Curtius-type reaction

Scheme 9.134. A representation of the formation of phenyiisocyanate from the reaction between the acid anhydride of benzenecarboxylic acid [benzoic anhydride, (QH5C0)20] and sodium azide (NaNs) foiiowed by rearrangement of the benzoylazide (a Curtius-type reaction, vide supra).

N-benzylaniline with phosgene, and then with sodium azide to produce carbonyl azide 52. On heating, nitrogen is evolved and a separable mixture of nitrene insertion product 53 and the desired ketoindazole 54 results. The latter reaction appears to be a Curtius-type rearrangement to produce an N-isocyanate (54a), which then cyclizes. Alkylation of the enol of 54... 

Photolysis of pentacoordinate pentavalent phosphorus azides leads to a Curtius-type reaction36,66. Further investigations into the photolytic behaviour of 25-phosphorus azide derivatives showed that three reaction types can be observed, depending on the nature of the substituents (a) Curtius-type rearrangement (b) tautomeric equilibrium between cyclic and open azides and (c) hydrogen abstraction reaction66. 

Using a carboxamide group as a source of an amino group by applying Hoffman type reactions, it has been possible to prepare several purines. Thus 4-aminopyrimidine-5-carboxamide and alkaline hypochlorite gave, a 60% yield of 8-oxo-7,8-dihydropurine (302) (62CB956), and the same authors achieved a Curtius reaction with a 4-aminopyrimidine-5-carbohydrazide and nitrous acid (Scheme 113). 

Phthalein type dyes have been prepared from 2,3-dicarboxypyrazine by heating with phenols or aromatic amines and zinc chloride. For example, compound (25) was obtained with resorcinol (1353). Efforts to prepare 2,6-diaminopyrazine through a Curtius-Schmidt reaction on 2-acetamido-6-carboxypyrazine (with sodium azide, sulfuric acid, and trichloroacetic acid) proved unsuccessful (434). The preparation of bicyclic heterocyles from 2-amino-3-carboxypyrazines has been described in Section VIII. 1D(6). 

The first step is likely to be a so-called Hieber base reaction (0 in Scheme 1), describing a nucleophilic attack at metal-coordinated carbon monoxide by hydroxide. While eq. (3) is the prototypical example as first reported by Walter Hieber in 1932 [5], several other variants have since become known. For example, azides and alkyl/aryl anions attack metal carbonyls according to eqs. (4) and (5), yielding metal isocyanates (via a Curtius-type azide degradation step) and metal carbenes, respectively [6, 7]. 

Curtius discovered HN3 [1] by reacting benzoylhydrazine with nitrous acid (b + g-type reaction). The resulting benzoyl azide was saponified, and sodium azide was isolated from the alkaline mixture. In 1903 Wislicenus [14] synthesized sodium azide solely from inorganic compounds, namely, sodium metal, ammonia, and dinitrogen oxide (a + e). The reaction proceeds in two steps, first converting ammonia with sodium to sodamide, and then reacting this with dinitrogen oxide to yield sodium azide. Fifty percent of the sodamide is decomposed to hydroxide and ammonia, and the overall balance of the process is... 

Conversions of compounds 116, 120 and 123 into IP-2-ones described above belong to Hofmann-, Curtius- and Lossen-type reactions. Therefore the parent amides, hydroxamic acids and o-aminopyridinecarboxylic acid azides, may formally be regarded as derivatives of monoaminopyridines. The above compounds rearrange into o-diamines with various degrees of ease, while benzenesulphonate 121 is transformed into intermediate isocyanate 122 under extremely mild conditions (68JOC2543). 

In an early experiment, Abramovitch and Breslow observed the formation of traces of alkyl azides during Curtius-type rearrangement of sulfonyl azides. This formation was rationalized by a direct reaction between alkyl radicals and sulfonyl azides. Roberts examined the reaction of aryl and alkyl sulfonyl azides with allylstarmanes in order to... 

Several standard type organic reactions were successfully investigated, e.g., Reformatsky (58), Hofmann and Curtius (55), Willgerodt (7), (19), Glaisen Condensation, Pinacol Rearrangement (42) and Darzens Reaction (21). 

In a related type of reaction, the styryl isocyanates, readily available by Curtius rearrangement of cinnamoyl azides, undergo thermal cyclization to l-isoquinolones in good yield (equation 34) the reaction can also be carrried out using Friedel-Crafts catalysts. 2,3-Dihydro-4( 1//)- isoquinolones are obtained by Dieckmann cyclization of N- (o- carbalkoxy-benzyl)glycine ester derivatives (equation 35). The same reaction has been used for the synthesis of a range of non-aromatic heterocycles (equations 36 and 37). 

Treatment of 2-lithiofurans with ethyl borate and hydrolysis of the resultant boronic ester yields 2(3//)-furanones (69AK(29)229). 2,5-Dimethyl-3(2i/)-furanone (358) has been prepared by a Curtius reaction on the ester (359) and acid hydrolysis of the intermediate urethane (360) (Scheme 97). This type of reaction has been used to synthesize muscarine and its stereoisomers (61QR153). 

Several other synthetic sequences have been developed that lead to the production of potentially useful intermediates for the total synthesis of galanthamine-type alkaloids. For example, the 4-arylbutyric acid 348 has been converted to the tetrahydrobenzazepine 349 by a modified Curtius reaction followed by cycliza-tion of the intermediate isocyanate with polyphosphoric acid (168). N-Methyla-tion of 349 and photooxidation of the resulting tertiary lactam in the presence of NBS gave 350. 

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