Synthesis from chloroform

An early review on the chemistry of chloroformates ( esters of chloroformic acid ) covered the methods of synthesis, physical and chemical properties and highlighted the possibility of polymer synthesis from chloroformates [10]. An example of a classical chloroformate preparation by phosgenation of benzylic alcohol with phosgene gas is given in [11]. An improved procedure for the synthesis of benzyl chloroformate (1, Z-Cl) in 97% yield is given in [12]. 

Methods for synthesis of the thia olium ring also have matured technically based on the cost, throughput, and waste disposal issues of production. In earlier syntheses, the 2-carbon and the sulfur atom were suppHed as potassium dithioformate, made from chloroform and potassium sulfide. 

The addition of dichlorocarbene, generated from chloroform, to alkenes gives dichlorocyclopropanes. The procedures based on lithiated halogen compounds have been less generally used in synthesis. Section D of Scheme 10.9 gives a few examples of addition reactions of carbenes generated by a-elimination. 

This synthesis of ethyl orthoformate is more elegant and smooth than that from chloroform and sodium ethoxide. Ethyl orthoformate is used for preparing acetals of ketones, e.g. 

SYNTHESIS (from 5-MeO-DMT). To a solution of 0.10 g 5-methoxy-N,N-dimethyl tryptamine (see 5 MeO-DMT) in 5 mL benzene there was added 0.5 g 2,2,2-trichloroethyl chloroformate, and the resulting solution was held at reflux temperature for 2 days. After cooling there was added 5 mL Et20 and the organic phase washed with 2x20 mL 3N HCI followed by 20 mL H20. The solvent was then removed under vacuum. The residue (N-... 

Dihalocyclopropanes are generally prepared by the addition of dihalocarbenes to alkenic substrates. As indicated in the introduction, the first synthesis of a dihalocyclopropane was accomplished by Doering and Hoffmann by the addition of dichlorocarbene, generated from chloroform and potassium r-butoxide (Bu OK), to cyclohexene giving dichloronorcarane (1), as shown in equation (l).s... 

Siloxane Polymers. The synthesis of the ferrocene-modified siloxane polymers (A - E) has been described previously (25,27,32). Briefly, the methyl(2-ferrocenylethyl)-siloxane polymers were prepared by the hydrosilylation of vinylferrocene with the methylhydrosiloxane homopolymer or the methylhydrosiloxane-dimethylsiloxane copolymers (m n ratios of 1 1, 1 2, and 1 7.5 see Figure 1) in the presence of chloroplatinic acid as a catalyst. The methyl(9-ferrocenylnonyl)siloxane-dimethylsiloxane (1 2) copolymer was prepared via hydrosilylation of 9-ferrocenyl-l-nonene with the methylhydrosiloxane-dimethylsiloxane (1 2) copolymer. The molecular weight range of these ferrocene-modified siloxane polymers is approximately 5,000-10,000. Purification of the polymers was achieved by reprecipitation from chloroform solution, via dropwise... 

The leaves of Arnica montana L. contain a new alkaloid, N-ethoxycarbonyl-L-prolinamide (1). Its structure has been established by mass, i.r., and n.m.r. spectral analysis, and confirmed by synthesis from L-proline by conversion into the amide followed by reaction with ethyl chloroformate. The synthesis also settles the absolute configuration of the new alkaloid.3... 

This reaction is similar to the Williamson synthesis of ethers (method 115). Otthofotmates in which the alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and isoamyl have been prepared from chloroform. The yield of ethyl orthoformate is 45%. Mixed esters are obtained from a mixture of sodium alkoxides and chloroform. Benzotrichloride, C,HjCClj, is converted to methyl orthobenzoate in 86% yield by sodium methoxide in methanol, ... 

Tris(2,4-pentanedionato)molybdenum(III) is a dark purple crystalline solid, m.p. 228 to 230°. It reacts rapidly with atmospheric oxygen to form a diamagnetic brown product, m.p. 284 to 285° (decomp.), containing pentaposi-tive molybdenum. This oxidation state is determined by dissolution in concentrated hydrochloric acid to produce a solution which has the same absorption spectrum in the visible region as green oxopentachloromolybdate(V), by cerimetric titration of this concentrated hydrochloric acid solution after chloroform extraction of the liberated 2,4-pen-tanedione, and by independent synthesis from a brown... 

Tests for Primary Amines.—The constitution of R—NC for the isocyanides is supported also by their synthesis from primary amines. When a primary amine, R—NH2, is treated with chloroform in alkaline solution an iso-cyanide is formed. Chloroform (p. 183), is tri-chlor methane, CHCI3. The reaction is. 

Acidification of diazoketones The conversion of the diazoketone into a chloroketone is usually routine. Schoellman and Shaw (1963), in their synthesis of the chloromethyl ketone derived from phenylalanine, prepared an ethereal solution of the corresponding diazoketone and then treated it with dry HCl for 2 hr. The chloroketone could then be isolated following the removal of solvent. Visser et al. (1971) added concentrated HCl to an ethyl acetate solution of the diazoketone derivative of N-tosyl alanine until the evolution of nitrogen ceased. Removal of solvent, followed by crystallization from chloroform-heptane yielded an analytically pure product. A carbonyl absorption in the region of 1720 cm is diagnostic of haloketones. 

An alternate procedure was used by Shafer et al. (1966) in their synthesis of p-nitrophenyl diazoacetate. The key to this synthesis was the use of a chloroformate intermediate. To a 16-fold excess of diazomethane in ether (10 ml) was added dropwise a solution of 48.4 mg of p-nitrophenyl chloroformate. After the solution stood overnight at 4°C, the excess diazomethane was removed under a stream of N2 and the ether evaporated under reduced pressure. The residual yellow oil was dissolved in 2 ml of benzene and chromatographed on an alumina column using benzene as the eluant. The first fraction contained 48 mg of product which could be recrystallized from chloroform-hexane (m.p. 92-94°C). These authors reported that several other diazoacetates can be prepared by this procedure. 

The above conditions allow the synthesis of a large variety of a,a-dialkyl substituted ketones including spiro derivatives and cyclopentanones, cyclohexanones, cycloheptanones and cyclododecanones bearing two alkyl groups at die a-posidon (Scheme 162, e Scheme 165, c Scheme 166, e Scheme 186, a and b Scheme 187 Scheme 188, a Scheme 189, a and The reactions are less selective when the dichlorocarbene is generated from bromodichloromethane and lead to gem-dichlorocyclopropanes if the dichlorocarbene is produced from chloroform and potassium r-butoxide (Scheme 162, f Scheme 188, b Scheme 189, c). ... 

The preparation of orthoformic acid esters from chloroform and alkali metal alkoxides is a long known procedure, " which can be performed under phase transfer catalysis. If small amounts of alcohol are present in the phase-catalyz process, cyclopropanes (372 Scheme 67) can be produced by aHHifinn of dichlorocarbene to l,2-dialkoxy-l,2-dichloroethylenes, which are thought to be intermediates. " Al-kenes of this kind, e.g. (373 equation 176), have been observed as byproducts in the synthesis of tri-r-butylorthoformate from chlorodifluoromethane or dichlorofluoromethane and potassium r-butoxide. Trimethoxyacetonitrile was prepared from trichloroacetonitrile and sodium methoxide. ... 

Kolbe2 in his last papers described a compound with the same formula, formed by oxidation of isatin (3) with Cr03, and called it isatoic acid. Meyer3 proved the identity of both compounds, and Niementowski and Rozanski4 were the first to establish the correct formula (1) when they found a new synthesis from anthranilic acid (4) and ethyl chloroformate. 

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