Oxalates, methyl reduction

Several total syntheses of antirhine (11) and 18,19-dihydroantirhine (14) have been developed during the last decade. Wenkert et al. (136) employed a facile route to ( )-18,19-dihydroantirhine, using lactone 196 as a key building block. Base-catalyzed condensation of methyl 4-methylnicotinate (193) with methyl oxalate, followed by hydrolysis, oxidative decarboxylation with alkaline hydrogen peroxide, and final esterification, resulted in methyl 4-(methoxycar-bonylmethyl)nicotinate (194). Condensation of 194 with acetaldehyde and subsequent reduction afforded nicotinic ester derivative 195, which was reduced with lithium aluminum hydride, and the diol product obtained was oxidized with manganese dioxide to yield the desired lactone 196. Alkylation of 196 with tryptophyl bromide (197) resulted in a pyridinium salt whose catalytic reduction... 

Reduction of dispiro[bis(cyclopropane)indan]yl methyl oxalate 50 led to the formation of all three possible products derived from the cleavage of one cyclopropane ring. ... 

A novel syrTEhesis of the aporphine system has been achieved from the diphenylethylamine (149) by condensation with diethyl oxalate followed by Bischler-Napieralski ring closure to the dihydroisoquinoline (150) and further cyclisation with polyph-osphoric acid to the oxoaporphine (151). A -methylation and reduction of this gave the trimethoxyaporphine 0,iV-dimethyl-tuduranine (M. Grecke and A. Brossi, Helv., 1979, 62. 1549). 

Carbonylation acetic acid, acetic anhydride, methyl acetate, methyl formate Reductive carbonylation acetaldehyde, ethanol, ethyl acetate, ethylidene diacetate Oxidative carbonylation dimethyl carbonate, dimethyl oxalate... 

NOTE. Many esters reduce Fehling s solution on warming. This reduction occurs rapidly with the alkyl esters of many aliphatic acids, but scarcely at all with similar esters of aromatic acids (f.g., ethyl oxalate reduces, but ethyl benzoate does not). Note also that this is a property of the ester itself thus both methyl and ethyl oxalate reduce Fehling s solution very rapidly, whereas neither oxalic acid, nor sodium oxalate, nor a mixture of the alcohol and oxalic acid (or sodium oxalate), reduces the solution. 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

The first use of chiral oxazolines as activating groups for nucleophilic additions to arenes was described by Meyers in 1984. " Reaction of naphthyloxazoline 3 with phenyllithium followed by alkylation of the resulting anion with iodomethane afforded dihydronaphthalene 10 in 99% yield as an 83 17 mixture of separable diastereomers. Reductive cleavage of 10 by sequential treatment with methyl fluorosulfonate, NaBKi, and aqueous oxalic acid afforded the corresponding enantiopure aldehyde 11 in 88% yield. 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Redox titrants (mainly in acetic acid) are bromine, iodine monochloride, chlorine dioxide, iodine (for Karl Fischer reagent based on a methanolic solution of iodine and S02 with pyridine, and the alternatives, methyl-Cellosolve instead of methanol, or sodium acetate instead of pyridine (see pp. 204-205), and other oxidants, mostly compounds of metals of high valency such as potassium permanganate, chromic acid, lead(IV) or mercury(II) acetate or cerium(IV) salts reductants include sodium dithionate, pyrocatechol and oxalic acid, and compounds of metals at low valency such as iron(II) perchlorate, tin(II) chloride, vanadyl acetate, arsenic(IV) or titanium(III) chloride and chromium(II) chloride. 

The same group has also shown that mono- or dinuclear trisbipyridine-like complexes containing the ligand 2,2 -bis(l-methyl-benzimidazol-2-yl)-4,4 -bipyridine instead of unsubstituted 2,2 -bipyridine catalyze the reduction of C02 to oxalate (C2042-) in anhydrous MeCN at — 1.65 V and —1.55 V, respectively (vs. Ag AgCl) with a good current yield (r/ 70%). In contrast,... 

Wock-Hardt Ltd.54 reported a manufacturing process for the preparation of 2 (Scheme 8). In their approach, reductive amination of ketone 41 with dimethylamine hydrochloride using NaCNBH3 afforded amine 42 in 69% yield. The phenol was acylated with iV-ethyl-/V-methyl carbamoyl chloride (40) using KO/-Bu as the base instead of NaH to provide racemic carbamate 2 in 88% yield (98% pure by HPLC). Racemic 2 was further purified by making the oxalate salt, which provided 2 as a colorless crystalline oxalate salt in 100% purity. Resolution with DTTA followed by salt formation with tartaric acid afforded chiral tartrate salt 2. The overall yield of this process was 20%. 

Chromate(VI) has been reported to undergo reduction to Crv as a result of PET between its LMCT excited state and an external electron donor. In the study carried out for several aliphatic alcohols (methanol, ethanol, propan-2-ol, butan-1-ol, butan-2-ol, 2-methyl-propan-2-ol) two pathways of PET were identified one-electron transfer for intermolecular and two-electron transfer for intramolecular systems [96,97]. The intermolecular mechanism of the CrVI excited state quenching was also found for phenol or its derivatives [98], whereas in the case of an anion donor (such as oxalate) an effect of external cations was observed [99],... 

A new synthetic route to tetraaminoethene derivatives developed by Gorls and coworkers95 involves a reduction/substitution sequence the oxalic amidines, 123, were reduced with lithium under sonication affording 124, and the subsequent addition of phenyl isothiocyanate, 125, afforded the anionic bis(thiocarbamoyl) derivatives 126. Treatment of 126 with methyl iodide gave, in a nearly quantitative yield, the isothiourea derivative 127 (Scheme 40)96. 

The ethylene glycol and methyl alcohol (see below), which is also sometimes found in antifreeze, are poisonous because they are converted into more toxic products. Once inside the body, the ethylene glycol in the antifreeze is changed by metabolism into first one, and then several other chemicals. This requires the same enzyme that metabolizes the alcohol we consume in alcoholic drinks (ethyl alcohol). The ethylene glycol is converted into oxalic acid which is poisonous, and other poisonous products are also produced. Oxalic acid is also found in rhubarb leaves, which is what makes them poisonous. The result of these metabolic conversions is that the acidity of the blood increases (the pH decreases) and normal metabolic processes are inhibited. The oxalic acid formed can crystallize in the brain and the kidneys, causing damage. The oxalic acid also reacts with calcium and removes it from the body. The reduction of calcium... 

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