Carboxylic acids, anhydrides equation

Carboxylic acid anhydrides. Carboxylic acids are converted to the symmetrical anhydride by reaction with 1 and triethylaminc in acetone or methylene chloride at room temperature (equation I). 

Furopyrylium salts (43, 55) have been repeatedly mentioned in the foregoing subsections. They may be prepared from acetonylfurans (42,54) and carboxylic acid anhydrides in the presence of perchloric acid. Benzofuro[3,2-6]pyrylium salts have been synthesized from /3-coumaranone and /3-diketones, e.g. equation (15) (B-78MI31704). 

A common synthetic method is that of equation (9), where X = MeC02,168 PhS03,169 NO3170 or C104,171 and relies on the precipitation of silver chloride. A variation of this method is the synthesis of the ring complex (5), by the reaction (10).172 In other cases, the synthesis may involve mercury(II) salts or sodium salts (equations 11 and 12).173,174 Another useful synthetic method involves reaction of alkyl- or aryl-gold(I) complexes with carboxylic acids or acid anhydrides (equations 13-15).176,177... 

A cyclization reaction involving the sulfonamide 267 finalized an efficient synthetic approach to the COX-inhihitor 268 after subsequent simultaneous ester hydrolysis and detosylation (Equation 82) <2003JOC4104>. Indoles have also been prepared by reaction of (2-aminobenzyl)triphenylphosphonium salts with carboxylic acid anhydrides in the presence of a base <2002TL2885>. Exposure of o-(benzoylamino)benzonitriles to a-bromoketones under basic conditions gives 3-aminoindole derivatives <2001BML2169>. 

Symmetrical and unsymmetrical anhydrides can be prepared in quantitative yields by the reaction of Tl(l) carboxylates with carboxylic acid chlorides (equation 28). 

In general, salt-free solutions of ylides do not react with methyl or ethyl esters of carboxylic acids. Better results can be obtained when activated esters (e.g. phenyl or pyridyl esters) are used for acyl-ation. " Acylation with carboxylic acid anhydrides also requires only one mole of starting ylide (equation 73). ... 

Carbonyl dichloride can be taken similarly to form acid anhydrides (equation 31). Via a mixed anhydride and in the presence of triethylamine, it is possible to prepare symmetrical anhydrides in high yield. ° °° A variation provides ethyl chloroformate as reagent.In a first step the carboxylic acid is ethoxycarbonylated in the presence of triethylamine and then reacted with free caiiioxylic acid to form the acid anhydride (equation 32). As the intermediate can be isolated, this is a good method of forming mixed anhydrides.In addition it seems to be particularly suitable for functionalized carboxylic acids such as hydroxy acids." Polymer-bound chloroformates may be advantageous in some cases. " " ... 

Carbodiimides, in particular dicyclohexylcarbodiimide, have been applied in many syntheses where dehydration had to be performed under mild conditions. It is therefore no surprise that this reagent was also introduced for the synthesis of acid anhydrides from carboxylic acids." " In order to avoid N-acylation the reactions are carried out at low temperature. First 0-acylisoureas are formed, which then react further with free acid to the acid anhydride (equation 34). The reaction has been exploited in particular for the preparation of peptides." )V-alkoxycarbonyl-protected amino acids can be transformed in high yield to the corresponding anhydrides, which themselves are activated acid derivatives and may be converted to peptides. As in many other examples polymer-bound carbodiimides may prove superior sometimes, as the isolation of the products is facilitated. Easy preparation of acid anhydrides is possible in this way." ... 

Mild dehydrating agents are available in yneamines and 1-alkoxyalkynes. They have been applied occasionally to the preparation of acid anhydrides.The great advantage of these reagents is that the reaction takes place under neutral conditions and, therefore, acid anhydrides of acid sensitive compounds can be obtained. An extension of this approach was described recently. Trimethylsilyl-ethoxyacetylene, which can be prepared from ethoxyacetylene, serves as a very mild dehydrating agent.By means of this compound various types of acid sensitive carboxylic acid anhydrides can be made quantitatively or almost quantitatively (equation 40). Some examples are collected in Table 11. 

Orthoesters react with primary amines to give imino esters (238 equation 129). The condensation proceeds usually at temperatures above 100 C and can be catalyzed by mineral acids, sulfonic acids, Lewis acids and carboxylic acid anhydrides. 

Only a limited amount of work has been published concerning the reactions of phosgene with carboxylic acid anhydrides, despite the fact that the product acid chlorides, formed as illustrated in Equation (10.23), are generated without concomitant formation of co-product hydrogen chloride, as in the case for the corresponding reaction of the carboxylic acids. 

The Perkin reaction involves the condensation of a carboxylic acid anhydride and an aldehyde in the presence of a weak base, often the sodium or potassium salt of the acid or triethylamine, to give unsaturated carboxylic acids (equation 1). The first example of this reaction was described by Perkin in 1868 and involves a synthesis of coumarin by heating the sodium salt of salicylaldehyde with acetic anhydride (equation 2). The reaction is generally applicable only to aromatic aldehydes and is particularly useful for the preparation of substituted cinnamic acids, as illustrated by equation (3). ... 

Acyloxysilatranes (658) can be obtained from 1-ethoxysilatrane (657) with carboxylic acids in the presence of the corresponding acid anhydride (equation 337)377. Transetherification of 657 by means of triphenylsilanol (659) gives rise to l-(tri-phenylsiloxy)silatrane (660) (equation 338)377. 

Acid chlorides are the most common source of compounds for Friedel-Crafts acylations but they are not the sole source. Carboxylic acid anhydrides are also used in this capacity, the other product being a carboxylic acid. The general equation for this type of reaction is ... 

Problem 16.47. Amides can also be synthesized by using the acid chloride or acid anhydride instead of the carboxylic acid. Give equations for the synthesis of formamide from formyl chloride and formic anhydride. 

The first example of an indole-2,3-quinodimethane (IQM) undergoing a Diels-Alder cycloaddition to furnish a carbazole was reported by Plieninger and coworkers in 1964 [9], Thus, indole-3-acetic acid was readily converted to pyrano[3,4-fe]indol-3-ones upon treatment with carboxylic acid anhydrides (Scheme 1, equation 1). These stable synthetic equivalents of IQMs undergo Diels-Alder reactions with electron-deficient dienophiles (A-phenytma-leimide,maleicanhydride,dimethylacetylenedicarboxylate) (equation 2). Plieninger s discovery notwithstanding, it was Moody and coworkers who parlayed this chemistry into a powerful carbazole synthesis (equations 3,4) [10-18],... 

The process of substitution undertaken on carboxylic acids and the derivatives of carboxylic acids (anhydrides, acid halides, esters, amides, and nitriles) generally involves a series of replacement processes. Thus, individually, substitution may involve replacement of (a) the proton attached to oxygen of the -OH group (i.e., ionization of the acid) (b) the hydroxyl (-OH) portion of the carboxylic acid (or derivative) (e.g., esterification) (c) the carbonyl oxygen and the hydroxyl (-OH) (e.g., orthoester formation, vide infra) (d) the entire carboxylic acid functionality (e.g., the Hunsdiecker reaction, already discussed Scheme 9.101) and the decarboxylation of orotic acid (as orotidine monophosphate) to uracil (as uridine monophosphate)—catalyzed by the enzyme orotidine monophosphate decarboxylase (Scheme 9.115) or (e) the protons (if any) on the carbon to which the carboxylic acid functional group is attached (e.g., the Dieckman cycUzation, already discussed earlier, c Equation 9.91). Indeed, processes already discussed (i.e., reduction and oxidation) have also accomplished some of these ends. Some additional substitutions for the carboxylic acid group itself are presented in Table 9.6, while other substitutions for derivatives of carboxylic acids are shown in Tables 9.7-9.10 and discussed subsequently. 

Chlorosulfonic acid is widely used in organic qualitative analysis to prepare solid derivatives from liquid or low melting aromatic compounds, e.g. hydrocarbons, halides and ethers." The procedure involves conversion of the aromatic compound into the sulfonyl chloride, which is subsequently reacted with ammonia to yield the solid sulfonamide derivative which is suitable for melting point determination, Chlorosulfonic acid reacts with carboxylic acid anhydrides to give excellent yields of the acid chlorides (Equation 11). 

As mentioned in the Introduction (p 5), chlorosulfonic acid reacts easily with carboxylic acid anhydrides giving excellent yields of the corresponding alkanoyl chlorides, which provides a useful synthetic route to these compounds. For example, butanoic anhydride 134 by treatment with chlorosulfonic acid (0.8 equivalents) at —5 °C, followed by vacuum distillation, afforded butanoyl chloride 135 (95% yield) (Equation 54). ... 

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)... 

Theperfluoroorganozmc compounds have limited application in organic syn thesis because of their lack of reactivity However, heptafluoro I methylethylzinc iodide reacts with acyl fluorides or anhydrides of carboxylic acids in the presence of pyndine to give the corresponding ketones [7S] (equations 28 and 29) In the presence of zinc fluoride, acyl chlorides can be used as substrates [7d]... 

Catalysis in Transacylation Reactions. The principal objective of the study was to evaluate 4 as an effective organic soluble lipophilic catalyst for transacylation reactions of carboxylic and phosphoric acid derivatives in aqueous and two-phase aqueous-organic solvent media. Indeed 4 catalyzes the conversion of benzoyl chloride to benzoic anhydride in well-stirred suspensions of CH2CI2 and 1.0 M aqueous NaHCC>3 (Equations 1-3). The results are summarized in Table 1 where yields of isolated acid, anhydride and recovered acid chloride are reported. The reaction is believed to involve formation of the poly(benzoyloxypyridinium) ion intermediate (5) in the organic phase (Equation 1) and 5 then quickly reacts with bicarbonate ion and/or hydroxide ion at the interphase to form benzoate ion (Equation 2 and 3). Apparently most of the benzoate ion is trapped by additional 5 in the organic layer or at the interphase to produce benzoic anhydride (Equation 4), an example of normal phase-... 

Equation 1 expresses a state of equilibrium between an alcohol A. on a molecule whose degree of polymerization is j, the catalyst C and the alkoxide anion A.C. In Relation 2 this activated intermediate reacts with monomeric anhydride A, forming an acid adduct A.AC, which dissociates, forming an unassociable carboxylic acid A.A. Reactions 3-5 depict the union of a carboxylic intermediate with a monomeric epoxide E, or with pendant oxiranes on macromole- ... 

In a similar approach (Equation 53), the use of a resin-bound nitrile allowed access to the corresponding resin-bound amidoximes 274, which could be converted into 1,2,4-oxadiazoles 275 via acylation with either an appropriate acid halide/ anhydride in the presence of a base or a carboxylic acid in the presence of a coupling reagent followed by cyclization, where the latter step was performed by heating in pyridine or diglyme and could be accelerated by the use of a microwave oven. Cleavage from the resin was easily achieved by the use of TFA in dichloromethane <2000BML1431>. 

For both reactions a RhCl3/CH3l/TPO catalyst in acetic acid as reaction solvent affords propionic acid in more than 80 % yield according to the respective stoichiometries of Equations 12 and 13. Although acetic acid is present in excess in the reaction medium, it does not participate in the homologation as reactant. Only traces of propionic acid are produced in the absence of methyl acetate, ethyli-dene diacetate or acetic anhydride under our reaction conditions. Homologation of carboxylic acids has been reported by Knifton (10) to require more severe reaction conditions (220 °C, > 100 bar). 

Preparations of pyridazino[3,4- [l,3]oxazines by ozonolysis of pyrrolo[2,3-b]pyridazine-3-carboxylates and from the reaction of A -(4-ethoxycarbonylpyridazin-3-yl)phosphinimines with acyl halides were described in CHEC-II(1996) <1996CHEC-11(7)737>. A simpler form of the latter approach has now been reported <1994CC2451>, wherein the 1-A -oxide of 3-aminocinnoline-4-carboxylic acid undergoes cyclization with acetic anhydride (Equation 126). The isomeric pyridazino[4,3-, [l,3]oxazines have been prepared in a similar manner (Equation 127) <1997PHA838>. 

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