Schotten-Bauman conditions

Zugravescu et al. (263) showed that ethyl chloroformate reacts on the exocyclic nitrogen of 2-amino-4-methylthiazole to yield the carbamate (101) (Scheme 70) (see also Refs. 264 and 265). With an excess of chloroformate (2 moles for one of the thiazole) under Schotten-Bauman conditions the jV.A -dicarbamate of 2-imino-4-methylthiazoline (102) is obtained (263),... 

By far the most common method for preparation of amides is the reaction of ammonia or a primary or secondary amine with one of the reactive reagents described in Section 3.4.1. When acyl halides are used, some provision for neutralizing the hydrogen halide is necessary, because it will otherwise react with the reagent amine to form the corresponding salt. Acid anhydrides give rapid acylation of most amines and are convenient if available. The Schotten-Bauman conditions, which involve shaking an amine with excess anhydride or acyl chloride and an alkaline aqueous solution, provide a very satisfactory method for preparation of simple amides. 

Several attempts to prepare typical alcohol derivatives of [Cr(HO-A)2]-were unsuccessful these include Schotten-Bauman conditions (acetyl chloride in chloroform shaken with cold, aqueous alkaline solution of complex), refluxing in acetyl chloride, in glacial acetic acid, acetyl chloride in hot dimethyl formamide, acetyl chloride and pyridine in acetonitrile, and acetic anhydride in acetonitrile. The failure of refluxing acetyl chloride to effect acetylation brings to mind the work of Keller and Edwards (4) the acetyl chloride system is completely heterogeneous and consequently not conducive to reaction. However, even the homogeneous reaction of [Cr(HO-A)2] — with acetyl chloride in acetonitrile failed to give a measurable quantity of the diester. 

Reaction of L-glutamic acid with /7-nitrobenzoyl chloride under Schotten-Bauman conditions gave (29), from which the diester (30) was obtained using refluxing 5 % ethanolic HC1. Catalytic reduction of the nitro group then yielded (31) [48] Scheme 3.4). 

A photoaddition-fragmentation sequence similar to that described in Scheme 17 was subsequently reported by Schell and Cook, who described the isolation of ketoimine 77 on irradiation of secondary vinylogous amide photosubstrate 75 in f-butanol (Scheme 18). The observed product was presumed to form via the intermediacy of cyclobutane 7639. Exposure of 77 to Schotten-Bauman conditions produced the diketo-amide 78. 

The reported ee of ID-47 was determined via conversion of the final product to the Mosher amide under Schotten-Bauman conditions [121]. The desired product was observed as a single peak, >99 % diasteromerically pure. 

In one synthetic approach (Veld 1990, 1992), alanine is first converted to the bromo derivative via the reaction of the diazonium salt of the amine with hydrogen bromide. In the next step the acid functionality is activated by converting it to the acid chloride using thionyl chloride. The activated acid is condensed with a protected a-amino acid to yield the dipeptide intermediate which is then cyclized by heating in presence of Celite (ion exchange resin) to yield the final product. However, the overall yield of this reaction is fairly low. A more elegant approach is shown in Scheme 5. In this approach, an a-amino acid wth a protected side chain (e.g., e-Z-lysine) is reacted with 2-bromo-propionyl bromide under Schotten-Bauman condidons (Fischer 1908) to yield the intermediate 5a, which is then cyclized under basic conditions to the depsipeptide 5b. 

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