Diethyl carbonate, hydrolysis

Dihydroxyimidazoles are involved in keto-enol tautomerism, and the diketo structure, which is known as hydantoin (9.42), is favored. This is the framework for many valuable compounds with anticonvulsant activity. These are nonh5 notic and are used in the treatment of epilepsy. Dilantin (9.55) is the best known of these. Its synthesis is shown in Scheme 9.29. The Strecker reaction of benzophenone with HCN gives an alpha-aminonitrile, which adds ammonia to form compound 9.54 (an amidine). The ring is then closed with phosgene or diethyl carbonate. Hydrolysis gives phenytoin (dilantin, Pfizer, Inc.). 

This approach has been extended by Tieckelmann, Mulvey, and Gottis to 2-amino-5-cyanonicotinamides (16 and 18), whiob were prepared directly by partial hydrolysis of the corresponding dir itriles. Diethyl carbonate, ethyl orthoacetate, and ethyl orthoformate all underwent reaction to yield the corresponding pyrido[2,3-( ]pyri-midines (17 and 19). 

The earliest method used at PicArsn was in 1933 It consisted of treating ethylenediamine with diethyl carbon ate to obtain ethyleneurea, followed by nitration to obtain Dinitroediyleneurea, which on hydrolysis gave Ethylenedinitramine. This process suffered from two disadvantages the overall yield was only 42% of the theoretical amt and the initial step, the reaction between ethylenediamine and diethyl carbon a re, required the use of high pressures and temperatures over an extended period of time. However, the expl props of EDNA were of sufficient in-, terest ro justify further study (Ref 4). See also Aaronson (Ref 5)... 

Exercise 14-29 Addition of Grignard reagents, RMgX, to diethyl carbonate, 0=C (OC2H5)2, gives tertiary alcohols, R3COH, on hydrolysis. Write the steps involved in this reaction. 

A variant of this route to 2-unsubstituted chromones employs oxalic acid half-ester half-acid chloride, which gives a 2-ethoxycarbonyl-chromone, hydrolysis and decarboxylation of which achieves the required result. Diethyl carbonate as the ester gives rise to 2,4-dioxygenated heterocycles, which exist as 4-hydroxy-coumarins. The condensation of a salicylate with an ester, using three mole equivalents of base also leads through to 4-hydroxy-coumarins, as illustrated below. ... 

Condensation of 4,6-dimethoxy-2-hydroxyacetophenone with diethyl carbonate and an alkoxide ion has now been shown to give the coumarin-3-carboxylic ester (245), and not 4-hydroxy-5,7-dimethoxycoumarin (246), as originally reported. Heating the ester with aqueous alkali resulted in hydrolysis and decarboxylation to (246). The well-established acid cyclization of salicyl-aldehyde with ethyl cyanoacetate to give coumarin-3-carboxylic acids has been studied in alkaline media and found to give the ester (247 X = O) and the imino-ester (247 X = NH). When the proportion of the cyano-ester was increased, high yields of the latter were obtained. "... 

Of the enzymes listed in Table 10.1, Upases are the woikhorses. The employment of Upases in non-aqueous media is an estabUshed art, with over 25 years of research serving as a foundation. Lipases are abundant and relatively inexpensive enzymes that require no co-factors and are easily immobilized. Lipases from several thermophiUc organisms have been isolated, cloned, and mass produced via recombinant DNA technology in common vectors such as Escherichia coli. Some of the examples in Table 10.1 are surfactants formed from enzymatic hydrolysis of oleochemical feedstocks, such as MAG formed from lipase-catalyzed hydrolysis of TAG, and lysophospholipids via hydrolysis by Upases or phosphoUpase A. Ui the foUowing sections some specific examples from the literature are given of enzyme-catalyzed synthesis of bio-based surfactants. Other examples not described, such as the oxidation of fatty alcohols to aldehydes (OrUch et al., 2000) and the covalent attachment of fatty alcohols and bio-based diethyl carbonate (Banno et al., 2007, 2010 Matsumura 2002 Lee et al., 2010) are covered in the references provided. 

The preparation of perfluoroalkanecarboxylic adds and their alkali-metal salts via reaction of perfluoroalkylmagnesium bromides (generated from perfluoroalkyl iodides and phenylmagnesium bromide) with diethyl carbonate followed by hydrolysis, has been described in the patent literature. ... 

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

In 1897, Reissert reported the synthesis of a variety of substituted indoles from o-nitrotoluene derivatives. Condensation of o-nitrotoluene (5) with diethyl oxalate (2) in the presense of sodium ethoxide afforded ethyl o-nitrophenylpyruvate (6). After hydrolysis of the ester, the free acid, o-nitrophenylpyruvic acid (7), was reduced with zinc in acetic acid to the intermediate, o-aminophenylpyruvic acid (8), which underwent cyclization with loss of water under the conditions of reduction to furnish the indole-2-carboxylic acid (9). When the indole-2-carboxylic acid (9) was heated above its melting point, carbon dioxide was evolved with concomitant formation of the indole (10). 

Plant Diaziuou was rapidly absorbed by and translocated in rice plants. Metabolites identified in both rice plants and a paddy soil were 2-isopropyl-4-methyl-6-hydroxypyrimidine (hydrolysis product), 2-(l -hydroxy-l -methyl)ethyl-4-methyl-6-hydroxypyrimidine, and other polar compounds (Laanio et al, 1972). Oxidizes in plants to diazoxon (Laanio et al., 1972 Ralls et al, 1966 Wolfe et al., 1976) although 2-isopropyl-4-methylpyrimidin-6-ol was identified in bean plants (Kansouh and Hopkins, 1968) and as a hydrolysis product in soil (Somasundaram et al., 1991) and water (Suffet et al., 1967). Five d after spraying, pyrimidine ring-labeled C-diazinon was oxidized to oxodiazinon which then hydrolyzed to 2-isopropyl-4-methylpyrimidin-6-ol which, in turn, was further metabolized to carbon dioxide (Ralls et al, 1966). Diazinon was transformed in field-sprayed kale plants to hydroxydiazinon 0,0-diethyl-0-[2-(2 -hydroxy-2 -propyl)-4-methyl-6-pyrimidinyl] phosphorothioate which was not previously reported (Pardue et al., 1970). 

A completely different approach to lithium homoenolate synthons uses a carbon-oxygen bond cleavage. Lithiation of acrolein diethyl acetal 180 with lithium and a catalytic amount of DTBB (2.5%) in the presence of different carbonyl compounds in THF at 0°C gave, after final hydrolysis, the corresponding y-products 181 in different diastereomeric ratios (Z/ 3/1 to 20/1) (Scheme 63) . 

The acidic aqueous layer from the aqueous acetic acid/sodium acetate/pentane hydrolysis of 2-alkylcyclo-hexanonc imines is neutralized with solid potassium hydroxide to pH 14, and then saturated with sodium chloride. This aqueous solution is extracted with four portions of diethyl ether, and the combined ethereal layer is washed with brine. Drying over potassium carbonate and concentration gives an oil which is distilled 85% recovery bp 57-59 °C/0.02 Torr [x]D — 13.75 (c = 5.8, benzene). If the rotation of the distilled amine is lower than 13.40, it is purified via its hydrochloride. Thus, a solution of the amine in ice-cold diethyl ether is treated with dry hydrogen chloride by bubbling through a fritted disk. The amine hydrochloride is collected by filtration and recrystallized from ethanol mp 151-152°C. 

Diphenylacetic acid has been obtained by the reduction of benzilic acid with hydriodic acid and red phosphorus 1 by the treatment of phenylbromoacetic acid with benzene and zinc dust,2 or with benzene and aluminum chloride 3 by the hydrolysis of diphenylacetonitrile 4 by heating a-diphenyldichloroethyl-ene with alcoholic sodium ethylate 5 by heating benzilic acid 6 from diphenylmethane, mercury diethyl, sodium and carbon dioxide 7 by the oxidation of a,a,5,S-tetraphenyl- 8-butine 8 by the decomposition of some complex derivatives obtained from diphenylketene 9 by the hydrolysis of diphenyl-5,5-hydan-toin 10 by the treatment of diphenylbromoacetic acid with copper 11 by the oxidation of dichlorodiphenylcrotonic acid.12... 

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