Amines acyl halides

FIGURE 4.14 Reactions of activated A-alkoxycarbonylamino acids in the presence of tertiary amine. Acyl halides and mixed and symmetrical anhydrides generate 2-alkoxy-5(4/7)-oxazolone in the presence of tertiary amine. Aminolysis of 2-alkoxy-5(47f)-oxazolone in the presence of E N led to partially epimerized products. OAct = activating group. 

Quatemization involves the reaction of a tertiary amine with an alkylating agent. Typically, primary and some secondary alkyl halides are used for this purpose, although alkyl sulfates have also been used. Tertiary hahdes are not useful because they undergo elimination rather than substitution. The reaction, which is an example of an Sn2 process, proceeds readily to give crystalline, stable, and still-aromatic quaternary salts (Scheme 6.6). These have been used for many years to characterize amines. Acyl halides also react in a similar manner with pyridine, but the resulting salts are unstable and generally not isolated. 

Ketenes undergo rapid addition by nucleophilic attack at the sp-carbon atom. The reaction of tertiary amines and acyl halides, in the absence of nucleophiles, is a general preparation for ketenes. ... 

Lehn s approach is slightly more complex than that illustrated above in that the diol is chloromethylated and then treated with cyanide. Hydrolysis then affords the diacid which may be carried through as shown. It should also be noted that once the bis-acyl halide is in hand, it may be treated directly with an open-chained amine to yield a lipophilic diazacrown, after reduction ... 

Acylation of various oxygen functions by use of common and commercially available fluonnated carboxylic acid denvatives such as trifluoroacetic anhydride or the corresponding acyl halides have already been discussed sufficiently in the first edition [10] Therefore only exceptional observations will be described in this section In the past 15 years, many denvatizations of various nonfluonnated oxygen compounds by fluoroacylation were made for analytical purposes. Thus Mosher s acid chlorides for example became ready-to-use reagents for the determination of the enantiomeric purity of alcohols and amines by NMR or gas-liquid chromatographic (GLC) techniques [//] (equation 1)... 

Ruonnated carboxylic anhydrides and acyl halides as common acylating reagents to convert amines to amides and to acy late suitable heterocyclic nitiogen atoms have already been described in the first edition [10] Like in the acylation at oxygen, much synthetic activity was concentrated m the past few years on the denvatization of biomolecules by fluoroacylation reactions, that is, tnfluoroacetylation of amino sugars,... 

The Cunius degradation of acyl azides prepared either by treatment of acyl halides with sodium azide or trimethylsilyl azide [47] or by treatment of acyl hydrazides with nitrous acid [f J yields pnmarily alkyl isocyanates, which can be isolated when the reaction is earned out in aptotic solvents If alcohols are used as solvents, urethanes are formed Hydrolysis of the isocyanates and the urethanes yields primary amines. 

In the course of this study, the authors determined /Lvalues for dibenzyl, methyl phenyl, methyl p-nitrophenyl, di-p-tolyl, di-isopropyl and tetramethylene sulphoxides and for diethyl, dipropyl and dibutyl sulphites. The /Lscales are applied to the various reactions or the spectral measurements. The /Lscales have been divided into either family-dependent (FD) types, which means two or more compounds can share the same /Lscale, family-independent (FI) types. Consequently, a variety of /Lscales are now available for various families of the bases, including 29 aldehydes and ketones, 17 carboxylic amides and ureas, 14 carboxylic acids esters, 4 acyl halides, 5 nitriles, 10 ethers, 16 phosphine oxides, 12 sulphinyl compounds, 15 pyridines and pyrimidines, 16 sp3 hybridized amines and 10 alcohols. The enthalpies of formation of the hydrogen bond of 4-fluorophenol with both sulphoxides and phosphine oxides and related derivatives fit the empirical equation 18, where the standard deviation is y = 0.983. Several averaged scales are shown in Table 1588. 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

The treatment of acyl halides with ammonia or amines is a very general reaction for the preparation of amides.The reaction is highly exothermic and must be carefully controlled, usually by cooling or dilution. Ammonia gives unsubstituted amides, primary amines give A-substituted amides, and secondary amines give N,N-disubstituted amides. Arylamines can be similarly acylated. In some cases aqueous... 

In an indirect amination process, acyl halides are converted to amino acids. Reaction of the acyl halide with a chiral oxazolidinone leads to a chiral amide, which reacts with the N=N unit of a dialkyl azodicarboxylate [R"02C—N=N—CO2R ]. Hydrolysis and catalytic hydrogenation leads to an amino acid with good enantioselectivity. ... 

The reaction of enamines with ketenes can be conveniently carried out by generating the ketene in situ from an acyl halide and a tertiary amine. 

Ketenes can be prepared by treatment of acyl halides with tertiary amines. The scope is broad, and most acyl halides possessing an a hydrogen give the reaction, but if at least one R is hydrogen, only the ketene dimer, not the ketene, is isolated. However, if it is desired to use a reactive ketene in a reaction with a given compound, the ketene can be generated in situ in the presence of the given compound. ... 

In a similar reaction, aromatic acyl halides are converted to amines in one laboratory step by treatment with hydroxylamine-O-sulfonic acid. " ... 

Survey of Organic Synthesis , by Buehler and Pearson, Wiley, New York, 2 vols., 1970, 1977, discusses hundreds of reactions used to prepare the principal types of organic compounds. The arrangement is by chapters, each covering a functional group (e.g., ketones, acyl halides, and amines). Each... 

Acyl halides and anhydrides are the most reactive class of carboxylic acid derivatives, and readily react with amines to give amides. It should be noted that in both cases the leaving group is a conjugate base that, upon protonation during the reaction, will become an... 

Esters also react smoothly with amines, which is a useful reaction if the corresponding acyl halides or anhydrides are not easily available. The reaction proceeds through the anticipated tetrahedral anionic intermediate. There are two possible leaving groups... 

There are other activation procedures which generate acyl halides in situ in the presence of the nucleophile. Refluxing a carboxylic acid, triphenylphosphine, bromotri-chloromethane, and an amine gives rise to the corresponding amide103. 

By far the most common method for preparation of amides is the reaction of ammonia or a primary or secondary amine with one of the reactive reagents described in Section 3.4.1. When acyl halides are used, some provision for neutralizing the hydrogen halide is necessary, because it will otherwise react with the reagent amine to form the corresponding salt. Acid anhydrides give rapid acylation of most amines and are convenient if available. The Schotten-Bauman conditions, which involve shaking an amine with excess anhydride or acyl chloride and an alkaline aqueous solution, provide a very satisfactory method for preparation of simple amides. 

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