Bromohydrin

Several cortisone derivatives with glucocorticoid effects are most active, if they contain fluorine in the 9or-position together with an Il(9-OH group. Both substituents are introduced by the cleavage of a 9,11 -epoxide with hydrogen fluoride. The regio- and stereoselective formation of the -epoxide is achieved by bromohydrination of a 9,11-double bond and subsequent alkali treatment (J. Fried, 1954). 

FIGURE 6 13 Mechanism of bromohydrin formation from cyclopentene A bridged bromonium ion is formed and is attacked by a water molecule from the side opposite the carbon-bromine bond The bromine and the hydroxyl group are trans to each other in the product... 

Begin by asking the question What kind of compound is the target molecule and what methods can I use to prepare that kind of compound The desired product has a bromine and a hydroxyl on adjacent carbons it is a vicinal bromohydrin The only method we have learned so far for the preparation of vicinal bromohydrms involves the reaction of alkenes with Bi2 m water Thus a reasonable last step is... 

Branched chain carbohydrate (Section 25 12) Carbohydrate in which the main carbon chain bears a carbon substituent in place of a hydrogen or hydroxyl group Bromohydrin (Section 6 17) A halohydnn in which the halo gen IS bromine (see halohydnn)... 

Bromohydrins can be prepared direcdy from polyhydric alcohols using hydrobromic acid and acetic acid catalyst, followed by distillation of water and acetic acid (21). Reaction conditions must be carehiUy controlled to avoid production of simple acetate esters (22). The raw product is usually a mixture of the mono-, di-and tribromohydrins. 

Electrochemical Process. Applying an electrical current to a brine solution containing propylene results in oxidation of propylene to propylene oxide. The chemistry is essentially the same as for the halohydrin process. AH of the chemistry takes place in one reactor. Most of the reported work uses sodium or potassium bromide as the electrolyte. Bromine, generated from bromide ions at the anode, reacts with propylene and water to form propylene bromohydrin. Hydroxide generated at the cathode then reacts with the bromohydrin to yield propylene oxide (217—219). The net reaction involves transfer of two electrons ... 

In the olivanic acid series of carbapenems the ( )-acetamidoethenyl grouping can be isomerised to the (Z)-isomer (19) (22) and reaction with hypobromous acid provides a bromohydrin that fragments to give a thiol of type (20) when R = H, SO H, or COCH. The thiol is not isolated but can react to provide new alkyl or alkenyl C-2 substituents (28). In the case of the nonsulfated olivanic acids, inversion of the stereochemistry at the 8(3)-hydroxyl group by way of a Mitsunobu reaction affords an entry to the 8(R)-thienamycin series (29). An alternative method for introducing new sulfur substituents makes use of a displacement reaction of a carbapenem (3)-oxide with a thiol (30). Microbial deacylation of the acylamino group in PS-5 (5) has... 

Note 8). After two distillations the fraction boiling at 55-59°/22 mm. (Note 9) is pure ethylene bromohydrin. The yield is 327-345 g. (S7-92 per cent of the theoretical amount). 

When the bromohydrin is removed by the first treatment with ether, the ethereal layer is on the bottom. Subsequent ethereal extractions float on the aqueous layer. 

Ethylene bromohydrin has been prepared by the reaction between ethylene glycol and hydrobromic acid and phosphorus tribromide. It has also been prepared by the direct addition of hypobromous acid to ethylene, and by the reaction between ethylene and dilute bromine water. With ethylene oxide now available at a reasonable price, the method described is probably the best because of the high yields and the convenience of reaction. 

The presence of an a-bromo substituent may cause anomalies. With NaBH4, 2a-bromo-5a-cholestan-3-one gives a mixture of epimers, in which the 3p-o predominates. 4 -Bromo-17)5-hydroxy-5)5-androstan-3-one acetate gives 25% of the 315,4 -bromohydrin and 34% of the 3a,4)5-compound. Reduction of 7a-bromo-3)5,5a-diacetoxycholestan-6-one gives exclusively 7a-bromocholestane-3)5,5a,6a-triol 3,5-diacetate,whereas reduc-... 

The reductive elimination of halohydrins provides a means of introduction of double bonds in specific locations, particularly as the halohydrin may be obtained from the corresponding a-halo ketone. This route is one way of converting a ketone into an olefin. (The elimination of alcohols obtainable by reduction has been covered above, and other routes will be discussed in sections IX and X.) An advantage of this method is that it is unnecessary to separate the epimeric alcohols obtained on reduction of the a-bromo ketone, since both cis- and tran -bromohydrins give olefins (ref. 185, p. 251, 271 cf. ref. 272). Many examples of this approach have been recorded. (For recent examples, see ref. 176, 227, 228, 242, 273.) The preparation of an-drost-16-ene (123) is illustrative, although there are better routes to this compound. 

The pure olefin is best prepared via the bromohydrin (131) a more direct route from the tosylate (129) yields a mixture of (132) and its A -isomer. The indirect method is most suitable for preparing A -olefins in the 5jS-series. 

The formation of a bromohydrin via the addition of hyprobromous acid to olefins complements the above mentioned route. This reagent adds to the double bond in a tm/w-diaxial manner, the addition being initiated by the attack of a positive bromonium ion from the less hindered side. The... 

A variety of conditions has been used to prepare oxiranes from trans-hxomo-hydrins. In general, bromohydrins are heated in a solution of 5-10% methanolic potassium hydroxide for 30 min to 8 hr. Longer reflux times are required for bromohydrins which are not anti-coplanar, e.g., diequatorial bromohydrins. A 5 % solution of potassium acetate in boiling ethanol can be used to cyclize steroidal bromohydrins containing base sensitive groups. The use of 1.1 equivalents of sodium methoxide per equivalent of steroid in methanol solution is especially recommended for 9a-bromo-l lj5-hydroxy steroids. 

Selectivity between A -olefins and other double bonds can often be excellent S-keto-A, A and A systems are relativelyunreactive, and functional groups at C-21 e.g., OH, OAc) or at C-20 e.g., CN, Br) normally do not interfere. With functional groups at C-20, the final products are 20-ketones rather than 20-aIcohols, the intermediate bromohydrin or cyanohydrin cleaving during workup to the ketone. 

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