Acid anhydride, amides from reaction with alcohols

The reaction of N-arylsulfonylsuinmides with a range of trivalent phosphorus compounds gave near quantitative yields of the phosphinimides and the sulfide. I Addition of protic solvents led to reduction products, which contain, besides the original sulfides, an alkyl-exchanged sulfide in which the alkyl group derived from the alcohol. 126.127 other derivatives, (acid anhydride, amide, ester or thioester) were formed in the presence of carboxylic acid derivatives. 128,129 xhese reactions were favoured by the dipolar nature of the intermediately formed sulfurane. 127... 

In the first case, reaction with amines leads to amides amido acids formed when amines react with cyclic anhydrides can be recyclized to cyclic imides (p. 344). When mixed acyclic or asymmetrical cyclic anhydrides react, a mixture of products can be formed, although the stronger acid usually gives an ester (or amide) (56). Reaction of alcohols with anhydrides very often takes place even in the cold certain anhydrides, however, are resistent to heat and can be crystallized from ethanol (57) they can be cleaved by heating with sodium ethoxide in ethanol or benzene. If the acids formed by hydrolysis are solid and suitable for identification, this procedure can be considered as the simplest for identification purposes. When anhydrides of liquid acids are to be identified, the reaction with aromatic amines is generally employed mixed anhydrides are best identified by chromatography of acids formed on alkaline hydrolysis. 

In general, the reactions of the perfluoro acids are similar to those of the hydrocarbon acids. Salts are formed with the ease expected of strong acids. The metal salts are all water soluble and much more soluble in organic solvents than the salts of the corresponding hydrocarbon acids. Esterification takes place readily with primary and secondary alcohols. Acid anhydrides can be prepared by distillation of the acids from phosphoms pentoxide. The amides are readily prepared by the ammonolysis of the acid haUdes, anhydrides, or esters and can be dehydrated to the corresponding nitriles (31). 

The latter, on reaction with methylamine yielded via the P-epoxide 373, the trans-a aminoalcohol 374, which was N-acylated to the amide 375. Acid-catalysed dehydration of the tertiary alcohol 375, led to the olefin 375, from which the key radical precursor, the chlorothioether377 was secured in quantitative yield by reaction with N-chlorosuccinimide. In keeping with the earlier results recorded for structurally related compounds, 377 on heating in the presence of ruthenium dichloride and triphenylphosphine also underwent a 5-exo radical addition to generate the cyclohexyl radical 378 which recaptured the chlorine atom to furnish the a-chloro-c/5-hydroindolone 379. Oxidation of thioether 379 gave the corresponding sulfoxide 380, which on successive treatment with trifluoroacetic anhydride and aqueous bicarbonate led to the chloro-a-ketoamide 381. The olefin 382 resulting from base induced dehydrochlorination of 381, was reduced to the hydroxy-amine 383, which was obtained as the sole diastereoisomer... 

It will be noted that in all of the reactions of the anhydrides the tendency is to reform the acid by removing one hydrogen from the other compound present. The remaining acyl group then unites with the residue of the reagent and a new compound is formed. The character of the new compound depends upon the residue of the reagent. With water H—OH we obtain the hydroxyl compound of the acyl radical, that is, the acid itself, while with alcohols we obtain the alkyl-oxy compound of the radical, i.e.y an ester, and with ammonia the amino, (—NH2), compound of the acyl radical, i.e., an amide. 

Related anchored l,l,3,3-tetraphenyl-2-oxa-l,3-diphospholanium bis-triflate (39) has been prepared by reaction of brominated poly(styrene-co-divinylbenzene) resin 38 with the phosphorous anion generated from l,2-bis(diphenylphosphino)ethane and sodium naphthalenide followed by further oxidation and reaction with triflic anhydride (Scheme 7.13) [55]. This supported reagent has also been employed, to a lesser extent than 37, for the formation of esters and amides by reaction of carboxylic acids with primary alcohols and amines, respectively. 

Since the discovery of the synthesis of 1,3,5-triazine-2,4-diamines from biguanide and its derivatives,328-329 a large variety of carboxylic acid derivatives, e.g. acid chlorides,332 342,346 lactones,333 amides,334,335 imides,336,337 ortho esters,338 amidines,338 esters334, 339- 343 and acid anhydrides,332,344,345 have been used as starting materials in the preparation of these triazines (Table 8).330,331 The preferred procedure is the reaction of biguanides 1 with esters 2 in alcoholic solution, sometimes in the presence of a basic catalyst. The reaction mechanism is thought to be as indicated.341... 

Local anesthetics are divided into two groups according to their basic chemical structure. These are esters and amides. An ester is a chemical compound formed from the reaction between an acid and an alcohol. Amides are an oiganic chemical compound formed by reaction of an acid chloride, acid anhydride, or ester with an amine. Amides have a lower incidence of causing an allergic reaction than esters. 

Thioesters have the general formula RCSR. They resemble their oxygen counterparts RCOR (oxoesters) in structure and reactivity more than other carboxylic acid derivatives such as acyl chlorides, acid anhydrides, and amides. Thioesters can be prepared from thiols by reaction with acyl chlorides or acid anhydrides in much the same way as oxoesters are prepared from alcohols. 

This chapter will revisit the lUPAC nomenclature system for aldehydes, ketones, and carboxylic acids, as well as introduce nomenclature for the four main acid derivatives acid chlorides, anhydrides, esters, and amides. The chapter will show the similarity of a carbonyl and an alkene in that both react with a Br0nsted-Lowry acid or a Lewis acid. The reaction of a carbonyl compound with an acid will generate a resonance stabilized oxocarbenium ion. Ketones and aldehydes react with nucleophiles by what is known as acyl addition to give an alkoxide product, which is converted to an alcohol in a second chemical step. Acid derivatives differ from aldehydes or ketones in that a leaving group is attached to the carbonyl carbon. Acid derivatives react with nucleophiles by what is known as acyl substitution, via a tetrahedral intermediate. 

Anhydrides are formed from the reaction of acid chlorides with acids, and an ester is formed from the reaction of acid chlorides or anhydrides with alcohols. Amides may be formed by the reaction of ammonia or an amine with acid chlorides, acid anhydrides, or esters. The nitrogen atom of ammonia or an amine is a good nucleophile, and it attacks the acyl carbon of an acid derivative in a now familiar sequence (see 60 62) to give the amide. A typical example reacts... 

This disappointing result is unfortunately quite neral. Secondary amines react with crown ether acid chlorides to give N-alkyl amides, but the slower reaction with crown ether anhydrides results in much poorer yields and significant competing epimerization via deprotonation-ieprotonation at the carbon adjacent to the carboxylic acid. The monoamide-triadd (above R-H) can be prepared from the corresponding primary amino-alcohol. The more reactive amine steers the dominant reaction towards amide formation without epimerization. 

The reactions of HN3 with cyclic alcohols to yield mixtures of ketones, amines, and products with an enlarged ring are catalyzed by H2SO4 [1]. Tertiary alcohols are converted to azides in the presence of acid [12] or TiCU [13]. Aldehydes and ketones with HN3 undergo a Schmidt-type reaction by liberating N2 and inserting NH In the presence of H or Lewis acids [14]. Ketones yield secondary amides and, in the case of cyclic ketones, lactames. Aldehydes are converted to nitriles or N-formylamines. Tetrazole derivatives result with excess HN3 [1, 15]. However, a-azido ethers are obtained from aldehydes and HN3 in the presence of alcohols by catalysis of TiC [16]. Carboxylic acids and anhydrides form amines, N2, and CO2 in Schmidt reactions with HN3. Intermediates are carbamic acids which form by insertion of NH into the R-COOH bond [1, 14]. High yields result for acids of arenes [17]. 

Much more important than these reactions, however, are the reactions of CDI and its analogues with carboxylic acids, leading to AAacylazoles, from which (by acyl transfer) esters, amides, peptides, hydrazides, hydroxamic acids, as well as anhydrides and various C-acylation products may be obtained. The potential of these and other reactions will be shown in the following chapters. In most of these reactions it is not necessary to isolate the intermediate AAacylazoles. Instead, in the normal procedure the appropriate nucleophile reactant (an alcohol in the ester synthesis, or an amino acid in the peptide synthesis) is added to a solution of an AAacylimidazole, formed by reaction of a carboxylic acid with CDI. Thus, CDI and its analogues offer an especially convenient vehicle for activation of... 

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