Glyoxylic acid chloride

C. Crotyl diazoacetate. A solution of 10.0 g. (0.038 mole) of the />-toluenesulfonylhydrazone of glyoxylic acid chloride in 100 ml. of methylene chloride is cooled in an ice bath. Crotyl alcohol (2.80 g. or 0.038 mole) (Note 7) is added to this cold solution, and then a solution of 7.80 g. (0.077 mole) of redistilled triethyl-amine (b.p. 88.5-90.5°) in 25 ml. of methylene chloride is added to the cold reaction mixture dropwise and with stirring over a 20-minute period. During the addition a yellow color develops in the reaction mixture and some solid separates near the end of the addition period. The resulting mixture is stirred at 0° for 1 hour and then the solvent is removed at 25° under reduced pressure with a rotary evaporator. A solution of the residual dark orange liquid in approximately 200 ml. of benzene is thoroughly mixed with 100 g. of Florisil (Note 8) and then filtered. The residual Florisil, which has adsorbed the bulk of the dark colored by-products, is washed with two or three additional portions of benzene of such size that the total volume of the combined benzene filtrates is 400-500 ml. This yellow benzene solution of the diazoester is concentrated under reduced pressure at 25° with a rotary evaporator, and the residual yellow liquid is distilled under reduced pressure. (Caution This distillation should be conducted in a hood behind a safety shield) (Note 9). The diazo ester is collected as 2.20-2.94 g. (42-55%) of yellow liquid, b.p. 30-33° (0.15 mm.), n T) 1.4853 - 1.4856 (Note 10). 

Glyoxylic acid chloride />-toluene-suUonylhydrazone, 49, 23 reaction with crotyl alcohol, 49, 24 Glyoxylic acid, condensation with p-toluenesulfonylhydrazide, 49, 22 Glyoxylic acid, />-toluenesulfonylhydra-zone, 49, 22... 

In the following year, this method was also applied to the total synthesis of tjipanazole FI (371) (784). For this synthesis, the required bisindole 1444 was obtained starting from 5-chloroindole (1440) in three steps and 47% overall yield. Acylation of 1440 with oxalyl chloride led to the glyoxylic acid chloride 1441. Transmetalation of indolylmagnesium bromide with zinc chloride, followed by addition of the acid chloride, provided the ot-diketone 1443. Exhaustive reduction of 1443 with lithium aluminum hydride (LiAlFl4) afforded the corresponding bisindolylethane 1444. Executing a similar reaction sequence as shown for the synthesis of tjipanazole F2 (372) (see Scheme 5.243), the chloroindoline (+ )-1445 was transformed to tjipanazole FI (371) in two steps and 50% overall yield (784) (Scheme 5.244). 

The esters are prepared by reaction of the allylic or homoallylic alcohol with the tosylhydrazone of glyoxylic acid chloride- and N,N-dimethylaniline as a base, followed by elimination of /j-toluenesulfinic acid (triethylamine). Yields of —75% can be obtained. 

B. The p-toluenesulfonylhydrazone of glyoxylic acid chloride. Caution Since hydrogen chloride and sulfur dioxide are liberated during this reaction, it should be conducted in a hood. To a suspension of 50.2 g. (0.21 mole) of glyoxylic acid / -toluenesulfonyl-hydrazone in 250 ml. of benzene is added 30 ml. (49 g. or 0.42 mole) of thionyl chloride (Note 5). The reaction mixture is heated under reflux with stirring until vigorous gas evolution has ceased and most of the suspended solid has dissolved (about... 

Tribromobenzoic acid has been prepared by the deamination of 2,4,6-tribromo-3-aminobenzoic acid (reagents not specified), by hydrolysis of 2,4,6-tribromobenzonitrile, " and by oxidation of the tribromotoluene, the benzyl chloride, the aldehyde,and the glyoxylic acid.i The present method is a modification of that of Bunnett, Robison, and Pennington.i ... 

Hanessian reported the synthesis of enantiomerically pure or highly enriched allylglycine and its chain-substituted analogs from the reaction of the sultam derivatives of O-benzyl glyoxylic acid oxime with ally he bromides in the presence of zinc powder in aqueous ammonium chloride (Eq. 11.41).72 Brown noticed the critical importance of water in the asymmetric allylboration of /V-trimethylsilyIbcnzaldimines with B-allyldiisopinocampheylborane.73 The reaction required one equivalent of water to proceed (Eq. 11.42). 

Glyoxal-sodium bisulfite, 30, 86 Glyoxylic acid, w-butyl ester, 35, 18 ethyl ester, diethyl acetal, 35, 59 Grignard reaction, addition to ethyl sec-butylidenecyanoacetate, 35, 7 allylmagnesium bromide with of,(3-di-bromoethyl ethyl ether, 36, 61 allylmagnesium chloride with a,/3-di-bromoethyl ethyl ether, 36, 63 ethylmagnesium bromide with tin tetrachloride, 36, 86... 

Mesitoic acid has been prepared by carbonation of mesityl-magnesium bromide 2-4 by hydrolysis of its amide prepared by condensation of mesitylene with carbamyl chloride under the influence of aluminum chloride 6 by oxidation of isodurene with dilute nitric acid 6-7 by distillation of 2,4,6-trimethylmandelic acid (low yield) 8 by dry distillation of 2,4,6-trimethyIphenyl-glyoxylic acid 9 by oxidation of the latter with potassium permanganate 10 and by treating 2,4,6-trimethylphenylglyoxylic acid with concentrated sulfuric acid in the cold11 or with heating.12... 

Cleavage of the oxirane C-0 bond produces a zwitterionic intermediate (Fig. 10.22), which that can undergo chloride shift (Pathway a) to 2,2-dich-loroacetyl chloride (10.90) followed by hydrolysis to 2,2-dichloroacetic acid (10.91). Furthermore, the zwitterionic intermediate reacts with H20 or H30+ (Pathway b) by pH-independent or a H30+-dependent hydrolysis, respectively. The pH-independent pathway only is shown in Fig. 10.22, Pathway b, but the mechanism of the H30+-dependent hydrolysis is comparable. Hydration and loss of Cl, thus, leads to glyoxylyl chloride (10.92), a reactive acyl chloride that is detoxified by H20 to glyoxylic acid (10.93), breaks down to formic acid and carbon monoxide, or reacts with lysine residues to form adducts with proteins and cytochrome P450 [157], There is also evidence for reaction with phosphatidylethanolamine in the membrane. 

Although the present procedure illustrates the formation of the diazoacetic ester without isolation of the intermediate ester of glyoxylic acid />-toluenesulfonylhydrazone, the two geometric isomers of this hydrazone can be isolated if only one molar equivalent of triethylamine is used in the reaction of the acid chloride with the alcohol. The extremely mild conditions required for the further conversion of these hydrazones to the diazo esters should be noted. Other methods for decomposing arylsulfonyl-hydrazones to form diazocarbonyl compounds have included aqueous sodium hydroxide, sodium hydride in dimethoxyethane at 60°, and aluminum oxide in methylene chloride or ethyl acetate." Although the latter method competes in mildness and convenience with the procedure described here, it was found not to be applicable to the preparation of aliphatic diazoesters such as ethyl 2-diazopropionate. Hence the conditions used in the present procedure may offer a useful complement to the last-mentioned method when the appropriate arylsulfonylhydrazone is available. 

Biological. Vinyl chloride was reported to be a biodegradation product from an anaerobic digester at a wastewater treatment facility (Howard, 1990). Under aerobic conditions. Pseudomonas putida oxidized 1,1,2-trichloroethane to chloroacetic and glyoxylic acids. Simultaneously, 1,1,2-trichloroethane is reduced to vinyl chloride exclusively (Castro and Belser,... 

From Catechol. Several routes have recently been developed for the synthesis of heliotropin from catechol. In one such route, catechol is converted into 3,4-dihydroxymandelic acid with glyoxylic acid in an alkaline medium in the presence of aluminum oxide. 3,4-Dihydroxymandelic acid is oxidized to the corresponding keto acid (e.g. with copper-(II) oxide), which is decarboxylated to 3,4-dihydroxybenzaldehyde [176]. The latter product is converted into heliotropin, for example, by reaction with methylene chloride in the presence of quaternary ammonium salts [177]. 

In another route, catechol is first reacted with methylene chloride and converted into 1,2-methylenedioxybenzene [177]. Reaction with glyoxylic acid in strongly acidic media yields 3,4-methylenedioxymandelic acid [178]. Subsequent oxidation and decarboxylation with nitric acid affords heliotropin. 

The statine-like moiety in one of the first drugs, saquinovir (23-8), comprises a transition state mimic for the cleavage of phenylalanylprolyl and tyrosylprolyl sequences. Constmction starts with the protection of the amino group of phenylalanine as its phthaloyl derivative (Phth) by reaction with phthalic anhydride this is then converted to acid chloride. The chain is then extended by one carbon using a Friedel-Crafts-like reaction. The required reagent (21-2) is prepared by reaction of the enolate obtained from the /7A-silyl ether (21-3) of glyoxylic acid and lithio... 

Synthesis (Tull et al. (Merck Co.), 1975 1976) Friedel-Crafts reaction of fluorobenzene and a-bromoisobutyryl bromide gives 5-fluoro-2-methylindan-1-one, which is treated with 4-methylthiobenzylmagnesium chloride to yield 5-fluoro-2-methyl-1-(4-methylthiobenzyl)indene. Condensation with glyoxylic acid in the presence of N-benzyltrimethyl ammonium hydroxide (Triton B) gives 3-carboxy methylene-5-fluoro-2-methyl-1 -(4-methylthio-ben-zyl) indene, which is isomerized in acid to 5-fluoro-2-methyl-1-(4-methylthiobenzylidene)indene-3-acetic acid. Oxidation with hydrogen peroxide affords sulindac. 

Colloidal particles of CdS were examined by Eggins et al. [131]. In C02-saturated aqueous solutions containing tetramethyl ammonium chloride, illumination with an arc-lamp produced formic acid and formaldehyde along with glyoxylic acid and acetic acid. Either hydroquinone or Na2S03 was used as the hole scavenger to increase yields. When CdSe colloids were examined for C02 photoreduction, those with a particle size <50 A were seen to produce formic acid under illumination in aqueous solution, whilst larger particles exhibited no photoreduction [132],... 

Reductive dechlorination also produces inorganic chloride ion, but glyoxylic acid [Eq. (63)] rather than formic acid. As with the halomethanes, peroxyl radical formation is an important intermediate. Oxygen is clearly important to achieving dechlorination in aqueous solution. 

Phenyl-1,3,4-thiadiazole (3, R = Ph) was first prepared by Ohta et al. by thioformylation of benzhydrazide with sodium dithio-formate, followed by dehydrating cyclization in sulfuric acid. In the same way the 2-benzyl and some aromatic analogs were obtained. Holmberg prepared 3 (R = Ph) by oxidation of l-methylene-2-thiobenzoylhydrazine (9) and of glyoxylic acid thiobenzhydrazone (10) with ferric chloride, and finally by reaction between thiobenz-hydrazide (11) and formic acid. 

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