A-Epoxides

Although acetonitrile is one of the more stable nitriles, it undergoes typical nitrile reactions and is used to produce many types of nitrogen-containing compounds, eg, amides (15), amines (16,17) higher molecular weight mono- and dinitriles (18,19) halogenated nitriles (20) ketones (21) isocyanates (22) heterocycles, eg, pyridines (23), and imidazolines (24). It can be trimerized to. f-trimethyltriazine (25) and has been telomerized with ethylene (26) and copolymerized with a-epoxides (27). 

Medroxyprogesterone acetate (74) is stmcturaHy related to and has been prepared from hydroxyprogesterone (39) (Fig. 10). Formation of the bis-ketal accomplishes the protection of the ketones and the required migration of the double bond. Epoxidation with peracetic acid produces a mixture of epoxides (75), with a predominating. Treatment of the a-epoxide with methyl magnesium bromide results in diaxial opening of the epoxide. Deprotection of the ketones provides (76), which is dehydrated to (77) by treatment with dilute sodium hydroxide in pyridine. Upon treatment with gaseous hydrochloric... 

Mention has already been made of epoxide stabilisers. They are of two classes and are rarely used alone. The first class are the epoxidised oils, which are commonly employed in conjunction with the cadmium-barium systems. The second class are the conventional bis-phenol A epoxide resins (see Chapter 22). Although rarely employed alone, used in conjunction with a trace of zinc octoate (2 parts resin, 0.1 part octoate) compounds may be produced with very good heat stability. 

Heat aging resistance does not appear to be as good as with the bis-phenol A epoxide but outdoor weathering is said to be superior. 

The immediate product of opening of the a-epoxide (160) is the chlorohydrin (161) which slowly eliminates to give the olefin. In contrast, the epimeric chlorohydrin (165) formed from the jS-epoxide (164) eliminates spontaneously to give the same product (162). This difference is explicable by the known enolization preferences of 5oc- and 5/3-3-ketones. 

In general, epoxidation of steroids with trans-anti-trans ring fusions leads to exclusive formation of the a-oxirane. Steroid Reactions lists examples of exclusive a-epoxide formation from 2-, 4-, 6-, 7-, 8(9)-, 14-, 16- and 17(20)-unsaturated steroids. Further examples of a-epoxidation of steroid 1-enes, 3-enes, 8-enes, 9(ll)-enes, 8(14)-enes and 16-enes have been reported. The preferred attack by the reagent on the a-side of the steroid nucleus can be attributed to shielding of the -side of the molecules by the two angular methyl groups. 

Several steroid olefins, especially A -steroids, do not give exclusive a-epoxidation. The a-oxirane usually predominates in the epoxidation mixture, its proportion varying from 50% to 90% or greater when either perbenzoic acid or monoperphthalic acid is employed. The claims that the ratio of a- to p-epoxide is high in compounds containing a keto group d or a j5-substituent at may be misleading since epoxidation of 17a,20 20,... 

However, suitably located hydroxyl and acetoxyl functions can assist the cisoid approach of the peracid reagent. While 4jS-acetoxycholest-5-ene gives a 9 1 ratio of the a- and jS-epoxides, the 4a-acetoxy-5-ene yields the a-epoxide exclusively. The directive effect can be used to prepare and /9-oxiranes from A -steroids as illustrated by the epoxidation of (16) and (18). 

The alkaline epoxidation of A -3-ketones proceeds with variable stereoselectivity, although the -epoxide is usually the major product. Cholest-4-en-3-one (57) for example, gives almost exclusively the jS-oxirane. ° On the other hand, androst-4-ene-3,ll,17-dione (59) furnishes the a-epoxide in 86% yield. The yield of a-epoxide appears to vary with the distance by... 

Three possible mechanisms for the Serini reaction were originally suggested. These proceed via (a) a A -enol acetate, (b) a A -epoxide, or (c) a cyclic orthoester ... 

As with i -substituted allyl alcohols, 2,i -substituted allyl alcohols are epoxidized in excellent enantioselectivity. Examples of AE reactions of this class of substrate are shown below. Epoxide 23 was utilized to prepare chiral allene oxides, which were ring opened with TBAF to provide chiral a-fluoroketones. Epoxide 24 was used to prepare 5,8-disubstituted indolizidines and epoxide 25 was utilized in the formal synthesis of macrosphelide A. Epoxide 26 represents an AE reaction on the very electron deficient 2-cyanoallylic alcohols and epoxide 27 was an intermediate in the total synthesis of (+)-varantmycin. 

A cement slurry additive consisting of methylcellulose, melamine-formaldehyde resin, and trioxane has been proposed for better bonding of cement to the casing string [20]. Bisphenol-A epoxide resins, with amine-based curing agents, sand filler, and a mixture of n-butanol and dimethyl benzene as a diluent, have been proposed as additives to increase adhesion properties of cement [572]. 

Conditions Method A Epoxidation using Sharpless reagent method B addition of 0.05-0.1 equivalent of calcium hydride and 0.1-0.15 equivalent of silica gel to the Sharpless reagent, ee = Enantiomeric excess. 

A. Epoxide Ring Opening with Nonstabilized Organoiithium Reagents. . 1195... 

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