Chlorohydrins cyclization

The product from the reaction of chloro-l,3,2-diazaphospholan with a chlorohydrin cyclizes in acetonitrile to give a bicyclic salt (75) which is in a tautomeric equilibrium (see Scheme 5) <77TL1583>. This represents another example of the transannular interactions exhibited by the phosphatranes. 

Formation of chlorohydrins from alkenes Chlorination with solvent participation and cyclization Formation of chlorohydrins in acidic aqueous solution. 

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...

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... 

Alkenes are converted to halohydrins by the treatment of halides and water. When halohydrins are treated with a strong base (NaOH), an intramolecular cyclization occurs and epoxides are formed. For example, 1-butene can be converted to butylene oxide via butylene chlorohydrin. 

The chlorohydrins show different rates of cyclization, reflecting... 

In the steroid series photochemical rearrangement of hypochlorites of the type A - B (X = halogen) were first used successfully at the Institute to functionalize the 18- and 19-methyl groups.51-63 Thus the hypochlorite (5) on irradiation gave the corresponding chlorohydrin which was smoothly cyclized to the ether (6, X = H2) oxidation of the ether to the lactone (6, X = O) constituted a formal proof of its structure. 

Ethylene was reacted with chlorine water, or with a mixture of hydrated lime and chlorine. In the latter case the Ca(OCl)2 formed decomposes to yield HOC1. The aqueous opening of the intermediate chloronium ion leads to the formation of the product. Ethylene chlorohydrin then was cyclized to ethylene oxide by addition of calcium hydroxide. 

Chiral halohydrins epoxides.1 The esters (2) of the chiral alcohol 1 derived from camphor-10-sulfonic acid, are converted to a-chloro esters (3) by O-silylation and reaction with NCS with high diastereoselectivity. Reduction of 3 with Ca(BH4)2 results in the recovered auxiliary and the chlorohydrin 4 with clean retention. Cyclization of 4 to the terminal epoxide 5 proceeds with clean inversion. 

Dansette and Jerina25 found that cis- 1,2-glycols (34) on treatment with trimethyl orthoacetate in refluxing benzene containing a trace of benzoic acid are converted to an enantiomeric mixture of 2-methyl-2-methoxydioxolanes (orthoesters) (35 and 36). On reaction of this mixture with trimethylsilyl chloride, substitution with inversion takes place, and trans-chlorohydrin acetate (37) is formed. The chlorohydrin acetate is cyclized to an arene oxide on treatment with sodium methoxide. 

A fractionation of deuterium has been observed when a nearly 1 1 mixture of NaB1H4 and NaB2H4 has been used in the second reduction step of equation 17 and the cumulative amounts of sodium boro[2H + 1H]hydride and ketone 64 used in the test reaction were equal to 1.963 mmoles and 2.0 mmoles, respectively. After complete reduction of ketone 64 and of the cyclization of chlorohydrin 65 to epoxide 66, the integration of the multiplet centred at 5 3.44 in the JH NMR spectrum of the obtained mixture of the [JH]- and [2H]-epoxides, corresponding to the 2-H of the side chain, showed that this mixture contained 61% of [1H]-epoxide and 39% [2H]-epoxide. Neglecting the fractionation of deuterium between C(2)—H and O—H bonds the observed (61%/39% = 1.564) ratio (at hydride conversion equal to about 0.5) leads to / 1.9. Therefore, to minimize the losses of 3H the excess of 64 has been treated witn NaB[3H]4, followed after a short period by addition of excess of NaBJH4 to... 

Manganese (III) acetate or chloride salts [Mn30(0Ac) H0Ac, MnCb] can react with alkenes to afford 1,2-dichlorides and chlorohydrin acetates (equation 16). i The manganese(III) reagent promotes the chlorination of 1,6-heptadiene (42) to afford almost equal amount of open chain and cycliz dichlorides... 

Reactions with Nucleophiles. The epoxide is, by far, the more reactive site and a wide variety of nucleophiles have been used (eq 2) to open the ring at C-3 such as HCl (96%), HOAc (>50%), H2S (65% as cyclized product 3-thietanol), HCN (66%), ethanol (90%), t-butanol (86%), phenyl or benzyl thiol (99% or 93%, respectively), and phenyl selenide (generated in situ from the diselenide and sodium hydroxymethyl sulfite) (>55%). If desired, the epoxide is easily formed from the chlorohydrin by treatment with excess KOH or Et3N. 

Finally, mention may be made of those articles in which this method is utilized in the synthesis of optically active oxiranes for example, the simple synthesis of monosubstituted (S)-oxiranes and the asymmetric cyclization of some chlorohydrins catalyzed by optically active cobalt (salen)-type complexes, or in the enantiomeric selection of racemic oxiranes via halohydrins and /3-hydroxy sulfides. A useful three-step synthesis has been worked out from (S)-amino acids to (R)-alkyloxiranes as well as enantiomer resolution for chiral oxiranes by complexation gas chromatography. ... 

In an interesting application of Lewis acid-mediated oxirane ring openings, diazomethyl-chlorohydrins, formed from a,/ -epoxy diazomethylketones with SnCl4, cyclize to 3-oxetanones (Scheme 15) <92T9985>. 

The rate of reaction of chlorine with propylene is much slower, though 7-8% by weight propylene chloride (1,2-dichloropropane) is also formed. In a second stage the propylene chlorohydrin is contacted with lime slurry in water, which cyclizes the chlorohydrin to the epoxide (Eq. 19.46). 

A macrocyclic dibenzobisamide system has also been studied. A bisamide-containing bis-phenol was first prepared quantitatively from a benzolactone and ethylenediamine. This bis-phenol was cyclized in 12-16% yields with either a glycol dichloride or a chlorohydrin (method T-7) (Ashby et al., 1974). 

In two separate routes the aminoepoxides were obtained by highly stereoselective methods. Chlorination of iV -benzoylquinotoxine (5) with iV -chlorodiisopropylamine in 100% phosphoric acid in the dark gave an amorphous mixture of the epimeric a-chloroketones 85 and 86 (Scheme 8) [10). Reduction with sodium borohydride or with lithium tri-i-butoxyaluminum hydride afforded stereoselectively a mixture of the threo chlorohydrins 87 and 88. Treatment of 87 and 88 with aqueous potassium hydroxide at 20°C gave smoothly a mixture of the erythro iV-benzoylepoxides 89 and 90. The benzoyl groups were removed reductively with diisobutylaluminum hydride to give the aminoepoxides 81 and 82 which were cyclized in refluxing toluene-methanol (100 1). This reaction yielded 9-ep -quinine (12) and 9-epi-quinidine (13) in a ratio of 2 1. The overall yield of 12 and 13 from 87 and 88 was 50%. Only traces of the erythro products quinine and quinidine were observed. 

Synthesis of Oxirans by Halohydrin Cyclizations and Related Reactions. One of the oldest commercial methods for the production of ethene oxide is the chlorohydrin route, involving chlorohydration of ethene followed by dehydrochlorination. An improved procedure for the second stage of this process has been reported in which a basic ion-exchange resin is used to... 

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