Nitriles reaction with epoxides

Epoxides also participate in the Ritter reaction with nitriles. An investigation of the ring opening of several alkyl-substituted glycidic esters and amides 181 showed that this transformation occurs with inversion and is completely regiospecific. ° Esters appeared to be somewhat more reactive than amides. However, phenyl-substituted glycidic esters and amides 184 are almost totally nonstereoselective. In addition, the oxazolines 186 are isolated in low yield due to the propensity of intermediate 185 to generate an aldehyde byproduct 187 (Scheme 8.53). 

The reactions of Grignard reagents with aldehydes and ketones give alcohols, reaction with acid chlorides and esters give tertiary alcohols, reaction with carbon dioxide to give carboxylic acids, reaction with nitriles give ketones, and reaction with epoxides give alcohols. 

The zwitterion (6) can react with protic solvents to produce a variety of products. Reaction with water yields a transient hydroperoxy alcohol (10) that can dehydrate to a carboxyUc acid or spHt out H2O2 to form a carbonyl compound (aldehyde or ketone, R2CO). In alcohoHc media, the product is an isolable hydroperoxy ether (11) that can be hydrolyzed or reduced (with (CH O) or (CH2)2S) to a carbonyl compound. Reductive amination of (11) over Raney nickel produces amides and amines (64). Reaction of the zwitterion with a carboxyUc acid to form a hydroperoxy ester (12) is commercially important because it can be oxidized to other acids, RCOOH and R COOH. Reaction of zwitterion with HCN produces a-hydroxy nitriles that can be hydrolyzed to a-hydroxy carboxyUc acids. Carboxylates are obtained with H2O2/OH (65). The zwitterion can be reduced during the course of the reaction by tetracyanoethylene to produce its epoxide (66). 

Other modifications of the polyamines include limited addition of alkylene oxide to yield the corresponding hydroxyalkyl derivatives (225) and cyanoethylation of DETA or TETA, usuaHy by reaction with acrylonitrile [107-13-1/, to give derivatives providing longer pot Hfe and better wetting of glass (226). Also included are ketimines, made by the reaction of EDA with acetone for example. These derivatives can also be hydrogenated, as in the case of the equimolar adducts of DETA and methyl isobutyl ketone [108-10-1] or methyl isoamyl ketone [110-12-3] (221 or used as is to provide moisture cure performance. Mannich bases prepared from a phenol, formaldehyde and a polyamine are also used, such as the hardener prepared from cresol, DETA, and formaldehyde (228). Other modifications of polyamines for use as epoxy hardeners include reaction with aldehydes (229), epoxidized fatty nitriles (230), aromatic monoisocyanates (231), or propylene sulfide [1072-43-1] (232). 

Insertion of phenyl, trimethylsilyl, and nitrile-stabilized metalated epoxides into zircona-cyclcs gives the product 160, generally in good yield (Scheme 3.37). With trimethylsilyl-substituted epoxides, the insertion/elimination has been shown to be stereospecific, whereas with nitrile-substituted epoxides it is not, presumably due to isomerization of the lithiated epoxide prior to insertion [86]. With lithiated trimethylsilyl-substituted epoxides, up to 25 % of a double insertion product, e. g. 161, is formed in the reaction with zirconacyclopentanes. Surprisingly, the ratio of mono- to bis-inserted products is little affected by the quantity of the carbenoid used. In the case of insertion of trimethylsilyl-substituted epoxides into zirconacydopentenes, no double insertion product is formed, but product 162, derived from elimination of Me3SiO , is formed to an extent of up to 26%. 

Cleavage of epoxidesThe aiiion (2) of 1 reacts with carbonyl compounds to give a,/(-unsaturated nitriles and LiOSi(CH3)3, as expected.2 The reaction with epoxides is unexpected the products are y-trimethylsilyloxynitriles, which are useful precursors to -/-lactones (equation I). The formulation indicates that a 1,4-migration of the trimethylsilyl group is involved.2... 

Scheme 5.9 shows a possible mechanism for this epoxidation reaction. First, H202 reacts with a base site on the HT surface to form a HOO species, which attacks a nitrile to generate peroxycarboximidic acid as an active intermediate oxidant. The oxygen of the peroxycarboximidic acid is transferred to an olefin molecule. Interestingly, the resulting amide can be further employed for the epoxidation of olefins in the presence of a HT catalyst [44b]. 

Epoxides react with cyanide under basic reaction conditions to yield 3-hydroxypro-pionitriles by nucleophilic attack at the sterically less demanding carbon atom (Scheme4.86). Me3SiCN can also be used as reagent, but trimethylsilyl ethers will be the main products. With some types of epoxide (e.g. styrene oxide [372]) the products readily dehydrate to yield ,/i-unsaturated nitriles [373] (Scheme4.86). 

Under acidic reaction conditions the formation of isonitriles can compete efficiently with nitrile formation (Scheme 4.87) [377]. Particularly effective reagents for the formation of isonitriles are mixtures of Me3SiCN with Lewis acids such as Zn(II), Pd(II), or Sn(II) salts. Aluminum-derived Lewis acids with Me3SiCN, on the other hand, mediate the conversion of epoxides into nitriles [378, 379]. 

Under alkaline conditions, H202 produces perhydroxide anion, which playing the role of the intermediate substance epoxidizes a-unsaturated ketones and interacts with nitriles giving amides and 02 [59], In the two latter cases, the perhydroxide anion helps in setting the inter-reaction communication required for conjugation. 

Oxazolines.1 Reaction of 1,1-disubstituted epoxides with nitriles and SiF4 (1 equiv.) provides fluorohydrins, which oti further exposure to SiF4 are converted into 2-oxazolines, in which the nitrogen is attached to the substituted carbon. In the example cited, the yield is increased to 81% from reactions conducted at 80°. 

Alkyl halides (particularly bromides) undergo oxidative addition with activated copper powder, prepared from Cu(I) salts with lithium naphthalenide, to give alkylcopper species10. The alkyl halides may be functionalized with ester, nitrile and chloro functions ketone and epoxide functions may also be tolerated in some cases11. The resulting alkylcopper species have been shown to react efficiently with acid chlorides, enones (conjugate addition) and (less efficiently) with primary alkyl iodides and allylic and benzylic bromides (equations 5 and 6). If a suitable ring size can be made, intramolecular reactions with epoxides and ketones are realized. 

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