Hydrazine phosphorus chloride

Next the product is acylated with bromoacetyl chloride and the glycine equivalent is constructed in place by a Gabriel amine synthesis (phthalamide anion followed by hydrazine) subsequent to which cyclization to benzodiazepine occurs. The synthesis of the tranquilizer quazepam (88) is finished by thioamide conversion with phosphorus pentasulfide. ... 

Hydrogen chloride Phosphorus oxychloride Benzoyl chloride Maleic acid Hydrazine... 

Tetrahydroimidazo[5,l-c][l,2,4]triazine 474 was prepared (79KGS1540) by treating imidazole derivatives 472 or 473 with hydrazine. Compound 473 was obtained by reaction of the respective imidazole with 1,2-dibromoethane or by the reaction of the alcohol derivative 471 with phosphorus tribromide. On the other hand, chlorination of471 with thionyl chloride gave 472 (Scheme 100). 

Hydrazine 835 underwent ring closure with one carbon cyclizing reagents to afford 837 and/or /V-acyl derivatives 836. The N-acyl derivatives underwent cyclization on treatment with phosphorus oxychloride. They were also prepared by the reaction of hydrazones 838 with thionyl chloride (84JHC1565). Compound 835 underwent ring closure with carbon disulfide and ethyl chloroformate to give 839 (Scheme 169). 

Dihydralazine (67-3) is the less important of the two phthalazine antihypetensive agents its preparation is however recorded first because of its simplicity. Thus, reaction of phthaUiydrazide (67-1) with phosphorus oxychloride leads to the by now very famihar conversion of the amide functions to enol chlorides (67-2). The displacement of halogen by hydrazine leads directly to the antihypertensive agent dihydralazine (67-3) [76]. 

Much the same activity is retained when the nitrogen atoms in the heterocyclic nucleus are shifted around. The convergent scheme to this related compound starts with the acylation of alanine (35-1) with butyryl chloride (35-2). The thus-produced amide (35-3) is then again acylated, this time with the half-acid chloride from ethyl oxalate in the presence of DMAP and pyridine to afford the intermediate (35-4). In the second arm of the scheme, the benzonitrile (35-5) is reacted with the aluminate (35-6), itself prepared from trimethyl aluminum and ammonium chloride, to form the imidate (35-7). Treatment of this intermediate with hydrazine leads to the replacement of one of the imidate nitrogen atoms by the reagent by an addition-elimination sequence to form (35-8). Condensation of this product with (35-4) leads to the formation of the triazine (35-9). Phosphorus oxychloride then closes the second ring... 

The key intermediate chloromethyloxadiazole 18 was prepared in two steps from inexpensive, commercially available materials as shown in Scheme 5.10. Bishydrazide 19 was prepared in a one-pot procedure by reaction of 35% aqueous hydrazine with ethyl trifluoroacetate in acetonitrile and subsequent addition of chloroacetyl chloride and base. This procedure affords the unsymmetrical bis(hydrazide) 19 in higher than 95% assay yield. While a number of dehydrating agents were found to be effective in the dehydration to prepare 18, phosphorus oxychloride was chosen because of its low cost and relatively benign waste stream. Sub-stoichiometric (0.3 equiv.) amounts were found to be as effective as full equivalents in the reachon when used in conjunction with catalyhc amounts of DMAP as a nucleophilic catalyst. The entire sequence was transformed into a one-pot through process in order to improve efficiency. Following the cyclization, an aqueous work-up was performed and the organic extracts carried directly into the next step. 

Rather than yielding sulfonylhydrazide, the action of hydrazine on o-esters of benzenesulfonyl chloride 10 effects cyclization to benzothia-diazine 11 (62JOC1703). The action of the phosphorus pentachloride on the sodium salt of hydrazone 12 gives up to an 80% yield of benzothia-diazine 13 (R = H) (69CC33), which can also be made from the reaction of hydrazine with o-formylbenzenesulfonyl chloride (79MI1). 

Phthalazone Hydrazine hydrate Phosphorus oxychloride Hydrogen chloride... 

Thiazolecarboxylic acids, esters or acid chlorides react readily with ammonia or various amines, affording the corresponding carboxamides. Dehydration of the amides with phosphorus pentoxide or phosphoryl chloride occurs readily and gives the corresponding nitriles (Scheme 99). Thiazolecarboxylic acid hydrazides are obtained in a similar way, using hydrazine or substituted hydrazines instead of ammonia or amines. The Raney nickel reduction of cyanothiazoles leads to the corresponding amino compounds, the 4-cyano derivative being the isomer most readily reduced. 

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