Halohydrins preparation

Propylene oxide has found use in the preparation of polyether polyols from recycled poly(ethylene terephthalate) (264), haUde removal from amine salts via halohydrin formation (265), preparation of flame retardants (266), alkoxylation of amines (267,268), modification of catalysts (269), and preparation of cellulose ethers (270,271). 

Uses. /-Butyl hypochlorite has been found useful in upgrading vegetable oils (273) and in the preparation of a-substituted acryflc acid esters (274) and esters of isoprene halohydrins (275). Numerous patents describe its use in cross-linking of polymers (qv) (276), in surface treatment of mbber (qv) (277), and in odor control of polymer latexes (278). It is used in the preparation of propylene oxide (qv) in high yield with Httle or no by-products (269,279). Fluoroalkyl hypochlorites are useful as insecticides, initiators for polymerizations, and bleaching and chlorinating agents (280). 

The reductive elimination of halohydrins provides a means of introduction of double bonds in specific locations, particularly as the halohydrin may be obtained from the corresponding a-halo ketone. This route is one way of converting a ketone into an olefin. (The elimination of alcohols obtainable by reduction has been covered above, and other routes will be discussed in sections IX and X.) An advantage of this method is that it is unnecessary to separate the epimeric alcohols obtained on reduction of the a-bromo ketone, since both cis- and tran -bromohydrins give olefins (ref. 185, p. 251, 271 cf. ref. 272). Many examples of this approach have been recorded. (For recent examples, see ref. 176, 227, 228, 242, 273.) The preparation of an-drost-16-ene (123) is illustrative, although there are better routes to this compound. 

The following section describes the preparation of epoxides by the base-promoted ring closure of vicinal halohydrins. Because vicinal halohydrins are customarily prepared from alkenes (Section 6.17), both methods—epoxidation using peroxy acids and ring closure of halohydrins—are based on alkenes as the starting materials for preparing epoxides. 

Another method for the synthesis of epoxides is through the use of halo-hydrins, prepared by electrophilic addition of HO-X to alkenes (Section 7.3). When a halohydrin is treated with base, HX is eliminated and an epoxide is produced. 

This is a special case of 10-71 and is frequently used for the preparation of halohydrins. In contrast to the situation with open-chain ethers and with larger rings,... 

Hydratropaldehyde has been prepared by hydrolysis of phenylmethylglycidic ester,2 3 4 by chromyl chloride oxidation of cumene,5 by the elimination of halogen acid or water from halohydrins or glycols,5 8 and by the distillation at ordinary pressure of methylphenylethylene oxide.9,10... 

Halohydrin dehalogenase activity was determined by monitoring halide liberation at 30 °C in tris-S04 buffer (50 mM, pH 8.0) containing 5 mM 1,3-dichloropropanol or 1,3-dibromopropanol as the substrate. All buffers used for activity assay were prepared with bidest water. From the incubation mixture, 0.5 ml samples were taken and mixed with 1.6 ml of H2O, 0.2 ml or halide reagent 1 and 0.2 ml of halide reagent II. Absorbances were read at 460 nm. A calibration curve of 0-1 mM of chloride or bromide was used to calculate the concentration of halide. The extinctions at 460 nm should be below 0.4 (for chloride) or 0.8 (for bromide). 

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. 

Addition of halides and water to alkenes preparation of halohydrins... 

No attempt will be made here to cite every recorded instance of the preparation of a halohydrin from an olefin. It will be sufficient to consider (1) the various moans employed to generate hypohakuw acids (2) the mechanism of the reaction and (3) a few representative examples of its application. 

The AT-halophtha1imides, A -haloacetanilides,180 and AMialo-txmzonoeulfonamides10 8-7M 1 u have Been only limitod service as reagonts for the preparation of halohydrins. 

Enantioselective reductions. The neat reagent (1), prepared from ( + )-< -pinene, reduces aryl a-halomethyl ketones slowly but in high chemical yield to (R)-halohydrins in 90-96% ee, but optical induction is mediocre in the case of aliphatic a-halo ketones (35-66% ee). The chiral halohydrins are useful precursors to chiral epoxides. 

The first examples of the synthesis of CCs from halohydrins appeared during the early 1930s. In this case, vic-halohydrins were reacted with sodium hydrogen carbonate [190, 191] or sodium alkyl carbonates [192] to afford CCs in good yield (82%), especially when the reaction was carried out under high pressure and temperature. When tetramethylammonium hydrogen carbonate was used in acetonitrile (Equation 7.18) [193], the relevant carbonate could be prepared in high yields under mild conditions. 

Normant, J. F. Preparation of propargylic carbenoids and reactions with carbonyl compounds. A stereoselective synthesis of propargylic halohydrins and oxiranes. Eur. J. Org. Chem. 2001, 3295-3300. 

Several recent publications describe cleavage of 1,3,2-dioxathiolane. S -dioxides (cyclic sulfates) by halide nucleophiles that furnish halohydrines, which can be used as synthetic intermediates, primarily for preparation of corresponding epoxides or for further reactions with nucleophiles (Table 6). Similar reactions with chloride have been studied for 1,3,2-dioxathiolane J-oxides (cyclic sulfites) <1996ACS832>. 

Three inosamines were obtained in the course of efforts to synthesize myo-inositol by the nitro-sugar cyclization (see p. 142). However, the methods which have been the most productive of new inosamines are those which are well known as means of preparing amino sugars and aminopolyhydric alcohols, namely, reduction of imine derivatives of carbonyl compounds (in this case, inososes) and ammonolysis of halohydrins and epoxides. 

PEG proves to be an efficient reaction medium for the reaction of vicinal halohydrin with carbon dioxide in the presence of a base to synthesize cyclic carbonates (Scheme 5.9) [42], Notably, PEG400 (MW = 400) as an environmentally friendly solvent exhibits a unique influence on reactivity compared with conventional organic solvents. Various cyclic carbonates can be prepared in high yield employing this protocol. The process presented here has potential applications in the industrial production of cyclic carbonates because of its simplicity, cost benefits, ready availability of starting materials, and mild reaction conditions. 

One of the major uses of these halohydrins is for the preparation of epoxides. Treatment of the halohydrin with base, such as NaOH or KOH, results in deprotonation of the alcohol followed by an intramolecular nucleophilic substitution (see Section 10.3), as shown in the following example. Remember that the nucleophilic oxygen must displace the chlorine from the opposite side, resulting in inversion of configuration at that carbon. 

Several examples of halohydrin formation from styrene derivatives and saccharides catalyzed by CPO are reviewed by Adam and coworkers [23], Formation of bromohydrin derivatives of some saccharides can be of interest for the preparation of bioactive compounds [72]. 

Since esmolol is marketed as its racemic mixture, there were no stereochemical issues associated with the Payne-like [21] formation of the intermediate aryloxyep-oxide, particularly when the coupling reaction was carried out under the K2C03/ acetone conditions conducive to the formation of epoxides from alpha-halohydrins (see discussion in Chapter II-8). Likewise, even though over-alkylation had been a major problem when preparing the N-extemal ester targets because the N-alkyl-... 

Thiiranes are prepared by two major pathways. The first pathway is the conversion of alkenes to intermediates, such as dihaiides, halohydrins or epoxides, followed by nucleophilic attack and subsequent... 

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