Carboxylic acids a-methyl

C4HioO+- C3H602+- ethers methyl esters of carboxylic acids, a-methyl carboxylic acids... 

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

In man, the metabolic pathways of mepirizole were distinct from those in experimental animals, since hydroxylation on each of the aromatic rings did not occur in man. Compound (752) was obtained by oxidation of the 3-methyl group to the carboxylic acid (a similar process occurs with 5-methylpyrazole-3-carboxylic acid, an active metabolite of 3,5-dimethylpyrazole). However, the carboxylic acid metabolite of mepirizole had no analgesic activity and did not decrease blood glucose. 

Merck and Maeder have patented the manufacture of arecaidine by loss of water from l-methyl-4-hydroxypiperidine-3-carboxylic acid. A method of producing the latter has been describd by Mannich and Veit and has been developed by Ugriumov for the production of arecaidine and arecoline. With the same objective, Dankova, Sidorova and Preobrachenski use what is substantially McElvain s process,but start by converting ethylene oxide, via the chlorohydrin and the cyanohydrin, into -chloropropionic acid. The ethyl ester of this with methylamine in benzene at 140° furnishes methylbis(2-carbethoxyethyl) amine (I) which on refluxing with sodium or sodium Moamyloxide in xylene yields l-methyl-3-carbethoxy-4-piperidone (II). The latter is reduced by sodium amalgam in dilute hydrochloric acid at 0° to l-methyl-3-carbethoxy-4-hydroxypiperidine (III) which on dehydration, and hydrolysis, yields arecaidine (IV R = H), convertible by methylation into arecoline (IV R = CH3). 

The 2-methylthioethyl ester is prepared from a carboxylic acid and methyl-thioethyl alcohol or methylthioethyl chloride (MeSCH2CH20H. TsOH, benzene, reflux, 55 h, 55% yield MeSCH2CH2Cl, Et3N, 65°, 12 h, 50-70% yield). It is cleaved by oxidation [H2O2, (NH4)6Mo7024, acetone, 25°, 2 h, 80-95% yield —> pH 10-11, 25°, 12-24 h, 85-95% yield] and by alkylation followed by hydrolysis (Mel, 70-95% yield pH 10, 5-10 min, 70-95% yield). ... 

In 1883, Bottinger described the reaction of aniline and pyruvic acid to yield a methylquinolinecarboxylic acid. He found that the compound decarboxylated and resulted in a methylquinoline, but made no effort to determine the position of either the carboxylic acid or methyl group. Four years later, Doebner established the first product as 2-methylquinoline-4-carboxylic acid (8) and the second product as 2- methylquinoline (9). Under the reaction conditions (refluxing ethanol), pyruvic acid partially decarboxylates to provide the required acetaldehyde in situ. By adding other aldehydes at the beginning of the reaction, Doebner found he was able to synthesize a variety of 2-substituted quinolines. While the Doebner reaction is most commonly associated with the preparation of 2-aryl quinolines, in this primary communication Doebner reported the successful use of several alkyl aldehydes in the quinoline synthesis. 

Methyl-3,4-dihydro-j3-carboline-3-carboxylic acid has been reported to undergo photochemical and pyrolyticoxidation to yield a mixture containing l-methyl-j8-carboline and l-methyl-j8-carboline-3-carboxylic acid. The methyl ester of this 3,4-dihydro-j8-carboline acid appears to be oxidized to methyl l-methyl-j8-carboline-3-carboxylate on alumina chromatography. ... 

Related to a class of a,y-diketoacids that has previously been shown to bind to NS5B [64], is the mono-ethyl ester of meconic acid 25. This compound was identified as a selective inhibitor of NS5B HCV polymerase (IC50 = 2.3 pM) and is competitive with the diketoacids. SAR studies have demonstrated the requirement for the carboxylic acid. A variety of different permutations of esters, acids, amides, and decarboxylated compounds were prepared without any improvement in binding affinity or in the cell-based replicon assay [65]. The 4,5-dihydroxypyrimidine-6-carboxylic acids, a hybrid of the a,y-diketoacids and meconic acid, envisioned as chelators of the essential Mg2+ ions in the active site of NS5B, are also active in the polymerase assay (26, IC5o = 5.8pM). While alkylation of the phenol of the hybrid is tolerated, methylation of the heterocyclic hydroxyl groups or the carboxylic acid, as well as decarboxylation, leads to... 

The geometric isomers 464 and 467 of 5(47/)-oxazolones prepared from acetophenones can be separated. Alternatively, the mixture can be isomerized under the appropriate reaction conditions to obtain the pure of (Z) or ) isomer. Each isomer can be converted to a pair of enantiomers 466 and 469 (only one enantiomer shown) (Scheme 7.152). The p-methyl phenylalanine analogues thus obtained are constrained phenylalanines and the effect of incorporation of a p-MePhe or p-MeTyr residue on the biological properties of H-Tyr-Tic-Phe-Phe-NH2 (TIPP, where Tic = l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) a delta opioid receptor antagonist, has been studied. ... 

J 4-Hydroxy-2-methyl-1,1-dioxo-1,2-di hydro-116-benzo[e][1,2]thiazine-3-carboxylic acid (5-methyl-thiazol-2-yl)-amide, 4-hydroxy-2-methyl-A/-(5-methyl-2-thiazoyl)-2H-1,2-benzothiazine-3-carboxamide-1,1 -dioxide, C14H13N3O4S2, Mr 351.40, mp 264 °C (decomp.)... 

Chakraborti, A. K. Basak, A. Grover, V. Chemoselective protection of carboxylic acids as methyl esters a practical alternative to the diazomethane protocol. J. Org. Chem. 1999,... 

A TLC method has been developed to determine etodolac and its metabolites (6-OH-etodolac and 7-OH-etodolac) in biological fluids and extracts (before and after enzyme hydrolysis) [15]. The method used silica gel plates and hexane-ethyl acetate-acetic acid (60 40 2, v/v) and hexane-ethyl acetate (70 30, v/v) solvent systems to separate the free carboxylic acid and methyl esters of etodolac and the two metabolites. The relative retention (Rf) values obtained under these conditions were 0.29,0.20 and 0.24 for etodolac, 6-OH-etodolac, and 7-OH-etodolac respectively. An Rf value of 0.45 was obtained for methyl ester of etodolac. 

Figure 5. Stereospecific hydroxylation of cyclopentane carboxylic acid (a) and 4-methyl-2-pentanone (b) by two fungus species using the docking/protecting group concept.

Phenanthridones and benzophenanthridones undergo ready alkylation on treatment with dialkyl sulfates in alkali.113, 126 As in the case of other, similar, ambident nucleophiles, V-alkylation normally predominates, although with diethyl sulfate 2-nitrophenanthridone gives a significant amount (27%) of 6-ethoxy-2-nitrophenanthri-dine,126 and, more recently, O-methylation has been observed in the reactions between both the methyl ester and the pyrrolidine amide of phenanthridone-4-carboxylic acid with methyl iodide in the presence... 

Alkynes upon heating with HTI in methanol underwent an oxidative rearrangement to methyl carboxylates which were hydrolysed in situ to afford carboxylic acids a typical procedure is given. 

Lesser tea tortrix. A minor component of the sex pheromone blend of this moth is 10-methyl-l-dodecanol acetate, V, (Figure 10) (48). Mori has synthesized the enantiomers both compounds were constructed from (R)-(+)-citronellol (49). The racemic target compound was synthesized by alkylating 10-undecenoic acid (as its dianion) with ethyl iodide (50). Reduction of the carboxyl to a methyl group was accomplished by standard procedures. Hydroboration of the olefinic link with disiamylborane and oxidative workup yielded the primary alcohol which was then acetylated to give the racemic pheromone structure. The overall yield from undecenoic acid was 40-45% without any extensive effort to optimize. 

Seeds of Areca catechu (betel nut) (Palmae) contain the simple jV-methyltetrahydropyridine 3-carboxylic acid (jV-methyl-A -tetrahydronicotinic acid) arecaidine and arecoline (arecai-dine methyl ester) (Section 1, Appendix) that are mACh-R agonists and accordingly parasympathetic stimulants. Betel nut also yields guvacine (A -tetrahydronicotinic acid) that is an anti-epileptic GABA transport inhibitor. Conversely the jV-methyl dihydropyridone derivative ricinine from seeds of Ricinus communis (castor seed) (Euphorbiaceae) is a stimulatory agonist acting at the benzodiazepine site of the GABA(A) receptor. 

The presence of oxygenates, even at low concentrations, and in particular the presence of carboxylic acids and methyl alkyl ketones in the Fischer-Tropsch product obtained by catalysis on iron, is a strong indication that CO insertion can occur (Figure 5). 

FIGURE 5 Anderson-Schulz-Flory distribution of the linear hydrocarbons, linear oxygenates (n-alcohols, n-aldehydes, and linear carboxylic acids), and methyl alkyl ketones formed in the Fischer-Tropsch synthesis on an iron-containing Fischer-Tropsch catalyst operating at a temperature of 498 K (plotted using log(lO)). 

Song, A. M. Zhang, J. H. Lam, K. S. Synthesis and reaction of 7-fluoro-4-methyl-6-nitro-2-oxo- 2H l-benzopyran-3-carboxylic acid A novel scaffold for combinatorial synthesis of coumarins. J. Com. Chem., 2004, 6(1) 112-120. 

Dialkyl ketones have been little studied as precursors in this reactioiL Selenium dioxide with hydrogen peroxide and r-butyl alcohol effects a similar reaction with these substrates to give 35-40% yield of the conesponding carboxylic acid. In methyl alkyl ketones, the regioselectivity is of the order of 5 1 in favor of meAyl migration. ... 

---