A-Chlorohydrin

A chlorohydrin has been defined (1) as a compound containing both chloio and hydroxyl radicals, and chlorohydrins have been described as compounds having the chloro and the hydroxyl groups on adjacent carbon atoms (2). Common usage of the term appHes to aUphatic compounds and does not include aromatic compounds. Chlorohydrins are most easily prepared by the reaction of an alkene with chlorine and water, though other methods of preparation ate possible. The principal use of chlorohydrins has been as intermediates in the production of various oxitane compounds through dehydrochlorination. 

Chloro-l,2-propanediol [96-24-2] HOCH2CHOHCH2CI, a liquid with = 1.4831 (6), boils at 213°C and 101.3 kPa (1 atm) with decomposition. It can be distilled at 114—120°C at 1.87 kPa (14 mm Hg). Synonyms for this compound include 3-chloro-l,2-dihydroxypropane, glycerol monochlorohydrin, a-chlorohydrin, and 3-chloropropylene glycol. It is miscible in water, ethanol, ethyl ether, and acetone [67-64-1] (8) and is soluble in hot... 

An improved method iavolves the reaction of a chlorohydrin and CO2 ia the presence of an amine, which gives cycHc carbonate selectivities of... 

Almost 40 years later the Lummus Co. patented an integrated process involving the addition of chlorine along with the sodium chloride and sodium hydroxide from the cathode side of an electrolytic cell to a tertiary alcohol such as tertiary butanol to produce the tertiary alkyl hypochlorite. The hypochlorite phase separates, and the aqueous brine solution is returned to the electrolytic cells. The alkyl hypochlorite reacts with an olefin in the presence of water to produce a chlorohydrin and the tertiary alcohol, which is returned to the chlorinator. With propylene, a selectivity to the chlorohydrin of better than 96% is reported (52). A series of other patents covering this technology appeared during the 1980s (53—56). 

Iodine monochloride adds unidirectionally to perfluoropropene-2-ol to form a chlorohydrin, which easily dehydrochlonnates to yield lodopentafluoroacetone [/5] (equation 8). 

The use of peroxides for the oxidation of propylene produces propylene oxide. This compound is also obtained via a chlorohydrination of propylene followed by epoxidation. 

Due to the presence of a terminal double bond in 1-butene, oxidation of this isomer via a chlorohydrination route is similar to that used for propylene. 

Isobutylene oxide is produced in a way similar to propylene oxide and butylene oxide by a chlorohydrination route followed by reaction with Ca(OH)2. Direct catalytic liquid-phase oxidation using stoichiometric amounts of thallium acetate catalyst in aqueous acetic acid solution has been reported. An isobutylene oxide yield of 82% could be obtained. 

Fig. 10.18. Metabolism of epichlorohydrin (10.70), showing the sequential steps of hydration to a-chlorohydrin (10.71), cyclization with loss ofHCl to form glycidol (10.72), and hydration...

Although not in the top 50, it is an important monomer for making epoxy adhesives as well as glycerine (HO-CH2-CHOH-CH2-OH). Propylene is first chlorinated free radically at the allyl position at 500°C to give allyl chloride, which undergoes chlorohydrin chemistry as discussed previously to give epichlorohydrin. The student should review the mechanism of allyl free radical substitution from a basic organic chemistry course and also work out the mechanism for this example of a chlorohydrin reaction. 

The dihydrofuran derivative 35 was also employed for the synthesis of ethyl 3-amino-3-deoxy-/3-DL-arafiino-pentofuranoside (40b). The synthesis was accomplished27 in three stages. By the action of calcium hypochlorite on 35, a chlorohydrin intennediate was formed which, on treatment with a base, afforded a mixture of the epoxides 37, 38,... 

Dihydroxypropyl)glutathione, V-(2,3-dihydroxypropyl)cysteine and [3-ehlo-rolactic acid are the major metabolites isolated from rat urine after intraperitoneal administration of glycidol. The generation of [3-ehlorolaetic acid is presumably a result of initial formation of a-chlorohydrin, with subsequent oxidation by alcohol and aldehyde... 

Jones, A.R. O Brien, R.W. (1980) Metabolism of three active analogues of the male antifertility agent a-chlorohydrin in the rat. Xenobiotica, 5, 365-370 Kaplan, D.L., Cornell, J.H. Kaplan, A.M. (1982) Biodegradation of glycidol and glycidyl nitrate. Appl. environ. Microbiol., 43, 144-150... 

The reaction involves a chlorohydrin intermediate, which is then treated with a base to give the resulting epoxy compound. 

After an oral dose of 6 mg/kg bw to rats, approximately 38% of the dose was exhaled as CO2, 50% was excreted as metabolites in the urine and 3% was present in faeces (Gingell et al., 1985). Concentrations were highest in liver, kidney and forestomach. The initial metabolic reactions are conjugation of the epoxide with glutathione, which is probably a chemical, not enzymatic, reaction, and hydration of the epoxide by epoxide hydrolase. The major metabolites in urine are jV-acetyl-5 -(3-chloro-2-hydroxypropyl)-L-cysteine (36% of the dose) and 3-chloro-1,2-propanediol (a-chlorohydrin) (4%). 

This methodology has been used for an iterative synthesis of the tricyclopenta-noid hirsulene (6), as outlined in equation (II).2 Two steps in the synthesis involve conversion of an -chloro ketone to an alkcne. This reaction was accomplished by reduction to a chlorohydrin followed by treatment with chromium(ll) perchlorate.1... 

Marmor and Maroski2 investigated the reaction of four hindered alkenes with IIOCI in acetone-water (homogenous conditions), but the reaction led to a chlorohydrin in only one case l-chloro-2,4,4-trimcthyl-2-pentanol (34% yield). The products in general are vinyl chlorides. 

The raw material from which dinitrochlorohydrin is produced is chlorohydrin, made by treating glycerine with hydrochloric acid at a temperature of 100-120°C under pressure [20]. The substitution product is a mixture of a- and /S-isomers. (The boiling point of a-chlorohydrin is 130°C at 18 mm Hg that of -chlorohydrin is 146°C at 18 mm Hg). 

In the five-membered series, Bartlett and White 6 converted 2-chlorocyclopentanone into a chlorohydrin on treatment with methyl-magnesium bromide, but this product too failed to yield an epoxide because of the cis-disposition of hydroxyl and chlorine substituents (Eq. 177). 

More recently Bradley and co-workers288 demonstrated a fourth significant product in this reaction to be l,3-dichloro-2-propanol. formed by addition of hydrochloric acid to epiehlorohydrin. These authors then showed that under suitable conditions phenyl glycidyl ether can be mode to react wjth a chlorohydrin. There are formed in this manner a new epoxide and l-chloro-D-phenoxy-2-propanol, ah... 

Chlorohydrin(Called Chlorpropandiol, Mono-chlorhydrin, Glycerinchlorhydrin or Chlor-propylenglykol in Ger), Cl.CsHs(OH)2 mw 110.54. Two isomers are known, both of which are present in the commercial product 3-Chloropropane-1,2-diol or a-Chlorohydrin, Cl.CH2.CH(OH).CH2.OH, col to pale-yel si viscous liq having a pleasant odor, bp 213°... 

B) Examination of the Solvents insoluble in Water. These may be carbon disulphide, chloroform, carbon tetrachloride, a chloro-derivative of ethane or ethylene, a chlorohydrin, amyl alcohol, amyl acetate, ether, benzene or a homologue, oil of turpentine, pinewood oil, light mineral oil, resin oil, tar oil, shale oil, or camphor oil. 

The investigations of Lucas and his coworkers with 2,3-disubstituted butanes have contributed much to the clarification of the mechanism of ring closure and ring opening of ethylene oxides and ethylene imines. D-Mreo-2,3-Butanediol (XV) is converted into a chlorohydrin (XVII) via the diacetate (XVI).24 In the formation of the chlorohydrin (XVII) a Walden inversion occurs.26 The dehydrochlorination of XVII with... 

The kinetics of the alkylation of tertiary amines with l,3-dichloropropan-2-ol have been studied.39 The mechanism is thought to involve a chlorohydrin-epoxide equilibrium. 

Chlorohydrins are compounds characterized by alpha halo-alpha alkoxy groups bound to a common carbon atom. These compounds undergo rapid hydrolysis at this shared carbon atom. Bis(2-chloroisopropyl)ether, a chlorohydrin, has two such carbon atoms, and both react very rapidly with water. In fact, the reactions are so fast that acid and alkaline contributions have not been determined. It is likely, however, that base accelerates the reaction kinetics. The proposed reaction pathway for this compound is based on the reported pathway for bis(chloroethyl)ether (Figure 13.4). The reported rate constant for bis(chlorome-thyl)ether, of 0.23 sec-1 was based on an observed half-life of a few minutes. Similarly, for bis(2-chloroisopropyl)ether, both of the chloro substituents are reactive, and a half-life of a few minutes can be assigned to this compound, as well. 

Chloromethylation.1 Chloromethyl methyl ether has been generally used for electrophilic aromatic chloromethylation, but it is highly toxic and now considered a carcinogen. Chloromethylation can be effected by use of a trimethylsilyl ether (1) of a chlorohydrin prepared as shown from trioxane and chlorotrimethylsilane in the presence of stannic chloride in chloroform. This reagent, generated in situ, is effective for chloromethylation of styrene in the presence of SnCl4 any excess is easily decomposed by hydrolysis. Bromomethylation is possible by replacement of ClSi(CH3)3 by BrSi(CH3)3. 

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