Ketene aminals reactions with isocyanates

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

Several approaches to the 1,2,3-triazole core have been published in 2000. Iodobenzene diacetate-mediated oxidation of hydrazones 152 led to fused 1,2,3-triazoloheterocycles 153 <00SC417>. Treatment of oxazolone 154 with iso-pentyl nitrite in the presence of acetic acid gave 1,2,3-triazole 155, a precursor to 3-(W-l,2,3-triazolyl)-substituted a,P-unsaturated a amino acid derivatives <00SC2863>. Aroyl-substituted ketene aminals 156 reacted with aryl azides to provide polysubstituted 1,23-triazoles 157 <00HC387>. 2-Aryl-2T/,4/f-imidazo[43-d][l,2,3]triazoles 159 were prepared from the reaction of triethyl AM-ethyl-2-methyl-4-nitro-l//-imidazol-5-yl phosphoramidate (158) with aryl isocyanates <00TL9889>. 

Tetrakis(dimethylamino)titanium converts DMF to tris(dimethylamino)methane (529 equation 236). This compound is also formed in the reaction of V-tetramethyloxamide with the titanium reagent, whereas amides which have a-CH bonds are converted to ketene aminals. Cyclic and spitocyclic compounds, containing the substitution pattern of a trisamino compound, are formed in the reaction of IVA -dialkylformamides or A/ -aryl-(VJV-dialkylformamidines with aryl isocyanates. Similar compounds, e.g. (530 equation 237), are produced in the reaction of imidazolines or lactamid-ines with isocyanates. 

This paper will describe the reactions of ketene aminals, 1, more highly activated electron-rich alkenes, with isocyanates to again afford amide products. We shall initially discuss the chemistry of the ketene aminal/isocyanate reaction, the preparation of these activated monomers and sane properties of solution-derived model "hard segments". 

Our investigations have shown additionally that the reaction between various ketene aminals and two equivalents of isocyanate is rapid, exothermic and essentially quantitative with or without the use of solvent. No catalysis is required to achieve quantitative results. 

Although there is no reaction directly related to the Breckpot )0-actam synthesis, other methods of preparing )0-lactams include the cycloaddition of imino compound with ketene, the reaction between diazomethane and isocyanate and the use of bromomalonic ester and primary amine. ... 

Reactions. As with other tertiary alcohols, esterification with carboxylic acids is difficult and esters are prepared with anhydrides (181), acid chlorides (182), or ketene (183). Ca.rba.mic esters may be prepared by treatment with an isocyanate (184) or with phosgene followed by ammonia or an amine (185). 

What is the mechanism of the coupling reaction of Rgure 23.47 Remember that other cumulated double bonds (p. 512) such as ketenes (p. 515), isocyanates (p. 918), and isothiocyanates (p. 1198) all react rapidly with nucleophiles. The related DCC is no exception, and it is attacked by amines to give molecules called guanidines. Carboxylates are nucleophiles too, and will also add to DCC (Fig. 23.48). 

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