Pyrazole thioamides

JOC3904>. Pyrazole thioamides 22 were transformed into pyrazolothiazoles 23 via a cyclization/dehydration sequence <02S1079>. l-Acetyl-2-methoxyazulene (24) reacted with arylhydrazines in refluxing ethanol to give 1 -aryl-3-methylazuleno[ 1,2-r/]pyrazoles 25 in moderate to high yields <02H(56)497>. 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

Acyloin 213 with thioamides, thiosemicarbazides, and methyl dithio-carbazate in trifluoroacetic acid give photochromic thiazole-, thiadiazine-, and pyrazole-bridged dihetarylethenes 254,255, and 256-258, respectively (Scheme 72) (OlIZVllS, 06ZOR882). 

Compound 12 cyclizes with hydrazine to give a pyrazoline which can be dehydrogenated to afford pyrazole 12. Many trifluoromethylated pyrazoles are known as described in an excellent review (ref. 27). Alcohols U can be methylated using NaH/TfOMe. These methyl ethers could not be hydrolyzed to the corresponding Mosher acid. As the hydroxyl is now protected by an alkyl group, the thioamide moiety can be chlorinated to give the amide chloride 14- This unstable compound was directly cyclized with benzothiazole (Scheme 35). 

A four-component domino reaction of isatin 58, phenylhydrazine, 3-aminocrotononitrile 117, and cyclic 3-diketones/amide/thioamide 118 in an aqueous medium in the presence of ( )-camphor-10-sulfonic acid on heating at 100 °C for 2-3 h afforded the spiro-fused 2-oxindoles 119 (Scheme 39) [94]. The reaction was successfully extended to 5-chloro- and 5-nitroisatins. According to the proposed mechanism, an acid-catalyzed reaction of phenylhydrazine with nitrile 117 affords the 5-amino-3-methyl-l-phenyl pyrazole 111 that adds to the carbonyl carbon of isatin giving rise to an intermediate product 120. The acid-catalyzed reaction of this intermediate (that has been isolated) with carbonyl compounds 118 affords another intermediate compound 121, which eventually furnishes the final products 119 by cyclodehydration forming tetrahydropyridine ring followed by subsequent dehydration (Scheme 40). 

Tominaga, Y., Y. Matsuoka, S. Kohra, and A. Hosomi. 1987. A novel preparation of polarized ethylenes by the reaction of thioamides or dithiocarboxylates with tetra-cyanoethylene oxide. Synthesis of pyrazoles and pyrimidines. Heterocycles 26 (3) ... 

Tominaga, Y., Y. Matsuoka, Y. Oniyama et al. 1990. Polarized ethylenes. IV. Synthesis of polarized ethylene using thioamides and methyl dithiocarboxylates and their application to syntheses of pyrazoles, pyrimidines, pyrazolo[3,4-d]pyrimidines and 5-aza[2.2.3] cyclazines. J Heterocycl Chem 27 (3) 647-660. 

---