Epoxide formation, from chlorohydrin

Epoxide formation from chlorohydrins is marked by an increase in rate with alkyl substitution (28) as shown in Figure 1. This phenomenon has been explained on the basis that steric crowding ia the chlorohydrin is somewhat reheved as the epoxide is formed, so that the greatest rehef of strain results from ring closure of the most crowded chlorohydrin (28). 

The alkyl groups generally favour ring closure, atleast in small and common rings as will be clear from epoxide formation from chlorohydrins in basic medium as illustrated below ... 

As was illustrated in the first survey, all known halogenated terrestrial diterpenes are chlorohydrins (1), and that continues to be mainly the case. Obviously, one must be alert to the possibility of artifact formation from ring opening of the corresponding epoxide during isolation. Many nonhalogenated terrestrial diterpenoids also continue to be isolated (622). 

The mechanism of dehydrohalogenation under basic conditions of trons-fused bicyclo[4,n,0]alkane halohydrins (563)—(565) has been studied. Three reaction types are noted (i) epoxide formation, (ii) ketone formation, and (iii) ring contraction. trans-Diaxial chlorohydrins corresponding to (563)—(565) gave epoxides (566)—(568) with relative rates (derived from bimolecular rate constants) of 1 3 17. This rate sequence was rationalized in terms of deformation of the cyclohexane ring brought about by the nature of the fused ring. In particular, deformation is probably towards the half-chair conformation favoured by the cyclohexane epoxide which is formed in the slow step. trans-Diequatorial chlorohydrins represented by (563)—(565)... 

The disadvantage of the chlorohydrin process is the use of toxic, corrosive, and expensive chlorine the major drawback of the peroxide process is the formation of co-oxidates in larger amounts than the desired PO. The direct epoxidation of propylene using 02 (i.e., partial oxidation of propylene) from air has been recognized as a promising route. 

For 1,2-disubstituted epoxides, the regiochemical outcome of nucleophilic attack becomes less predictable. However, in the case of epoxy ethers chelation control can be used to deliver the nucleophile preferentially to the epoxide carbon away from the ether moiety. Thus, treatment of epoxy ether 61 with an imido(halo)metal complex, such as [Cr(N-t-Bu)Cl3(dme)], leads to the clean and high-yielding production of the chlorohydrin 64. The regioselectivity is rationalized in terms of initial formation of a chelated species (62), followed by attack at C-3 to form the more stable 5-membered metallacyclic alkoxide 63 <00SL677>. 

Formation of Acetylenic Epoxides from the Corresponding Chlorohydrines and KOH... 

Chiral alkenyl and cycloalkenyl oxiranes are valuable intermediates in organic synthesis [38]. Their asymmetric synthesis has been accomplished by several methods, including the epoxidation of allyl alcohols in combination with an oxidation and olefination [39a], the epoxidation of dienes [39b,c], the chloroallylation of aldehydes in combination with a 1,2-elimination [39f-h], and the reaction of S-ylides with aldehydes [39i]. Although these methods are efficient for the synthesis of alkenyl oxiranes, they are not well suited for cycloalkenyl oxiranes of the 56 type (Scheme 1.3.21). Therefore we had developed an interest in the asymmetric synthesis of the cycloalkenyl oxiranes 56 from the sulfonimidoyl-substituted homoallyl alcohols 7. It was speculated that the allylic sulfoximine group of 7 could be stereoselectively replaced by a Cl atom with formation of corresponding chlorohydrins 55 which upon base treatment should give the cycloalkenyl oxiranes 56. The feasibility of a Cl substitution of the sulfoximine group had been shown previously in the case of S-alkyl sulfoximines [40]. 

Cyclodehydration. The reaction of this reagent with 1,4-diols results mainly in cyclodehydration to tetrahydrofuranes. Extent of formation of cyclic ethers decreases in order of the ring sizes 5 > 6 > 4 = 7. The reaction with 1,2-diols or 1,3-diols results in chlorohydrins as the major products. If the reaction is conducted in the presence of solid K,CO, in CCI4 (reflux), epoxides become the major products formed from 1,2-diols. 

Synthesis of Epoxides from Chiral Chlorohydrins. Asymmetric halogenation of CSA-derived esters allows for the formation of enantiomerically pure halohydrins and terminal epoxides (eq 23). ... 

Compared to EO, propylene oxide (PO) is less reactive and less hazardous. PO is mainly used for the production of polyether, polyols, polyurethane, glycols, and ethers. Direct oxidation of propylene with air or pure oxygen is not efficient, and PO is produced either by the chlorohydrin process (46% share) or by indirect oxidation. Indirect oxidation of propylene proceeds in two steps. The first step is the formation of a peroxide from iso-butane or ethylbenzene by oxidation with air/oxy-gen (peroxides tert-butyl hydroperoxide and ethylbenzene hydroperoxide, respectively). The second step is the catalytic epoxidation of propylene to propylene oxide by oxygen transfer from the peroxide. In future, oxidation processes based on H2O2 will probably also play an important role. In 2008, the first commercial plant of this kind went on stream. 

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