3-Aryl-5-mercapto

Solid-phase library synthesis of triazolopyridazines via a [4+2] cycloaddition strategy has been accomplished <99TL619>. Intramolecular bis-Mannich reaction of 3-aryl-5-mercapto-13,4-triazole, formaldehyde and a-phenylethylamine yields chiral 5-aryltriazolo[3,4-ft]-[133]thiadiazine derivatives. These compounds have been screened for antibacterial activities and some of them show potent biological activity <99SC2027>. 

Amidoximes (46) were first used as a source of 1,2,4-thiadiazoles in 1889 their condensation with carbon disulfide or with an excess of aryl isothiocyanate yields 3-aryl-5-mercapto- (47)6 -73 or 3-aryl-5-aryl-amino- 1,2,4-thiadiazoles (50),71,74,75 respectively. The latter reaction has been reexamined and discussed by Gheorgiu and Barbos76 who suggest that an initial addition of two moles of phenyl isothiocyanate to one of benzamidoxime is followed by cyclization of the intermediate (49), with elimination of phenylthiocarbamic acid (51). Decomposition of the latter gives rise to the by-products observed (cf. following scheme). 

Condensation of 2-bromodimedone 202 and 3-aryl-5-mercapto-l,2,4-4H-triazoles 207 in THF at room temperature afforded intermediates 5a-hydroxy-l,2,4-4H-triazolo[3,2-t>]benzothiazoles 208 rather than [3,4-b] isomers 209 polarity of different solvents did not affect the outcome (95M759). A one-pot synthesis of 208 was achieved by heating a mixture of 1, NBS, and 207 in benzene containing traces of benzoyl peroxide. Dehydration of 208 on heating in PPA at 150 °C afforded 210, which also... 

Disubstituted tetrahydro-r-triazolo[3,4-3][l,3,5]thiadiazines 272 have been synthesized in 50-85% yield by the double Mannich reaction of 3-aryl-5-mercapto-l,2,4-triazoles 273 with various aromatic amines and formaldehyde in the presence of ethanolic HCl, as shown in Scheme 57 <1996MOL89>. 

Other sulfur compounds such as thiourea, ammonium dithiocarbamate, or hydrogen sulfide also lead to 2-mercaptothiazoles. Thus thiourea has been used in the syntheses of 4,5-dimethyl (369) and 4-aryl-2-mercapto-thiazoles (Table 11-30) (519). The reactions were carried out by condensing the ia -thiocyanatoketones with thiourea in alcohol and water acidified with hydrochloric acid. By this procedure, 4-aryl-2-mercaptothiazoles were obtained in yields of 40 to 80% with bis-(4-aryl-2-thiazolyl) sulfides as by-products (519). These latter products (194) have also been observed as a result of the action of thiourea on 2-chloro-4-arylthiazole under the same experimental conditions. They can be separated from 2-mercaptothiazoles because of their different degrees of solubility in sodium hydroxide solution at 5%. In this medium bis-(4-phenyl-2-thiazolyl)sulfide is... 

When benzaldehyde or its substituted derivatives are added to carbon disulfide and a-aminonitrile, the corresponding 2-mercapto-5-(p-R-benzylideneamino)thiazoles (215), R = hydrogen atom or a propenyl or phenyl group and Ar = aryl, are obtained (Scheme 112) (393, 442, 694). Yields ranged from 40 to 60% (Table II-34b). 

A large number of variously 2-, 4-, and 5-substituted thiazoles with alkyl, aryl, hydroxy, methylthio, mercapto, halo, and nitro groups have been analyzed by thin-layer chromatography on silica and alumina by the Stahl s technique (167, 170, 172). Among the many systems recommended for the elution of these compounds are the following ... 

Mercapto derivatives of furan, thiophene, selenophene (77ACS(B)198) and pyrrole (72AJC985) all exist predominantly in the thiol form. 2-Mercaptobenzothiophene is also a thiol (70JCS(C)243i) whereas 2-mercaptoindole is mainly indoline-2-thione (89) (69CPB550). The finely balanced nature of this system is indicated by the fact that a 3-aryl, but not a 3-alkyl, substituent will stabilize the 2-thiol form, whereas for 3-aryl-fV-methyl derivatives the 2-thione tautomer is preferred (71CC836). 

Isothiazole, 4-aryl-3-hydroxy-5-mercapto-methylation, 6, 160 synthesis, 6, 166... 

Thiazoline, trans-2-amino-4,5-dimethyl-synthesis, 6, 310 2-Thiazoline, 2-aryl-synthesis, 6, 307, 308, 309 2-Thiazoline, 2-arylamino-tautomerism, 6, 248 2-Thiazoline, 2-dialkylamino-synthesis, 6, 308 2-liiiazoline, 5-imino-synthesis, 5, 461 2-"niiazoline, 2-mercapto-hydrolysis, 6, 272 oxidation, 6, 272 synthesis, 6, 307 2-Thiazoline, 2-methyl-aldehyde synthesis from, 1, 469 2-Thiazoline, 2-methyl-acetylation, 6, 270 acylation, 6, 270 H NMR, 6, 243... 

Alkyl-(2-mercapto-athyl)-benzyl- 247 Alkyl-phenyl- 259 Allyl- 118, 579 Allyl-benzyl- 350 Allyl-butyl-(3-oxo-butyl)- 659 Aryl- 498, 536, 568... 

In 2000, Woodward et al. reported that LiGaH4, in combination with the S/ 0-chelate, 2-hydroxy-2 -mercapto-1,1 -binaphthyl (MTBH2), formed an active catalyst for the asymmetric reduction of prochiral ketones with catecholborane as the hydride source (Scheme 10.65). The enantioface differentiation was on the basis of the steric requirements of the ketone substituents. Aryl w-alkyl ketones were reduced in enantioselectivities of 90-93% ee, whereas alkyl methyl ketones e.g. i-Pr, Cy, t-Bu) gave lower enantioselectivities of 60-72% ee. 

The kinetics of the reaction of trialkyl phosphites, dialkyl aryl-phosphonites, alkyl diarylphosphinites, and triarylphosphines with Sg has been studied the effects of structural changes on the rate (Ph2POR > PhP(OR>2 > P(OR)g > Ph P) and on the Hammett p values are interpreted with respect to the mechanism. A general method to displace mercapto groups from carbon with clean inversion includes... 

Phenyl-l,2,3,6-tetrahydropyrido[2,l- ][l,3]thiazino[3,2- ]quinolin-6-ones were prepared by the reaction of 2-mercapto-5-phenyl-l,4-dihydroquinolin-4-ones with 1,3-dihalopropane <1997JAK97/278780>. 7-Acetyl-2-aryl-9-cyano-6-methyl-8-phenyl-3,4-dihydro-277,877-pyrido[2,l- ][l,3]thiazin-4-ones were obtained from 5-acetyl-3-cyano-6-methyl-4-phenyl-l,2,3,4-tetrahydropyridine-2-thione with 3-aryl-2-propenoyl chloride <2002CHE761>. Reaction... 

Mercapto- benzothiazolates Dialkyl- dithiophosphates Dialkyl(aryl)- monothiophosphates Fatty carboxylates... 

Compound 98 reacts with carbon disulfide in the presence of an alkali solution to give 3 -mercapto-l,2,4-triazolo[4, 5 l,5][l,2,4]triazolo[3,4-A]benzothiazole 247. Treatment of product 98 with urea at 200°C for 4h affords 3 -hydroxy-l,2,4-triazolo[4, 5 l,5]-l,2,4-triazolo[3,4-A benzothiazole 99 (Scheme 20). Finally, the addition of concentrated phosphoric acid in the presence of sodium nitrite to compound 98 produces 1,2,3,4-tetra-zolo[l, 5 l,5]-l,2,4-triazolo[3,4- ]benzothiazole 248, and refluxing substituted benzaldehydes in acetic acid provides an easy access to 3 -aryl-l,2,4-triazolo[4, 5 l,5]-l,2,4-triazolo[3,4-A benzothiazoles 249 (Scheme 20) (Table 50) <2005IJC(B)625>. 

In a study on [l,2,4]triazolo[3,4-3][l,3,5]thiadiazines, mass spectral fragmentation of the 3-aryl-6-methyl derivative 33 (see Scheme 2) has been determined by Wang et al. <2001SC2841>. These authors found that elimination of the methylimine formaldehyde takes place first to form a thiazetidine ring 34 and, finally, removal of a CH2 group the 2-mercapto-5-aryl[l,2,4]triazole 35 can be observed. 

Ring closure to [l,2,4]triazolo[3,4- ][l,3,5]thiadiazines by utilizing the Mannich reaction has been published by a Chinese team <1999SC2027, 2001SC2841, 2001JF1C929> (Scheme 23). 5-Aryl-substituted 3-mercapto[l,2,4]tri-azoles 123 were treated with formaldehyde and primary amines under acidic conditions to yield the fused thiadiazines 124. The reaction was interpreted to proceed via formation of intermediate 125 upon the reaction of 123 with a... 

Thus, 5-aryl-3-hydrazino[l,2,4]triazine 200 was reacted with acid chlorides to yield 201 <2004AF42>, and reaction of 5,6-diphenyl-3-hydrazino[l,2,4]triazine 202 with carbon disulfide yielded a 3-mercapto product 203 <2000PJS214>. 

In West Germany pyridazinium compounds as represented by formula (120, R1 = halogen, alkyl, aryl R2 = H, alkyl R3 = substituted amino R4 = substituted alkyl, cycloalkyl) have been claimed as antibacterial agents [338]. In Australia, mercapto derivatives of several nitrogen heteroaromatics including pyridazine-derived compounds (121, R = CONH2, CH2NMe2) have been prepared in a search of amplifiers of phleomycin [339] however, only low activity has been observed in this series. 

Among 5-alkyl- or 5-aryl-substituted 4-pyrimidinecarboxylic acids screened for antiviral, antimalarial and antimicrobial activities [213], 2-mercapto-5-methyl-6-amino-4-pyrimidinecarboxylic acid (XlVa) is active against influenza... 

The activity of tetrahydropyrimidines is presented in the order of substitution at the 2-position 2-unsubstituted, 2-alkyl (and 2-alkenyl), 2-aralkyl, 2-aryl, 2-hydroxy, 2-mercapto, 2-amino, etc. 

Coumarinyl-substituted thiazolo[3,2-h][l,2,4]triazoles have also been reported. They are available in one step by reaction of 5-aryl-3-mercapto[l,2, 4]triazoles with 3-bromoacetylcoumarin (ethanol, reflux, 8 h yield 44-65%) (81AP435) or in a two-step reaction from the corresponding S-alkylated intermediates with PPA [93MI2 94IJC(B)579]. 2-Aminothiazolo[3,2-h][l,2,4]triazoles are also available from 3-mercaptotriazoles. Treatment of 5-amino-3-mercaptotriazole with chloroacetone (DMF, K2CO3) and subsequent acid-catalyzed cyclization yields 146 [90JAP(K)02/142797]. 

Simple considerations such as these account adequately for many of the familiar reactions of substituted 7r-deficient heterocycles, such as nucleophilic displacement, tautomerism in hydroxy, mercapto and amino heterocycles, facile deprotonation of alkyl substituents, decarboxylation of carboxymethyl groups and electrophilic substitution of benzo-fused and aryl-substituted heterocycles. These individual effects are discussed separately in the following subsections. 

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