Carboxylic acids with addition

Carboxylic Acids with Additional Electrophilic Croups... 

Carboxylic acids from ketones. White and Wu have described a new conversion of ketones into carboxylic acids with addition of one carbon atom. The... 

In carboxylic acids with additional phenolic hydroxyl groups the carboxyl groups are more acid than the phenolic groups and can be specifically methylated by a very short treatment (5 to 10 s) with diazomethane at 0 °C. Some phenolic groups are difficult to methylate and need reaction times up to 24 h at room temperature. 

The formulated mechanism is supported by the finding that no halogen from the phosphorus trihalide is transferred to the a-carbon of the carboxylic acid. For instance, the reaction of a carboxylic acid with phosphorus tribromide and chlorine yields exclusively an a-chlorinated carboxylic acid. In addition, carboxylic acid derivatives that enolize easily—e.g. acyl halides and anhydrides—do react without a catalyst present. 

Esters are usually prepared from carboxylic acids by the methods already discussed. Thus, carboxylic acids are converted directly into esters by SK2 reaction of a carboxyfate ion with a primary alkyl halide or by Fischer esterification of a carboxylic acid with an alcohol in the presence of a mineral acid catalyst. In addition, acid chlorides are converted into esters by treatment with an alcohol in the presence of base (Section 21.4). 

The Hell-Volhard-Zelinskii reaction is a bit more complex than it looks and actually involves substitution of an acid bromide enol rather than a carboxylic acid enol. The process begins with reaction of the carboxylic acid with PBr3 to form an acid bromide plus HBr (Section 21.4). The HBr then catalyzes enolization of the acid bromide, and the resultant enol reacts with Br2 in an cr-substitution reaction to give an cv-bromo acid bromide. Addition of water hydrolyzes the acid bromide in a nucleophilic acyl substitution reaction and yields the a-bromo carboxylic acid product. 

Alpha hydrogen atoms of carbonyl compounds are weakly acidic and can be removed by strong bases, such as lithium diisopropylamide (LDA), to yield nucleophilic enolate ions. The most important reaction of enolate ions is their Sn2 alkylation with alkyl halides. The malonic ester synthesis converts an alkyl halide into a carboxylic acid with the addition of two carbon atoms. Similarly, the acetoacetic ester synthesis converts an alkyl halide into a methyl ketone. In addition, many carbonyl compounds, including ketones, esters, and nitriles, can be directly alkylated by treatment with LDA and an alkyl halide. 

Ester enolates which contain the chiral information in the acid moiety have been widely used in alkylations (see Section D.1.1.1,3.) as well as in additions to carbon-nitrogen double bonds (sec Section D.1.4.2.). Below are examples of the reaction of this type of enolate with aldehydes720. The (Z)-enolate generated from benzyl cinnamate (benzyl 3-phenylpropcnoate) and lithium (dimethylphenylsilyl)cuprate affords the /h/-carboxylic acid on addition to acetaldehyde and subsequent hydrogenolysis, The diastereoselectivity is 90 10. 

In another approach, a glucose-derived titanium enolate is used in order to accomplish stereoselective aldol additions. Again the chiral information lies in the metallic portion of the enolate. Thus, the lithiated /m-butyl acetate is transmetalated with chloro(cyclopentadienyl)bis(l,2 5,6-di-0-isopropylidene- -D-glucofuranos-3-0-yl)titanium (see Section I.3.4.2.2.I. and 1.3.4.2.2.2.). The titanium enolate 5 is reacted in situ with aldehydes to provide, after hydrolysis, /i-hydroxy-carboxylic acids with 90 95% ee and the chiral auxiliary reagent can be recovered76. 

A similar case of enolatc-controlled stereochemistry is found in aldol additions of the chiral acetate 2-hydroxy-2.2-triphenylethyl acetate (HYTRA) when both enantiomers of double deprotonated (R)- and (S)-HYTRA are combined with an enantiomerically pure aldehyde, e.g., (7 )-3-benzyloxybutanal. As in the case of achiral aldehydes, the deprotonated (tf)-HYTRA also attacks (independent of the chirality of the substrate) mainly from the /te-side to give predominantly the t/nii-carboxylic acid after hydrolysis. On the other hand, the (S)-reagcnt attacks the (/ )-aldebyde preferably from the. S7-side to give. s wz-carboxylic acids with comparable selectivity 6... 

When chiral additives such as ( —)-sparteine has added to the initial reaction with the organolithium reagent, quenching with CO2 produces carboxylic acids with good asymmetric induction. 

Oxidative addition of the O-H bond to transition metal complexes gives hydrido(hy-droxo), hydrido(alkoxo) or hydrido(carboxylato) complexes (Eq. 6.1), but web-characterized complexes obtained as primary products from the reaction of the compound, XO-H (XO-H = water, alcohol, and carboxylic acid) with late transition metals are quite rare [1]. Furthermore, the crystal stractures of very few complexes of this type have been reported. In this section we will survey late transition metal complexes resulting from activation of water, alcohol, and carboxylic acid. 

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... 

A special case of amide formation was observed in the reaction of a furan-2-carboxylic acid with two moles of CDI and subsequent conversion with amines, hi this reaction, besides formation of the imidazolide, addition of imidazole also takes places.1-1411... 

There are obvious similarities in the derived relative flux expressions for the MMHS model and the precursor HWPH model. The second term on the right-hand side of Eq. (11) accounts for the increase in dissolution observed near the pKa of the acid. Addition of the ionization reaction [Eq. (9)] provides the added flexibility and accountability so that dissolution at low pH s can be accurately predicted. The agreement between theoretical predictions and experimental results for three carboxylic acids with intrinsic solubilities ranging from 10 2 to 10 M over a pH range of 2-12 was good (see Fig. 2). Computationally, the MMHS model was also quite reasonable to use the roots for a quadratic expres-... 

Similar experiments performed with other aldehydes and primary alcohols indicate that their electrooxidation on platinum produce primarily the corresponding carboxylic acid in addition to C02,... 

In Arndt-Eistert synthesis, and acyl chloride is converted to a carboxylic acid with one additional carbon atom. 

The patented preparation of peroxyacids [2] by interaction of carboxylic acids with hydrogen peroxide in presence of metaboric acid needs appropriate safeguards to prevent accidental separation of the cone, peroxyacids [3], Much descriptive data on stabilities of a wide selection of peroxyacids has been summarised [4], A general method of preparation of peroxyacids involving addition of e.g. the anhydrides of acetic, maleic, phthalic or trifluoroacetic acids to a suspension of 90%... 

CASRN 133-06-2 molecular formula C9H8CI3NO2S3 FW 300.57 Biological. In water, captan reacted with the fungicide i-cysteine forming a compound with an absorption maximum of 272 mm which was identified as 2-thiazolidinethione-4-carboxylic acid. In addition, tetrahydrophthalimide also formed (Lukens and Sisler, 1958). 

Mechanism of esterification of carboxylic acids The esterification of carboxylic acids with alcohols is a kind of nncleophilic acyl snbstitntion. Protonation of the carbonyl ojq gen activates the carbonyl gronp towards nncleophilic addition of the alcohol. Proton transfer in the tetrahedral intermediate converts the hydrojq l group into - 0H2 group, which, being a better leaving group, is eliminated as neutml water molecule. The protonated ester so formed finally loses a proton to give the ester. 

In the aerobic oxidation of the non-activated aliphatic primary and secondary alcohols to the corresponding aldehydes and ketones, co-catalysts or other additives are normally required 223-226). The catalytic aerobic oxidation of aromatic aldehydes to the corresponding carboxylic acids with Ni(acac)2 in ionic liquids was the first example of an aerobic oxidation in ionic liquids 227). 

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