Nitriles unsaturated addition

F. F. Fleming, Q. Wang, Unsaturated Nitriles Conjugate Additions of Carbon Nucleophiles to a Recalcitrant Class of Acceptors, Chem. Rev. 2003, 103, 2035-2077. 

The ease of reaction depends both on the CH acidity of the addend and on the polarizability of the ethylenic double bond of the acceptor. Thus, in general, only such compounds function as addend in which a methylene or methine group is activated by two neighboring carbonyl or nitrile groups, as, for example, in malonic esters, malonodinitrile, cyanoacetic esters, 1,3-dioxo compounds and 3-oxo carboxylic esters, and their monoalkyl substitution products. The ethylenic double bond of the acceptor is polarized by conjugation with a polar multiple bond, so that the olefinic component is usually an unsaturated ketone, an, / -unsaturated ester, or an, / -unsaturated nitrile. The addition is catalysed by bases such as potassium hydroxide solution, sodium ethoxide, and amines. 

The introduction of a bromo atom into the a-position of an unsaturated ketone or carbonyl group, in general, inverts the nitrile oxide addition completely, and a Michael addition to the activated double bond of aUene 355 directs the subsequent cycloaddition into the p,y-double bond generating adduct 358, which cannot be obtained from 355 directly [125aj. 

However, the term saturated is often applied to compounds containing double or triple bonds which do not easily undergo addition reactions. Thus ethanoic acid is termed a saturated carboxylic acid and acetonitrile a saturated nitrile, whereas a Schiff base is considered to be unsaturated. 

The addition of active methylene compounds (ethyl malonate, ethyl aoeto-acetate, ethyl plienylacetate, nltromethane, acrylonitrile, etc.) to the aP-double bond of a conjugated unsaturated ketone, ester or nitrile In the presence of a basic catalyst (sodium ethoxide, piperidine, diethylamiiie, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields trlcarballylic acid ... 

One development involves the use of vitamin B 2 to cataly2e chemical, in addition to biochemical processes. Vitamin B 2 derivatives and B 2 model compounds (41,42) cataly2e the electrochemical reduction of alkyl haUdes and formation of C—C bonds (43,44), as well as the 2inc—acetic acid-promoted reduction of nitriles (45), alpha, beta-unsaturated nitriles (46), alpha, beta-unsaturated carbonyl derivatives and esters (47,48), and olefins (49). It is assumed that these reactions proceed through intermediates containing a Co—C bond which is then reductively cleaved. 

Because nitrile rubber is an unsaturated copolymer it is sensitive to oxidative attack and addition of an antioxidant is necessary. The most common practice is to add an emulsion or dispersion of antioxidant or stabilizer to the latex before coagulation. This is sometimes done batchwise to the latex in the blend tank, and sometimes is added continuously to the latex as it is pumped toward further processing. PhenoHc, amine, and organic phosphite materials are used. Examples are di-Z fZ-butylcatechol, octylated diphenylamine, and tris(nonylphenyl) phosphite [26523-78-4]. All are meant to protect the product from oxidation during drying at elevated temperature and during storage until final use. Most mbber processors add additional antioxidant to their compounds when the NBR is mixed with fillers and curatives in order to extend the life of the final mbber part. 

The two major methods of preparation are the cycloaddition of nitrile oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamines. Additional methods include reaction of /3-haloketones and hydroxylamine, the reaction of ylides with nitrile oxides by activation of alkyl nitro compounds from isoxazoline AT-oxides (methoxides, etc.) and miscellaneous syntheses (62HC(i7)i). 

Powdered potassium permanganate (94 mg) is added to an ice-cold, stirred solution of 0.1 g of the unsaturated nitrile in 3.5 ml of acetone containing 0.11 ml of piperidine. The reaction mixture is stirred at 0° for 1.5 hr, allowed to warm to room temperature (30 min) and then treated with 0.02 ml of acetic acid in 0.2 ml of acetone. After stirring at room temperature for an additional 1.5 hr the mixture is treated with chloroform, aqueous sodium bisulfite and sufficient 1 N sulfuric acid to reduce all of the manganese dioxide. 

Among the most successful classes of asymmetric acyl anion equivalents are the dioxane-containing a-amino nitriles 99 introduced by Enders and coworkers. These are deprotonated by EDA, and the resulting anions act as efficient equivalents of RCO for addition to a, (3-unsaturated esters [90AG(E)179],... 

Recently, the Michael addition of the optically active Q ,y-disubstituted tetronic acids 146c,e with a variety of Q ,/3-unsaturated aldehydes, ketones, esters, and nitriles was studied (Scheme 53) (99H1321). 

Enamines react with acceptor-substituted alkenes (Michael acceptors) in a conjugate addition reaction for example with o ,/3-unsaturated carbonyl compounds or nitriles such as acrylonitrile 8. With respect to the acceptor-substituted alkene the reaction is similar to a Michael addition ... 

Formal oxidation of pyrrolidine to the succinimide stage affords a series of compounds used as anticonvulsant agents for treatment of seizures in petit mal epilepsy. Knoevnagel condensation of benzaldehyde with ethyl cyanoacetate affords the unsaturated ester, 9. Conjugate addition of cyanide ion leads to the di-nitrile ester (10). Hydrolysis in mineral acid affords the succinic acid (11), presumably by decarboxylation of the intermediate tricarboxyllie acid. Lactamization with methylamine gives phensuximide (12). ... 

The titanium(IV) chloride catalyzed addition of allylic silanes to (E)-(2-nitroethenyl)benzene affords y,<5-unsaturated nitronates which, on treatment with low valent titanium species [generated in situ from titanium(IV) and zinc], give y,<5-unsaturated nitriles. For example, [(Zs)-2-butenyl]-(dimethyl)phenylsilane underwent reaction with ( )-(2-nitroethenyl)benzene to give 3-methyl-2-phenyl-4-pentenenitrile in 65 % yield as a 3 1 mixture of diastereomers of unassigned configuration22. 

The catalytic conditions (aqueous concentrated sodium hydroxide and tetraalkylammonium catalyst) are very useful in generating dihalo-carbenes from the corresponding haloforms. Dichlorocarbene thus generated reacts with alkenes to give high yields of dichlorocyclopropane derivatives,16 even in cases where other methods have failed,17 and with some hydrocarbons to yield dicholromethyl derivatives.18 Similar conditions are suited for the formation and reactions of dibromocar-benc,19 bromofluoro- and chlorofluorocarbene,20 and chlorothiophenoxy carbene,21 as well as the Michael addition of trichloromethyl carbanion to unsaturated nitriles, esters, and sulfones.22... 

There is generally little or no competition from 1,2 addition (to the C=0). However, when R is allylic,l,4 addition is observed with some substrates and 1,2 addition with others. The compound R2CuLi also add to a,P-unsaturated sulfones but not to simple aP-unsaturated nitriles. Organocopper reagents RCu (as well as certain R2CuLi) add to ocP-unsaturated and acetylenic sulfoxides. ... 

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