Aryl carboxylic esters, formation

Hydrazinolysis of the imidate and carboxylic ester functions of 1-aryl-oxycarbonyl-l,6-dihydro-2-methoxypyrimidines (61) with 1 molar equivalent of hydrazine hydrate culminated in the formation of the 1,2,4-tria-zolo[4,3-a]pyrimidine-3-ones 63 [89GEP(0)3839711] (Scheme 25). 

In the presence of alkyl halides and base, alkyltetracarbonylcobalt complexes are formed with Co2(CO)8 these species [RCo(CO)4] carbonylate a wide range of aryl halides or heterocyclic halides to various products, which depend upon the specific conditions. In the presence of alcohols, carboxylic esters are formed. Under phase transfer conditions and with iodomethane, mixtures of methyl ketone and carboxylic acid formation are realized (equation 207). In the presence of sodium sulfide or NaBH4 in water-Ca(OH)2 (equation 208) good amounts of double carbonylation are realized under very mild conditions412-414. 

Other methods that can be used to prepare thiol esters from carboxylic acids include the use of aryl thiocyanates,12 thiopyridyl chloroformate,13 2-fIuoro- V-methylpyridinium tosylate,14 1-hydroxybenzotriazole, 5 and boron thiolate.16 Direct conversion of 0-esters to 5-esters can also be effected via aluminum and boron reagents.17 However, the applicability of these 1217 and other more recent methods18 to the selective thiol ester formation discussed above has not been clearly defined. 

Dihydrooxazoles 275 can be made by the condensation of aryl nitriles with amino alcohols catalyzed by Bi(iii) salts <2005SL2747> or acidic clay <1998TL459> in good yields (Bi salts - 70-92% kaolinitic clay -56-96%) (Equation 16). The use of Bi salts is only applicable to the formation of 2-aryloxazolines while the latter method works well for both aromatic as well as aliphatic substrates. The conversion of carboxylic esters to 2-oxazolines 276 in good (44-82%) yields with lanthanide chloride as catalyst <1997TL7019> has also been described (Equation 17). 

We have previously seen (10-70) that dianions of carboxylic acids can be alkylated in the a position. These ions can also be acylated on treatment with a carboxylic ester ° to give salts of p-keto acids. As in 10-70, the carboxylic acid can be of the form RCH2COOH or RR CHCOOH. Since p-keto acids are so easily converted to ketones (12-40), this is also a method for the preparation of ketones R C0CH2R and R COCHRR, where R can be primary, secondary, or tertiary alkyl, or aryl. If the ester is ethyl formate, an a-formyl carboxylate salt (R = H) is formed, which on acidification spontaneously decarboxylates into an alde-hyde. ° This method accomplishes the conversion RCH2COOH RCH2CHO, and is an alternative to the reduction methods discussed in 19-39. When the carboxylic acid is of the form RR"CHCOOH, better yields are obtained by acylating with acyl halides rather than esters. 

Thiol esters are reduced at less negative potentials than carboxylic esters and can be cleaved in protic (e.g., methanol) [141] or aprotic [123, 142] media. Aroyl and benzylox-ycarbonyl groups may thus be used for protection of sulfhydryl groups in MeCN the radical anion of an arylthioic 5 -ester is usually cleaved to alkylthiolate and aryl radical if it is relatively stable (minutes) it reacts eventually with oxygen with formation of an arylcarboxylate [43]. 

Suzuki and Stille couplings. For coupling of aryl chlorides with arylboronic acids the catalytic system contains (CyjPjjPdClj, CsF in NMP. co-Arylalkanoic acids are prepared by coupling of aryl halides with carboxylic esters bearing a 9-BBN substituent at the other terminus, and saponification. A biaryl synthesis from two different aryl halides is accomplished with in situ boronate formation which depends on the (dppfjPdClj catalyst. For access to aryl boronates either the coupling of aryl triflates with bis(pinacolato)diboron" or that of aryl iodides with pinacolborane may be employed. 

Modifications at the carboxyl group include reduction (with dibor-ane or borohydride, after activation with soluble carbodiimide ), esterification (with diazomethane,or acyl or aryl chlorides ), and formation of amide esters. ... 

In addition to direct formation from an arylhydrazine and a carbonyl compound, iV-aryl-hydrazones can be prepared from aryldiazonium ions by coupling with enolates or enamines (Japp-Klingemann reaction). This reaction has most frequently been applied to j -ketoesters. The coupling product undergoes deacylation so that the ultimate product of Fischer cycUzation is an indole-2-carboxylate ester (Scheme 58) <92JMC4823>. 

The synthesis of 86 commenced with oxazole carboxylic acid 87. Base-catalyzed lithiation and coupling with isatin 88 followed by methyl ester formation and Boc deprotection provided tertiary alcohol 89. A second coupling of the amine 89 with carboxylic acid 90 followed by chlorination afforded chloride 91. Treatment of 91 with TBAF gave a 1 1 mixture of O-aryl ether 92 (CIO) in excellent yield. Refluxing 92 in chloroform resulted in the formation of 93 (70%, with 30% of the isomer), which was subjected to a three-step reaction sequence to furnish intermediate 86 (Scheme 16). 

One particular radical decarboxylation reaction, which is used in the synthesis of alkyl or aryl bromide (Hunsdiecker reaction), involves reaction of the silver salt of a carboxylic acid with bromine, and results overall in loss of CO2 to form the corresponding alkyl or aryl bromide (Scheme 4.47). When silver carboxylate is treated with I2 ester formation occurs (Simonini reaction). 

Aiming to overcome the limitations of the previous protocols, GooKen et al. then extended their own studies using easily available carboxylic esters [29], This indeed paved the way to waste-minimized Mizoroki-Heck reactions, in which any byproduct was efficiently recyclable such that waste formation was limited to carbon monoxide and water (47->48 Scheme 7.10). Subsequently, this technique has proven to be viable for converting various 4-nitrophenyl esters 47 in the presence of a PdCfi-LiCl-isoquinoline catalyst system into styrenes 48. Under Lewis acid catalysis, 4-nitrophenol (49) cleanly reacts with benzoic acid at the same temperature required for the Mizoroki-Heck arylation (49 47), thereby regenerating 4-nitrophenyl ester 47. 

Matsumoto and Mochida [33], using NMR with a hydrogenated coal tar pitch mesophase carbon fiber, showed that the initial attack by oxygen was on -CH3 and -CH2- groups, with the gradual formation of carboxyls, esters and aryl carbonyls. Fairly stable cross-links were formed via phenols, ethers and esters. The workers also found that slower heating rates (0.5°C/min instead of 2.0°C/min) produced better mechanical properties and that the final choice would be controlled by the desired target properties and economics. 

Formation of carboxylic acids ami their derivatives. Aryl and alkenyl halides undergo Pd-catalyzed carbonylation under mild conditions, offering useful synthetic methods for carbonyl compounds. The facile CO insertion into aryl- or alkenylpalladium complexes, followed by the nucleophilic attack of alcohol or water affords esters or carboxylic acids. Aromatic and a,/ -unsaturated carboxylic acids or esters are prepared by the carbonylation of aryl and alkenyl halides in water or alcohols[30l-305]. 

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