50 (m, IH, CH=CH2), 7.15-8.10 (m, 7H, aryl H), 9.15 (d, 1 H, J = 8 Hz, aryl H). - I3C NMR (CDCI3): 6 = 55.23 (OCH,), 55.59 (C-a), 113.73 (C-3'), 117.65 (C-y), 127.89 (C-2'), 128.67 (C-44, 131.07 (C-7), 134.14 (C-l'), 134.22 (C-p), 141.88 (C-8a), 155.05 (C-2), 160.59 (C-4'), 188.54 (C-4), others: 128.03, 129.34, 129.42 (aryl carbons). - MS (70 eV): m/z (%) = 308 (M+) (37), 307 (47), 294 (19), 283 (Mi - 15) (IOO), 275 (17), 235 (25).

CI8Hl6N20S (308.4) Calcd. C 70.10 H 5.23 N 9.08 Found C 70.23 H 5.12 N 8.84

3-Allyl-2-methyl-4[3H)-quinazolinethione (6e): Yield 69%; m. p. 6 6 T , yellow needles. - IR: 1596 cm-', 1557, 1470, 1358, 1332, 1206, 1145, 1085, 968, 946, 855, 838, 777, 764, 643. - 'H NMR (CDCI,): 6 = 2.80 (s, 3H, CH3), 5.00-5.40 (m, 2H, CH=CH2), 5.50-5.70 (m, 2H, CH,-CH=CH2), 5.90-6.50 (m, 1H, CH=CH2), 7.45-8.10 (m, 3H, aryl H), 8.97 (d, l H , J = 8.5 Hz, aryl H). - ',C NMR (CDCIJ: 6 = 24.08 (CH,), 53.09 (C-a), 117.57 (C-y), 127.29 (C-5), 127.60 (C-6), 128.48 (C-44, 130.27 (C-8), 131.45 (C-7), 134.31 (C-p), 142.23 (C-8a), 153.13 (C-2), 188.70 (C-4). - MS (70 eV): m/z (YO) = 216 (M+) (29), 215 (lo), 202 (14), 201 (M+ - 15) (loo), 183 (15), 182 (9), 143 (6), 102 (8).

Ct2H12N2S (216.3) Calcd. C 66.64 H 5.59 N 12.95 Found C 66.50 H 5.71 N 13.03

5- Aryl-2- (bromomethyl) -2,3-dihydrothiazolo(3,2-c]quinrr;olin-4~ ium Bromides 7. - General Procedure: A solution of bromine (4 mmol) in acetic acid (20 ml) was added dropwise to a well-stirred solution of the appropriate thione 6 (4 mmol) in the same solvent (40 ml) at room temperature. The reaction mixture was stirred at room temperature for 2 h and the yellow solid which gradually separated during the reaction was collected by filtration, washed with water, and recrystallized from methanol to give 7.

2- (Bromomethyl)-2,3-dihydro-5-phenylthiazolo[3,2-c]quinazolin- 4-ium Bromide (7a): Yield 71%; m.p. 230"C, colorless prisms. - IR: 1613 cm-', 1596, 1579, 1562, 1483, 1353, 1240, 1024, 962, 820,

(dd, l H , JAx = 4.8 Hz, J M x = 11.8 Hz, CH,Br), 3.94 (dd, l H ,

JAx = 13.4 Hz, = N + -CH2-CH), 5.22-5.37 (m, IH, 2-H), 5.55

7.60-7.83 (m, 5H, aryl H), 8.00 (t, l H , J = 7 Hz, aryl H), 8.15-8.40 (m, 3H, aryl H). - 13C NMR (CDCl, + CF3C02H): 6 = 34.26 (CH2Br), 48.59 (C-2), 63.51 (C-3), 118.66 (C-lOa), 128.16

(C-9), 132.58 (C-4'), 141.23 (C-8), 147.50 (C-lob), 153.20 (C-6a), 175.20 (C-5). - MS (70 eV): m/z (%) = 359 (M+ + 2) (6), 357 (M+) (6), 277 (27), 263 (5) , 238 (29), 206 (17), 205 (loo), 103 (4), 102 (13), 82 (51), 81 (12), 80 (50), 79 (12), 77 (8).

781, 707, 633, 611. - 'H NMR (CDC13 + CF3C02H): 6 = 3.85

JAM = 4.4 Hz, JXM = 11.8 Hz, CH2Br), 5.12(dd, lH, J M x = 3.3 Hz,

(dd, l H , J x A = 13.4 Hz, J M A = 8.5 Hz, = N + -CHZ-CH),

(C-lo), 128.70 (C-3'), 129.33 (C-7), 129.58 (C-2'), 131.10 (C-l'), 131.90

Cl7HI4Br2N2S (438.1) Calcd. C 46.60 H 3.22 N 6.39 Found C 46.30 H 3.09 N 6.52

2- (Bromomethyl)-5- (4-chlorophenyl)-2,3-dihydrothiazolo[3,2-c]- quinazolin-4-ium Bromide (7b): Yield 63%; m. p. 302"C, colorless prisms. - TR: 1596 cm-', 1562, 1481, 1403,1349, 1301, 1084,1016,

3.75-4.10(m, 2H, CH2Br), 4.90-5.65 (m, 3H, = N + -CH2-CH), 7.50-8.6 (m, 8H, aryl H).

823, 779, 728, 708. - 'H NMR (CDCI, + CFjC02H): 6 =

C17Hl3Br2C1N2S (472.6) Calcd. C 43.20 H 2.77 N 5.93 Found C 43.31 H 2.82 N 6.09

2- (Bromomethyl) -2,3-dihydro-5- (4-methylphenyl) thiazolo- (3,2-c/quinazolin-4-ium Bromide (7c): Yield 67%; m.p. 188 "C, co- lorlessprisms. - IR: 1609 cm-', 1589,1562,1404,1350,1343,1304, 1227, 1188, 1173, 1119, 957, 853, 818, 730, 726. - 'H NMR (CDC13 + CF3C02H): 6 = 2.55 (s, 3H, CH,), 3.80-4.20 (m, 2H, CH,Br), 5.10-5.80(m, 3H, = N + -CH2-CH), 7.50-8.70(m, 8H, aryl H). - MS (70 eV): m/z (%) = 373 (M+ + 2) (5) , 371 (M+) (5) , 291 (30), 277 (6), 252 (37), 220 (18), 219 (loo), 116 (14), 82 (73), 81 (37), 80 (71), 79 (36).

CI8Hl6Br2N2S (452.2) Calcd. C 47.81 H 3.57 N 6.19 Found C 47.92 H 3.40 N 6.24

2- (Bromomethyl) -2,3-dihydro-5- (4-melhoxyphenyl) thiazolo- [3,2-c]quinazolin-4-ium Bromide (7d): Yield 63%; m.p. 240"C, co- lorlessprisms. - TR: 1608 cm-', 1557, 1512, 1478, 1404, 1344, 1256, 1179, 1020, 964, 842, 773, 746, 625. - 'H NMR (CDCl, + CF3C02H): 6 = 3.75-4.15 (m, 2H, CH,Br), 4.05 (s, 3H, OCH3), 5.05-5.80 (m, 3H, =N+-CH,-CH), 7.43-8.75 (m, 8H, aryl H). - MS (70 eV): m/z (%) = 389 (M+ + 2) (9), 387 (M') (9), 307 (52), 293 (91 268 (42), 236 (18), 235 (loo), 133 (4), 132 (7), 82 (29), 81 (lo), 80 (30), 79 (9).

C18H16Br2N20S (468.2) Calcd. C 46.18 H 3.44 N 5.98 Found C 46.30 H 3.51 N 6.07

2-Aryl-4-(propargylthio)~u~~uzolines 8. - General Procedure: To a solution of the appropriate thione 1 (4 mmol) in benzene (30 ml), triethylamine (4 mmol) and propargyl bromide (4 mmol) were ad- ded. After 3 h of heating under reflux, triethylammonium bromide was deposited. The salt was separated by filtration, and the filtrate was kept at 0°C for about 12 h. The separated yellow solid was filtered off and recrystallized from ethanol to give 8.

2-Phenyl-4- (propargylthiolquinazoline (8a): Yield 82%; m. p. 11O"C, yellow needles. - IR: 3166 cm-', 1602, 1568, 1500, 1466, 1449, 1347, 1223, 1149, 1030, 888, 815, 764, 701. - 'H NMR

2.6 Hz, CH2-C=CH), 7.37-7.55 (m, 4H, aryl H), 7.68-7.94 (m, 3H, aryl H), 8.50-8.60 (m, 2H, aryl H). - I3C NMR (CDC13): 6 = 18.07 (C-cc), 70.97 (C-y), 79.03 (C-p), 122.07 (C-4a), 123.39 (C-5),

133.67 (C-7), 137.76 (C-I,), 149.00 (C-8a), 158.77 (C-4), 168.80 (C- 2). - MS (70 eV): m/z (YO) = 277 (M+ + 1) (8), 276 (M') (27) 275 (loo), 274 (16), 238 (5), 206 (5) , 205 (15), 77 (30).

(CDCI?): 6 = 2.22 (t, l H , J = 2.6 Hz, C=CH), 4.20 (d, 2H, J =

126.69 (C-6), 128.39 (C-3'), 128.54 (C-2') 129.01 (C-8), 130.53 (C-4'),

CI7Hl2N2S (276.4) Calcd. C 73.89 H 4.38 N 10.14 Found C 73.91 H 4.43 N 10.01

2-[4-Chlorophenyl)-4-(propargylthio)quinazoline (8 b): Yield 87%; m.p. 156"C, yellow needles. - IR: 3228 cm-', 1562, 1540, 1381, 1326, 1223, 1098, 843, 764, 741. - 'H NMR (CDC1,): 6 = 2.26 (t, l H , J = 2.6 Hz, CECH), 4.24 (d, 2H, J = 2.6 Hz, CH2-C-CH), 7.49(d, 2H, J = 8.7 Hz, 3'-H, 5'-H), 7.46-7.58 (m, l H , aryl H), 7.80-7.93 (m, IH, aryl H), 8.00 (d, 2H, J = 8.4 Hz, aryl H), 8.58 (d, 2H, J = 8.7 Hz, 2'-H, 6'-H). - I3C NMR (CDCl,): 6 = 18.06 (C-a), 70.89 (C-y), 78.53 (C-p), 122.03 (C-4a), 123.40 (C-

7). - MS (70 eV): m/z (YO) = 312 (M+ + 2) (lo), 311 (39), 310 (M+) (31), 309 (loo), 274 (3), 272 (6), 241 (6), 239 (17), 113 (3), 111 (9).

5), 126.91 (C-6), 128.58 (C-2'), 128.90 (C-8), 129.78 (C-3'), 133.85 (C-

C17HllClN2S (310.8) Calcd. C 65.70 H 3.57 N 9.01 Found C 65.82 H 3.41 N 8.88

2-(d-Methylphenyll-4- (propargy1thio)quinazoline (8c): Yield 72%; m.p. 128-13OCC, yellow needles. - IR: 3222 cm-', 1608, 1562, 1540, 1455, 1342, 1262, 1177, 996, 871, 837, 758, 736. - 'H NMR (CDC13): 6 = 2.37 (t, 1 H, J = 2.6 Hz, C=CH), 2.40 (s, 3H, CH3), 4.21 (d, 2H, J = 2.6 Hz, CH~-CECH), 7.32 (d, 2H,

Liebigs Ann. Chem. 1987. 103 - 109

108 P. Molina, A. Arques, M. V. Vinader

J = 8.1 Hz, 3'-H, 5'-H), 7.35-7.45 (m, l H , aryl H), 7.77-7.98 (m, 3H, aryl H), 8.52 (d, 2H, J = 8.1 Hz, 2'-H, 6'-H). - 13C NMR

CF3C02H): 6 = 4.05 (s, 3H, OCH3), 5.15 (d, 2H, CH2Br), 6.8 (t, 1 H, 2-H), 7.20-9.00 (m, 8H, aryl H).

Cl8HI4Br2NZOS (466.2) Calcd. C 46.38 H 3.03 N 6.01 Found C 46.12 H 3.12 N 5.89

(CDC13): 6 = 17.66 (C-a), 21.39 (CH,), 70.88 (C-y), 79.04 (C-p), 121.34 (C-kd), 123.34 (C-5), 126.44 (C-6), 128.45 (C-3'), 128.85 (C-8), 129.13 (C-2'), 133.59 (C-7), 134.97 (C-l'), 140.75 (C-4'), 148.97 (C-8a), 158.80 (C-4), 168.54 (C-2). - MS (70 ev): m/z (Yn) = 291 (Mi + 1) (9), 290 (M+) (32), 289 (loo), 288 (15), 258 (3, 252 (7), 220 (71. 219 (231. 91 (151. 39 (13).

Imidazoles 10 and 11. - General Procedure: To a suspension of the appropriate 1,3-benzothiazine 5 (4 mmol) in ethanol (40 ml), propargylamine (4 mmol) was added. The reaction mixture was

~I ~, ~I

refluxed for 6 h, the solution was cooled at O T , and the yellow Precipitated solid was filtered off and recrystallized from ethanol to give 10.

CI8Hl4N2S (290.4) Calcd. C 74.45 H 4.86 N 9.65 Found C 74.33 H 4.90 N 9.51

2- (4-Methoxyphenyl) -4- (propurgylthio) quinazoline (8d): Yield 75%; m.p. 126"C, yellow needles. - IR: 3296 cm-', 1608, 1562, 1540, 1517, 1483, 1353, 1336, 1257, 1166, 1030, 990, 837, 772, 752, 718, 650. - 2.6 Hz, C=CH), 3.81 ( s , OCH3), 4.15 (d, 2H, J = 2.6 Hz, CH~-CCCH),

'H NMR (CDC13): 6 = 2.22 (t, l H , J =

6.94 (d, 2H, J = 8.9 Hz, 3'-H, 5'-H), 7.18-7.89 (m, 4H, aryl H), 8.48 (d, 2H, J = 8.9 Hz, 2-H, 6'-H). - MS (70 eV): m/z (Yn) = 307 (M' + 1) (ll), 306 (M') (39), 305 (IOO), 290 (5), 262 (13), 261 (lo), 235 (25), 134 (lo), 39 (15).

C18H14N20S (306.4) Calcd. C 70.56 H 4.61 N 9.14 Found C 70.34 H 4.42 N 9.35

5-Aryl-3-(bromomethyl)thiazolo[3,2-c]quinazolin-4-ium Bromi- des 9. - General Procedure: A solution of bromine (2 mmol) in carbon tetrachloride (10 ml) was added dropwise to a well-stirred suspension of the appropriate quinazoline 8 (2 mmol) in the same solvent (20 ml). The reaction mixture was stirred at room temper- ature for 3 h and the precipitated solid collected by filtration to give 9.

3-(Bromornethyl)-5-phenylthiuzolo[3,2-c]quinazolin-4-ium Bro- mide (9a): Yield 73%; m.p. 166"C, yelow prisms. - IR: 1619 cm-',

'H NMR (CDCI, + CF3C02H): 6 = 5.1 (d, 2H, CH,Br), 6.5 (t, 1 H, 2-H), 7.65-8.95 (m, 9H, aryl H). - MS (70 eV): m/z (%) = 357 (M+ + 2) (6), 355 (M') (6), 276 (18), 275 (M+ - HBr) (72), 205 (13), 362 (42), 160 (89), 158 (46), 82 (loo), 80 (100).

1596, 1531, 1494, 1359, 1342, 1274, 996, 758, 701, 679, 650. -

CI7Hl2Br2N2S (436.2) Calcd. C 46.81 H 2.77 N 6.42 Found C 46.72 H 2.87 N 6.30

3-(Bromomethyl) -5- (4-chlorophenyl) thiazolo[3,2-c]quinazolin-4- ium Bromide (9b): Yield 70%; m.p. 173-178°C. - IR: 1619 cm-', 1608, 1557, 1540, 1499, 1404, 1348, 1313, 1268, 1245, 1155, 1013, 837, 820, 792, 667. - MS (70 eV): m/z (%) = 393 (M' + 4) (3), 392 (2), 391 (M + + 2) (7), 390 (2), 289 (M+) (6), 312 (ll), 311 (40), 310 (35), 309 (M+ - HBr) (loo), 241 (7), 239 (20), 113 (6), 111 (17).

C17HllBr,C1N,S (470.6) Calcd. C 43.30 H 2.36 N 5.95 Found C 43.48 H 2.40 N 6.12

3-(Bromomethyl)-5- (4-methylphenyl) thiazolo[3,2-c]quinazolin- 4-ium Bromide (9c): Yield 70%; m.p. 175- 177"C, yellow prisms. - IR: 1620 cm-', 1608,1557,1494,1410,1347,1319,1302,1247,1251, 1189, 1030, 1002, 826, 764, 724, 622. - 'H NMR (CDC13 + CF~COZH): 6 = 2.5 (s, 3H, CH3), 5.10 (s, 2H, CH2Br), 7.0 (s, 1 H, 2-H), 7.5-9.3 (m, 8H, aryl H). - MS (70 eV): m/z (YO) = 371 (2), 369 (M') (2), 290 (30), 289 (M+ - HBr) (loo), 219 (18), 91 (Il), 82 (15), 80 (11).

C18Hi4Br2N2S (450.2) Calcd. C 48.02 H 3.13 N 6.22 Found C 47.89 H 3.30 N 6.32

3- (Bromomethyl) -5- (methoxyphenyl) thiazolo[3,2-c]quinazolin- 4-ium Bromide (9d): Yield 67%; m.p. 177- 179"C, yellow prisms. - IR: 1619 cm-', 1608,1557,1517,1404,1347,1325,1268,1217,1183, 1019, 1002, 866, 837, 764, 724, 622. - 'H NMR (CDCI, +

2- (5-Methyl-2-phenyl- IH-imidazol-1-yl) dithiobenzoic Acid (10 a): Yield 68%; m.p. 128"C, yellow needles. - IR: 1620 cm-', 1597,

'H NMR (CDCI,): 6 = 2.55 (d, 3H, J = 1 Hz, CH3), 7.30-8.70 (m, 9H, aryl H), 10.10 (d, l H , J = 4.5 Hz, aryl H), 14.40 (s, broad, IH, CSSH). - I3C NMR (CDC13): 6 = 11.60 (CH,), 121.59 (C-4), 122.00 (C-CSSH), 133.80 (C-5), 144.04 (C-2), 197.39 (C=S), others: 125.25, 127.46, 128.06, 128.61, 129.50, 130.62, 137.67, 139.89, 166.46 (aryl carbons). - MS (70 eV): m/z (%) = 310 (M+) (4), 309 (6), 278 (22), 277 (loo), 121 (lo), 77 (7).

1548, 1477, 1470, 1359, 1306,1215, 1140,973,836,768,751,689. -

C17H14N2S2 (310.4) Calcd. C 65.78 H 4.55 N 9.02 Found C 65.81 H 4.42 N 8.90

2-15- Methkf-2- (4-methylphenyl) -1 H-imidazol-1-yl/dithiobenzoic Acid (lob): Yield 72%; m.p. 142"C, yellow needles. - IR: 1630 cm-', 1602,1562,1472,1404,1376,1308,1211,1143,996,973, 843, 769, 747, 633. - 'H NMR (CDClJ: 6 = 2.52 (d, 3H, J = 1.2 Hz, CHI), 7.20-8.30 (m, 8H, aryl H), 9.98 (d, IH, J = 8 Hz, aryl H), 14.45 (s, broad, 1 H, CSSH). - MS (70 eV): m/z (YO) = 345 (3), 344 (M+) (3), 343 (7), 314 (7), 313 (35), 312 (21), 311 (loo), 113 (31, 11 1 (9).

C17H13CIN2SZ (344.9) Calcd. C 59.21 H 3.80 N 8.12 Found C 59.03 H 3.73 N 8.28

2-[2- (4-Chlorophenyl) -5-methyl-1 H-imidazol-i -yl/dithiobenzoic Acid (1Oc): Yield 70%; m.p. 115-119"C, yellow needles. - IR: 1619 cm-', 1597,1552,1529,1352,1304,1206,1184,1144,991,976,

aryl CHJ, 2.40 (d, 3H, J = 1.1 Hz, 5-CH3), 7.25-8.20 (m, 8H, aryl H), 9.95 (dd, l H , J = 8.2 Hz, J = 1.3 Hz, aryl H), 14.40 (s, broad, l H , CSSH). - MS (70 eV): m/z (%) = 324 (M') (4), 323 (5), 292 (19), 291 (SO), 270 (21), 269 (loo), 237 (14), 236 (13), 194 (8), 193 (37), 192 (24), 91 (13).

Cl8Hl6N2S2 (324.5)

835, 816, 769, 718, 640. - 'H NMR (CDCI3): 6 = 2.36 (s , 3H,

Calcd. C 66.63 H 4.97 N 8.63 Found C 66.44 H 4.92 N 8.81

2-(2- (4-Methoxyphenyl)-5-methyl-l H-imidazol-l-yljdithioben- zoic Acid (10d): Yield 53%; m.p. 96-98"C, yellow needles. - IR: 1625 cm-', 1602, 1591, 1506, 1421, 1365, 1308, 1257, 1183, 1143, 991, 837, 804, 753, 719, 690. - 'H NMR (CDC13): 6 = 2.39 ( s , 3H, CH3), 3.79 (s, 3H, OCH3), 6.79-8.02 (m, 8H, aryl H), 9.58 (d, l H , J = 8.0 Hz, aryl H), 14.35 (s, broad, 1 H, CSSH).

Cj8H16NZOS2 (340.5) Calcd. C 63.50 H 4.74 N 8.23 Found C 63.62 H 4.50 N 7.98

To a solution of potassium hydroxide (2 mmol) in ethanol (30 ml), the appropriate imidazole derivative 10 (1 mmol) and methyl iodide (2 mmol) were added. The reaction mixture was stirred at room temperature for 30 min, and the precipitated solid was collected by filtration and recrystallized from ethanol to give 11.

Methyl 2-(5-Methyl-2-phenyl-lH-imidazol-l-yl)dithiobenzoate ( l la): Yield 80%; m.p. 161"C, yellow prisms. - IR: 1653 cm-', 1602, 1585, 1568, 1489, 1443, 1381, 1279, 1223, 1092, 973,956, 922,

Liebigs Ann. Chem. 1987, 103 - 109

2,3-Dihydrothiazolo[3,2-c]quinazolinium Salts 109

769, 747, 701, 634. - 'H NMR (CDC13): 6 = 2.48 (d, 3H, J = 2.1 Hz, CH,), 2.60 (s, 3H, SCH,), 6.40-6.70 (m, IH, aryl H), 7.02-7.30 (m, 2H, aryl H), 7.42 (s, 5H, aryl H), 7.55 (d, 1 H, J = 1.2 Hz, aryl H), 8.31 (dd, IH, J = 3.5 Hz, J = 3.7 Hz, aryl H). - MS (70 eV): m/z (%) = 324 (M+) (2), 323 (4), 322 (7), 309 (4), 278 (23), 277 (loo), 103 (7), 102 (9), 77 (12).

m/z (Yo) = 354 (M+) (4), 339 (3), 308 (21), 307 (IOO), 173 (12), 107 (7).

CiYHl8N20S2 (354.5) Calcd. C 64.38 H 5.12 N 7.90 Found C 64.42 H 5.25 N 7.60

CAS Registry Numbers

Cj8Hl6N2S2 (324.5) Calcd. C 66.63 H 4.97 N 8.63 Found C 66.37 H 4.75 N 8.79

l a : 6483-99-4 I 1 b: 105250-97-3 / 1c: 105250-98-4 / Id: 20800- 41-3 / 2a: 33238-84-5 / 2b: 105250-99-5 / 2c: 105251-00-1 / 2d: 105251-01-2 / 3a: 33399-80-3 / 3b: 105251-02-3 / 3c: 105251- 03-4 j 3d: 105251-04-5 / 4a: 105251-05-6 / 4b: 105251-06-7 / 4c:

5 ~ : 53628-15-2 i 5d: 17240-31-2 i 5e: 32524-48-4 / 6a: 105251- 2-[2-f4-Ch1oro~heny1~-5-methy1-iH-imidazo1-1-y1/dithio- 105251-07-8 / 4d: 105251-08-9 1 s a : 17240-30-1 / 5b: 17240-32-3 /

benzoate (llb): Yield 86%; m.p. 118"C, yellow PriSms. - IR: 1659 cm-', 1602,1585,1562,1489,1398,1279,1123,1098,979,837, 826,775, 758,735,633. - 'H NMR (CDCI,): 6 = 2.53 (s, 3H, CH,), 2.62 (s, 3H, SCH,), 6.30-6.60 (m, IH, aryl H), 6.90-7.40 (m, 6H, aryl H), 7.65 (d, l H , J = 1.3 Hz, aryl H), 8.25-8.50 (m, IH, aryl H). - MS (70 eV): m/z (%) = 358 (M+) (I), 343 (I), 314 (9), 313 (34), 312 (23), 311 (loo), 173 (lo), 113 (2), 111 (7).

Cl8HI5C1N2S2 (358.9) Calcd. C 60.24 H 4.21 N 7.81 Found C 60.12 H 4.32 N 7.64

Methyl 2-[5-Methyl-2- (4-methylphenyl) - I H-imidazol-f - y l /d i - thiobenzoate (llc): Yield 83%; m.p. 143"C, yellow prisms. - IR: 1642 cm-', 1602, 1562, 1472, 1443, 1279, 1240, 1183, 968,939, 860,

aryl CH,), 2.55 (d, 3H, J = 1.2 Hz, CH,), 2.65 (s, 3H, SCH,), 6.30-6.65 (m, lH,aryl H), 6.90-7.40(m, 6H, aryl H), 7.70(d, l H , J = 1.2 Hz, aryl H), 8.50 (dd, l H , J = 3.8 Hz, J = 6.2 Hz, aryl H). - MS (70 eV): nzjz (%) = 338 (M+) (3), 292 (26), 291 (loo), 173 (7), 91 (4).

820, 758, 724, 684, 633. - 'H NMR (CDCI,): 6 = 2.30 (s, 3H,

ClYHl8N2S2 (338.5) Calcd. C 67.42 H 5.36 N 8.28 Found C 67.53 H 5.42 N 8.03

Methyl 2-[2-(4-Methoxyphenylj-5-methyl-lH-imidazol-l-yl]di- thiobenzoate (lld): Yield 88%; m.p. 129"C, yellow prisms. - IR: 1608 cm-I, 1562, 1506, 1303, 1262, 1240, 1172, 1025,968,961, 843,

SCH3), 3.80 (s, 3H, OCH,), 6.30-6.55 (m, l H , aryl H), 6.65-7.80 (m, 7H, aryl H), 8.40-8.60 (m, IH, aryl H). - MS (70eV):

758, 679. - 'H NMR (CDC13): 6 = 2.55 (s, 3H, CH,), 2.65 (s, 3H,

09-0 / 6b: 105251-10-3 / 6c: 105251-11-4 / 6d: 105251-12-5 / 6e: 105251-13-6 / 7a: 105251-34-7 / 7b: 105251-15-8 / 7c: 105251- 16-9 / 7d: 105251-17-0 / 8 a : 105251-18-1 / 8b: 105251-19-2 1 8c: 105251-20-5 / 8d: 105251-21-6 / 9a: 105251-22-7 1 9b: 105251- 23-8 / 9 c : 105251-24-9 / 9 d : 105251-25-0 1 10a: 105251-26-1 / lob: 105251-27-2 / 1Oc: 105251-28-3 / 10d: 105253-29-4 / l l a : 105251-

BrCH2CH=CH2: 106-95-6 / H2NCH2CH=CH2: 107-11-9 / BrCH2C = CH: 106-96-7 / H2NCH2C E CH: 2450-71-7

30-7 / l l b : 105251-31-8 / 1 1 ~ : 105251-32-9 / l l d : 105251-33-0 /

L. Legrand, N. Lozac'h, Bull. SOC. Chim. Fr. 1961, 618; ibid. 1961, 1400 ibid. 1961,2088; ibid. 1982, 133; Phosphorus Sulfur 5 (1978) 209.

2, A Sammour. M. L. Selim. A. F. M. Fahmv. K. Elewa. Indian J. Chem. 21 (1973) 437. '

3, P. Molina, A. Arques, I. Cartagena, M. V. Valcarcel, J. Hete- rocycl. Chem. 23 (1986) 43.

4, P. Molina, A. Arques, I. Cartagena, M. V. Valcarcel, Heterocyc- les 23 (1985) 2357. P. Molina. A. Araues, I. Cartagena, M. V. Valcarcel, Synthesis - 1984, 881.

6, P. Molina, A. Arques, I. Cartagena, M. V. Valcarcel, J. Hete- rocycl. Chem. 22 (1985) 1189.

7, H. Singh, S. K. Aggarwal, N. Malhotra, Heterocycles 22 (1984) 353; H. Singh, K. Deep, Tetrahedron 40 (1984) 4937.

') P. B. Talukdar, S. K. Sengupta, A. K. Data, T. K. Roy, Indian J. Chem., Sect B, 15B (1977) 41; K. T. Potts, D. R. Choudhury, J. Ory. Chem. 43 (1978) 2700. - K. T. Potts, P. Murphy, J. Chem. Soc., Chem. Commun. 1984,1348. - K. T. Potts, K. Bor- deaux, W. Kuehnling, R. L. Salsbury, J. Chem. Soc., Chem. Com- mun. 1984, 213; J. Org. Chem. 50 (1985) 1666.

9, P. Molina, M. Alajarin, M. J. Perez de Vega, Synth. Commun. 1983, 933.

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