Mechanisms of Diazoalkane Syntheses

In this section we will review mechanistic investigations on some synthetic routes to diazoalkanes. 

As discussed in Chapter 2, diazotization of primary aliphatic amines generally does not lead to diazoalkanes, because the intermediate alkanediazonium ion loses the diazonio group faster than a proton of the C(a)-atom. Diazoalkane formation is dominant if the deprotonation rate is increased by acidifying substituents in the a-position (see Sect. 2.3). Curtius synthesis of ethyl diazoacetate (1883) is the classical example. Hart and Brewbaker (1969) showed clearly that acidifying substituents favor diazoalkane formation over dediazoniation electron-donating substituents exert the opposite effect. 

One might expect that diazotization of aliphatic amines under alkaline conditions or in the presence of strong proton acceptors used for general base catalysis might also yield diazoalkanes. This alternative route, however, has not been successful so far, as shown by the experiments of Maltz et al. (1971), who nitrosated amines with disodium pentacyanonitrosyl ferrate (Fe[CN]5NO Na2 ) at pH up to 12.7 (see Sect. 2.3). 

Under alkaline conditions, on the other hand, diazenols and diazenolates may also be involved, in particular, as well known for diazoalkane formation via the N-alkyl-A -nitrosoamides, -urethanes and related A -nitroso compounds (see Sect. 2.4). The intermediacy of diazenolates already has been observed qualitatively by Hantzsch and Lehmann (1902). The investigation of hydrolytic partitioning of alkyl-diazenolates into diazoalkanes and dediazoniation products (4-15) was started by Moss (1966) and Kirmse and Wachterhauser (1967). With R = methyl, benzyl, or allyl in (4-15), the diazoalkane is the main product with R = alkyl a rather even partition between the two pathways was found secondary alkyldiazenolates gave almost exlusively dediazoniation products. It is interesting to note that most of the investigations were carried out in the years in which primary interest on these reactions concentrated on carbocation chemistry and less on diazoalkane formation (see, e.g., review by Moss, 1974). We refer also to the corresponding discussion (Sects. 7.2-7.5). 

The diazo transfer reactions, discussed in the synthesis Sections 2.6-2.8 clearly indicate that arylsulfonyl azides and other compounds with the azido group act as electrophilic reagents, that add to nucleophiles, e.g., to C-anions of so-called active methylene compounds. This result is qualitatively easy to comprehend, since the N()8) and N(y)-atoms of the azides are electronically similar to the diazonio group, as shown in the mesomeric structures 4.20b-4.20c. 

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