Phenyl alkanoates

The method described here belongs to a group of recently developed procedures comprising the spontaneous intramolecular acylation of active derivatives of metalated p-hydroxy alkanoates. These compounds are available by reactions of carbonyl compounds with ester enolates prepared from S-phenyl alkanethioates6 or phenyl alkanoates,15 as well as by Reformatsky16 or Darzens17 reactions of carbonyl compounds with phenyl a-halo alkanoates. 

Alkyl alkanoates are reduced only at very negative potentials so that preparative scale experiments at mercury or lead cathodes are not successful. Phenyl alkanoates afford 30-36% yields of the alkan-l-ol under acid conditions [148]. Preparative scale reduction of methyl alkanoates is best achieved at a magnesium cathode in tetrahydrofuran containing tm-butanol as proton donor. The reaction is carried out in an undivided cell with a sacrificial magnesium anode and affords the alkan-l-ol in good yields [151]. In the absence of a proton donor and in the presence of chlorotrimethylsilane, acyloin derivatives 30 arc formed in a process related to the acyloin condensation of esters using sodium in xylene [152], Radical-anions formed initially can be trapped by intramolecular addition to an alkene function in substrates such as 31 to give aiicyclic products [151]. 

The function of allomones in invertebrate defense is well established, but there is some evidence that such chemicals also occur in vertebrates, mainly in mustelids 316-325), but also in turtles Sterno-therus odoratus from which Eisner et al. 326) isolated four co-phenyl alkanoic acids identified as phenylacetic, 3-phenylpropionic, 5-phenyl-pentanoic and 7-phenylheptanoic acid. 

Some others (alkyl-phenyl)-alkanoic acids) are formed when linolenic acid is warmed at... 

In the hody, aspirin (a relatively reactive phenyl alkanoate, see Prohlem 59) acts as an acetylating agent of the enzyme cyclooxygenase (COX). It does so by transesterification with the hydroxyl function of the amino acid serine of the polypeptide chain in the active site (see below). Inta-estingly, while sahcylic acid itself is also a COX inhibitor, it works by a different mechanism, namely, suppression of the genetic information that encodes the enzyme, thus attenuating its production. 

As a children s medicine, acetaminophen (Tylenol) has a major marketing advantage over aspirin Liquid Tylenol preparations (essentially, acetaminophen dissolved in flavored water) are stable, whereas comparable aspirin solutions are not. Indeed, phenyl alkanoates undergo hydrolysis (and transesteriflcation) considerably more rapidly than alkyl alkanoates, reactivity that underlies the mechanism of action of aspirin (Real Life 22-2). Explain. 

From a study of the decompositions of several rhodium(II) carboxylates, Kitchen and Bear [1111] conclude that in alkanoates (e.g. acetates) the a-carbon—H bond is weakest and that, on reaction, this proton is transferred to an oxygen atom of another carboxylate group. Reduction of the metal ion is followed by decomposition of the a-lactone to CO and an aldehyde which, in turn, can further reduce metal ions and also protonate two carboxyl groups. Thus reaction yields the metal and an acid as products. In aromatic carboxylates (e.g. benzoates), the bond between the carboxyl group and the aromatic ring is the weakest. The phenyl radical formed on rupture of this linkage is capable of proton abstraction from water so that no acid product is given and the solid product is an oxide. 

Deacylation of hydrophobic p-nitrophenyl alkanoates Hydroxamic acid and phenyl ester derivatives had alkyl or fluoroalkyl substituents. Rate effects depend on selectivity of binding of fluoro- and hydro-carbon derivatives Kunitake et ai, 1984... 

LSER Approach The LSER approach has been described for aqueous solubility in Section 11.4. He et al. [18] have derived the following relationship for phenyl-sulfonyl alkanoates ... 

Analogous to the use of chiral enoates (see previous section), a, -unsaturated carboxylic amides, prepared from chiral amines, may be utilized in asymmetric 1,4-additions. When Grignard reagents are added to unsaturated amides (21), derived from (-)-ephedrine (20),25 highly optically active fi-sub-stituted alkanoic acids (22 R and R = alkyl or phenyl) are obtained in a variety of cases, after hydrolysis of the initially formed adducts (Scheme 7). This method was used for the synthesis of the antibiotic (-) malyngolide and its stereoisomers.26 Recrystallization of the intermediate (saturated) amide was necess-... 

Highly stereoselective aldol reactions of lithium ester enolates (LiCR1 R2CC>2R3) with (/0-2-(/ -tolylsulfiny I (cyclohexanone have been attributed to intermediacy of tricoordinate lithium species which involve the enolate and the sulfinyl and carbonyl oxygens of the substrates.43 The O-metallated /<-hydroxyalkanoatcs formed by aldol-type reaction of carbonyl compounds with enolates derived from esters of alkanoic acids undergo spontaneous intramolecular cyclization to /1-lactones if phenyl rather than alkyl esters are used the reaction has also been found to occur with other activated derivatives of carboxylic acids.44... 

CMCs of these polyfluorinated surfactants are of the order of 10 5 m.47 Plots of the observed H chemical shifts versus surfactant concentration of cetyl trimethyl ammonium chloride, cetyl pyridinium chloride, cetyl dimethyl phenyl ammonium chloride, cetyl dimethyl benzyl ammonium chloride, cetyl dimethy 1-2-phenyl ethyl ammonium chloride, and cetyl dimethyl-3-phenyl propyl ammonium chloride, are sigmoidal and were fitted to a model based on the mass action. The H chemical shift-based CMC values are in excellent agreement with those determined by the surface tension method.48 The micellization processes of dodecyl trimethyl ammonium halides (chloride and bromide) studied by calorimetric titration show different behaviors at 298 K. However, these disappear at 313 K, while the results measured by the chemical shift versus surfactant concentration do not show this difference.49 The CMC of 3-aminopropyl triethoxy silane in toluene is ca. 0.47m, measured by H and l3C chemical shifts.50 The CMC of optically active potassium A -n-dodecanoyl alaminate measured by H and l3C chemical shifts is lower (11-15 him) in D20 than that in a mixed solvent of 1,4-dioxane and D20 (19mM).-51 The H chemical shift shows that the CMC of resorcinol-type calix[4] phosphoric esters having four alkyl side-chains, [4]Ar 5P-R-n, is insensitive to the length of the side-chains, n.52 The CMC values of a family of surfactants, the sodium cyclohexyl alkanoates, with different lengths of the alkanoate side-chains, were obtained from 13C chemical-shift measurements. The results show that these amphiphiles have high CMCs (0.12-1.02 m).-53... 

Methyl 2-Methoxycarbonvl-5-oxo-3- 2-oxo-4-phenvl-3-oxazolidiny])alkanoates 8 General Procedure for Carboacylation of 4-Phenyl-3-vinyl-2-oxazolidinones 716 ... 

Often the phenyl group is treated as a substituent, and the name is derived from the appropriate alkanoic acid parent chain. For example ... 

Metalation of chiral oxazolines, derived from (15,25)-l-phenyl-2-amino-1,3-propanediol, followed by alkylation and hydrolysis, leads to optically active dialkylacetic acids, e.g. eq 22, 2-substituted butyrolactones and valerolactones, p-hydroxy and -methoxy acids, 2-hydroxy carboxylic acids, and 3-substituted alkanoic acids (eq 23). ... 

In the preparation of various unsaturated amides, the dianion of -phenyl-2-(phenyIsulphonylmethyl)propenamide (49) proved to be a versatile synthon. Borohydride reduction of alkylation products of the dianion occurred in high yield to afford moderate overall yields of ,B-unsaturated amides.The dianion of the corresponding phenyl sulphide alkylated poorly giving small amounts of oth a- and y-alkylation products, whereas the sulphone-ester corresponding to (49) was found to be labile under the deprotonation conditions. Compound (49) was also employed in the development of a general strategy for the synthesis of 3,4-epoxy-2-methylene-alkanoic acid amides (Scheme 29). ... 

Arylsulphenylation of 1,3-dicarbonyl compounds cm be effected at room temperature in an Et4N+ F" emulsion, but dianions R CHCOCHCOR, formed by successive treatment with NaH and Bu"Li, are sulphenylated at the alternative site by RbSSPh. 8-Keto-esters, malonates, and a-cyanoalkanoates can be sulphenylated and decarbalkoxylated in a one-pot process by reaction at 150—160 C, in HMPA, with PhSSPh and Nal, providing a-(phenylthio)alkyl ketones, cp(phenylthio)alkanoates, and tf-cyanoalkyl phenyl sulphides. 

Additions of PhCu.BFs, n-Bu"BF3, and MeCuBFs to /rans-S-phenyl-methylenolates are shown to proceed with high chiral induction. Saponification of the resulting adducts leads to enantiomerically pure /3-substituted alkanoic acids (Scheme 19)/ ... 

C7-C9 alkanes (3) benzene, toluene, ethylbenzene, xylenes 4-methylcyclohexyl alkanoates (10) (4-ethoxyphenylazo)phenyl heptanoate (N, I) [548]... 

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