Anti-chlorohydrin

Another example of the reduction of a-chloroketone involves dynamic kinetic resolution. The reduction of an a-chloroketo ester by M. racemosus and R. glutinis resulted in optically active syn- and anti-chlorohydrin, respectively, as shown in... 

HOCHj CHjOH. Colourless, odourless, rather viscous hygroscopic liquid having a sweet taste, b.p. 197 C. Manufactured from ethylene chlorohydrin and NaHC03 solution, or by the hydration of ethylene oxide with dilute sulphuric acid or water under pressure at 195°C. Used in anti-freezes and coolants for engines (50 %) and in manufacture of polyester fibres (e.g. Terylene) and in the manufacture of various esters used as plasticizers. U.S. production 1979 1 900 000 tonnes. 

CH3 CH0H CH20H, a colourless, almost odourless liquid. It has a sweet taste, but is more acrid than ethylene glycol b.p. 187. Manufactured by heating propylene chlorohydrin with a solution of NaHCO under pressure. It closely resembles dihydroxyethane in its properties, but is less toxic. Forms mono-and di-esters and ethers. Used as an anti-freeze and in the preparation of perfumes and flavouring extracts, as a solvent and in... 

Nitroimidazoles substituted by an aromatic ring at the 2-position are also active as antitrichomonal agents. Reaction of p-fluorobenzonitrile (83) with saturated ethanolic hydrogen chloride affords imino-ether 84. Condensation of that intermediate with the dimethyl acetal from 2-aminoacetaldehyde gives the imidazole 85. Nitration of that heterocycle with nitric acid in acetic anhydride gives 86. Alkylation with ethylene chlorohydrin, presumably under neutral conditions, completes the synthesis of the anti-... 

The principle of the method is that once a substance crystallizes, the interconversion of the various conformers stops and so the crystals correspond to one discrete conformation or another. This has established, that 1,2-dichloroethane crystallises exclusively in the anti form, while ethylene chlorohydrin crystallizes in a gauche form because of intra molecular hydrogen bonding. But when the molecule crystallizes in two or more conformations, we say that it shows polymorphism. 

A related allenylzinc reagent was prepared by the addition of LDA to a solution of trimethylsilylpropargyl chloride and ZnBr2 in THF at -78°C (Eq. 9.128) [107], Anti propargylic chlorohydrins adducts were obtained when aldehydes were allowed to react with this reagent. Subsequent treatment with DBU gave the alkynyloxiranes (Eq. 9.129). 

The reaction of sulfoximine 6 with ClC02CH(Cl)Me proceeded readily and gave, besides 54, the chlorohydrins 57, as mixtures of the anti and syn diastereo-mers in ratios of 78 22 and 73 27, respectively, in good yields. Treatment of the mixture of chlorohydrins with DBU furnished oxiranes 58 as mixtures of trans and as isomers in ratios of 78 22 and 73 27, respectively, in good yields. 

Resin 60 was successively treated at -78 °C with n-BuLi, ClTi(NEt2)3, and benz-aldehyde in THF to afford the polymer-bound homoallyl alcohol 61. The cleavage of the linker group of 61 was achieved through treatment with ClC02CH(Cl)Me in CH2CI2 at room temperature. Thereby a mixture of chlorohydrins syn-57 and anti-57 in a ratio of 2 1 was obtained. These chlorohydrins were treated with DBU, which gave oxiranes trans-SS and cis-58 in a ratio of 2 1 in an overall yield of 34% based on sulfoximine 12. 

Cklorohydrins. Chloramine-T reacts with olefins in an acidic medium to form chlorohydrins in 40 75% isolated yield. The reaction involves a /ran.v-addition Terminal olefins give a mixture of Markovnikov and anti-Markovnikov adducts in a ratio of 4 1. ... 

Hypochlorous acid and hypobromous acid react with acyclic alkenes to give Mar-kovnikov products. In striking contrast, exclusive anti-Markovnikov orientation was observed in the transformation of methylenecycloalkanes with HOBr, and mixtures of chlorohydrins were formed with HOC1 146... 

A convenient synthesis of chlorohydrins is based on the use of Chlorine T (TosNCINa) as the positive chlorine source in water-acetone.147 It adds to a variety of alkenes to form Markovnikov and anti-Markovnikov products in a ratio of 4 1. 

One further point. We have encountered the two-step addition of unsym-metrical reagents in which the first step is attack by positive halogen formation of halohydrins (Sec. 6.14), and ionic addition of IN3 and BrN3 (Problem 7, p. 247). The orientation is what would be expected if a carbonium ion were the intermediate. Propylene chlorohydrin, for example, is CH3CHOHCH2CI IN3 adds to terminal alkenes to yield RCH(N3)CH2l. Yet the exclusively anti stereochemistry... 

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... 

Another investigation (equation 9.19), reported by Backvall and Akermark,53 described an anti attack on a fram-dideuterioethylene Pd complex. In the presence of high concentrations of Cu(II) and Cl , the final product after oxidative cleavage (Section 8-4-1) was the chlorohydrin, 25, rather than the aldehyde. Treatment of the chlorohydrin with base gave dideuterioethylene oxide, 26, in which the two deuterium atoms were cis. This result is again consistent with attack by an external nucleophile. 

A stereochemical study reported by Henry illustrated that the formation of aldehyde and formation of chlorohydrin occur with different stereochemistry, and this result implies that one process occurs by syn addition and one by anti addition of water and palladium across the olefin. This study is summarized in Scheme 16.24. Oxidation of the non-race-mic, chiral allyl alcohol in the absence of added chloride forms the (R)-(E)-alcohol, whereas reaction of the allyl alcohol in the presence of added chloride forms the product with stereochemistry resulting from the opposite mode of attack. Because it is known that the allylic alcohol binds to palladium with hydrogen bonding between the hydroxyl group and the bound chloride, Henry concluded that the reaction conducted in the presence of high concentrations of added diloride occurs by external attack of the oxygen nucleophile, while the reaction with low concentrations of added chloride occurs by insertion of the olefin into a Pd-0 bond. ... 

The next major project for the Industrial Testing Laboratory was an attempt to improve the process of making ethylene glycol from ethylene via the hydrolysis of ethylene chlorohydrin. In his attempt to produce this "anti-freeze" by hydrolysis of ethylene dichloride with sodium polysulfide, "Doc" Patrick obtained a gummy gunk which he named "Thiokol" based on the greek word theion (sulfur) and kommi (gum). 

The mystery becomes the reason for the anti stereochemistry observed at high chloride and cupric chloride concentrations, conditions for ethylene chlorohydrin formation. An examination of the early data of Stangl and lira provide a clue. Thus in Table 1 the data indicate that the chlorohydrin is formed only when both [CUCI2] and [Cr] concentrations are high. 

The creation of a bromonium ion in alkene brominations suggests that, in the presence of other nucleophiles, competition might be observed in the trapping of the intermediate. For example, bromination of cyclopentene in water as solvent gives the vicinal bromoalcohol (common name, bromohydrin). In this case, the bromonium ion is attacked by water, which is present in large excess. The net transformation is the anti addition of Br and OH to the double bond. The other product formed is HBr. The corresponding chloroalcohols (chlorohydrins) can be made from chlorine in water through a chloronium ion intermediate. 

Umani-Ronchi adapted the Furstner protocol to achieve the first catalytic, enantioselective variant of this reaction. The chiral chromium salen complex was prepared from the in situ reduction of the anhydrous CrCb to CrCl2 with an excess of manganese metal, followed by complexation with the salen ligand 8 in the presence of catalytic triethylamine." Then the addition of allylic chloride (9) to aldehydes 10 to give the allylic alcohols 11 in moderate yields and in up to 95% ee. The same groups employed the same conditions for the addition of 2-butenyl bromides to aldehydes to achieve up to 83 17 syn/anti of allylic alcohol products and for the addition of 1,3-dichloropropene to aromatic aldehydes to obtain the syn chlorohydrin adduct in modest yield which were further converted to optically active vinyl epoxides. The [Cr(salen)]-catalyzed addition of propargyl halides to aromatic aldehydes allowed the synthesis of enantiomerically enriched homopropargyl alcohols in moderate yields with up to 56% ee. ... 

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