Ethylation chloroformate

Colourless prisms m.p. 49-50 C, b.p. 184 C. Prepared by the action of ammonia on ethyl chloroformate. Used as a long-acting anaesthetic for laboratory animals. 

The ester 870 is prepared by the cross-coupling of the chloroformate 869 with an organotin reagent. Some chloroformates are easily decomposed by a Pd catalyst, and hence the reaction should be carried out by slow addition of the chloroformates. Similarly, the amide 872 is prepared by the reaction of the carbamoyl chloride 871 [742]. The coupling of alkylcopper with ethyl chloroformate catalyzed by Pd affords esters[743]. 

Phenyl-3-oxopropanoic acid (25 mmol) and EtjN (87.5 mmol) were dissolved in THF (150 ml) and cooled to —40°C. Ethyl chloroformate (27.5 mmol) was added dropwise to this solution and then the reaction mixture was stirred for 30 min at —20°C. Di-n-hexylamine (27.5 mmol) was added to the suspension and it was stirred at room temperature for an additional hour. The reaction mixture was diluted with water (100 ml) and extracted with ether (400 ml). The extract was washed with aq. 5% HCl (100 ml) and brine (2 X 100 ml) and dried over NajSO. The crude amide was obtained by removal of the solvent in vacuo and phenylhydrazine (25 mmol) was added. The mixture was heated to 100°C for 30 min. The residue was held in vacuo to remove the water formed and then powdered ZnCl2 (125 mmol) was added. The mixture was heated at 170"C with manual stirring for 5 min. The cooled residue was dissolved in acetone (100 ml) and diluted with ether (500 ml). Water (100 ml) was added. The organic layer was separated and washed successively with 5% aq. HCl (100 ml) and brine (2 x 100 ml) and dried over NajSO. The solvent was removed in vacuo, and the residue was recrystallized from EtOAc-hexane. The yield was 79%. 

Zugravescu et al. (263) showed that ethyl chloroformate reacts on the exocyclic nitrogen of 2-amino-4-methylthiazole to yield the carbamate (101) (Scheme 70) (see also Refs. 264 and 265). With an excess of chloroformate (2 moles for one of the thiazole) under Schotten-Bauman conditions the jV.A -dicarbamate of 2-imino-4-methylthiazoline (102) is obtained (263),... 

The reaction between ethyl chloroformate and 2-aminothiazoles provides easy synthetic access to thiazolyl 2-carbamaies (269) (Scheme 163)... 

Ethyl chloroformate is used in the manufacture of ore flotation agents by reaction with various xanthates (48). 

Unlike simple alkyl halides, ethyl chloroformate appears to react with primary and secondary amino groups in any position to give directly the corresponding urethane, e.g. (258) (64JMC364). Such alkylations proceed in pyridine, aqueous alkali or even warm benzene (62JOC982). 

Other applications of this conceptual approach are found throughout the various chapters, and the range of potential 1,1-bielectrophiles, e.g. ethyl chloroformate, will be readily apparent. 

Ethyl chloroformate [541-41-3] M 108.5, m -81 , b 94-95 , d 1.135, n 1.3974. Washed several times with water, redistd using an efficient fractionating column at atmospheric pressure and a CaCl2 guard tube to keep free from moisture [Hamilton and Sly J Am Chem Soc 47 435 1 925 Saunders, Slocombe and Hardy, J Am Chem SocT3 3796 1951]. LACHRYMATORY AND TOXIC. 

After cooling to room temperature, a solution of 58 g. (51 cc., 0.53 mole) of freshly distilled ethyl chloroformate (b.p. 92.5-93.5°) in 160 cc. of absolute ether is added dropwise in the course of one-half hour (Note 3). The mixture is heated on the steam bath for one and one-half hours and then allowed to stand overnight at room temperature. 

Tricarbethoxymethane has been prepared by the action of ethyl chloroformate upon sodiomalonic ester in benzene suspension and by distillation of ethyl ethoxalylmalonate. The present method has been described briefly by one of the authors." It is simpler and gives better yields than the method described in Org. Syn. 13, 100, for the preparation of the corresponding methyl ester. 

In the sjmthesis of evodiamine effected by Asahina and Ohta,i N-methylanthranilic acid was converted by ethyl chloroformate into N-methylisatoic anhydride, which, on treatment with 3- -aminoethylindole, furnished 3-/3-o-methylaminobenzoylaminoethylindole (III), and this with ethyl orthoformate at 175-180° gave dZ-evodiamine, m.p. 278°, convertible by boiling alcoholic hydrogen chloride into Zsoevodiamine, m.p. 147°, as shown above. 

Treatment of /j -dehydroquinoli2idine with ethyl chloroformate furnishes upon basiflcation l-carbethoxy-/J -dehydroquinolizidine (126). 

The ethoxycarbonyl group was developed for the protection of phosphonates. The derivative is prepared by reaction of tris(trimethylsilyl) phosphite with ethyl chloroformate and can be cleaved by hydrolysis of the ester followed by silyla-tion with bistrimethylsilylacetamide. ... 

Ethoxycarbonyl-2-methylindole (222) and l-ethoxycarbonyl-3-methylindole (223) were the main products said to be obtained by the action of ethyl chloroformate on the 2- and 3-methylindole Grignard... 

In the case of 1,3-diphenylisoindole (29), Diels-Alder addition with maleic anhydride is readily reversible, and the position of equilibrium is found to be markedly dependent on the solvent. In ether, for example, the expected adduet (117) is formed in 72% yield, whereas in aeetonitrile solution the adduet is almost completely dissociated to its components. Similarly, the addition product (118) of maleic anhydride and l,3-diphenyl-2-methjdi.soindole is found to be completely dissociated on warming in methanol. The Diels-Alder products (119 and 120) formed by the addition of dimethyl acetylene-dicarboxylate and benzyne respectively to 1,3-diphcnylisoindole, show no tendency to revert to starting materials. An attempt to extrude carbethoxynitrene by thermal and photochemical methods from (121), prepared from the adduct (120) by treatment with butyl-lithium followed by ethyl chloroform ate, was unsuccessful. 

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