P. Molina, A. Arques, I. Cartagena, M. A. Alias, M. de la Concepcion Foces-Foces, F. H. Cano

Preparation of 2-Substituted 1,3,4-Thiadiazoles and Mesoionic 1,3,4-Thiadiazole[3,2-c]quinazolines from 4H-3,1-Benzothiazine-4-thiones or 3-Amino-4( 3H)-quinazolinet hiones Pedro Molina” ’, Antonio Arquesa, Inmaculada Cartagena”, Maria Asuncion Alias“, Maria de la Concepci6n Foces-Focesb, and Felix Hernandez Cano

Departamento de Quiniica Organica, Facultad de Ciencias, Universidad de Murcia”, 30001, Murcia, Spain

Departamento de Rayos X, Instituto de Quimica Fisica “Rocasolano”b. Serrano 119, 28006, Madrid, Spain

Received July 30, 1987

Reaction of 4H-3.1-benzothiazine-4-lhiones 1 with S-methyliso- thiosemicarbazide hydroiodide yields bamino-1.3.4-thiadiazoles 2 insteud of the espected 1.2,4-triazolo[3,2-c]quinazolines. Struc- tures of compounds 2 have been established by mcans of ‘>C- N M R analysis and X-ray crystallography. 3-Arnino-4(3/f )-quin- azolinethiones 4 react with ketcne dithioacetals 5 to give the new mesoionic t,3,~thiadiazolo[3.2-c]quinazolinylium-2-methanides 6 which undergo ring opening by the action or hydrochloric acid to givc z-methylene- 1,3.4-thiadiamles 7. Compounds 2 are con- vcrted into the corresponding oxygen analog 9 by treatment with hydrochloric acid.

The reaction of primary amines with 4H-3,1-benzothia- zine-4-thiones to give 4(3H)-quinazolinethiones is well-doc- umented. In this context, we have studied the reaction with several bifunctionalized nitrogen nucleophiles giving fused quinazoline derivatives’). On the other hand, we have re- ported the preparation of mesoionic 1,2,4-triazolo[3,2-c]- quinazolines from 3-amino-4(3H)-quinazolinethiones and aromatic isothiocyanates” or diaryl~arbodiimides~). We re- port here attempts to synthesize 2-substituted S-aryl-l,3,4- thiadiazoles by two approaches: a) from 4H-3,l-benzothia- zine-4-thiones and S-methylisothiosemicarbazide to give 2- amino-l,3,4-thiadiazoles and b) via mesoionic 1,3,4-thiadia- zolo[3,2-c]quinazolines to give 2-methylene-l,3,4-thiadi- azoles.

In general, the most common procedure for the synthesis of 5-substituted 2-amino-l,3,4-thiadiazoles is the acylation of thiosemicarbazide or derivatives followed by dehydration under acidic conditions4). However, no general useful pro- cedure for the preparation of 2-methylene-l,3,4-thiadiazoles has hitherto been reported, it has only been briefly mentioned 5,6) the preparation of mesoionic heptafulvenes de- rived from the 1,3,4-thiadiazole ring system.

Our approach to the preparation of 5-aryl-2-amino-1,3,4- thiadiazoles is based on the ring opening of 4H-3,l-benzo- thiazine-Cthiones by the action of thiosemicarbazide deriv- atives. Thus, the reactions between 1 and S-methylisothio- semicarbazide hydroiodide7) in ethanolic solutions in the

133

Herstellung Zsubstituierter 1,3.4-Thiadiazoie und mesoionkcher 1$,4-Tb~diazol[3,Z-c)cbi~zoliw nus 4H-3,1-Benzothinzin-4- tbionen odor 3-Amino-4(3H)-chinazoliithio~n

4n-3,I-Benzothiatin-4-thione vom Typ 1 reagieren mit S-Methyl- isothiosemicarbazid-hydroiodid zu ?-Amino- I ,3,4-thiadiazolrn 2 an Stelle der crwartctcn 1.2,4-Triazolo[3,Z-c]chinazoline. Dic Strukturauklhng von 2 gelang durch Rantgcnstrukturanalyse und ‘3C-NMR-Spektroskopie. Die .l-Amino-4(3H~chinlvolin- thione 4 reagieren mit Keten-dithioacetalen 5 zu ncuartigen meso- ionischen t ,3,CThiadiazolo[ 3.2-c]chinazolinylium-l-met hanidcn 6. Letztere erleiden RingiitTnung durch Salzsaurc unter Bildunp von 2-Methylen-l,3,4thiadiazolen 7. Die Verbindungen 2 lassen sich durch Behandlung mil Salzsiure in die entsprechenden 0- Analoga 9 umwandeln.

SCHI x y R \ -I- H2N-N=C-NH2.1H I

S

I 1

bJ 2

1. 2

a b C

d

SCH3 3

R

‘gH5 4-C1-C6H4 4-H3C-C H

(CH313C 6 4

presence of sodium acetate run in a different way compared with the previously described reaction of 1 with primary amino groups. The reaction products are found to be 5-aryl- 2-amino-l,3,4-thiadiazoles 2 instead of the expected l,2,4-

Liebigs Ann. Chem. 1988, 133- 139 0 VCH Verlagsgesellschaft mbH, D-6940 Weinheim, 1988 0170-2041/88/0202-0233 $ 02.50/0

134 P. Molina, A. Arques, I. Cartagena, M. A. Alias, M. de la Concepcion Foces-Foces, F. H. Can0

triazolo[3,2-c]quinazoline derivatives 3. For instance, in the case of the 4H-3,1-benzothiazine-4-thione 1 a, compound 2a was isolated. The mass spectra (EI and FAB) show the ex- pected molecular ion peaks, the base peak is due to the fragment (M+ - SH), peaks are also found for M + - 32 (loss of sulfur) and for (R-CS). The thiocarbonyl group signal shows up characteristically in the 13C-NMR spectra at 6 = 199 - 182, the quaternary carbon signals (C-2 and C-5) in the thiadiazole ring appear at 6 = 169 and 6 = 153 respectively, in addition in 2 d the aliphatic carbon signals appear at 6 = 30 and 6 = 45, respectively.

To identify unambigously this compound, an X-ray struc- ture determination has been performed. The final atomic coordinates for the nonhydrogen atoms are given in Table 1, according to the numbering scheme shown in Figure 1. Table 2 gives a selection of the geometrical features in the molecular structure.

Figure 1. A PLUTO view’) of the two independent molecules of 2a showing the numbering system

The bond length distributions are equal, within the achieved accuracy, between both independent molecules, and they agree with those in the literature’). The most re- markable feature in the constitution is the aperture of the C-N-C angle at N13 and N 13’ (see Table 2). A search in the Cambridge Data File’), concerning the thioamide group, shows that there are precedents of this and it is present even in some amides ‘,12313,14).

The two molecules used in the crystallographic analysis have opposite conformation, their degree of puckering being a bit different, and mainly held through the torsion around the alterning bonds C16-Cl4, N13-C8, C5-C7, and the corresponding dashed ones (see Table 2). The puckering sit- uates the molecules approximately at two levels of the b axis, as defined by the phenyl rings and the thiadiazolyl ring systems. An intramolecular hydrogen bond, joining N13 with N4, supports the planarity of these parts of the molecule^'^). The crystal structure contains a network of intermolecular hydrogen bonds (see Table 3).

Presumably, the conversion 1+2 involves initial addition of one amino group of the S-methylisothiosemicarbazide to the thiocarbonyl group of 4H-3,1-benzothiazine-4-thione (1) and subsequent ring opening to give an open-chain inter- mediate which undergoes cyclization and elimination of methanethiol to give 2.

SCH, I

H~N-NzC-NH~. IH 1

sH 1 KyR q = C - R

- 2 -H,CSH N-N N H ~

SH V N H z SCH,

HS NH-N

Our approach to 2-methylene-l,3,4-thiadiazoles either with mesoionic or neutral character is based on the struc- tural similarity between the N-amino heterocycle 4 and N- thioacylhydrazines, which are useful starting materials for the preparation of the mesoionic 1,3,4-thiadiazolium system16). On the other hand, it is well-known that the re- action of polarized ethylenes bearing push-pull substituents with bifunctionalized nucleophiles allows the preparation of a variety of heterocyclic compounds 17s1’). Thus, when the thiones 4 are treated with ketene dithioacetals 5 in dry di- methylformamide in the presence of potassium tert-butox- ide, the new mesoionic 1,3,4-thiadiazolo[3,2-c]quinazoliny- lium-2-methanides 6 are isolated as crystalline solids in

S

L

6

- a b C

d

e f

9 h

1

j k 1 m n

5

R

‘sH5

‘6’5 ‘6’5

4-H3C-C6H4

4-H3C-C H 6 4 4-H3C-C6H4

4-H3CO-C6H4 4-H3CO-C6H4

4-H3CO-C H 6 4

CH3 CH3

(CH3)3C (CH3 C (CH3l3C

CN 6

X

CN COOCH3 CONHZ

CN

COOCH3 CONH2

CN COOCH.,

CONH2 COOCH3

CONH2 CN

COOCH3 CONHZ

20- 86% yields. The IR spectra of the four dicyanomethan- ides 6a, 6d, 6g, and 61, show two intense absorptions re- sulting from the symmetrical and asymmetrical stretching vibrations of nitrile groups in the region 2210-2175 cm-l, whereas the monocyanomethanides show one band in this region. The carbonyl stretching band of compounds 6b, 6e, 6h, 6j, and 6m appear in the region 1650-1640 cm-‘, a considerable shift to lower wave number compared with the normal value for a methoxycarbonyl group. This suggests the contribution of a dipolar mesoionic structure. Strong

Liebigs Ann. Chem. 1988, 133-139

2-Substituted 1,3,4-Thiadiazoles and Mesoionic 1,3,4-Thiadiazole[3,2-c]quinazolines 135

absorption due to the stretching vibration of the exocyclic carbon -carbon bond appears at 1580 - 1560 cm-I. In the electronic spectra the long wave-length maxima lie in the range 273 and 325 nm. Mass spectra show the expected molecular ion peaks in high intensities, and the fragmen- tation pattern is in accord with the proposed structure.

8

b 1 4-H:C-C6H4 I COC€H3

C 4 - H C-C6H4 CONH2

b I 4-H3CO-C6H4 I COOCH3

L J

9

Compounds 6, by action of hydrochloric acid, undergo hydrolytic cleavage to give 5-aryl-2-methylene-1,3,4-thiadi- azoles 7 in moderate to good yields. The above results show so far unrevealed high reactivity at position 2 of the pyrimi- dine ring in fused 1,3,4-thiadiazolo[3,2-c]quinazoline deri- vative~'~). On the other hand, compounds 7 by treatment with phosphorus pentasulfide are transformed into the cor- responding thio analog 8 in fair yields. Finally we have found that compounds 2 by action of hydrochloric acid undergo desulfurization to give the oxygen analogs 9 in excellent yields. It is conceivable that the conversion 2+9 could be due to the initial formation of bicyclic salts (1,3,4- thiadiazolo[3,2-c]quinazolinium chloride) which by nucleo- philic attack of water on position 2 of the pyrimidine ring undergo ring opening to give 9.

We thank to the Comisidn Asesora de Znvestigacion Cientifica y Te'cnica for financial support (project number 2019/83).

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

NMR spectra: Varian FT-80 instrument. - IR spectra: Nicolet- 5 DX, nujol used in all cases. - Mass spectra: Hewlett-Packard 5993 C. - UV spectra: Hitachi U-3200 spectrophotometer. - Melting points (uncorrected): Kofler hot-stage apparatus. 2-Aryl-4H-3,1-benzothiazine-4-thione~~~), 2-aryl-3-amino-4(3H)-

quinazolinethiones"), and ketene dithioacetals 22) were prepared fol- lowing the methods described in the literature.

X-ray Crystallography: Ct5H12N4S2 (31 2.41), monoclinic, space group P2,/c, a = 19.1259(14), b = 7.4728(3), c = 21.6850(20) A, p = 112.373(6)", Dc = 1.448 g ~ m - ~ , Z = 8. Cell constants ob- tained from a least-squares fit using 84 reflexions up to 0 = 45" and CuK, radiation. A transparent prism-like sample (0.33 x 0.27 x 0.10 mm) was used for the analysis on a Philips PW 1100 diffractometer, with CuK, radiation, graphite monochromator. 13/20 scans, bisecting geometry, 1 x 1" detector apertures, 1.5" scan width and using 1 min per reflexion. Good stability of the sample was checked every 90 min. - A 30(4 criterion gave 3657 observed reflexions, up to 65" in 0. Empirical absorption cor- rection resulted with a range of transmission factors between 0.577 and 1.385. The structure was solved by direct methods and refined by two block matrix least-squares procedures for 475 parame- ters. - All the hydrogen atoms were located by a difference syn- thesis. An empirical weigthing scheme, so as to give no trends in (wA2F) vs. (I F,I) and (sin @)/A), was introduced. The final shift/ error was 0.05 with maximum peak in the final AF of 0.29 e k 3 . The maximum thermal factor is U22(N6) = 0.116(4) w2. The final R and Rw values were 0.058 and 0.065 respectively. All the calcu- lations were performed on a VAX 11/750 computer through the use of the following software: XRAY System23), PLUTO9), MULTAN DIRDIF25) and DIFABS26). The atomic scattering factors were taken from the International Tables2'). - Two crys- tallographically independent molecules are present in the structure, the ones chosen for the X-ray analysis being approximately related by an extra, pseudoglide plane on a, quasinormal to b, in such a way that the coordinates of these molecules are related by: x' x

2-Amino-5-[2-(thioacylamino)phenyl]-f,3,4-thiadiazoles 2. -

General Procedure: To a solution of 1 (1 g, 3 mmol) in ethanol (20 ml), a solution of S-methylisothiosemicarbazide hydroiodide (1.60 g, 6 mmol) and sodium acetate (1.13 g, 6 mmol) in water (15 ml) was added dropwise. The reaction mixture was stirred at reflux temperature for 4 h. After cooling, the yellow precipitate was collected by filtration, dried, and recrystallized from ethanol to give 2.

2-Amino-S-[2-(thiobenzoylamino)phenyl]-1,3,4-thiadiazole (2a): Yield 88%; m.p. 183-185"C, yellow needles. - IR: 3466 cm-', 3256, 1625, 1596, 1551, 1506, 1486, 1472, 1370, 1206, 996, 752, 690. - 'H NMR ([D6]DMSO): 6 = 7.3-8.4 (m, 11 H, aryl-H, 2 NH), 10.3 (s broad, 1 H, NH, interchangeable with D20). - "C-

0.45 + X, y' x 0.46 - y , Z' = Z.

NMR ([DJDMSO): 6 = 127.2, 127.7, 128.0, 128.3, 128.8, 129.9, 131.3, 137.4, 141.2, 153.2 (C-5), 169.6 (C-2), 199.3 (C=S). - MS (70 eV): m/z (%) = 312 [M'] (S), 280 (18), 279 (loo), 261 (36), 260 (lo), 238 (58), 237 (9), 206 (17), 205 (95), 121 (22), 103 (S), 102 (13), 77 (22), 76 (25).

C15H12N4S2 (312.4) Calcd. C 57.66 H 3.87 N 17.93 Found C 57.69 H 3.84 N 17.94

Liebigs Ann. Chem. 1988, 133- 139

136 P. Molina, A. Arques, I. Cartagena, M. A. Alias, M. de la Concepcihn Foces-Foces, F. H. Can0

Table 1. Final atomic coordinates and thermal parameters as in: U,, = (1/3); C [ U , a*, a*, a, a, cos (a,, aJl

ATOM x/a y/b Z/C ueq.104

Table 2. Selected geometrical parameters [A, "1 of 2a

Mo lecu 1 e undashed dashed

s1-a 1.729r 4) s1 c2 N3 N4 c5 N6 c7 C8 c9 c10 c11 c1z N13 C14 S15 C16 C17 C18 c19 c20 c21 S1' c2 ' N3 ' N4 ' c5 ' N6 ' c7 C8 ' c9 ' c10 C11' c12 * N13' C14' S 1 5 ' C16' C17 ' C18' C 1 9 ' C20' C21'

0.03997( 6 ) 0.13711( 23) 0.17312( 18) 0.12384( 18) 0.05248( 20) 0.172'7( 21) -0.00928( 21) 0.00029( 21) -0.06114( 2 5 ) -0.13249( 2 5 ) -0.14323( 25) -0.08239( 23) 0.07481( 17) 0.10236( 23) 0.05323( 7) 0.18705( 23) 0.22707( 30) 0.30661( 35) 0.34569( 31) 0.30567( 28) 0.22663( 24) 0.52725( 6 ) 0.62388( 22) 0.66221( 18) 0.61594( 18) 0.54435( 20) 0.65707( 21) 0.48485( 20) 0.49775( 20) 0.43872( 2 5 ) 0.36786( 27) 0.35375( 25) 0.41147( 2 2 ) 0.57228( 19) 0.59923( 22) 0.54725( 7) 0.68376( 23) 0.72189( 35) 0.80136( 36) 0.84192( 3 5 ) 0.80498( 28) 0.72617( 2 5 )

0.41889( 16) 0.43611( 61) 0.44664( 53) 0.44280( 49) 0.42961( 50) 0.43975( 69) 0.42667( 5 1 ) 0.39448( 5 1 ) 0.40253( 67) 0.43832( 8 2 ) 0.46727( 8 5 ) 0.46265( 64) 0.35968( 44) 0.28763( 5 2 ) 0.20841( 21) 0.28073( 49) 0.31769( 62) 0.31824( 66) 0.28130( 68) 0.24039( 65) 0.23980( 5 8 ) 0.01133( 14) -0.01110( 56) -0.02301( 5 2 ) -0.01598( 48) 0.00126( 49) -0.01548( 58)

0.00500( 47) 0.04870( 47) 0.04001( 65) -0.01060( 78) -0.04987( 76) -0.04471( 5 8 ) 0.09772( 44) 0.19999( 49) 0.30700( 16) 0.21293( 48) 0.24310( 61) 0.25225( 71) 0.23296( 66) 0.20582( 67) 0.19624( 60)

~

0.17710( 5 ) 469( 4) 0.20305( 21) 498( 16) 0.26773( 16) 513( 14) 0.30013( 16) 475( 1 3 ) 0.26074( 18) 376( 13) 0.16053( 18) 703( 18) 0.28433( 19) 412( 14) 0.35099( 19) 410( 14) 0.36980( 23) 566( 18) 0.32304( 27) 688( 22) 0.25727( 27) 719( 2 2 ) 0.23830( 2 2 ) 541( 17) 0.39698( 15) 419( 1 2 ) 0.45853( 19) 439( 15) 0.50074( 7) 710( 6 ) 0.48646( 19) 429( 14) 0.55325( 23) 632( 19) 0.57808( 28) 782( 23) 0.53856( 34) 752( 24) 0.47270( 29) 672( 22) 0.44632( 2 2 ) 523( 17) 0.17738( 5 ) 440( 4) 0.19915( 21) 458( 1 5 ) 0.26359( 17) 512( 14) 0.29914( 16) 465( 13) 0.26190( 18) 369( 13) 0.15480( 18) -34( 15) 0.28860( 19) 382( 14) 0.35508( 20) 390( 14) 0.37758( 24) 574( 19) 0.33472( 30) 705( 23) 0.26875( 2 8 ) 673( 22) 0.24599( 24) 514( 16) 0.39753( 16) 412( 12) 0.45302( 19) 406( 14) 0.48755( 6 ) 584( 5 ) 0.48135( 19) 440( 15) 0.54876( 24) 632( 21) 0.57646( 30) 784( 24) 0.53758( 32) 759( 24) 0.47017( 30) 671( 22) 0.44207( 24) 528r 1 7 )

2- Amino-5-( 2-[ (4-chlorothiobenzoyl) aminolpheny1)- I ,3,4-thiadi- azole (2 b): Yield 60%; m. p. 184- 186"C, yellow needles. - IR: 3432 cm-', 3239, 3143, 3080, 1636, 1596, 1500, 1409, 1381, 1206, 1092,1013,990,837, 815,752,730,718. - 'H NMR ([D6]DMSO): 6 = 7.2-8.5 (m, 10H, aryl-H, 2 NH), 10.5 (s broad, I H , NH, in- terchangeable with D20). - I3C NMR ([D6]DMSO): 6 = 127.9, 128.1, 128.8, 128.9,129.5, 129.9,136.9, 137.1, 139.7, 153.1 (C-5), 169.5 (C-2), 197.6 (C=S). - MS (70 eV): m/z (%) = 348 [M+ + 21 (3), 346 [M'] (9), 316 (7), 315 (39), 314 (19), 313 (IOO), 297 (9), 295 (20), 274 (51, 272 (13, 241 (8), 239 (21), 157 (4), 155 (Il) , 113 (4), 111 (lo), 76 (8).

C1&llClN& (346.9) Calcd. C 51.94 H 3.20 N 16.15 Found C 51.84 H 3.15 N 16.28

2- Amino-5-(2-[ (4-methylthiobenzoyl)amino]phenyl)-l,3,4-thia- diazole (2c): Yield 61%; m.p. 182-183"C, yellow needles. - IR: 3375 cm-', 3284, 3109, 1629, 1592, 1544, 1503, 1469, 1347, 1303,

2.58 (s, 3H, CH3), 7.3-8.7 (m, 10H, aryl-H, 2 NH), 12.3 (s broad, IH, NH, interchangeable with D20). - 13C NMR ([D,]DMSO):

153.3 (C-5), 169.6 (C-2), 183.0 (C=S). - MS (70 eV): m/z (%) = 326 [M'] (S), 294 (Il), 293 (56), 275 (31), 252 (67), 235 (23), 220 (19), 219 (loo), 135 (9), 118 (lo), 102 (lo), 91 (16), 76 (28).

CI6Hl4N4S2 (326.4) Calcd. C 58.87 H 4.32 N 17.16 Found C 58.69 H 4.24 N 17.33

1201, 1120, 1055, 987, 807, 742. - 'H NMR ([DdDMSO): F =

6 = 21.0 (CH,), 127.2, 127.9, 128.0, 128.8, 129.9, 137.5, 138.4, 141.7,

2-Amino-5-[2-(thiopivaloylamino)phenyl]-l,3,4-thiadiazole (2d): Yield 63%; m.p. 216-218"C, yellow needles. - IR: 3296 cm-', 3239, 3216, 3069, 1619, 1585, 1540, 1511, 1353, 1149, 1058, 1013,

Table 3. Hydrogen bond characteristics [A, "1 of 2a (Roman num- bers indicate the symmetry operations given below)

X-H.. .Y X-H x.. .Y H.. .Y X-H.. .Y

N13-H13....N4i 0.95(5) 2.679(6) 1.89(5) 139f3) N13'-H13'..N4'i 0 . 8 3 ( 5 ) 2.707(6) 2.02(5) 140f4) N6-H6A.....N3'ii 0.97(6) 2.965(5) 2.02(5) 166(63 N6'-H6'A. ..N3iii 0.84(5) 3.049(5) 2.24(4) 160(5) N6-H6B. .... 515iv 0.83(4) 3.525(4) 2.73(4) 162(5) N6'-H6'8 ... S15'iv 0.92(5) 3.767(4) 2.91(5) 156(4)

i : x. y, z iii: 1-x,-1/2+y. 1/2-z ii : 1-x, 1/2ty, 1/2-z iv : x, 1/2-y,-1/2+z

985, 752, 724, 679. - 'H NMR ([D,]DMSO): 6 = 1.46 [s, 9H, C(CH,),], 7.4-7.8 (m, 4H, aryl-H), 7.9-8.3 (m, 2H, NH, inter- changeable with DzO), 11.6 (s broad, 1 H, NH, interchangeable with

126.8, 127.3, 127.9, 128.8, 129.7, 137.8, 153.5 (C-5), 169.5 (C-2), 187.2 (C=S). - MS (70 ev): m/z (YO) = 292 [M '1 (5), 260 (16), 259 (IOO), 235 (37), 203 (46), 161 (16), 160 (13), 129 (32), 102 (20), 101 (5), 57

CI3Hl6N4S2 (292.4) Calcd. C 53.39 H 5.52 N 19.16 Found C 53.50 H 5.49 N 19.29

D2O). - 13C NMR ([D,j]DMSO): 6 = 30.1 (CH,), 45.1 C(CH&,

(36).

1,3,4-Thiadiazolo[3,2-c/quinazolinylium-2-methunides 6. - Gen- eral Procedure: To a well stirred solution of potassium tert-butoxide (3.45 g, 10 mmol) in dry dimethylformamide (50 ml) the correspond- ing thione 4 (10 mmol) was added. The resultant mixture was stirred under nitrogen at room temperature for 30 min, and the appro- priate ketene dithioacetal 5 (20 mmol) was added. Stirring was continued for 2 h, then the solution was poured into cold water (50 ml) and the yellow precipitated solid was collected by filtration, washed with water (2 x 20 ml), benzene (2 x 20 ml) and recrys- tallized from acetonitrile to give 6.

Liebigs Ann. Chem. 1988, 133-139

2-Substituted 1,3,4-Thiadiazoles and Mesoionic 1,3,4-Thiadiazole[3,2-c]quinazolines 137

S-Phenyl-l,3,4-thiadiazolo~3,2-c]quinazolinylium-2- (dicyano- methanide) (64: Yield 30%; m.p. 296-298"C, yellow needles. - IR: 2209 cm-', 2186,1557, 1511,1467,1353, 1319, 1257,1103, 770, 704,692. - MS (70 eV): m/z (%) = 328 (21), 327 [M'] (loo), 238 (25), 237 (14), 206 (12), 205 (71), 103 (4), 102 (12), 77 (9).

CIBHPN5S (327.4) Calcd. C 66.04 H 2.77 N 21.39 Found C 65.92 H 2.81 N 21.43

5-Phenyl-l,3,4-thiadiazolo[3.2-c]quinazolinylium-2-[cyano (meth- oxycarbonyl)methanide](6b): Yield 50%; m. p. 305 - 307"C, yellow needles. - IR: 2197 cm-', 1649,1608,1563,1489,1472,1319, 1280,

CF3COOH): 6 = 3.95 (s, 3H, OCH,), 7.63-7.91 (m, 3H, aryl-H), 8.0-8.8 (m, 6H, aryl-H). - UV (ethanol): h,,, (Ig E ) = 273 nm (3.783), 317 (3.586). - MS (70 eV): m/z (%) = 361 (24), 360 [M'] (loo), 330 (12), 329 (53), 316 (28), 302 (17), 301 (16), 277 (30), 261 (22), 238 (24), 237 (lo), 205 (50), 102 (5), 77 (9).

C,9H,ZN402S (360.4) Calcd. C 63.32 H 3.36 N 15.55 Found C 63.18 H 3.41 N 15.62

1195, 1155, 1070, 775, 759, 702. - 'H NMR (CDCI3 +

5-Phenyl-1,3,4-thiadiazolo[3,2-c]quinazolinylium-2-[ (aminocar- bony1)cyanomethanidel (6c): Yield 26%; m. p. 296-298 "C, yellow needles. - IR: 3466 cm-', 3302,3177,2197,1659,1636, 1591, 1574,

UV (ethanol): h,,, (Ig E) = 280 nm (4.176), 312 (4.152). - MS (70 eV): m/z (%) = 346 (12), 345 [M'] (58), 330 (8), 329 (40), 301 (4), 238 (20), 237 (lo), 206 (14), 205 (loo), 102 (29), 77 (56).

Cl8HllN5OS (345.4) Calcd. C 62.60 H 3.21 N 20.27 Found C 62.81 H 3.24 N 20.17

5- (4-Methylphenyl)-l,3,4~thiadiazolo[3.2-c]quinazolinylium-2- (dicyanomethanide) (6d): Yield 30%; m. p. 245 - 247 "C, yellow needles. - IR: 2197 cm-', 2175,1608,1580,1557,1352,1323, 1252, 1189, 1143, 838, 821, 759, 737, 692. - 'H NMR (CDCI3 + CF3COOH): 6 = 2.6 (s, 3H, aryl-CH3), 7.3 - 8.6 (m, 8H, aryl-H). - MS (70 eV): m/z (%) = 342 (25), 341 [M'] (loo), 252 (28), 251 (l l) , 250 (lo), 220 (16), 219 (74), 123 (23), 118 (12), 117 (9), 102 (l l) , 91

(12)' CI9HllN5S (341.4)

1495, 1416,1353,1314, 1280,1195, 1161,951,877,764,725,708. -

Calcd. C 66.84 H 3.25 N 20.51 Found C 66.73 H 3.19 N 20.63

5- (4-Methylphenyl) - 1 ,3,4-thiadiazolo[3,2-c]quinazolinylium-2- /cyano(methoxycarbonyl)methanide] (6e): Yield 79%; m. p. 304 to 306"C, yellow needles. - IR: 2209 cm-', 1648, 1557, 1495, 1382, 1319, 1274, 1194, 1182, 1065, 912, 812, 764, 720. - 'H NMR (CDCI, + CF3COOH): 6 = 2.56 (s, 3H, aryl-CH,), 4.03 (s, 3H, OCHJ), 7.35-7.65 (d, 2H, J = 8.3 Hz), 8.0-8.55 (m, 6H, aryl- H). - UV (ethanol): A,,, (Ig E ) = 281 nm (4.452), 317 (4.335). - MS (70 eV): m/z (%) = 375 (21), 374 [M'] (85), 344 (12), 343 (SO), 316 (22), 315 (S) , 291 (50), 252 (lo), 251 (lo), 219 (loo), 118 (28), 91

C20H14N402S (374.4) Calcd. C 64.16 H 3.77 N 14.96 Found C 64.24 H 3.65 N 15.07

(1 8).

5- (4-Methylphenyl) -1,3,4-thiadiazolo[3,2-c]quinazolinylium-2- [(aminocarbonyl)cyanomethanide] (60: Yield 32%; m. p. 303 to 305"C, yellow needles. - IR: 3483 cm-', 3347, 3239, 3194, 2186,

(CDCI, + CF3COOH): 6 = 2.65 (s, 3H, aryl-CH3), 7.4-8.5 (m, 8H, aryl-H). - MS (70 eV): m/z (%) = 360 (l l) , 359 [M'] (loo), 343 (32), 315 (5), 252 (14), 251 (9, 220 (ll), 219 (49), 120 (12), 102 (18), 91 (37).

1632,1559, 1328,1284, 1191, 1089, 826, 818, 766, 721. - 'H NMR

C19H,3N50S (359.4) Calcd. C 63.50 H 3.64 N 19.48 Found C 63.43 H 3.74 N 19.37

5- (4-Methoxyphenyl)-l,3,4-thiadiazolo[3,2-c]quinazolinylium-2- (dicyanomethanide) (6g): Yield 22%; m. p. 278 -280"C, yellow

needles. - IR: 2203 cm-', 2180,1670,1584,1557,1349,1312,1249,

6 = 4.0 (s, 3H, aryl-OCH,), 7.40 (d, 2H, J = 8 Hz), 7.9-8.4 (m, 4H, aryl-H), 8.55 (d, 2H, J = 8 Hz). - MS (70 eV): m/z (%) = 358 (lo), 357 [M'] (46), 300 (20), 299 (5 ) , 286 (lo), 268 (43), 236 (20), 235 (loo), 192 (37), 139 (61), 134 (12), 133 (15), 120 (13), 107 (8), 103 (13), 102 (20).

C19HllNSOS (357.4) Calcd. C 63.85 H 3.10 N 19.59 Found C 63.92 H 3.13 N 19.43

1177,1027,843,826,760,722. - 'H NMR (CDCI3 + CF3COOH):

5- (4-Methoxyphenyl)-l,3,4-thiadiazolo[3,2-c]quinazolinylium-2- [cyano(methoxycarbonyl)methanide] (6h): Yield 86%; m. p. 323 to 325"C, yellow needles. - IR: 2203 cm-', 1642, 1557, 1495, 1325, 1195, 1126, 1064, 1025,838, 776, 759, 736. - 'H NMR (CDCI, + CF3COOH): 6 = 4.03 (s, 3H, aryl-OCH,), 4.1 (s, 3H, COOCH,), 7.23 (d, 2H, J = 9 Hz), 8.0-8.45 (m, 4H, aryl-H), 8.66 (d, 2H, J = 9 Hz). - UV (ethanol): h,,, (Ig E ) = 287 nm (4.208), 325 (4.173). - MS (70 eV): m/z (%) = 391 (15), 390 [M'] (55), 359 (25), 332 (lo), 307 (27), 268 (lo), 235 (50), 139 (loo), 133 (16), 120 (23), 102 (15).

CZ0Hl4N4O3S (390.4) Calcd. C 61.53 H 3.61 N 14.35 Found C 61.47 H 3.68 N 14.43

5- (4-Methoxyphenyl)-l,3.4-thiadiazolo[3,2-c]quinazolinylium-2- [(am~nocarbonyl)cyanomethanide] (6i): Yield 20%; m. p. 298 to 300"C, yellow needles. - IR: 3960 cm-', 3307, 3177, 2186, 1648, 1552,1353,1268,1189, 1030,843,764. - 'H NMR (CDCI, + CF3- COOH): 6 = 4.01 (s, 3 H, aryl-OCH,), 7.1 3 - 7.41 (d, 2 H, J = 9 Hz), 8.0-8.73 (m, 6H, aryl-H). - UV (ethanol): h,,, (Ig E ) = 291 nm (3.875), 323 (3.843). - MS (70 eV): m/z (YO) = 376 (1 l), 375 [M'] (70), 359 (33), 331 (lo), 268 (15), 236 (13), 235 (48), 220 (lo), 192 (30), 139 (loo), 133 (21), 120 (21), 107 (18), 102 (20).

Cf9HI3N5O2S (375.4) Calcd. C 60.79 H 3.49 N 18.65 Found C 60.83 H 3.42 N 18.57

S-Methyl-l,3,4-thiadiazolo[3,2-c]quinazolinylium-2-[cyano (me- thoxycarbonyljmethanide] (6j): Yield 31 %; m. p. > 350"C, yellow needles. - IR:2194cm-', 1643,1619,1561,1350,1297,1192,1157,

6 = 2.34 (s, 3H, C-CH3), 3.86 (s, 3H, OCH3), 7.25-8.55 (m, 4H, aryl-H). - MS (70 eV): m/z (%) = 299 (13), 298 [M'] (73), 267 (67), 240 (21), 215 (58), 143 (loo), 120 (15), 102 (42), 90 (20), 76 (15).

Cf4HION402S (298.3) Calcd. C 56.37 H 3.38 N 18.78 Found C 56.42 H 3.29 N 18.84

1133,1028,987,875,782,758. - 'H NMR (CDC13 + CF3COOH):

5- Methyl- 1 ,3,4-thiadiazolo[3,2-c]quinazolinylium-2-[ (aminocar- bony1)cyanomethanidel (6k): Yield 20%; m.p. > 350°C, yellow needles. - IR: 3421 cm-', 3313,3239,2180,1648,1625,1580,1461, 1314, 1285, 1189, 1166, 1115, 770, 719,696. - 'H NMR (CDCI, + CF3COOH): 6 = 2.40 (s, 3H, C-CH,), 7.30-8.45 (m, 4H, aryl- H). - MS (70 eV): m/z (%) = 284 (15), 283 [M'] (92), 267 (loo), 143 (61), 102 (24), 90 (8), 76 (10).

CI3H4N5OS (283.3) Calcd. C 55.11 H 3.20 N 24.72 Found C 55.24 H 3.16 N 24.63

5-tert-Butyl-l,3,4-thiadiazolo[3,2-c]quinazolinylium-2- (dicyano- methanide) (61): Yield 20%; m.p. >35O"C, yellow needles. - IR: 2197cm-', 2175,1591,1557,1518,1495,1285,1149,1127,770,719.

7.93-8.18 (m, 4H, aryl-H). - MS (70 eV): m/z (%) = 308 (lo), 307 [M'] (48), 252 (15), 251 (loo), 161 (12), 129 (48), 102 (24), 90

Cf6H13NSS (307.4) Calcd. C 62.52 H 4.26 N 22.78 Found C 62.48 H 4.31 N 22.65

- 'H NMR (CDCI3 + CFjCOOH): 6 == 1.70 [s, 9H, C(CH,),],

(lo), 57 (55).

5-tert-Butyl- 1,3,4-thiadiazolo[3,2-clquinazolinylium-2-[cyano- (metho.xycarbonyl)methanide] (6m): Yield 30%; m. p, 332-334"C,

Liebigs Ann. Chem. 1988, 133 - 139

138 P. Molina, A. Arques, I. Cartagena, M. A. Alias, M. de la Concepcibn Foces-Foces, F. H. Can0

yellow needles. - IR: 2197 cm-', 1642, 1614, 1591, 1563, 1438, 1342, 1183, 1149, 1110, 922, 759. - 'H NMR (CDCl, + CFj- COOH): 6 = 1.85 [s, 9H, C(CH,),], 4.0 (s, 3H, COOCH3), 8.05 to 8.55 (m, 4H, aryl-H). - MS (70 eV): m/z (YO) = 341 (20), 340 [M'] (IOO), 309 (15), 284 (12), 253 (56), 201 (69), 146 (43), 129 (76), 102

Cl7Hl6N4O2S (340.4) Calcd. C 59.98 H 4.74 N 16.46 Found C 59.85 H 4.69 N 16.57

(35), 57 (54).

5- tert-Butyl-1,3,4-thiadiazolo[3,2-c]quinazolinylium-2-[ (amino- carbonyl)cyanomethanide] (64: Yield 27%; m. p. 303 - 305 "C, yel- low needles. - IR: 3421 cm-', 3313, 3200,2191, 1642, 1585, 1557, 1415, 1399, 1195, 1155, 1098, 753, 725. - 'H NMR (CDC13 + CF,COOH): 6 = 1.8 [s, 9H, C(CH,),], 7.95-8.3 (m, 4H, aryl- H). - MS (70 eV): m/z (%) = 326 (16), 325 [M'] @I), 269 (35), 253 (loo), 129 (68), 102 ( 3 3 83 (15), 57 (47).

Ci6H15N50S (325.39) Calcd. C 59.06 H 4.65 N 21.52 Found C 58.93 H 4.59 N 21.62

2 (3H) -Methylene-5-[2- (acylamino)phenyl]-l,3,4-thiadiazoles 7. - General Procedure: To a well-stirred suspension of the appro- priate methanide 6 (2 mmol) in ethanol (40 ml), conc. hydrochloric acid (4 ml) was added. The resultant solution was stirred at reflux temperature for 1 h. After cooling, the precipitated solid was col- lected by filtration, washed with water (3 x 20 ml) and recrystal- lized from ethanol to give 7.

Methyl 2-(5-[2-(Benzoylamino)phenyl]-1,3,4-thiadiazol-2(3H)- ylidene)-2-cyanoacetate (7a): Yield 96%; m. p. 270- 272 "C, color- less needles. - IR: 3341 cm-', 3120, 2212, 1686, 3674, 1613, 1593, 1551,1337,1315,1271,1144,1134,1015,759,731,700. - 'H NMR (CF3COOH): 6 = 4.0 (s, 3H, COOCH3), 7.35-8.3 (m, 7H, aryl- H), 8.75-8.9 (m, 2H, aryl-H). - MS (70 eV): m/z (%) = 378 [M'] (15), 346 (4), 241 (5), 105 (IOO), 77 (35).

C19Ht4N403S (378.4) Calcd. C 60.31 H 3.73 N 14.81 Found C 60.47 H 3.92 N 14.72

Methyl 2-Cyano-2-(5-[2-(4-methylbenzoylamino)phenyl]-~,3,4- thiadiazol-2(3H)-ylidene)acetate (7b): Yield 50%; m.p. 251 to 253 "C, colorless needles. - IR: 3443 cm-', 3324,3302,2208, 1670, 1657,1614,1586,1551,1331,1273,1198,1136,756,745. - 'HNMR ([D,]DMSO): 6 = 2.46 (s, 3H, aryl-CH,), 3.80 (s, 3H, COOCHJ, 6.1 (s broad, 1 H, NH interchangeable with DzO), 7.4 - 8.63 (m, 8 H, aryl-H), 11.15 (s broad, 1 H, NH interchangeable with D20). - MS (70 eV): m/z (%) = 392 [M'] (lo), 360 (5), 149 (S), 120 (15), 110 (loo), 91 (30).

CZOHI6N4O3S (392.4) Calcd. C 61.21 H 4.11 N 14.28 Found C 61.32 H 4.24 N 14.09

2-Cyano-2-(5-[2- (4-methylbenzoylamino)phenyl]-1,3,4-thiadi- azol-2(3H)-ylidene)acetamide (7c): Yield 87%; m. p. 261 -263"C, yellow prisms. - IR: 3466 cm-', 3319,3166,2192,1682,1648,1591,

aryl-CH,), 7.1 - 8.7 (m, 11 H, aryl-H, NH), 11.4 (s broad, 1 H, NH interchangeable with DzO). - MS (70 eV): m/z (YO) = 377 [M'] (lo), 334 (5) , 120 (15), 119 (IOO), 91 (33).

CI9Hl5N5O2S (377.4) Calcd. C 60.46 H 4.00 N 18.55 Found C 60.39 H 3.92 N 18.47

1529, 1319, 1274, 759. - 'H NMR ([D6]DMSO): 6 = 2.46 (s, 3H,

Methyl 2-Cyano-2-(5-[2-(4-methoxybenzoylamino)phenyl]- 1,3,4-thiadiazo1-2-(3H)-ylidene)acetate (7d): Yield 45%; m. p. 264 to 266"C, colorless needles. - IR: 3330 cm-', 3115, 2208, 1675, 1670, 1601, 1557, 1530, 1335, 1298, 1189, 1134, 1030, 843, 754. - 'H NMR ([D,]DMSO): 6 = 3.85 (s, 3H, aryl-OCH3), 4.0 (s, 3H, COOCH,), 6.5 (s broad, l H , NH interchangeable with DzO), 7.45 - 8.70 (m, 8 H, aryl-H), 11.2 (s broad, 1 H, NH interchangeable

with D20). - MS (70 eV): m/z (YO) = 408 [M'] (5), 390 (5), 350 (5), 135 (loo), 107 (15), 77 (15).

C20H16N404S (408.4) Calcd. C 58.81 H 3.95 N 13.72 Found C 58.69 H 3.78 N 13.91

Methyl 2-Cyano-2-(5-[2-(pivaloylamino)phenyl/-l,3,4-thiadi- azol-2(3H)-ylidene)acetate (7e): Yield 70%; m.p. 248-250°C, col- orless needles. - IR: 3341 cm-', 2208,1688,1674,1584,1545,1336,

6 = 1.95 [s, 9H, C(CH,),], 3.95 (s, 3H, aryl-OCH3), 6.9 (s broad, l H , NH interchangeable with D20), 7.80-8.55 (m, 4H, aryl-H), 11.4 (s broad, lH, NH interchangeable with D20). - MS (70 eV): m/z (%) = 358 [M'] (lo), 301 (5) , 274 (30), 269 (24), 243 (lo), 242 (50), 150 (21), 85 (15), 57 (IOO), 55 (39).

C17H18N403S (358.4) Calcd. C 56.97 H 5.06 N 15.63 Found C 56.82 H 5.12 N 15.53

1297,1195,1166,1149,1030, 1019,764. - 'H NMR ([D,]DMSO):

2 ( 3 H ) -Methylene-5-[2- (thioacylamino)phenyl]-l,3,4-thiadi- azoles 8. - General Procedure: To a hot solution of the appropriate 1,3,4-thiadiazole 7 (2 mmol) in dry pyridine (20 ml) phosphorus pentasulfide (0.88 g, 4 mmol) was added. The reaction mixture was heated under reflux temperature for 3 h. After cooling, the solution was poured into ice-water (50 ml) and the precipitated solid was separated by filtration, washed with water (3 x 20 ml), dried and recrystallized from ethanol to give 8.

Methyl 2-Cyano-2-(5-[2-(thiobenzoylamino)phenyl]-1,3,4-thia- diazol-2(3H)-ylidene)acetate (8a): Yield 60%; m.p. 311 -313"C, brown prisms. - IR: 2197 cm-', 1636,1591,1552,1348,1280,1195,

6 = 3.9 (s, 3H, COOCHJ, 6.2 (s broad, 1 H, NH interchangeable with DzO), 7.4-8.2 (m, 7H, aryl-H), 8.5-8.7 (m, 2H, aryl-H), 10.7 (s broad, 1 H, NH interchangeable with DzO). - MS (70 eV): m/z (%) = 394 [M'] (9, 361 (15), 360 (72), 329 (42), 277 (49), 205 (IOO), 134 (20), 120 (20), 111 (25), 102 (40), 77 (65).

1135, 1064, 1030, 911, 781, 760, 698. - 'H NMR ([D,]DMSO):

CI9Hl4N4O2S2 (394.5) Calcd. C 57.86 H 3.58 N 14.20 Found C 57.78 H 3.68 N 14.42

Methyl 2-Cyano-2-( 542- (4-methoxythiobenzoylamino)phenyl]- 1,3,4-thiadiazol-2(3H)-ylidene)acetate (8b): Yield 50%; m. p. 256-258"C, brown prisms. - IR: 3239 cm-', 2207, 1665, 1602,

DMSO): 6 = 3.85 (s, 3H, aryl-OCH3), 4.05 (s, 3H, COOCH3), 5.9 (s broad, 1 H, NH interchangeable with DzO), 7.3 - 8.7 (m, 8 H, aryl- H), 10.9 (s broad, IH, NH interchangeable with D20). - MS (70 eV): m/z ('YO) = 424 [M'] (3), 391 (lo), 390 (62), 359 (25), 307 (32), 268 (47), 236 (20), 235 (loo), 134 (15), 76 (17).

C20H16N403SZ (424.5) Calcd. C 56.59 H 3.80 N 13.20 Found C 56.69 H 4.03 N 13.16

1552, 1331, 1257, 1178, 1030, 843, 758, 685. - 'H NMR ([D6]-

2-Amino-5-[2-(acylamino)phenyl]-l,3,4-thiadiazoles 9. - Gen- eral Procedure: To a solution of the appropriate 1,3,4-thiadiazole 2 (2 mmol) in methanol (40 ml), conc. hydrochloric acid (2 ml) was added. The reaction mixture was heated under reflux for 1 h. After cooling, the solvent was removed under reduced pressure, and the residual material was treated with ether (20 ml), the separated solid was collected by filtration, dried and recrystallized from methanol/ ether (1 : 1, v/v) to give 9.

2-Amino-5-[2- (benzoylamino)phenyl]-1,3,4-thiadiazole (9 a) : Yield 70%; m.p. 150-152"C, orange prisms. - IR: 3415 cm-l, 3235, 1693,1636, 1585,1342,1262, 1211, 1166,786,752,718. - 'H NMR ([D6]DMSO): 6 = 7.2-8.1 (m, 11H, aryl-H, 2 NH), 10.5 (S

broad, lH, NH interchangeable with D20). - MS (70 eV): m/z (%I = 296 IM'1 (141, 279 (261, 238 (511, 221 (20), 205 (loo), 121 (571, 105 (49), 77 (20).

C I ~ H I Z N ~ O S (296.4) Calcd. C 60.79 H 4.08 N 18.91 Found C 60.83 H 3.94 N 18.79

Liebigs Ann. Chem. 1988, 133-139

2-Substituted 1,3,4-Thiadiazoles and Mesoionic 1,3,4-Thiadiazole[3,2-c]quinazolines 139

2-Amino-5-(2-[ (I-methylbenzoyl)amino]phenyl)-1,3,4-thiadi- azole (9b): Yield 85%; m.p. 166-168"C, orange prisms. - IR: 3313 cm-', 2274, 1676, 1653, 1636, 1551, 1279, 1053,894, 758, 741, 707. - 'H NMR ([D6]DMSO): 6 = 2.57 (s, 3 H, aryl-CH3), 7.2-8.5 (m, 10H, aryl-H, 2 NH), 10.7 (s broad, 1 H, NH interchangeable with D20). - MS (70 eV): m/z (%) = 310 [M'] (37), 293 (5 ) , 277 (lo), 219 (15), 120 (12), 119 (100), 91 (43), 65 (17).

Cl6HI4N40S (310.4) Calcd. C 61.92 H 4.55 N 18.05 Found C 61.79 H 4.58 N 17.93

2- Amino-S-[ 2- (pioaloylamino) phenyll- 1,3,4-thiadiazole (9 c) : Yield 95%; m.p. 150-152"C, colorless prisms. - IR: 3313 cm-', 3154, 1749, 1642, 1511, 1342, 1200, 1160, 1064, 1019, 985, 764,

(m, 4H, aryl-H), 8.0-8.3 (m, 2H, NH interchangeable with D20), 10.9 (s broad, 1 H, N H interchangeable with D20). - MS (70 eV): m/z = 276 [M'] (5), 220 (Il) , 219 (loo), 192 (24), 150 (22), 57 (22).

CI3Hl6N40S (276.4) Calcd. C 56.50 H 5.84 N 20.27 Found C 56.35 H 6.04 N 20.13

724. - 'H NMR ([D,]DMSO): 6 = 1.5 [ s , 9H, C(CH3)J, 7.6-7.9

CAS Registry Numbers

l a : 17240-30-1 / l b : 17240-32-3 / l c : 53628-15-2 / Id: 57623-30-0 / 2a: 111324-13-1 J 2 b : 111324-14-2/2~: 111324-15-3/2d: 111324-

4 (R = 4-MeOC6H4): 93945-96-1 / 4 (R = Me): 66645-54-3 / 4 (R = CMe3): 91644-29-0 / 5 (X = CN): 5147-80-8 / 5 (X = CO- OMe): 3490-92-4 / 5 (X = CONH2): 17823-69-7 / 6a: 111324- 17-5 / 6b: 111324-18-6 / 6c: 111324-19-7 / 6d: 111324-20-0 / 6 e :

24-4 / 6 i : 111324-37-9 / 6 j : 111324-25-5 / 6k: 111324-38-0 / 61: 111324-26-6 / 6m: 111324-27-7 / 6n: 111348-89-1 / 7a: 111324- 28-8 / 7 b : 111324-29-9 / 7c: 111324-30-2 / 7d: 111324-31-3 / 7e: 111324-32-4 / 8 a : 111324-33-5 / 8b: 111324-34-6 / 9a: 111324- 35-7 / 9b: 11 1324-36-8 / 9c: 11 1378-70-2 / S-methylisothiosemicarb- azide hydroiodide: 35600-34-1

16-4 1 4 (R = C6H5): 13961-55-2 / 4 (R = 4-MeC6H4): 92555-57-2 /

111324-21-1 / 6f : 111324-22-2 / 6 g : 111324-23-3 / 6h: 111324-

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