Hydrazine reaction with, phosgene

Acetazolamide Acetazolamide is 5-acetamido-l,3,4-thiadiazole-2-sulfonamide (9.7.5). The synthesis of acetazolamide is based on the production of 2-amino-5-mercapto-l,3, 4-thiadiazole (9.7.2), which is synthesized by the reaction of ammonium thiocyanate and hydrazine, forming hydrazino-N,N -( ji-(thiourea) (9.7.1), which cycles into thiazole (9.7.2) upon reaction with phosgene. Acylation of (9.7.2) with acetic anhydride gives 2-acetylamino-5-mercapto-l,3,4-thiadiazol (9.7.3). The obtained product is chlorinated to give 2-acetylamino-5-mercapto-l,3,4-thiadiazol-5-sulfonylchloride (9.7.4), which is transformed into acetazolamide upon reaction with ammonia (9.7.5) [24,25]. 

The imonium salt (199), obtained from ynamines and phosgeneimonium chloVide, underwent ready reaction with monosubstituted hydrazines to give the 3,5-bis(dimethyl-amino)pyrazole (200) (68T4217, 69T3453). Similarly, the adduct (201), resulting from the addition of phosgene to ynamines, likewise reacted with sym-disubstituted hydrazines to give pyrazoles (202). With hydroxylamine derivatives the isoxazolinone (203) was obtained. 

The bicyclic meso-ionic 3-oxo-l,2,4-triazolo[4,5-a]pyridines (206) have been prepared by the following methods (i) the reaction of the hydrazines (207, X = H) with phosgene, (ii) heating the amide (207, X = CONH2) or the carbamate (207, X = COjEt), and (iii) alkylation or acylation of 3-oxo-l,2,4-triazolo[4,5-a]pyridine (208). The isomeric meso-ionic 2-oxo-l,3,4-triazolo[4,5-a]pyridines (209) are formed from the carbamoyl chlorides (210) and sodium azide. ... 

The synthesis of a triptan with a chiral side chain begins by reduction of the carboxylic acid in chiral 4-nitrophenylalanine (15-1). The two-step procedure involves conversion of the acid to its ester by the acid chloride by successive reaction with thionyl chloride and then methanol. Treatment of the ester with sodium borohy-dride then afford the alanilol (15-2). Reaction of this last intermediate with phosgene closes the ring to afford the oxazolidone (15-3) the nitro group is then reduced to the aniline (15-4). The newly obtained amine is then converted to the hydrazine (15-5). Reaction of this product with the acetal from 3-chloropropionaldehyde followed by treatment of the hydrazone with acid affords the indole (15-6). The terminal halogen on the side chain is then replaced by an amine by successive displacement by means of sodium azide followed by catalytic reduction of the azide. The newly formed amine is then methylated by reductive alkylation with formaldehyde in the presence of sodium cyanoborohydride to afford zolmitriptan (15-7) [15]. 

Carbamyl chlorides, available by the reaction of phosgene on secondary amines, can react with hydrazines to give good yields of 1,1-dialkylsemi-carbazides [31] (Eq. 24). 

Reactions of phosgene with Group IS hydrides 9.10.2.1 Reactions of phosgene with ammonia and hydrazine... 

Purine derivatives have also been formed by the reaction of phosgene with heterocyclic hydrazine derivatives [1161b] ... 

Reaction between hydrazine hydrate and ammonium thiocyanate yields 1,1-his (thiocarbamoyl) hydrazine which on treatment with phosgene undergoes molecular rearrangement through loss of ammonia to yield 5-amino-2-mercapto-l, 3, 4-thiadiazole. This on acylation gives a corresponding amide which on oxidation with aqueous chlorine affords the 2-sulphonyl chloride. The final step essentially consists of amidation by treatment with ammonia. 

Thiadiazolidines can be obtained from aliphatic aldehydes or ketones and disubstituted hydrazine derivatives (Scheme 29). A typical preparation of a mesoionic compound consists in the reaction of 1-methylthioacylhydrazine and phosgene (Scheme 31a). Syntheses by three-bond formation are rare for example, a one-pot reaction of an aldehyde with hydrazine and sulfur. A typical ring transformation reaction is the irradiation of 1,3,4-oxadiazoles to yield 1,3,4-thiadiazoles. 

The parent molecule, 1,3,4-thiadiazole (174), was first synthesized in 1956 by a four-step reaction sequence starting from thiosemicarbazide. A second procedure utilizes hydrazine and potassium dithioformate. A later procedure is shown in Scheme 19. Dehydration of DMF with thionyl chloride or phosgene gives the formamidoyl chloride (172) which on... 

Preparative Methods The title reagent is prepared by reaction of (IR, 2S)-2-phenyl-l-cyclohexanol with excess phosgene in the presence of quinoline to afford a chloroformate which is treated directly with hydrazine monohydrate (0.5 equiv) to afford di-(—)-(IR, 25)-2-phenyl- 1-cyclohexyl diazanedicarboxy-late. Oxidation of the diazanedicarboxylate to the diazenedicarboxylate is then readily effected using N-bromosuccinimide and pyridine (eq 1). 

Although the most extensively recorded aspect of phosgene chemistry is its interaction with compounds at a nitrogen centre, only three reactions of carbonyl chloride fluoride with amines have been reported. No reports have appeared concerning the reactions of COCIF with tertiary amines, amino acids, hydrazine derivatives, imino compounds or nitrogen-containing heterocycles, to name but a few unstudied reagents. 

Oxatriazines. (1) Reaction of benzonitrile oxides with hydrazones (Equation 16) - this method gives 3-aryl derivatives (2) reaction of benzonitrile oxides with hydrazine carboxylates and cyclization (Scheme 33) (3) cyclic carbonylation of l,4-disubstituted-4-hydroxy-semicarbazides with (thio)phosgene (Scheme 41) - this method gives 3,6-dione-type derivatives. Methods (1) and (3) both appear quite general and high yielding, with precursors readily available. 

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