Diazo with carboxylic acids

With less electron-rich pyrroles, hydrochloric acid can be used in the diazotization. The diazo compounds were isolated after neutralization with aqueous ammonia [84H(22)2269]. 3-Diazo-2,5-diphenylpyrrole, although efficiently prepared by diazotization of the 3-aminopyrrole, can also be prepared by oxidation of the 3-nitrosopyrrole with dinitrogen trioxide (60JCS3270). Pyrrole-3-carboxylic acid, with buffered nitrous acid, gave the 3-diazo derivative 295 by displacement of the carboxyl group, together with the 3-diazo-2-carboxylic acid 296, obtained by further hydrolysis (62JCS1638) (Scheme 90). 

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. 

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... 

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... 

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

In a first step, the carboxylic acid 1 is converted into the corresponding acyl chloride 2 by treatment with thionyl chloride or phosphorous trichloride. The acyl chloride is then treated with diazomethane to give the diazo ketone 3, which is stabilized by resonance, and hydrogen chloride ... 

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). 

However, it may be that the acid catalysis mechanism is more complex than that described by Scheme 6-5. Broxton and McLeish (1983) investigated the (ii)-diazo ether of a benzene derivative with a carboxy group in the 2-position. They also observed acid catalysis by added carboxylic acids, but, interestingly enough, the reactivity decreased as the strength of the added acid increased. 

In his pioneering work, Sus (1944) assumed that the final product of photodediazoniation of 2,1-diazonaphthoquinone (10.75) is indene-l-carboxylic acid (10.79, not the 3-isomer 10.78). He came to this conclusion on the basis of some analogies (in addition to an elemental analysis). Cope et al. (1956) as well as Yates and Robb (1957) found that the infrared spectrum of the product was consistent with an a,P-unsaturated acid. Later, Melera et al. (1974) verified the structure 10.78 by H NMR spectroscopy. Friedrich and Taggart (1975) showed that the equilibrium between 10.78 and 10.79 at 233 K lies on the side of the latter, but 10.78 clearly predominates at or above 0°C. Ponomareva et al. (1980) showed that not only 2,1-, but also 1,2-diazo-naphthoquinone yields indene-3- and not -1-carboxylic acid. 

Reagents that provide UV adsorptive derivatives of carboxylic acids are fairly numerous. The preparation of the simple benzyl esters by reacting the carboxylic ion with alkyl halides or diazo compounds has been unsuccessful due to their having unacceptable toxicity. The... 

Alkylation of Carboxylic Acids With Diazo Compounds... 

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. ... 

Alkylation of carboxylic acids with diazo compounds... 

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