Chlorohydrin direct synthesis

On the other hand, in the absence of TMSCl, almost quantitative starting material was recovered. The use of BTSP offers a useful method for direct synthesis of chlorohydrins as shown in equations 44 and 45 and in Table 10. 

New routes to hydrogen peroxide new methods for direct synthesis of hydrogen peroxide (from hydrogen and oxygen) in a controlled, safe manner could provide a lower cost oxidant that reduces the use of chlorine. For example, in situ generation of hydrogen peroxide can be used to produce propylene oxide in place of the chlorohydrin route and... 

Shibasaki et al. developed a method for the direct synthesis of chlorohydrins or 2-acetoxy alcohols from disubstituted olefins [41). Various kinds of chlorohydrins are prepared from the corresponding alkenes with bis(trimethylsilyl)peroxide (BTSP) and chlorotrimethylsilane (TMSCl) in the presence of the catalyst (SnCU or (SnO) ). It is worth noting that 2-acetoxy alcohols could be obtained under similar reaction conditions using trimethylsilyl acetate (TMSOAc) instead of TMSCl with the promotion of Zr(0 Pr)4 in place of SnCU (Scheme 10.20). 

Commerciol Dichlorohydrin consists of the above two isomers, the proportions of which depend on method of prepn d 1.36-1.39, bp 175-80°, flash p 74°, Glycerol was the main source for the prepn of glycerol chloro-hydrins until the process for direct substitutive chlorination of propylene to allyl chloride paved the way for synthesis by chlorohydrination of allyl chloride. In the synthesis from glycerol, excess HCI is used in the presence of 4% acetic acid. The reaction is run at 130° to yield 90% of product which is mainly the a,y-form. Synthesis from propylene yields a mixt of approx 70% a,/8-form 8c 30% a,y-form. Addn of HCI to epichlorohydrin, CH2 CHCH> Cl, at... 

Ethylene Chlorohydrin. Two industrial processes were used in the synthesis of ethylene chlorohydrin,182 191 which, in turn, was transformed to ethylene oxide. Since the direct oxidation of ethylene to ethylene oxide is more economical, these technologies are being abandoned. 

Another significant application of the concept of relay deprotection comes from a synthesis of the antitumour macrolides Cryptophycins 1 and 8.644 The penultimate step required a mild method for the introduction of the epoxide ring in the side chain [Scheme 4.340]. A variant of a direct method for the conversion of diols to epoxides developed by Kolb and Sharpless645 was cleverly adapted to the case at hand. Thus diol 340.1 was treated with the 4-azido-1 1,1-tri-methoxybutane in the presence of chlorotrimethylsilane to give the cyclic orthoester 340.2, which decomposed under the reaction conditions with loss of Me SiOMe to give the chlorohydrin ester 3403 (inversion). Selective reduction... 

Asymmetric reduction of or y-functionalized alkyl aryl ketones provides a wide variety of chiral amino alcohols. Commercial -chloropropiophenone is reduced with borane-tetrahydrofuran adduct catalyzed by oxazaborolidine 45 to provide the chlorohydrin in over 99 % yield with 94 % ee. The resulting alcohol is a key intermediate for synthesis of the R form of fluoxetine (Prozac ), a serotonin-uptake inhibitor [53]. Using hydrogenation processes the functionalized amino ketones are converted directly into the respective products [8, 43e],... 

The catalyzed hydrocyana a stable (salen)aluminum c BUjSnCN. It is important to An asymmetric synthesi A -(benzyloxyiminoacety 1 )-bi Mo(CO) and LiOH sequenti Addition of allylmetals t directly attached to the yyn-chlorohydrins and anti-via two oxygen atoms and th useful for the synthesis of < en-4-ols, respectively. (-)-Sx A chiral reagent derived f tartrate reacts with aromahe alcohols sometimes in excel been conducted in the presei. Allylsilanes modified by a tai... 

Reduction of iodohydrins. In Cornforth s stereospecific synthesis of a cis or irons olefin, an intermediate is a chlorohydrin of predictable configuration which cannot be reduced directly to the olefin. The conversion is accomplished by three strictly stereospeciflc steps formation of the epoxide, cleavage with HI (Nal—AcOH—EtCOgH), and reduction of the resulting iodohydrin with stannous chloride, phosphoryl chloride, and pyridine. 

Ethylene chloride is not isolated directly since an azeotrope (b.p. 97.8°) of the chlorohydrin (42.5 %) and water distils from the reaction mixture. Instead, calcium hydroxide is added, the resulting alkaline medium causing formation of ethylene oxide (b.p. 10.7°) which can be easily separated. This is then led, together with the equivalent amount of HC1, into preformed ethylene chlorohydrin, whereupon ethylene chlorohydrin (b.p. 128.7°/760 mm) is formed quantitatively. For a synthesis of ethylene bromohydrin see McDowell.270... 

To complete the synthesis, the required 13a,17a-epoxide 187 was best obtained via the chlorohydrin 186 (and/or the isomeric 13a-hydroxy-17P-chloro structure) rather than by direct epoxidation, which gave mainly the -epoxide. Boron trifluoride catalyzed rearrangement of 187 then gave ( )-estrone 26 in 22% overall yield from 182 (R = H). 

Propylene is the starting material for the commercial propylene oxide synthesis. Direct oxidation only provides low yields, consequently the propylene is stoichiometrically oxidized with hydroperoxides such as /-butyl hydroperoxide or a-methyl benzyl hydroperoxide. Alternatively, hydrogen chloride can be eliminated from propylene chlorohydrin, CHa—CH(OH)—CH2CI. 

Propene oxide (methyl oxirane) is used on a large scale for the production of polyurethanes and is usually made using a chlorohydrin process. A greener alternative would be to use the direct gas-phase synthesis of methyloxirane from propene, using molecular oxygen in the presence of... 

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