Unsaturated nitriles alkylation

By-Products. Almost all commercial manufacture of pyridine compounds involves the concomitant manufacture of various side products. Liquid- and vapor-phase synthesis of pyridines from ammonia and aldehydes or ketones produces pyridine or an alkylated pyridine as a primary product, as well as isomeric aLkylpyridines and higher substituted aLkylpyridines, along with their isomers. Furthermore, self-condensation of aldehydes and ketones can produce substituted ben2enes. Condensation of ammonia with the aldehydes can produce certain alkyl or unsaturated nitrile side products. Lasdy, self-condensation of the aldehydes and ketones, perhaps with reduction, can lead to alkanes and alkenes. 

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. 

Much of the early work into the rhodium(II)-catalysed formation of oxazoles from diazocarbonyl compounds was pioneered by the group of Helquist. They first reported, in 1986, the rhodium(II) acetate catalysed reaction of dimethyl diazomalonate with nitriles.<86TL5559, 93T5445, 960S(74)229> A range of nitriles was screened, including aromatic, alkyl and vinyl derivatives with unsaturated nitriles, cyclopropanation was found to be a competing reaction (Table 3). 

The oxime 299 is silylated in the presence of catalytic amounts of TMSOTf 20 to 300, which affords, via the Beckmann fragmentation intermediate 301 and alkylation with allyltrimethylsilane 82, 66% of the seco nitrile 302 [101, 102] (Scheme 4.39). Tris(trimethylsilyl) ketenimine 303 reacts with aldehydes such as benzaldehyde in the presence of Bp3-OEt2, via the aldol adduct 304, to give the unsaturated nitriles 305, in 99% yield, and HMDSO 7 [103]. 

Mention should also be made of the DuPhos-type hybrid 10 that works well for the reductions of itaconic acids [62]. A recent addition to the general class is trichickenfootphos (11) this has been developed for the reduction of enamides, dehydroamino acids and a,/ -unsaturated nitriles [63, 64]. (Throughout this chapter, R in generic structures denotes an alkyl group unless otherwise stated.)... 

This has been applied to the cyclization of dihalides [45, 46], nonconjugated, unsaturated ketones [47] and esters [48], oxoalkylpyridinium salts [49], aldehydes and unsaturated nitriles [50], halides, and unsaturated esters [51], The umpoled acceptors, mostly radical anions or carban-ions (see Scheme 1), can also be used in intermolecular reactions such as acylation, alkylation, or carboxylation (Eq. 5). 

Cyanomethyl)zinc bromide, BrZnCH2CN (1). The reagent converts alkyl, ally lie, or propargylic iodides in the presence of HMPT to nitriles. The reaction is particularly useful for synthesis of y,5-unsaturated nitriles.5 Example ... 

Although ethers have been used less frequently than alcohols, it has recently been reported that tetrahydrofuran (THF) is photocatalytically activated by TBADT, and the alkylation of unsaturated nitriles is obtained in good yield [15]. As an alternative, the C—Br bond in various glycosyl bromides has been homolytically cleaved, and the resulting radical trapped by acrylonitrile to form the corresponding C-glycosides. The halogen abstraction step is initiated by a photolabile iron-based dimeric metal complex [16]. 

The concept of tungstate-catalyzed radical reactions was recently extended by Albini and coworkers to efficient radical addition reactions to electrophilic alkenes 147 (Fig. 40). Dondi et al. described the photocatalyzed addition of alkyl radicals generated by 310 nm irradiation of 2 mol% decatungstate 139 to ot,(3-unsaturated nitriles [241] or ot,(3-unsaturated ketones [242]. The yields of saturated nitriles 148a were 30-66%, while those of saturated ketones 148b amounted to 21-56% after... 

Giese and coworkers determined on the basis of experimental results obtained by Scheffold et al. [268, 299] that addition reactions of alkyl bromides 249 to a,p-unsaturated nitriles or esters 248 catalyzed by cobalamine 247 are free radical reactions (Fig. 61) [300], This conclusion was based on the similar cis/trans-selectivities in addition reactions of the 4-tert-butylcyclohexyl radical to different electron-poor alkenes 248 using 247 as a catalyst on one hand and classical tributyltin hydride conditions on the other. The kinetics of the radical addition was determined. 

A convenient synthesis of unsaturated nitriles by a stereospecific alkylative cleavage of pyridine ring via borate process has been reported. Namely, the reaction of 2-bromo-6-lithiopyridine with trialkylboranes affords 5-alkyl-5-dialkylboryl-2-(25--4-(E)-pentadienenitriles (28), which are versatile intermediates for the preparation of 5-alkyl-2-(Z)-4-(E)-pentadienenitriles (29), 5,5-dialkyl-4-pentenenitriles (SO), and 5,5-dialkyl-2,4-pentadienenitriles (SJ), as depicted in Eq. 65 . 

Certain unsaturated nitriles are prepared by the alkylation of reactive olefinic nitriles like vinylacetonitrile, 1-cycIohexenyIacetonitrile, and 3-ethyl-2-pentenonitrile. ... 

It is possible to replace just one halogen or both. In the latter case the two alkyl groups can be the same or different. When dialkylation is apphed to dihalo nitriles, the two alkyl groups can be primary or secondary, but with dUialo esters, dialkylation is limited to primary R. Another extension is the reaction of boranes (BR3) with y-halo-a,p-unsaturated esters.Alkylation takes place in the y position, but the double bond migrates out of conjugation with the COOEt unit [BrCH2 CH=CHCOOEt RCH=CHCH2COOEt]. In this case, however, double-bond... 

Triazolines have also been easily obtained in the reactions of azides with unsaturated nitriles with ethylenesulphonic acid derivatives and with maleimides . Steric hindrance caused by additional substitution by alkyl or aryl groups lowers the yields and also influences the orientation. The reaction of phenyl azide with j3-nitrostyrene proceeded only at 130° and yielded only 20% of the expected 1,5-diphenyl-4-nitrotriazoline (229), together with 1,4-diphenyl triazole (230), resulting from addition in the opposite direction ". ... 

In the benzoin condensation, one molecule of aldehyde serves as an electrophile. If a carbanion is generated from protected cyanohydrins, a-aminonitriles or dithioacetals, it can react with electrophiles such as alkyl halides, strongly activated aryl halides or alkyl tosylates to form ketones. Amongst other electrophiles which are attacked by the above carbanions are heterocyclic A -oxides, carbonyl compounds, a,p-unsaturated carbonyl compounds, a,3-unsaturated nitriles, acyl halides, Mannich bases, epoxides and chlorotiimethyl derivatives of silicon, germanium and tin. 

From a historical perspective, the a-(dialkylamino)nitrile anions were the first acyl anion equivalents to undergo systematic investigation. More recent studies indicate that anions of a-(dialkylamino)nitriles derived from aliphatic, aromatic or heteroaromatic aldehydes intercept an array of electrophiles including alkyl halides, alkyl sulfonates, epoxides, aldehydes, ketones, acyl chlorides, chloroformates, unsaturated ketones, unsaturated esters and unsaturated nitriles. Aminonitriles are readily prepared and their anions are formed with a variety of bases such as sodium methoxide, KOH in alcohol, NaH, LDA, PhLi, sodium amide, 70% NaOH and potassium amide. Regeneration of the carbonyl group can be achieved... 

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