Carboxylic esters conversion

The conversion of primary alcohols and aldehydes into carboxylic acids is generally possible with all strong oxidants. Silver(II) oxide in THF/water is particularly useful as a neutral oxidant (E.J. Corey, 1968 A). The direct conversion of primary alcohols into carboxylic esters is achieved with MnOj in the presence of hydrogen cyanide and alcohols (E.J. Corey, 1968 A,D). The remarkably smooth oxidation of ethers to esters by ruthenium tetroxide has been employed quite often (D.G. Lee, 1973). Dibutyl ether affords butyl butanoate, and tetra-hydrofuran yields butyrolactone almost quantitatively. More complex educts also give acceptable yields (M.E. Wolff, 1963). 

Replacement of a benzene ring by its isostere, thiophene, is one of the more venerable practices in medicinal chemistry. Application of this stratagem to the NSAID piroxicam, gives tenoxicam, 136, a drug with substantially the same activity, nie synthesis of this compound starts by a multi-step conversion of hydroxy thiophene carboxylic ester 130, to the sulfonyl chloride 133. Reaction of that with N-methylglycinc ethyl ester, gives the sulfonamide 134. Base-catalyzed Claisen type condensation serves to cyclize that intermediate to the p-keto ester 135 (shown as the enol tautomer). The final product tenoxicam (136) is obtained by heating the ester with 2-aminopyridine [22]. 

Another method for the conversion of alkyl halides to carboxylic esters is treatment of a halide wifh nickel carbonyl, Ni(CO)4, in the presence of an alcohol... 

For conversion of vinylic triflates to carboxylic esters and amides, see Cacchi, S. Morera, E. Ortar, G. Tetrahedron Lett., 1985, 26, 1109. 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives. Acyl halides can be a brominated or chlorinated by use of NBS or NCS and HBr or HCl. The latter is an ionic, not a free-radical halogenation (see 14-2). Direct iodination of carboxylic acids has been achieved with I2—Cu acetate in HOAc. " ° Acyl chlorides can be a iodinated with I2 and a trace of HI. Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium A-isopropylcyclohexylamide in THF and treatment of this solution at -78°C with... 

The Conversion of Organometallic Compounds to Ketones, Aldehydes, Carboxylic Esters, or Amides... 

This reaction has sometimes been performed on carboxylic esters, though these compounds very seldom undergo any addition to the C=0 bond. An example is the conversion of FsCCOOPh to FaCCClaOPh. " However, formates commonly give the reaction. 

Carboxylic esters undergo the conversion C=0— C=CHR (R = primary or secondary alkyl) when treated with RCHBr2, Zn, and TiCl4 in the presence of A,A,A, iV -tetramethylethylenediamine. Metal carbene complexes R2C=ML (L = ligand), where M is a transition metal such as Zr, W, or Ta, have also been used to convert the C=0 of carboxylic esters and lactones to CR2. It is likely that the complex Cp2Ti=CH2 is an intermediate in the reaction with Tebbe s reagent. 

Both the selenoxide and sulfoxide " reactions have been used in a method for the conversion of ketones, aldehydes, and carboxylic esters to their a, P-unsaturated derivatives (illustrated for the selenoxide). 

In the context of the preparation of a library of pyrazole-based cyclooxygenase II (COX-II) inhibitors, the Organ group has described the microwave-assisted decarboxylation of a pyrazole carboxylic ester with 20% sulfuric acid (Scheme 6.160 a) [49]. While the conventional protocol (reflux, 100 °C) required 96 h to provide a yield of 86%, full conversion could be achieved within 5 min at 200 °C under micro-wave heating, leading to an 88% isolated product yield. 

Conversion of MEM ethers to esters. 2-Methoxyethoxymethyl (MEM) ethers are converted into carboxylic esters by reaction with an anhydride in the presence of FeCl3 (0.4 equiv.) (equation I). Selective cleavage is possible in the presence of a benzyl ether but not in the presence of a f-butyl ether. Aromatic rings, if present, can undergo acylation. 

Reaction of the azophosphoranes (Scheme 7.32) with dichlorocarbene follows an interesting pathway to produce l-aryl-5-chloropyrazole-3-carboxylic esters. The initial displacement of the phosphine (probably as the oxide) has been confirmed by the isolation of the 3,3-dichloropropenic ester under mild conditions. Subsequent conversion into the pyrazole appears to involve reaction with a trichloromethyl anion followed by attack by a second dichlorocarbene, although evidence for the mechanism of these steps is circumstantial [40],... 

The diastereomerically related keto esters 53 and 55, activated for removal of the chiral auxiliary, were obtained from 5 and 9. The requisite nitrogen atom was introduced by an azide displacement of chloride and at an opportune stage of the synthesis an intramolecular aminolysis of the carboxylic ester provided the enantiomerically related keto lactams 54 and 56. Although shorter routes to these popular synthetic targets have been reported in recent years, the conversion of 9 to (—)-iso-nitramine (ten steps, 50% overall yield) clearly illustrates the efficiency of the asymmetric Birch reduction-alkylation strategy for construction of the azaspiroundecane ring system. 

Alkynenitriles, RC=CC=N, are generally prepared by dehydration of acid amides. RC=CC(=0)NH2, with phosphorous pentoxide. For HC=CC=N and NsCChCChN [130] this is the only available method it requires the previous synthesis of the carboxylic esters and their conversion into the acid amides. In principle it should be possible to prepare these useful... 

The relative stability of the oxiranes to bases at room temperature allows the selective ammonolysis of carboxylic ester groups with ammonia in methanol,49 and, conversely, free hydroxyl groups may be esterified with acid chlorides or anhydrides in pyridine without affecting the oxirane ring. Hydroxyl groups may also be converted into alkyl ethers by using either the Haworth50 or the Purdie-Irvine procedure.5152... 

In 1963, Elad and Youssefyeh80 described the photochemical conversion, in the presence of acetone, of a number of 2-alkyl- or 2-aryl-substituted 1,3-dioxolanes (see Scheme 3, n=0) or 1,3-dioxanes (Scheme 3, n = l) into carboxylic esters. They suggested that the reaction proceeds by initial, hydrogen abstraction from the acetal carbon... 

The Conversion of Anhydrides, Carboxylic Esters, or Amides to Ketones with Organometallic Compounds1659 Alkyl-de-acyloxy-substitution... 

Ketones can be a hydroxylated in good yields, without conversion to the enolates, by treatment with the hypervalent iodine reagents162 o-iodosobenzoic acid163 or phenyliodoso acetate PhI(OAc)2 in methanolic NaOH.164 The latter reagent has also been used on carboxylic esters.165 02 and a chiral phase transfer catalyst gave enantioselective a hydroxylation of ketones, if the a position was tertiary.166... 

BC13 convert 0=0 groups of ketones, lactones, and lactams to G=S groups119 and H2S-Me3SiCl-i-Pr2NLi converts carboxylic esters to thiono esters.120 Carboxylic acids RCOOH can be converted directly to dithiocarboxylic esters RCSSR, 120a in moderate yield, with P4S, and a primary alcohol R OH.121 Thioketones can also be prepared by treatment of ketones with P4SI0,122 and from oximes or various types of hydrazone (overall conversion C=N------> C=S).123... 

Conversion of Carboxylic Esters to Enol Ethers Methylene-de-oxo-bisubstitution... 

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