Hypochlorites: chlorohydrination with

Ghlorohydrination with er -All l Hypohalites. Olefins react with ethyl hypochlorite [624-85-1] to form the corresponding chlorohydrin (49). In 1938 both Shell Development Co. (50) and Arthur D. Litde, Inc. (51) patented the preparation of chlorohydrins by the reactions of olefins with tertiary alkyl hypochlorites. Examples with ethylene and propylene in the Shell patent reported chlorohydrin yields of greater than 95% with tert-huty hypochlorite [507-40-4]. 

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). 

In two proposed alternative processes, the chlorine is replaced in the hypochlorination reaction by hypochlorous acid [7790-92-3] HOCl, or tert-huty hypochlorite. In the first, a concentrated (>10% by weight) aqueous solution of hypochlorous acid, substantially free of chloride, chlorate, and alkah metal ions, is contacted with propylene to produce propylene chlorohydrin (113). The likely mechanism of reaction is the same as that for chlorine, as chlorine is generated in situ through the equiUbrium of chlorine and hypochlorous acid (109). 

In the second proposed alternative process, tert-huty hypochlorite, formed from the reaction of chlorine and tert-huty alcohol, reacts with propylene and water to produce the chlorohydrin. The alcohol is a coproduct and is recycled to generate the hypochlorite (114—116). No commercialisation of the hypochlorous acid and tert-huty hypochlorite processes for chlorohydrin production is known. 

The stepwise formation of epoxides through the reaction of alkenes with sodium hypochlorite with, or without, the isolation of the intermediate chlorohydrin has been subjected to catalysis with (V-benzylquininium chloride under liquiddiquid two-... 

ELECTROPHILIC ADDITIONS TO CARBON-CARBON MULTIPLE BONDS A. Chlorinating agents Sodium hypochlorite solution 7V-Chloro succi n i m i de Antimony pentachloride Formation of chlorohydrins from alkenes Chlorination with solvent participation and cyclization Controlled chlorination of acetylenes... 

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,... 

The final, critical oxidative spirocyclization of the 2,3-disubstituted indole to the spiro oxindole was effected by treatment of 124 with tert-butyl hypochlorite in pyridine to provide the labile 125 [Fig. (34)]. The Pinacol-type rearrangement was conducted by treating compound 125 with p-toluenesulfonic acid in THF/water. It is assumed that the chlorination of 124 proceeds from the least hindered face of the indole, to give the a-chloroindolene 125. The hydration of the imine functionality must also occur from the same a-face that is syn to the relatively large chlorine atom furnishing the syn-chlorohydrin 126, that subsequently rearranges stereospecifically to the desired spiro oxindole 127. 

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. 

Olefin inversion (c/. 7, 338). Trifluoroacetyl chloride reacts with 1,2-dialkyl epoxides in DMF stereospeciflcally by trans opening to give u/c-chlorohydrin trifluoroacetates. These products are reduced stcrcospccifically by Nal to alkenes with. ryn-elimination to give inverted alkenes. Reductions with zinc arc less selective. Inversion of olefins is also possible by addition of NCS in CFjCOOH (actual reagent is trifluoroacetyl hypochlorite) followed by reduction with Nal. 

The C = C bond in 3,3,3-trifluoro-2-methylprop-l-eneis readily oxidized in 76 % yield by bubbling the substrate into a cooled solution of hypochlorous acid (Table 6).98 Chlorohydrins together with 1,2-dichloro derivatives arc obtained by oxidation of alkenes with tert-butyl hypochlorite when the reaction is performed in acetic acid instead of water, chlorohydrin acetate is formed (Table 6)."... 

Polycyclic aromatic hydrocarbons (PAH), which are ubiquitous in the environment, including surface waters, undergo facile chlorination by hypochlorite when dissolved in humus-poor water to give a suite of chlorinated PAH (1660). It is therefore conceivable that this chlorination can occur under natural conditions, but this is yet to be determined. Another new possible source of natural chlorinated PAH is the reported in vitro reaction of benzo [a pyrene diol epoxide, the ultimate carcinogen of benzo aIpyrene with chloride ion to give chlorohydrin DDD, which has been isolated and identified as an intermediate en route to a benzol a pyrene-DN A adduct (1661). However, DDD is not considered to be a natural compound at this time. 

An altemative synthesis of fosfomycin has been effected by the halohydrin route. 9 Thus, treatment of ( ) (Z)-l-propenylphosphonic acid in aqueous solution with sodium hypochlorite gave t/zreo-l-chloro-2-hydroxypropylphosphonic acid (85%). Resolution is accomplished by means of (-)-a-phenylethylamine to yield (-i-)-chlorohydrin (80%), which is converted with 10 M aqueous NaOH into fosfomycin (85-90%). ... 

A variant of the chlorohydrin method consists in causing chlorine and caustic soda to react simultaneously with r-butyl alcohol to form t-butyl hypochlorite, which can act on propylene to regenerate t-butyl alcohol and produce chlorohydrin. This is then hydrolysed in the presence of caustic soda to produce the final propylene oxide (Lummus process). 

For addition of HOC1 the olefins are stirred with 0.125-0.5 m-HOCl at 10°. The yields of chlorohydrin from 1-alkenes of higher molecular weight are considerably increased by addition of pyridine and sulfuric acid (initial pH 6-6.5)278. Chlorohydrins of higher molecular weight are also, accessible by reaction of alkyl hypochlorites with the olefin in an aqueous medium tert-butyl hypochlorite (a yellow oil, b.p. 77-78°/760 mm) is suitable for this purpose it is obtained by passage of chlorine into tert-butyl alcohol in aqueous sodium hydroxide at 0-20°. 

Ethylene undergoes a variety of reactions to form highly toxic and/or flammable substances. It catalytically oxidizes to ethylene oxide (highly toxic and explosive gas) reacts with chlorine and bromine to form ethylene dichloride and ethylene dibromide (toxic and carcinogens) reacts with hypochlorite to form ethylene chlorohydrin (poisonous) reacts with chlorine in the presence of FICl and light or chlorides of copper, iron, or calcium to form ethyl chloride (flammable gas, narcotic) and hydrates in the presence of H2SO4 to form diethyl ether (highly flammable). 

In the reaction of chlorine dioxide with water, hypochlorous, hydrochloric and chloric acids are formed temporarily, and in alkaline solutions chlorites (C102 ), chlorates (ClOj ) and other products arise. The cation H20C1 formed in aqueous solutions of chlorine, chlorine dioxide and hypochlorites may react with alkenes and other unsaturated compounds. The electrophilic addition of HOCl to alkenes is an established reaction mechanism for a, P-chloroalcohol (chlorohydrin) and a, -dichloro derivative formation (Figure 11.16). The reaction yielding chlorohydrins follows the Markovnikov rule with the hydroxyl group adding to the more substituted carbon. Oxidation of chlorohydrins by hypochlorites... 

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