Acetals reaction with hydrazine

Hippuric acid, cyclization to 2 phenyl-5 oxazolone with acetic anhydride, 47,101 Holarrhimine, 46, 61 Hydrazine, reaction with cinnamalde-hyde, 47, 99... 

Dissolve 10 g. of chloro- 2,4-dinitrobenzenet in 50 ml. of dioxan in a 250 ml. conical flask. Dilute 8 ml. of hydrazine hydrate with an equal volume of water and add this slowly with shaking to the dioxan solution, keeping the temperature between zo " and 25°. Heat under reflux for 10 minutes to complete the reaction and then add 5 ml. of ethanol and heat again for 5 minutes. Cool and filter oflF the orange 2,4-dinitrophenylhydra-zine. Recrystallise the dry product from ethyl acetate m.p. 200° (decomp.). Yield, 7 g. 

The reaction represented is that with hydrazine solution, produced from hydrazine sulphate and sodium acetate in the presence of aqueous alcohol. Excellent results are also obtained by interaction of the commercially available 60-64 per cent, hydrazine solution with a solution of 2 4 dinitrochloro-benzene in triethylene glycol or in diethylene glycol at about 20°. 

Reaction of diacylfuroxans with hydrazine dihydrochloride gave furoxano-pyridazines (55JA4233, 77MI2, 99KGS1259), whereas treatment with hydrazine hydrate in acetic acid afforded furazanopyridazines (Scheme 63) (92JHC87). 

Hydrazinopyridazines such as hydralazine have a venerable history as anti hypertensive agents. It is of note that this biological activity is maintained in the face of major modifications in the heterocyclic nucleus. The key intermediate keto ester in principle can be obtained by alkylation of the anion of pi peri done 44 with ethyl bromo-acetate. The cyclic acylhydrazone formed on reaction with hydrazine (46) is then oxidized to give the aromatized compound 47. The hydroxyl group is then transformed to chloro by treatment with phosphorus oxychloride (48). Displacement of halogen with hydrazine leads to the formation of endralazine (49). ... 

A mixture of 16.3 g of 4-methyl-6-methoxy-2-pyrimidinyl-hydrazine, 13.7 g of ethyl acetoacetate and 16.3 ml of methanol was refluxed 2 hours on a water bath. After a mixture of 4.7 g of sodium hydroxide, 4.7 ml of water and 27 ml of methanol was added dropwise thereto at about 50°C, the reaction mixture was refluxed for 2 hours more, then methanol was distilled off and the residue was dissolved in 130 ml of water. The solution was adjusted to pH 6 with acetic acid. The precipitate was filtered, washed with water and dried to give 24 g (yield 95.3%) of crystals, MP 97° to 98°C. Recrystallization from ligroin gave 1-(4 -methyl-6 -methoxy-2 -pyrimidinyl)-3-methyl-3-pyrazoline-5-one, MP 102° to 103°C. 

In the above-mentioned reactions with hydrazine and hydroxylamine, the actual reducing species is diimide (NH=NH), which is formed from N2H4 by the oxidizing agent and from NH2OH by the ethyl acetate.The rate of this reaction has been studied.Although both the syn and anti forms of diimide are produced, only the syn form reduces the double bond, at least in part by a cyclic mechanism ... 

The Diels-Alder adduct, anhydride 63, on treatment with hydrazine hydrate in acetic acid for 20 min yielded 252 which on keeping in acetic acid for further 8 h gave the imide derivative 253. This adduct, imide 253, underwent retro-Diels-Alder reaction to eliminate furan giving amino maleimide derivative 254 (Scheme 45) <2005J OC4553>. 

Anthranilic acid reacts with the fused-ring chloroimine 155 in ethanol at 170°C to give the pentacycle 156 (Equation 38), and similar compounds can be prepared from the keto-ester 157 by reaction with hydrazine in acetic acid (Equation 39) <2003HC0181>. 

Treating 644 with triethyl orthoformate gave l,2-dihydro-l-oxo[l,2,4]-triazino[4,5-a]indole 648, whose reaction with phosphorus oxychloride or phosphorus pentasulfide gave 650 and 649, respectively. Both reacted with hydrazine to give 651, which then was converted into [l,2,4]triazolo[3, 4 -/][1,2,4]triazino[4,5-a]indoles 652 and 653 by reaction with formic or acetic acid, respectively (80JHC77). 

However, the reaction of 3,4-diacylfuroxans 60 with hydrazine hydrate in acetic acid affords 3-[4,5-bis(hydrox-imino)-4,5-dihydro-l//-pyrazol-3-yl]-4-methylfurazans 61 (Scheme 12) <2003T1059>. 

Starting from 1-substituted-16-(12/f-l l-oxa-17-thia-15-aza-cyclopenta[ ]phenathrene-16-yl)-hydrazines, the reaction with formic acid or acetic anhydride gave novel l-substituted-6//-5-oxa-7-thia-8,9,10a-triaza-pentaleno[4,5- ]-phenathrenes, and l-substituted-10-methyl-6/7-5-oxa-7-thia-8,9,10a-triaza-pentaleno[4,5- ]phenathrenes, whose in vitro antibacterial activity has been also evaluated 111 NMR and MS data are described <2006EJM891>. 

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]. 

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