Amines thiosemicarbazides

Acylation of thiosemicarbazide with propionyl chloride, interestingly, does not stop at the acylated product (124). Instead, this intermediate cyclizes to the thiadiazole, 125, under the reaction conditions. Hydrolysis then affords the heterocyclic amine, 126. Acylation by 88 followed by removal qf the acetyl group affords sulfaethidole (116) variation of thle acid chloride used in the preparation of the heterocycle leads to 117 and 118. 

Formaldehyde hydrazones react with N,AT -thiocarbonyldi-1,2,-4-triazole to give hydra-zones of thioglyoxalyl-1,2,4-triazoles, which react readily under displacement of 1,2,4-triazole with nucleophilic reagents such as amines and hydrazines but also with less nucleophilic compounds, including hydrazones, sulfonylhydrazides, thiosemicarbazides, and hydrazides.[10]... 

Amino-l,3,4-thiadiazol-2-yl)-l,2,5-oxadiazole-3-amine 175 was formed with a yield of more than 75% in a condensation of 3-amino 4-cyano-l,2,5-oxadiazole 174 with thiosemicarbazide in trifluoroacetic acid (Equation 30)... 

Thus, (dimorpholinophosphoryl)formonitrile oxide undergoes 1,3-addition reactions with HC1, HI, primary and secondary amines, acylhydrazines, and even with thiourea or thiosemicarbazide (Scheme 1.13) (98). The former gives (dimor-pholinophosphoryl)isothiocyanate and urea. Those products might arise from a retro destruction of the unstable 1,3,5-oxathiazoline. The latter transforms to the isothiocyanate, the product of addition of a second molecule of thiosemicarbazide. (98). 

Substitution of the 11-ethoxycarbonylmethylthio group of 64 with anilines, 3-dimethylaminopropylamine, thiosemicarbazide, acetylhydrazine, and dimethyl malonate gave the corresponding 11-amine 65 and ll-bis(di-methoxycarbonyl)methylene derivatives 66 (74JHC125). Deprotonation of the 11-amines 65 gave the 11-imino derivatives 67. 

The reaction of 1,4,2-dithiazolium salts with amines also leads to thiadiazoles. Thus treatment of the A,A-diethylamino dithiazolium salt (177) with an excess of hydrazine (Scheme 32) afforded 2,5-bis(diethylamino)-l,3,4-thiadiazole (180) together with thiobenzamide. The mechanism postulated is as follows in the first step, hydrazine causes rupture of the ring to liberate A,A-diethyl-thiosemicarbazide (178) which in turn reacts with another molecule of (177) to give the intermediate... 

Isatin reacts with formaldehyde and a variety of amines in the Mannich reaction to give compounds of type 42.181-193a A similar reaction takes place with isatin-3-thiosemicarbazone,185,187 or 42 can react with thiosemicarbazide to give a similar product.192 In the absence of an amine, isatin181 and substituted isatins157,193a with form-... 

PHA827). 3-Amino-6-phenylthieno[2,3-<7]pyrimidin-4-one-2(l H)-thione (17) was obtained similarly from isothiocyanate 15 (R1 = C02Et, R2 = H, R3 = Ph) via the thiosemicarbazide 16 (94PHA64). Isothiocyanate 15 [R1 = COPh, R2, R3 = (CH2)4] was reacted with hydrazine hydrate and various primary amines to give directly the 3-substituted 4-phenyl-2-thioxothieno[2,3-c/ pyrimidines 82b (90JHC269). 

Further nucleophilic reagents used to cleave 2-amino-l,3,4-oxadiazoles include alcoholic potash, primary amines, hydrazine hydrate, phenylhydrazine hydrochloride, acid hydrazides, semicarbazide, thiosemicarbazide, ammonium hydrogen sulfide, and hydrochloric acid. 

Bis(thiosemicarbazide)nickel(II) forms charge augmented double hydrogen-bonded chains with 1,4-terephthalate and trans-fumarate anions, which are further linked into sheets by hydrogen bonds between the N-H- -O units. The methylation of the primary amine disrupts these interactions markedly so that hydrogen-bonded sheets result, involving now molecules of water. ... 

The 4-formyl and 4-acyl-3-pyrazolin-5-ones react like normal carbonyl compounds with active methylene groups,898-1190 amines,107,1190 hydroxylamine,196 hydrazines196-201 and semicarba-zide,201 although some fail to react with thiosemicarbazide.799 They... 

Addition to the Carbonyl Group — The internal, cyclic hemiacetal formation is one of the illustrations of such addition. The H2N-X nucleophiles, with X being NH2 (hydrazine), NHAr (arylhydrazines), OH (hydroxylamine), NHCONH2 (semi-carbazide), NHCSNH2 (thiosemicarbazide), or alkyl (primary amine), produce hydrazones, arylhydrazones, oximes, semicarbazones, thiosemicarbazones, and alkyl imines (Schiff bases), respectively, following the following path 5.4 + 5.15 — 5.16 ->. .. -> 5.21. 

The periodate oxidation of 165 and its derivatives gave 195, which could be transformed into a variety of derivatives (194 and 196) (80MI8) upon reaction with amines, hydrazines, semicarbazide, or thiosemicarbazide (Scheme 44). The thiosemicarbazones 196 were cyclized to the thiadiazoles 199 and thiadiazolines 198, which are of chemotherapeutic interest (80MI8). The aldehyde also affords the expected dimedone derivative 197. 

Condensation reactions can be grouped into two categories. The first category involves pyrazol-3-ones with formyl, acyl, nitroso, a,jS-unsaturated oxo, 3-oxo-2-azobutyric acid ethyl ester or acetonitrile substituents at position 4 or formyl substituents at position 5 and their reaction with carbanions, heterocyclic methylcarbenium salts, primary and secondary amines, diamines, heterocyclic perchlorates, hydroxylamine, hydrazines, urea or thiosemicarbazide. The second category involves pyrazol-3-ones with amino, hydrazino, heteroaromatic amino, acetyl or acetonitiilo groups at position 4 and their reaction with aryl or heteroaromatic aldehydes or cyclic ketones. 

Reaction of the tetraketone 355 with nitroanilines in the presence of catalytic amount of P2O5 in ethanol gave 356. Reduction of the m-nitro group to the amine with Zn/HCl was successful whereas the p-nitro was unsuccessful. The reaction of 355 with N-amino ethyl piprazine or thiosemicarbazides in acetic acid gave the respective N-substituted acridines 356 (04ARK124). 

A generalized reaction scheme has been developed for the reactions of thiosemicarbazides with a-halocarbonyl compounds. Depending on whether condensation occurs at the N1, N2, or N4 atom, three different sulfur-containing heterocyclic rings may be expected after ring closure 1,3,4-thiadiazines, 2-alkyl(aryl)imino-2,3-dihydrothiazol-3-amines, and 3-alkyl(aryl)-2-hydra-zono-2,3-dihydrothiazoles as well as, with R3 = H, thiazole-2-hydrazines (see p 494). 

A noteworthy difference is observed in the condensation of thiosemicarbazide with aromatic a-halocarbonyl compounds in comparison to aliphatic a-halocarbonyl compounds. It has been found26 that the reaction of phenacyl bromide with thiosemicarbazide furnishes 5-phenyl-1,3,4-thiadiazin-2-amine together with a small amount of 5-phenylthiazolc-2-hydrazine, Similarly, the reactions of thiosemicarbazide with 2-bromo-l,2-diphenylethan-l-one,7 8,41 2-bro-mo-l-phenylpropan-l-one,10,41 and 2-bromo-l-phenylbutan-l-one 10,41 in ethanolic solution give 1,3,4-thiadizines. However, the main products are the thiazole-2-hydrazine derivatives (cf. Houben-Weyl, Vol. E8b, p 72ff). The addition of an equimolar amount of 48% hydro-bromic acid results in the exclusive formation of the 1,3,4-thiadiazines 2 a, c, and d. When the condensations of thiosemicarbazide with 2-bromo-l,2-diphenylethan-l-one, 2-bromo-1-phenylpropan-l-one or 2-bromo-l-phenylbutan-l-one are performed in ethanol at room temperature, the S-(oxoalkyl)-isothiosemicarbazide hydrobromides are formed as open-chain intermediates and also undergo cyclization in ethanol upon addition of an equimolar amount of 48% hydrobromic acid to furnish 2 a, c, and d. 

On condensation of a-chloro-a-phenylacetone with thiosemicarbazide, all three isomeric. S, jV-heterocyclic systems can be isolated by varying the reaction conditions.7 8 Reaction in ethanol at 20 °C gives 4-methyl-5-phenylthiazole-2-hydrazine in 60% yield, reaction in concentrated hydrochloric acid gives 2-imino-4-methyl-5-phenyl-2,3-dihydrothiazol-3-amine, and when a-chloro-a-phenylacetone is added dropwise to a boiling suspension of thiosemicarbazide in ethanol, 5-methyl-6-phenyl-6//-l,3,4-thiadiazin-2-amine (2b) is obtained in 50% yield. The previously not observed strong temperature dependence of the reaction is worthy of emphasis.7- 8... 

When 4-alkyl(aryl)thiosemicarbazides are reacted with 2-bromo-l,2-diphenylethan-l-onc, 2-bromo-l-phenylpropan-l-one, or phenacyl halides in neutral media, the A -alkyl-5-aryl-6/f-l,3,4-thiadiazin-2-amines 3a-q are formed as the major products.41 -43... 

Thiosemicarbazides bearing a bulky alkyl substituent in the 4-position behave similarly. Thus, in reactions of 4-(2,2,4-trimethylpent-4-yl), 4-terZ-butyl- or 4-isopropylthiosemicarbazide with 2-bromo-l,2-diphenylethan-l-one, 2-bromo-l-phenylpropan-l-one, or phenacyl bromides, the 2-(alkylimino)-4-aryl-2,3-dihydrothiazol-3-amines are always formed as side products and, in the case of 4-isopropyllhiosemicarbazide, additional, small amounts of the corresponding 2-hydrazono-3-isopropyl-4-phenyl-2,3-dihydrothiazole are also obtained.10 These side products can be isolated preparatively by chromatographic workup on Sephadex LH-20.43... 

In addition to amidrazones, the corresponding carbonic acid derivatives semicarbazide, thiosemicarbazide, selenocarbazide, guanidin-2-amine, guanidine-1,2-diamine and 3-methylisothiosemicarbazide can also be reacted with 1,2-dicarbonyl compounds, leading to the nonaromatic 1,2,4-triazin-3(2//)-oncs,451 1,2,4-triazine-3(2/f)-thiones,452 -3(2//)-selenones 5,453 or the aromatic l -triazin-S-amines,112 3-hydrazino-l,2,4-triazines,113 or 3-(methylsulf-anyl)-l,2,4triazines 6.114 The initially formed hydrazones can be isolated in most cases and cyclized in a second step, but isolation is not necessary as direct cyclization is usually achieved without problem. 

Similar cyclizations to form 3-substituted 4/7-1,2,4-triazoles 10 can be achieved by replacing 7 with semiearbazide, thiosemicarbazide or guanidin-l-amine.21... 

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