2-Amino-4-aryl-5 thiazoles

Aromatic thioamides react with MeC(0)CHClC(0)C02Et to give a 3 1 ratio of ethyl 5-acetyl-2-aryl-thiazole-4-carboxylates and the isomeric products (2). Modifications of the Hantzsch synthesis continue to appear. Thus, 2-aryl-5-aroyl-thiazoles may be prepared from the JV -thioaroyl-iViV-dimethyl-formamidines ArC(S)N=CHNMea and a-bromo-ketones [strictly speaking, this is a Type F (C—N—C—S + C) synthesis], whilst 5-amino-2-phenyl-l,2,3-thiadiazolium salts [e.g. (3)] and compounds with the general structure RCHgCN (e.g. R = CN or COaEt) yield 4-amino-thiazoles. ... 

Amino-4-aryl-thiazoles give Meisenheimer complexes with 2,4,6-trinitro-chlorobenzene. The tautomeric properties of thiazoles continue to attract attention. Unlike most 4-hydroxy-thiazoles, which prefer to exist in their keto-forms, 4-hydroxy-2-methyl-5-phenylthiazole exists as a stable enol. The spectroscopic properties of the meso-ionic thiazole (12 = Me, R = Ph, R = / -ClC H4),... 

Electrophilic Substitution.— 2-Amino-thiazoles and their or 4-substituted derivatives and 2-aryl-thiazoles and their 4-substituted derivatives undergo electrophilic substitution predominantly or exclusively in the 5-position. 2-Aryl-thiazoles may undergo substitution in the non-heteroaromatic ring, particularly (as in the case of 5-ethyl-2-phenylthiazole if the 5-position is blocked or if the non-heteroaromatic ring is activated. Mononitration of 2-(2-thienyl)thiazole occurs exclusively in the vacant a-position of the thiophen ring, and 2-(3-thienyl)-thiazole similarly gives the mononitro-compound (19). The situation is not... 

The action of ammonia on N-(aryl-i,3-oxathiol-2-ylidine) tertiary im-inium salts (254) yields linear intermediates (255) that cyclize to 2-amino-4-phenyl thiazoles (256) on crystallization from acetic acid (Scheme 129) (730). 

Diaza-1,3-butadienes reacts with A,A -diarylthioureas to give 2-(aryl-amino)-2,3-dihydro-1,3-thiazole derivatives (Scheme 59).142... 

Aryl-5,6-dihydrobenzo[4,5]imidazo[l,2-C]-quinazolines Isatoic anhydride could also be reacted with amino-, hydroxyl- or thiolanilines to form 2-(2-aminophenyl)benz-imidazoles, oxazoles or thiazoles, Scheme 5.38. In the case of 2-(2-aminophenyl)benzimidazoles (X=N), the product was formed after 3 min at 150°C in acetic acid. The products could subsequently be further elaborated 6-aryl-5,6-dihydrobenzo[4,5]imidazo[l,2-C]quinazolines, a four ring system, was formed by treatment of the 2-(2-aminophenyl) benzimidazole (X=N) with different aldehydes in acetic acid at 150°C for 5 min (J. Westman, and K. Orrling, Personal Chemistry, Uppsala, Sweden, unpublished results). Fifteen compounds were synthesised in 20-75% overall yield. This 3 + 5 min procedure should be compared to the conventional heating protocol developed by Devi and co-workers57, where each reaction step was run overnight to eventually afford the products in only 30-50% yield. 

The 1,2-hydrogen shift isomers of neutral (singlet and triplet) thiazole and its radical cation have been investigated87 by a combination of mass spectrometric experiments and hybrid density functional theory calculations. An unexpected isomerization of A-aryl-3-amino-4-nitroisothiazole-5(2//)-imines (71) to 2-(benzothiazol-2-yl)-2-nitro-ethene-1,1-diamines (72) has been reported.88... 

The secondary amino group of 3-(Al-ethylaminomethyl)-7-[2-(2-amino-thiazol-4-yl)-2-(Z-1 -carboxy-1 -methylethoxyimino)acetamido]ceph-3-em-3-carboxylic acid was arylated with 8-methylthiopyrido[l,2-a]pyrimidi-nium salt in dimethylformamide in the presence of triethylamine at 40°C (89MIP2). 

All available experimental data relative to protomerism of 2-amino-, 2-alkylamino-, 2-aryl or heterylamino-thiazoles or benzothiazole converge to the same result as that predicted by theoretical calculations these compounds exist predominantly in the amino form (8a X = NHR), associated in solution by hydrogen-bonding between the exocyclic NH groups and the ring nitrogen atoms. The same situation is observed in the case of the corresponding 2-alkylamino- and 2-arylamino-A2-thiazolines. 

A new efficient procedure has been proposed for the synthesis of 3-aryl-5-amino-l//-pyrazoles by reaction of a-chloro-/ -arylacrylonitriles with hydrazine hydrate <2004RJ01518>. Reaction of 2-(3,3-dicyano-2-propenylidene)-4,4,5,5-tetra-methyl-l,3-dioxolane 641 with hydrazine afforded 3-(2-hydroxy-l,l,2-trimethylpropoxy)pyrazole 642 (Equation 134) <2003RJ01016>. Treatment of ethyl 3,3-dicyano-2-methoxyacrylate with alkyl, aryl, heterocyclic, and sulfonyl hydrazines led to the synthesis of N-l-substituted 3-acyM-cyano-5-aminopyrazoles, which are versatile intermediates for the synthesis of many biologically active scaffolds <2006TL5797>. 2-Hydrazinothiazol-4(5//)-one reacted with a variety of cinnamonitrile derivatives and activated acrylonitriles to yield annelated pyrazolopyrano[2,3-rf thiazole <1998JCM730>. 

This type of approach constitutes a convenient synthesis of 5-functionalized thiazoles. 2,4-Diamino-S-acylthiazoles (292) can be prepared by reacting a-haloketones with alkyl- or aryl-3-amidinothioureas (290) in the presence of triethylamine <86S353> with iV-(anilino)benzylidenc-JV,iV -disubstituted thioiurcas (291), the reaction affords 2-amino-4-aryl-5-acyltWazoles (293). In contrast, the corresponding iV-benzoylthioureas (294) afford mainly 5-benzoyl derivatives (295)... 

The thiazolium-mediated three-component reaction of thiazolium salts 201, aryl aldehydes and dimethyl acetylenedicarboxylate provides a facile synthesis of 2-amino-2-arylfurans 202 <05OL1343>. The reaction pathway may involve the sequential nucleophilic addition of thiazol-2-ylidene 203 with the aldehyde and DMAD to form the spirocyclic intermediate 204 through the simultaneous formation of two C-C bonds and a C-O bond Selective ring opening of the spirocyclic intermediate 204 followed by hydrolysis leads to 3-aminofuran 202 via 205. 

Analog entstehen durch Reaktion von 2-Amino-1,3-thiazolen mit 2-Chlor-l,3,5-trinitro-benzol 2-Amino-5-(2,4,6-trinitro-phenyl)-l, 3-thiazole, haufig jedoch im Gemisch mit den N-Aryl-Derivaten182+. 

Gleiches trifft fiir die Umsetzung von 2-Amino-l,3-thiazolen mit Nitrit in Gegenwart von Arenen odcr Hetarcnen zu, bcidcr ebenfalls iiber l,3-Thiazolyl-Radikale2-Aryl- bzw. 2-lie tar yl-1,3-thiazole entstehen1176,1399,1405 ... 

Zur Einfiihrungder Amino-Gruppe hat sich hierbei die mechanistisch iiberraschende Umsetzung mit Aryl-aminen in Gegcnwart von 4-Dimethylamino-pyridinIS36 Oder aber die Uberfiihrung in 5-Azido-l,3-thiazole mit anschlieBender Reduktion bewahrt1834, 83S 1836 (s.S.288) z.B. ... 

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