Carboxylic acid amid hindered

It was reported (1+7) that salicylamide and other aromatic hydroxy carboxylic acid amides undergo autooxidation, when chromatographed in alkaline media. This autooxidation products hinder the development of the complex coloration with ferric ion. However, paper chromatographic separation of salicylamide and analogs in alkaline buffer media can be accomplished by ionophoresis (1+8). 

The presence of electron withdrawing groups at the a position (R3) of the acrylate derivative increases the reactivity of the reagent toward conjugate addition, while substituents in the ( position (R4) tend to provide steric constraints that hinder carbon-carbon bond formation (Scheme 3). Of the various acrylate derivatives employed in these reactions, the most frequently used have electron withdrawing functionality such as a carboxylic acid, amide, ester, or nitrile group or a combination of these. Direct pyridone formation can be achieved primarily through the use of either a,(J acetylenic esters or acrylate derivatives with P substituents (Y = SR, OR, NR2) that eliminate under the reaction conditions. 

Carboxylic acids from hindered carboxylic acid amides via N-subst. and N-nitroso-carboxylic acid amides... 

For less hindered carboxylic acids acylation of the imidate requires only 5 minutes. With this modification the /V-(a-methoxybenzyl)amides are prepared according to the above-mentioned procedure [R = CH3, CH(CH,)2. CH(CH, )OAc, CH(C H2)OAc yield 85-88%]. 

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. 

Nucleophilic attack only occurs upon heating the ammonium salt, resulting in overall dehydration of the salt. Consequently, it is usual to prepare amides by using a more favourable substrate than the carboxylic acid, one that is more reactive towards nucleophiles by virtue of possessing a better leaving group, and where salt formation does not hinder the reaction. 

The conversion of sterically hindered carboxylic acids to A-methoxy-A-methyl amides can be efficiently carried out with methanesulfonyl chloride, 3 equivalents of triethy-lamine and A-methoxy-A-methylamine. Yields for this process range from 59% to... 

Despite the huge structural diversity of known carboxylic acids, most of these are readily converted into esters or amides. Even sterically hindered acids, for example pivalic, triphenylacetic [1], or 2,6-disubstituted benzoic acids [1, 2], can be converted into suitable acylating reagents for alcohols or amines (Scheme 7.1). Esters of sterically demanding carboxylic acids can, alternatively, also be prepared by O-alkylation of the corresponding carboxylates [3, 4]. 

Figure 10.10 The synthesis of 2R-methylbutanoic acid, illustrating the use of a chiral auxiliary. The chiral auxiliary is 2S-hydroxymethyltetrahydropyrrole, which is readily prepared from the naturally occurring amino acid proline. The chiral auxiliary is reacted with propanoic acid anhydride to form the corresponding amide. Treatment of the amide with lithium diisopropyla-mide (LDA) forms the corresponding enolate (I). The reaction almost exclusively forms the Z-isomer of the enolate, in which the OLi units are well separated and possibly have the configuration shown. The approach of the ethyl iodide is sterically hindered from the top (by the OLi units or Hs) and so alkylation from the lower side of the molecule is preferred. Electrophilic addition to the appropriate enolate is a widely used method for producing the enantiomers of a-alkyl substituted carboxylic acids...

In addition to protonic acids, Lewis acids are the most common initiators of carbocationic polymerizations. Two mechanisms are possible. Direct initiation is rare and usually slow. The more prevalent mechanism is by cocatalysis in binary systems, with the Lewis acid acting as a coinitiator or catalyst rather than as initiator. Cationating or protonating species are the true initiators, which are therefore the species incorporated at the polymer s end group. The most common initiator is adventitious water in insufficiently dried systems. Thus, mechanistic studies should be performed under stringently dry conditions or in the presence of proton traps such as hindered pyridines. In addition to water, the protonating reagent may be an alcohol, carboxylic acid, amine, or amide [Eq. (28)]. 

These two compounds are superior to pyridine as catalysts for acylation of alcohols, particularly for tertiary and sterically hindered alcohols. Even axial lljS-hydroxyl groups of steroids can be acetylated in yields as high as 80%. Several useful C-acylations have been reported. The reagents catalyze the transformation of amino acids into or-acylamino ketones (equation II). They are superior to pyridine for reaction of isocyanates and carboxylic acids to form amides (equation III). 

Combination of silicon hydrides with catalytic amounts of a ruthenium(II) complex in tetrahydrofuran, chloroform or benzene has afforded a new reducing system capable of efficient reduction of a,p-unsatu-rated carboxylic acids, esters, amides, etc. Addition of a weak proton source, such as a sterically hindered phenol significantly increases reaction rates. The ruthenium mixture was found to exhibit the same regioselectivity observed with the above-described palladium systems. 

In conclusion, then, the available evidence concerning the structure of dimeric units suggests that many H bonding compounds form cyclic dimers (carboxylic acids, lactams, alcohols, phenols, and some steri-cally hindered amides) but that some form open dimers (most amides). This conclusion is reassuring to the many quantitative studies which have been based upon the tacit assumption that the v, absorption of monomeric species is not coincident with terminal O—H absorption of polymers. 

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. " ... 

---