Diones reaction with, phosgene

The cyclization of a-hydrazinohydrazones (653) with ketones has been used for the synthesis of 4-amino-2,3,4,5-tetrahydro-l,2,4-triazines (654), and their reaction with phosgene affords 4-amino-4,5-dihydro-1,2,4-triazin-3-ones (655) (78HC(33)189, pp. 608, 656). 3-Thioxo-l,2,4-triazine-5,6-dione (657) was obtained when oxamohydrazide (656) reacted with thiophosgene (76ACS(B)7l). 

Substituted-tetrahydropyridazine-3,6-dione-3-hydrazones 27 react with strong carboxylic acids and with some acyl chlorides to give A-acyiated products and/or triazolo[4,3-6]pyridazines. Derivatives of this type are also obtained in reactions of 27 with triethyl orthoformate and orthoacetate. In reactions with phosgene, triazolo[4,3-6]pyrazine-3,6-diones are obtained and with oxaly chloride pyridazino[6,1-c]triazine-3,4,7-triones are formed (Scheme 4) <96MI01 97CA( 126)251121>. 

King Jr reported a facile synthesis of chlorinated dioxo-lanones by a simple, one-pot, direct addition of phosgene to 1,2-diones (Ref. 225). Thus, the reaction of 2,3-butane dione with phosgene in the presence of pyridine affords trans-4,5-dichloro-4,5-dimethyl-1,3-dioxolane-2-one in 82% yield as shown in scheme 172. 

The presence of pyridine catalyses the cyclization step [1907], and the reaction is to be preferred, as a route to substituted 1,3-dioxolan-2,4-diones, to the reaction of phosgene with the free 2-hydroxycarboxylic acids (see Section 10.3.4.1), as there is no formation of R R"C(C1)C(0)C1 as by-product [1907]. 

This generalization does not extend to l,2,4-triazolidine-3,5-diones both the 1-phenyl-and 4-phenyl-urazoles (89) and (90) can be diacetylated to (91) and (92), respectively, as in Scheme 29 (70JHC821, 66AP44i) the first of these reactions occurs with a yield of 69% while the yield in the second is almost quantitative. Phosgene does not afford carbonyl-ditriazolidines but carbamyl chlorides such as (93) which are useful intermediates in the synthesis of areas and urethanes (74AP504). 

The first examples of the 1,5,2,4-dioxadiazine ring system to be prepared have been the 2,4-dialkyl-2//-l,5,2,4-dioxadiazine-3,6(4/f)-diones (65). The synthesis involves a two-stage reaction of an A -alkylhydroxylamine with two equivalents of phosgene (Scheme 12) <86JOC3355>. 

Compounds of this type are usually prepared from the corresponding quinoxaline-2,3-diones. A variety of chlorinating reagents have been used, including phosphoryl chloride," phosgene," thionyl chloride, and mixtures of phosphoryl chloride with N,N-dimethylaniline or N,N-diethylaniline" " or phosphorus pentachloride." The reactions are normally carried out under reflux in an open vessel for periods of about... 

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. 

Phosgene and several of its equivalents react with 1,2-binucleophiles 1109 forming 2-oxo-five-membered heterocycles. Oxazolidin-2-ones (1110, Nu = NH, Nu = O), thiazolidin-2-ones (1110, Nu = NH, Nu = S), imidazolidin-2-ones (1110, Nu, Nu = NH), and lH-benzo[d][l,3]oxazine-2,4-diones (1110, Nu = COO, Nu = NH) are the most important classes of reaction products. 

The preparation of 4-(3-pyridylmethyl)oxazolidine-2,5-dione 1194, the NCA of j8-pyridylalanine, is made difficult by the presence of a pyridyl group in the amino acid. The pyridyl group complicated attempts to phosgenate the amino acid, since hydrogen chloride generated in the phosgenation reaction formed insoluble salts with the amino acid and with any anhydride that may have formed [877]. 

A large-scale cyclization reaction of carbamates with functionalized butenoates, starting from carbamates prepared without phosgene, for the efEdent preparation of 3-(substituted phenyl)-5-isopropylidene-l,3-oxazolidine-2,4-dione derivatives (azaladones) having potent herbicidal adivity, has been described in a patent application [240]. By reacting an N-(substituted phenyl)carbamate 312 with a 2-hydroxy-3-alkenoic acid ester (for example, ethyl 2-hydroxy-3-methyl-3-butenoate) or a 3-alkoxy-2-hydroxyalkanoic add ester, at 210 °C for 15 h, azaladone 313 was formed in 71.5% yield. 

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