Hindered salts with carboxylic acids

The reaction of trialkyloxonium salts with carboxylic acids is a mild, general esterification procedure that does not require the use of more hazardous reagents such as Hexamethylphospho-lie Triamide-Thionyl Chloride, lodomethane. Dimethyl Sulfate, 3-Methyl-l-p-tolyltriazene, or Diazomethane. The reaction proceeds smoothly with sterically hindered acids, as well as with acids containing various functional groups such as amides or nitriles (eq 10). ... 

Sodium salts of carboxylic acids, including hindered acids such as mesitoic, rapidly react with primary and secondary bromides and iodides at room temperature in dipolar aprotic solvents, especially HMPA, to give high yields of carboxylic esters.679 The mechanism is Sn2. Another method uses phase transfer catalysis.680 With this method good yields of esters have been obtained from primary, secondary, benzylic, allylic, and phenacyl halides.681 In another procedure, which is applicable to long-chain primary halides, the dry carboxylate salt and the halide, impregnated on alumina as a solid support, are subjected to irradiation by microwaves in a commercial microwave oven.682 In still another method, carboxylic acids... 

Typical synthetic procedures include the reaction of alkyl halides with the silver salts of carboxylic acids, the reaction of carboxylate anions in alkali with an excess of a dialkyl sulphate, (especially dimethyl sulphate), and heating tertiary184 or quaternary ammonium salts of carboxylic acids. These routes are particularly valuable for the preparation of esters of seriously sterically hindered acids. For example, Fuson et al.iK made the methyl ester of 2,4,6-triethylbenzoic acid by heating the tetramethyl ammonium salt to 200-250°C, viz. 

The interaction of the metal alkoxides with the salts of carboxylic acids or with p-diketonates of other metals is especially attractive for the synthesis of bimetallic molecular precursors in the cases, when the preparation of the alkoxide of the other metal is somehow hindered or it is insoluble or irreactive under the conditions applied. This method has been widely used for the sol-gel preparation of HTSC materials (because of low solubility and reactivity of Cu(OR)2) and lead-containing ferroelectrics (in the view of difficult synthesis and low stability of Pb(OR)2). It should be mentioned that the reaction between a metal alkoxide and a functional derivative does far not always lead to the formation of a mixed-ligand bimetallic complex ... 

Salts of NH with carboxylic acids arising from the respective N-alkyl group, i.e. pN+H2OCOR] were identified. It was concluded that the N-alkyl is easily oxidized via the a-CH moiety [26,173]. The process accounts for oxidative dealkylation and formation of the mentioned salt. The latter does not hinder the stabilizing activity (see Sect. 3.3.2). Moreover, tertiary HAS offer more stabilizing steps than secondary HAS and may, therefore, impart a better stabilization effect. Similar mechanisms as proposed for transformation with ROOH [173] were reported for reactivity with free radicals, 02 and excited complexes (Scheme 14) [111,127,130,175]. 

Esterification (4, 247). Shaw and Kunerth have reported further studies on the esterification of sodium salts of carboxylic acids with alkyl halides in HMPT at room temperature. The method is applicable to the preparation of ethyl esters of hindered acids for example, ethyl mesitoate can be obtained in 99% yield. In the esterification of acids that undergo ready decarboxylation, anhydrous potassium carbonate rather than NaOH is used as base (equation I). Diesters can be obtained by reaction of sodium salts of acids with dibromo-methane (equation II). Phenols are converted by this method into ethers in... 

Additional acceleration of acylation can be obtained by inclusion of cupric salts, which coordinate at the pyridine nitrogen. This modification is useful for the preparation of highly hindered esters.122 Pyridine-2-thiol esters can be prepared by reaction of the carboxylic acid with 2,2 -dipyridyl disulfide and triphenylphosphine123 or directly from the acid and 2-pyridyl thiochloroformate.124... 

Chloro-4,6-dimethoxy-l,3,5-triazine (100) reacts with iV-methylmorpholine at 20 °C to yield an isolable quaternary triazinylammonium salt (101 R = Me, R, R = C4H8O). This salt can then be reacted with a carboxylic acid to yield a 2-acyloxy-4,6-dimethoxy-l,3,5-triazine (102), which, in turn, can be reacted with an amine to yield an amide (103). This sequence of reactions provides an explanation for the activation (formation of reactive ester) of the carboxylic acid function by 2-chloro-4,6-disubstituted-l,3,5-triazines (100) in the presence of hindered amines. Several other hindered amines may replace iV-methylmorpholine in the process, but unhindered amines such as triethylamine and tributylamine were inactive. ... 

Irradiation of matrix-isolated imidazole-2-carboxylic acid gave the 2,3-dihydro-imidazol-2-ylidene-C02 complex (31) characterized by IR spectroscopy and calculated to lie 15.9 kcal mol above the starting material. A series of non-aromatic nucleophilic carbenes (32) were prepared by desulfurization of the corresponding thiones by molten potassium in boiling THF. The most hindered of the series (32 R = Bu) is stable indefinitely under exclusion of air and water and can be distilled without decomposition. The less hindered carbenes slowly dimerize to the corresponding alkenes. Stable aminoxy- and aminothiocarbenes (33 X = O, S) were prepared by deprotonation of iminium salts with lithium amide bases. The carbene carbon resonance appears at 260-297 ppm in the NMR spectrum and an X-ray structure determination of an aminooxycarbene indicated that electron donation from the nitrogen is more important than that from oxygen. These carbenes do not dimerize. 

Especially for large-scale work, esters, may be more safely and efficiently prepared by reaction of carboxylate salts with alkyl halides or tosylates. Carboxylate anions are not very reactive nucleophiles so the best results are obtained in polar aprotic solvents54 or with crown ether catalysts.55 The reactivity for the salts is Na+ < K+ < Rb+ < Cs+. Cesium carboxylates are especially useful in polar aprotic solvents. The enhanced reactivity of the cesium salts is due both to high solubility and to the absence of ion pairing with the anion.56 Acetone has been found to be a good solvent for reaction of carboxylate anions with alkyl iodides.57 Cesium fluoride in DMF is another useful combination.58 Carboxylate alkylation procedures have been particularly advantageous for preparation of hindered esters that can be relatively difficult to prepare by the acid-catalyzed esterification method (Fischer esterification) which will be discussed in Section... 

Esterification (4, 528). Complete details are available for preparation of methyl and ethyl esters of carboxylic acids with trialkyloxonium salts. The reaction is rapid even with hindered acids and yields generally are in the range 80-95%. 

The carboxylic acid group in the starting material will also be converted to a salt in carbonate solution. Although phenoxide is a better nucleophile than carboxylate ion, this phenoxide may not react as rapidly as the carboxylate with benzyl bromide because it is much more sterically hindered (by the ortho methyl and nitro groups). 8, 2 reactions are slowed considerably by steric hindrance. 

Ketones can also be obtained by treatment of the lithium salt of a carboxylic acid with an alkyllithium reagent (16-28). For an indirect way to convert carboxylic esters to ketones, see 16-82. A similar reaction with hindered aryl carboxylic acids has been reported. " Treatment of a p-amido acid with two equivalents of M-butyllithium, followed by reaction with an acid chloride leads to a p-keto amide.Carboxylic acids can be treated with 2-chloro-4,6-dimethoxy[l,3,5]-triazine and the RMgX/Cul to give ketones. " ... 

Water-immiscible amines are highly selective in the differentiation between acids (selectivity of about 10 for HCI/H3PO4 separation [44] compared to <2 in extraction by alkanols) and between them and their salts. They are widely used in extraction of metals (their anionic complexes) and of carboxylic acids, but most of them are too strongly basic for mineral acids. The convex distribution curve shows that extraction is very efficient, but back-extraction in free acid form would require huge amounts of water, resulting in extremely dilute, useless back-extracts. Only the very weak amines—highly branched trialkyl amines [52,53] or amines with at least one aryl group—combine efficient extraction with reversibility. Only few such water-immiscible aniline derivates and sterically hindered amines are currently produced on an industrial scale. Adjustment of their properties to treat a variety of feeds would require laborious synthesis. 

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