Diazo reaction with carboxylic acids

These two reactions of diazo compounds with carboxylic acids give gaseous nitrogen and esters as products. In both cases the rate of the reaction is proportional to [diazo compound]-[RCC H], Use the data for each reaction to suggest mechanisms and comment on the difference between them. 

These two reactions of diazo compounds with carboxylic acids give gaseous nitrogen and esters as products. In both cases r--... 

These two reactions of diazo compounds with carboxylic acids... 

Preparation of Esters. The (V-silyl hydrazones react with (difluoroiodo)benzene in the presence of chloropyridine to form an intermediate diazo-species, which participates in typical esteri-flcation reactions with carboxylic acids (eq 1)7... 

Two methods for converting carboxylic acids to esters fall into the mechanistic group under discussion the reaction of carboxylic acids with diazo compounds, especially diazomethane and alkylation of carboxylate anions by halides or sulfonates. The esterification of carboxylic acids with diazomethane is a very fast and clean reaction.41 The alkylating agent is the extremely reactive methyldiazonium ion, which is generated by proton transfer from the carboxylic acid to diazomethane. The collapse of the resulting ion pair with loss of nitrogen is extremely rapid. 

The mechanisms of two other reactions described in Sect. 2.2 involve slow proton transfer to unsaturated carbon. The general acid catalysed cleavage of vinyl mercuric halides [42, 50] for example, allyl mercuric iodide, CH2=CHCH2HgI (XXII), gives Bronsted exponents around 0.7. Linear Bronsted plots are obtained with carboxylic acid catalysts but, as observed in other A—SE 2 reactions, general acids of different structural types (for example, hydronium ion or bisulphate ion) show substantial deviations. Bronsted catalysis of the hydrolysis of diazo compounds (N2 =CR X) has been studied by the groups of Albery and Kreevoy. With... 

One of the more commonly applied chain extension reactions for carboxylic acids utilizes die unique reactivity of diazoalkanes. This sequence, generally referred to as the Amdt-Eistert synthesis, is a two-step process which, in the first step, involves the formation of an a-diazo ketone by reaction of the corresponding acyl chloride with an excess of diazoalkane (Scheme In the second stage of the... 

The reactions with HCl, ArOH, or with carboxylic acids may serve for the identification of aliphatic diazo compounds ... 

An a-diazo ketone 1 can decompose to give a ketocarbene, which further reacts by migration of a group R to yield a ketene 2. Reaction of ketene 2 with water results in formation of a carboxylic acid 3. The Woljf re arrangement is one step of the Arndt-Eistert reaction. Decomposition of diazo ketone 1 can be accomplished thermally, photochemically or catalytically as catalyst amorphous silver oxide is commonly used ... 

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 ... 

To set the stage for the crucial aza-Robinson annulation, a reaction in which the nucleophilic character of the newly introduced thiolactam function is expected to play an important role, it is necessary to manipulate the methyl propionate side chain in 19. To this end, alkaline hydrolysis of the methyl ester in 19, followed by treatment of the resulting carboxylic acid with isobutyl chlorofor-mate, provides a mixed anhydride. The latter substance is a reactive acylating agent that combines smoothly with diazomethane to give diazo ketone 12 (77 % overall yield from 19). 

Carboxylic acids can be converted to esters with diazo compounds in a reaction essentially the same as 10-15. In contrast to alcohols, carboxylic acids undergo the reaction quite well at room temperature, since the reactivity of the reagent increases with acidity. The reaction is used where high yields are important or where the acid is sensitive to higher temperatures. Because of availability, the diazo compounds most often used are diazomethane (for methyl esters) ... 

The reaction between acyl halides and diazomethane is of wide scope and is the best way to prepare diazo ketones. Diazomethane must be present in excess or the HX produced will react with the diazo ketone (10-74). This reaction is the first step of the Amdt-Eistert synthesis (18-8). Diazo ketones can also be prepared directly from a carboxylic acid and diazomethane or diazoethane in the presence of dicyclohexyl-carbodiimide. ... 

Making use of the same reaction principle, disubstituted ketenes 66 have been reacted with aldehydes 80 to form p-lactones 81 [100], with diazo-compounds 82 to form 1,2-diazetidin-3-ones 83 [101] and with nitroso-compounds 84 to form 1,2-oxazetidin-3-ones 85 as precursors of a-hydroxy carboxylic acids (Fig. 42) [102],... 

Protected 6-amino-hexahydro-l,7-dioxopyrazolo[l,2-4]pyrazole-2-carboxylic acid 274 is available by a thermolytic decomposition of diazo compound 273 via the Wolff rearrangement. The starting compound is simply available by alkylation of racemic 272 with the corresponding bromoacetoacetate and subsequent diazo transfer reaction (Scheme 35) <1996TL4891>. 

---