Carboxylic acids diazo compounds

There are two catalytically active residues in pepsin Asp-32 and Asp-215. Their ionizations are seen in the pH-activity profile, which has an optimum at pH 2 to 3, and which depends upon the acidic form of a group of pKa 4.5 and the basic form of a group of pKa 1.1.160,161 The pKa values have been assigned from the reactions of irreversible inhibitors that are designed to react specifically with ionized or un-ionized carboxyl groups. Diazo compounds—such as A-diazoacetyl-L-phenylalanine methyl ester, which reacts with un-ionized carboxyls—react specifically with Asp-215 up to pH 5 or so (equation 16.28).162-164 Epoxides, which react specifically with ionized carboxyls, modify Asp-32 (equation 16.29). 

Supplement 1953 3242-3457 Hydroxy-carboxylic acids, 190 In i doxylic acid, 226. Carbonyl-carboxylic acids, 284. i Sulphonic acids, 386 Quinoline sul-phonic acid, 390. Amines, 419 2-Aminopyridine, 428. Amino-carboxylic acids, 541 Tryp- tophane, 545. Hydrazines, 563. Azo. compounds, 572. Diazo compounds, 590. ... 

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) ... 

Alkylation of carboxylic acids with diazo compounds... 

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],... 

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. 

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>. 

The use of copper as a catalyst in carbenoid transfer has its roots in the Amdt-Eistert reaction, Eq. 1 (3). Although the original 1935 paper describes the Wolff rearrangement of a-diazo ketones to homologous carboxylic acids using silver, the authors mention that copper may be substituted in this reaction. In 1952, Yates (4) demonstrated that copper bronze induces insertion of diazo compounds into the X-H bond of alcohols, amines, and phenols without rearrangement, Eq. 2. Yates proposal of a distinct metal carbenoid intermediate formed the basis of the currently accepted mechanistic construct for the cyclopropanation reaction using diazo compounds. 

The simple primary amines of the aliphatic series, then, do not form diazo-compounds because the reaction which would le, d to their formation only occurs at a temperature at which they are destroyed. The reactivity of the NH2-group can, however, be increased by a neighbouring carbonyl group. Thus we come to the case of the esters of the a-amino-carboxylic acids and of the a-amino-ketones. The ethyl ester of glycine can be diazotised even in the cold the diazo-compound which does not decompose under these conditions undergoes stabilisation by elimination of water and change into ethyl diazoacetate ... 

The catalytic activity of rhodium diacetate compounds in the decomposition of diazo compounds was discovered by Teyssie in 1973 [12] for a reaction of ethyl diazoacetate with water, alcohols, and weak acids to give the carbene inserted alcohol, ether, or ester product. This was soon followed by cyclopropanation. Rhodium(II) acetates form stable dimeric complexes containing four bridging carboxylates and a rhodium-rhodium bond (Figure 17.8). 

Types of compounds are arranged according to the following system hydrocarbons and basic heterocycles hydroxy compounds and their ethers mercapto compounds, sulfides, disulfides, sulfoxides and sulfones, sulfenic, sulfinic and sulfonic acids and their derivatives amines, hydroxylamines, hydrazines, hydrazo and azo compounds carbonyl compounds and their functional derivatives carboxylic acids and their functional derivatives and organometallics. In each chapter, halogen, nitroso, nitro, diazo and azido compounds follow the parent compounds as their substitution derivatives. More detail is indicated in the table of contents. In polyfunctional derivatives reduction of a particular function is mentioned in the place of the highest functionality. Reduction of acrylic acid, for example, is described in the chapter on acids rather than functionalized ethylene, and reduction of ethyl acetoacetate is discussed in the chapter on esters rather than in the chapter on ketones. 

In 2007, Maruoka et al. introduced chiral dicarboxylic acids consisting of two carboxylic acid functionalities and an axially chiral binaphthyl moiety. They applied this new class of chiral Brpnsted acid catalyst to the asymmetric alkylation of diazo compounds withA-Boc imines [91]. The preparation of the dicarboxylic acid catalysts bearing aryl groups at the 3,3 -positions of the binaphthyl scaffold follows a synthetic route, which has been developed earlier in the Maruoka laboratory [92]. 

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). 

Appropriately substituted diazo ketones have been converted into oxetanes in two instances by Wolf rearrangement processes. The structure of compound (52) was established by X-ray crystallography (69MI51300, 81CSC345). Reaction of 4,4-dibromo-2,2,5,5-tetramethyltetrahydro-3-furanone with aqueous base is a good method of preparation for 3-hydroxy-2,2,4,4-tetramethyloxetane-3-carboxylic acid (equation 90) (66JA1242). 

Alkylation of Carboxylic Acids with Diazo Compounds Hydro,acyloxy-de-dlazo-bisubstitution... 

Alcoholysis of trihalides 0-6 Hydrolysis of ortho esters 0-20 Alcoholysis of acyl halides 0-21 Alcoholysis of anhydrides 0-22 Esterification of carboxylic acids 0-23 Transesterification 0-24 Alkylation of carboxylic acid salts 0-25 Cleavage of ethers with anhydrides 0-26 Alkylation of carboxylic acids with diazo compounds... 

The cycloaddition of DMAD and EP to 7-acylamino-3-azidomethyl-3-cephem-4-carboxylic acid derivatives (88) gave the expected 1,2,3-triazole derivatives 89 and 90.813 A similar addition of MP to the diazo compound 91 gave 92,814 and the nitrone 93 gave 94 with DMAD, a rearrangement having taken place.815... 

Rh(II) carboxylates, especially Rh2(OAc)4> have emerged as the most generally effective catalysts for metal carbene transformations [7-10] and thus interest continues in the design and development of dirhodium(II) complexes that possess chiral51igands. They are structurally well-defined, with D2h symmetry [51] and axial coordination sites at which carbene formation occurs in reactions with diazo compounds. With chiral dirhodium(II) carboxylates the asymmetric center is located relatively far from the carbene center in the metal carbene intermediate. The first of these to be reported with applications to cyclopropanation reactions was developed by Brunner [52], who prepared 13 chiral dirhodium(II) tetrakis(car-boxylate) derivatives (16) from enantiomerically pure carboxylic acids RlR2R3CC OOH with substituents that were varied from H, Me, and Ph to OH, NHAc, and CF3. However, reactions performed between ethyl diazoacetate and styrene yielded cyclopropane products whose enantiopurities were less than 12% ee, a situation analogous to that encountered by Nozaki [2] in the first applications of chiral Schiff base-Cu(II) catalysts. 

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