Esters from chloroformates

Scheme 46 Preparation of cyanoformate esters from chloroformates.

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. ... 

Production of cellulose esters from aromatic acids has not been commercialized because of unfavorable economics. These esters are usually prepared from highly reactive regenerated cellulose, and their physical properties do not differ markedly from cellulose esters prepared from the more readily available aHphatic acids. Benzoate esters have been prepared from regenerated cellulose with benzoyl chloride in pyridine—nitrobenzene (27) or benzene (28). These benzoate esters are soluble in common organic solvents such as acetone or chloroform. Benzoate esters, as well as the nitrochloro-, and methoxy-substituted benzoates, have been prepared from cellulose with the appropriate aromatic acid and chloroacetic anhydride as the impelling agent and magnesium perchlorate as the catalyst (29). 

Amides are stable compounds. The lower-melting members (such as acetamide) can be readily purified by fractional distillation. Most amides are solids which have low solubilities in water. They can be recrystallised from large quantities of water, ethanol, ethanol/ether, aqueous ethanol, chloroform/toluene, chloroform or acetic acid. The likely impurities are the parent acids or the alkyl esters from which they have been made. The former can be removed by thorough washing with aqueous ammonia followed by recrystallisation, whereas elimination of the latter is by trituration or recrystallisation from an organic solvent. Amides can be freed from solvent or water by drying below their melting points. These purifications can also be used for sulfonamides and acid hydrazides. 

Preparation of Di-n-Propyl Acetyl Tropine Hydrochloride Tropine (11.12 grams) was dissolved in 100 ml of anhydrous pyridine and to this solution was added 15.64 grams of din-propyl acetyl chloride. The mixture was refluxed for 6 hours. This solution was then cooled and the pyridine removed in vacuo. The residue was dissolved in chloroform. The chloroform solution was washed with 10% hydrochloric acid to remove the residual trace of pyridine. The hydrochloride of the product ester is soluble in chloroform and is not extracted from chloroform by hydrochloric acid. This is an unexpected property. 

Arachidonate esters, linolenate esters from CisH3iC02Me, CisHjsCOjMe, CiyHjsCOjMe, CiyHjsCOjMe, CiyHjjCOjMe, Ci7H3iC02Me, arachidonate esters, linolenate esters NH4Y Chloroform [176]... 

An extremely mild method for the synthesis of nitrate esters from easily oxidized or acid-sensitive alcohols involves the decomposition of a nitratocarbonate (29). The nitratocar-bonate is prepared in situ from metathesis between a chloroformate (reaction between phosgene and an alcohol) and silver nitrate in acetonitrile in the presence of pyridine at room temperature. Under these conditions the nitratocarbonate readily decomposes to yield the corresponding nitrate ester and carbon dioxide. Few examples of these reactions are available in the literature and they are limited to a laboratory scale. 

The preparation of furyl phosphorodichioridate is based upon a method to prepare 2-chlorofuran (16% yield, Hormi, Nasman unpublished). Later the preparation was extended to a general method to prepare furyl esters from carboxylic acid chlorides lacking a-hydrogens and alkyl furyl carbonates from primary (other than methyl) and secondary alkyl chloroformates. Phosphoryl chloride was the only acid chloride except carbon analogues found to give a furyl ester by the amine-catalyzed reaction. 

Acetylenic Esters from Lithium Alkynylides and Alkyl Chloroformates... 

TABLE 2. Synthesis of a-amino esters from magnesium carbenoids by the reaction with A-hthio A-substituted arylamines followed by ethyl chloroformate... 

The apparent abnormal formation of ethyl pyrrole-2-carboxylate from the reaction of ethyl chloroformate and alkali metal salts of pyrrole could be accounted for by a thermal rearrangement during the isolation of the products. However, whilst this may be partly correct, an analysis of the reaction products prior to their isolation has established (77CJC4103) the formation of the thermodynamically more stable 2-carboxylic ester from the 1-isomer by a reaction sequence shown in Scheme 36. 

Blowing agents - [FOAMED PLASTICS] (Vol 11) - [PLASTICPROCESSING] (Vol 19) -from chloroformates [CARBONIC AND CARBONOCHLOFJDIC ESTERS] (Vol 5) -fluorine compounds [FLUORINE COMPOUNDS, ORGANIC - INPRODUCTION] (Vol 11) -HF mprdnof [FLUORINE COMPOUNDS, INORGANIC - HYDROGEN] (Vol 11) -hydrazines as [HYDRAZINE AND ITS DERIVATIVES] (Vol 13)... 

It is this equilibrium which renders difficult the explanation of the course of the reactions which take place when metallic sodium or sodium ethoxide and then alkyl or acyl halide are added to these compounds. At first it was thought that the sodio compound formed with acetoacetic ester was CH3.CO.CHNa.COOC2H5, because the reaction with alkyl and acyl halides always yielded a C-derivative, CH3.CO.CHR.COOC2H5. The first example of a different course of reaction was found in the formation of an O-derivative—/3-carhethoxyhydroxycrotonic ester from sodio-acetoacetic ester and chloroformic ester (J. pr., [2], 37, 473 B., 25,1760 A., 277, 64). This could only be explained by assigning an enol formula to the sodium salt—... 

The residue was dissolved in chloroform. The chloroform solution was washed with 10% hydrochloric acid to remove the residual trace of pyridine. The hydrochloride of the product ester is soluble in chloroform and is not extracted from chloroform by hydrochloric acid. This is an unexpected property. 

The chloroform solution of the hydrochloride was dried over anhydrous calcium sulfate, and evaporated to dryness, leaving a semisolid residue of product ester hydrochloride. This was recrystallized from chloroform-hexane mixture, MP 186°C. 

The above ester (10.24 g, 0.0200 mole) in 100 ml of a solution prepared from chloroform (210 ml), ethanol (100 ml) and concentrated aqueous ammonia (10 ml) was allowed to stand at room temperature for 2 h, diluted with chloroform (250 ml), and washed with dilute hydrochloric acid (2 N, 250 ml). The chloroform layer was dried and removed of chloroform under vacuum. A solution of the residue in dichloromethane (95 ml) and ether (5 ml) was passed through silica gel (50 g) using more dichloromethane-ether (19 1, 600 ml). Evaporation of the solvent and recrystallization of the residue from acetonitrile afforded (5a,17a)-l -(methylsulfonyl)-l H-pregn-20-yno[3,2-c]pyrazol-17-ol (7.07 g, 85% yield, MP 202°-203°C). It may be also made another way. 

A procedure for obtaining indole-3-carboxylate ester from the f-pyrrolidino-o-nitrostyrene intermediates in the Leimgruber-Batcho indole synthesis was demonstrated. Although ethyl chloroformate is evidently not reactive enough, phosgene followed by methanolysis effects f) -carbomethoxylation. Reductive cyclization then gives the indole esters. <95SC95>... 

The purity of the hemin ester can be checked by tic (silica gel, with CHC13/ methanol = 5 1), or by visible spectroscopy. A small amount of the hemin ester dissolved in pyridine can be reduced by sodium dithionite in a cuvette.1 2 The resultant hemochrome should exhibit two absorption maxima at 557 and 526 nm. If necessary, the product can be further purified by chromatography on an alumina (grade III) column (1X10 cm) using a mixture of chloroform and methanol (10 1) as eluent. However, the iron prophyrin compound obtained after chromatography exists as the p-oxo dimer, [Fe(III)-O-Fe(III)], which may be converted back to the chloride by treatment in CHC13 with dry HO followed by crystallization from chloroform/methanol. 

Other methods that can be used to prepare thiol esters from carboxylic acids include the use of aryl thiocyanates,12 thiopyridyl chloroformate,13 2-fIuoro- V-methylpyridinium tosylate,14 1-hydroxybenzotriazole, 5 and boron thiolate.16 Direct conversion of 0-esters to 5-esters can also be effected via aluminum and boron reagents.17 However, the applicability of these 1217 and other more recent methods18 to the selective thiol ester formation discussed above has not been clearly defined. 

Heterocyclic compounds containing a nitrogen atom commonly undergo N-alkylation or C-alkylation. N-Methyl pyrrole can be prepared by interaction of methyl iodide with potassium pyrrole (40%). N-Carbethoxy pyrrole is made from chloroformic ester and potassium pyrrole. The C-alkylation of pyrroles has been discussed. 3-Alkylindoles are made by the alkylation and decarboxylation of indole-2-carboxylic acid. The conditions for alkylation of pyrrolidine are analogous to those employed for the alkylation of a secondary amine. Thus, pyrrolidine on treatment with n-butyl bromide and potassium hydroxide in boiling benzene is con-... 

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, ... 

Apart from their behaviour as ligands in metal catalyst systems, studies of the reactivity of phosphites towards a wide variety of other substrates have attracted attention. New aspects and applications of the classical Michaelis-Arbuzov reaction and its variants continue to appear. Evidence of the thermal disproportionation of methyltriaryloxyphosphonium halides formed in the reactions of triarylphosphites with alkyl halides, together with the formation of P-O-P intermediates, has been reported. The Michaelis-Arbuzov reaction has been used in the synthesis of phosphonate-based styrene-divinylbenzene resins and polyphosphonated chelation therapy ligands.Treatment of electron-rich benzylic alcohols dissolved in triethylphosphite with one equivalent of iodine affords a low-temperature one-pot route to the related benzylic phosphonates, compounds which are otherwise difficult to prepare. Upper-rim chloromethylated thiacalix[4]arenes have also been shown to undergo phosphonation on treatment with a phosphite ester in chloroform at room temperature. The nickel(II)-catalysed reaction of aryl halides with phosphite esters in high boiling solvents, e.g., diphenyl ether, (the Tavs reaction), has also... 

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