Preparation chlorohydrins using

Organic solutions of HOCl can be prepared in near quantitative yield (98—99%) by extraction of CU -containing aqueous solutions of HOCl with polar solvents such as ketones, nitriles, and esters (131). These organic solutions of HOCl have been used to prepare chlorohydrins (132) and are especially useful for preparation of water-insoluble chlorohydrins. Hypochlorous acid in methyl ethyl ketone has also been used to prepare Ca(OCl)2, by reaction with CaO or Ca(OH)2 (133), and hydrazine by reaction with NH3 (134). 

Control Preparations Transfer 50.0-g portions of unmodified (underivatized) waxy corn starch into five separate pressure bottles, and add 125 mL of 2 N sulfuric acid to each bottle. Add 0.0, 0.5, 1.0, 2.0, and 5.0 mL of the Standard Preparation to the bottles, respectively, giving propylene chlorohydrin concentrations, on the starch basis, of 0, 0.5, 1, 2, and 5 mg/kg, respectively. Calculate the exact concentration in each bottle from the weight of Propylene Chlorohydrins used in making the Standard Preparation. Clamp the tops in place, swirl until the contents of each bottle are completely dissolved, and proceed with the hydrolysis, neutralization, filtration, extraction, extract concentration, and final dilution as directed under Sample Preparation. 

CH3 CH0H CH20H, a colourless, almost odourless liquid. It has a sweet taste, but is more acrid than ethylene glycol b.p. 187. Manufactured by heating propylene chlorohydrin with a solution of NaHCO under pressure. It closely resembles dihydroxyethane in its properties, but is less toxic. Forms mono-and di-esters and ethers. Used as an anti-freeze and in the preparation of perfumes and flavouring extracts, as a solvent and in... 

Propylene oxide [75-56-9] (methyloxirane, 1,2-epoxypropane) is a significant organic chemical used primarily as a reaction intermediate for production of polyether polyols, propylene glycol, alkanolamines (qv), glycol ethers, and many other useful products (see Glycols). Propylene oxide was first prepared in 1861 by Oser and first polymerized by Levene and Walti in 1927 (1). Propylene oxide is manufactured by two basic processes the traditional chlorohydrin process (see Chlorohydrins) and the hydroperoxide process, where either / fZ-butanol (see Butyl alcohols) or styrene (qv) is a co-product. Research continues in an effort to develop a direct oxidation process to be used commercially. 

Where X is Br or Q, the free acids may be obtained by acidification of the alkaline solution, but where X is I, the acids must be isolated as salts to avoid reduction of the arsonic acids by HI. Rather than using alkyl haUdes, alkyl or dialkyl sulfates or alkyl arenesulfonates can be used. Primary alkyl haUdes react rapidly and smoothly, secondary haUdes react only slowly, whereas tertiary haUdes do not give arsonic acids. AHyl haUdes undergo the Meyer reaction, but vinyl hahdes do not. Substituted alkyl haUdes can be used eg, ethylene chlorohydrin gives 2-hydroxyethylarsonic acid [65423-87-2], C2H2ASO4. Arsinic acids, R2AsO(OH), are also readily prepared by substituting an alkaU metal arsonite, RAs(OM)2, for sodium arsenite ... 

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. 

The chlorohydrin process (24) has been used for the preparation of acetyl-P-alkylcholine chloride (25). The preparation of salts may be carried out mote economically by the neutralization of choline produced by the chlorohydrin synthesis. A modification produces choline carbonate as an intermediate that is converted to the desired salt (26). The most practical production procedure is that in which 300 parts of a 20% solution of trimethyl amine is neutralized with 100 parts of concentrated hydrochloric acid, and the solution is treated for 3 h with 50 parts of ethylene oxide under pressure at 60°C (27). 

There have been a number of cell designs tested for this reaction. Undivided cells using sodium bromide electrolyte have been tried (see, for example. Ref. 29). These have had electrode shapes for in-ceU propylene absorption into the electrolyte. The chief advantages of the electrochemical route to propylene oxide are elimination of the need for chlorine and lime, as well as avoidance of calcium chloride disposal (see Calcium compounds, calcium CHLORIDE Lime and limestone). An indirect electrochemical approach meeting these same objectives employs the chlorine produced at the anode of a membrane cell for preparing the propylene chlorohydrin external to the electrolysis system. The caustic made at the cathode is used to convert the chlorohydrin to propylene oxide, reforming a NaCl solution which is recycled. Attractive economics are claimed for this combined chlor-alkali electrolysis and propylene oxide manufacture (135). 

Ethylene oxide [75-21-8] was first prepared in 1859 by Wurt2 from 2-chloroethanol (ethylene chlorohydrin) and aqueous potassium hydroxide (1). He later attempted to produce ethylene oxide by direct oxidation but did not succeed (2). Many other researchers were also unsuccesshil (3—6). In 1931, Lefort achieved direct oxidation of ethylene to ethylene oxide using a silver catalyst (7,8). Although early manufacture of ethylene oxide was accompHshed by the chlorohydrin process, the direct oxidation process has been used almost exclusively since 1940. Today about 9.6 x 10 t of ethylene oxide are produced each year worldwide. The primary use for ethylene oxide is in the manufacture of derivatives such as ethylene glycol, surfactants, and ethanolamines. 

The trimethylene chlorobromide used boiled at 142-1470. It may be prepared in 75-85 per cent yields from trimethylene chlorohydrin (p. 112) by the general method for the preparation of alkyl bromides described in Org. Syn. 1,1. 

The original preparation of y-crotonolactone by Lespieau involved a five-step sequence from epichlorohydrin and sodium cyanide. A recent detailed study of this procedure reported an overall yield of 25% for the lactone. Glattfeld used a shorter route from glycerol chlorohydrin and sodium cyanide hydrolysis and distillation of the intermediate dihydroxy acid yielded y-cro-tonolactone in 23% yield and -hydroxy-y-butyrolactone in 28% yield. The formation of y-crotonolactone in 15% yield has also been reported from pyrolysis of 2,5-diacetoxy-2,5-dihydrofuran at 480-500 . ... 

The formation of cholesterol chlorohydrins has been a subject of intense research [99-102]. The role of these compounds is not yet fully understood, but in addition to cytotoxicity and a possible action on atherosclerosis [100], they have been suggested to be biomarkers of myeloperoxidase-derived HOC1 [103]. Moreover, chlorohydrins and other halohydrins are useful intermediates for the synthesis of a vast range of biologically active natural and synthetic products [104, 105], In fact, considering the importance of these compounds, their preparation is of major interest. 

To investigate the catalytic activity of the materials prepared, hydrolytic kinetic resolution of terminal epoxides such as styrene oxide, 1,2-epoxyhexane, and epi-chlorohydrin was carried out using only water, which acts as a nucleophilic agent... 

Allylic chlorides Actually the reaction of HOG with highly substituted alkenes is a convenient route to allylic chlorides if CH2G2 is used as the organic cosolvent. The reagent is prepared by addition of dry ice to calcium hypochlorite (70%) in water. The reaction of 1-methylcyclohexene is typical (equation I). Chlorohydrins arc the main products only in the case of 1-alkenes and 1,2-disubstituted alkenes. 

Cross-linked, insoluble PEG can be prepared by copolymerizing PEG with epi-chlorohydrin [107,160] or with the tosylate of 3-methyl-3-(hydroxymethyl)oxetane [161,162], These supports are highly permeable and hydrophilic, and enable the use of... 

Lycorine chlorohydrin, formed by the action of POCl3 and HC1 on lycorine, has been used as a synthetic intermediate it was regarded as the ds-derivative (6). An alternative preparation now indicates that the chlorohydrin has the trans configuration (7), and this has been confirmed by X-ray analysis of the acetate... 

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. 

A microbial reduction with a Rhodococcus erythropolis strain was used by BMS scientists to prepare the chiral chlorohydrin from the chloroketone (Scheme 19.15). This intermediate is incorporated into the human immunodeficiency virus (HIV) protease inhibitor Atazanavir (26). This strain was identified through screening and provided >90% yield with a diastereomeric purity of >98% and an ee of >99%.62... 

Epoxides are important intermediates in many industrial processes. For example, the reaction of the simplest epoxide, ethylene oxide, with water is employed to produce ethylene glycol, which is used in antifreeze and to prepare polymers such as Dacron. One method for the preparation of ethylene oxide employs an intramolecular nucleophilic substitution reaction of ethylene chlorohydrin ... 

Several addition reactions have been or are currently used on a large scale in industrial chemical plants. For example, an older method for the preparation of ethylene oxide employed the addition of chlorine to ethylene in water to form ethylene chlorohydrin or 2-chloroethanol. (In industry, ethene is almost always called ethylene.) Treatment of the chlorohydrin with calcium hydroxide results in the formation of ethylene oxide, which is an important intermediate in the manufacture of ethylene glycol and other products (see the Focus On box on page 375). However, this method is wasteful of... 

Hydroxyalkyl celluloses are obtained in the reaction of cellulose with alkene oxides or their corresponding chlorohydrins. The reaction is a base-catalyzed SN2-type substitution, and the reaction rate is proportional to the product [epoxide][CelI—O3]. The commercial preparations include hy-droxyethyl- and hydroxypropylcellulose for which ethylene oxide and propylene oxide are used as reagents. Hydroxyethylcellulose is formed according to the following equation ... 

Calculation Prepare a standard curve for the summed signal areas for each of the controls against the calculated propylene chlorohydrin concentrations, in mg/kg, derived from the actual weight of chlorohydrin isomers used. Using the summed signal areas corresponding to the l-chloro-2-propanol and 2-chloro-1 -propanol from the sample, determine the concentration of mixed propylene chlorohydrins, in mg/kg, in the sample by reference to the calibration plot. 

Reduction of a-chloroacetophenone using the catalyst prepared from the related (5)-diphenylisoleucinol (4) and borane gives (5)-chlorohydrin (5), which is readily transformed to (S)-... 

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