Halo nitriles

Cyanohydrins react with hydrogen haUdes or PCl to give a-halo nitriles which can be further hydrolyzed to the a-halo carboxyUc acids. The a-hydroxy group of cyanohydrins can be esterified with an acid or acid chloride. Dehydration of cyanohydrins with phosphoms pentoxide gives >80% yields of alkylacrylonitriles (8). 

Trialkylboranes react rapidly and in high yields with a-halo ketones,a-halo esters, a-halo nitriles, and a-halo sulfonyl derivatives (sulfones, sulfonic esters, sulfonamides) in the presence of a base to give, respectively, alkylated ketones, esters, nitriles, and sulfonyl derivatives. Potassium tert-butoxide is often a suitable base, but potassium 2,6-di-tert-butylphenoxide at 0°C in THF gives better results in most cases, possibly because the large bulk of the two tert-buXy groups prevents the base from coordinating with the R3B. The trialkylboranes are prepared by treatment of 3 mol of an alkene with 1 mol of BH3 (15-16). With appropriate boranes, the R group transferred to a-halo ketones, nitriles, and esters can be vinylic, or (for a-halo ketones and esters) aryl. " °... 

Addition of Grignard reagents or organolithium reagents to co-halo nitriles leads to 2-substituted cyclic imines. 

Reaction between aldehydes and ketones, zinc, and halo nitriles... 

Reaction of halo nitriles or diazo nitriles with boranes... 

Reaction between aldehydes and ketones, zinc, and halo nitriles 6-41 Addition of nitriles to ketones 6-49 Addition of HCN to aldehydes or ketones... 

For Sn2 reactions the effect of electron-withdrawing groups is less easy to predict than for SnI reactions. a-Halo ketones, a-halo nitriles, or haloacetic acid derivatives undergo bimolecular substitutions at much higher rates than unfunctionalized alkyl halides (Scheme 4.42). 

Alicyclic nitriles are prepared by the intramolecular alkylation of halo nitriles. For example, cyclopropyl cyanide is obtained in 75-90% yield by the action of sodium amide on y-chlorobutyronitrile in ether or liquid... 

RC = CCH,X — RCX = C==CH,. /S.y- and 7,S-Acetylenic alcohols can be transformed to the halides in better yields by an alternative procedure, which consists in their esterification with p-toluenesulfonyl chloride and subsequent cleavage of the ester by the action of sodium iodide, lithium chloride, or calcium bromide in an appropriate solvent (60-90%). Halo ethers are prepared by the action of phosphorus tribromide on hydroxy ethers, as in the preparation of /3-ethoxyethyl bromide (66%). In a similar manner, /3-halo esters have been prepared without appreciable dehydration of the /3-hydroxy ester (40-60%). The reaction of cyanohydrins leads to a-halo nitriles. Treatment of 2-nitro-l-propanol with phosphorus pentachloride gives l-chloro-2-nitropropane (47%). ... 

Halo nitriles are prepared from the corresponding dihalides or from mixed halides by taking advantage of the different reactivities of two dissimilar halogen atoms. ... 

Potassium /-butoxide is used also as basic catalyst in a modified Darzens condensation in which a ketone is condensed with an a-halo nitrile rather than an a-halo ester to give a glycidonitrile. Sodium ethoxide is unsatisfactory since it leads to a mixture of the epoxynitrile (I) and the imido ester (II). 

Reaction of compound 8 with a-halo nitriles (R CHHalCN) gave the 3-amino compounds 7 after cyclization of the intermediate S-alkylated products 12 with aqueous potassium hydroxide. Similarly reaction of 2-amino-3-chloropyrazine (13) with the mercapto esters 14 in the presence of sodium ethoxide gave the 3-oxo derivatives 16 on refluxing in dioxan. The intermediates 15 are involved in the reaction. The most convenient synthesis of these compounds involves reaction of 2-amino-3-chloropyrazines with thioglycollic acid in alkali and acid-catalyzed cyclization of the carboxymethylthio derivative. ... 

Et3B is an effective tool for halogen atom transfer radical reactions (see also Chap. 1.5). Perfluoroalkyl iodide [29], a-halo nitrile and a-halo ester [30] added to alkenes and alkynes at low temperature. Not only terminal alkenes but also internal alkenes can be employed to furnish iodine atom transfer adducts (Scheme 23). Furthermore, addition of perfluoroalkyl iodide to silyl and germyl enolate provided a-perfluoroalkyl ketones [31]. The reaction would involve the elimination of a tri-... 

Alicyclic nitriles may be formed by intramolecular alkylation of halo nitriles, e.g., cyclopropyl cyanide from 4-chlorobutyronitrile (yields 74-79%)414... 

It has been known for some time that (144) will, in the presence of ba se, alkylate, or arylate (R=Ph) a-halo nitriles, esters and ketones. Brown has now extended this reaction to include the... 

Alkyl halides that are very reactive in S 2 reactions such as primary allylic and benzylic halides, a-halo ethers, a-halo esters, and a-halo nitriles. 

If two equivalents of the 2-halo-carbonyl compound (or 2-halo-nitrile) are utilised to react with an enolate/carbon disulfide adduct, double S-alkylation and then double ring closure produce thieno[2,3-h]thiophenes [129] Scheme 82 shows how this works. Taking this idea further, if a malonate is used as the 1,3-dicarbonyl component, 3,4-dihydroxythieno[2,3-h]thiophenes are the final result (Scheme 83) [130], the ring closure steps then having the character of Claisen condensations. If malononitrile is used instead of a 1,3-dicarbonyl compound, the product is a 3,4-diaminothieno[2,3-6]thiophene - product 60 in Scheme 84 is the result of using chloroacetonitrile in the alkylation step [131]. 

Reduction of oe-Halo Carbonyl Compounds and a-Halo Nitriles. A halogen substituent on the carbon next to a carbonyl or cyano group is reduced with Me6Si2 in the presence of Pd(PPh3)4 catalyst (eq 11). In the case of or-halo ketones, oxy-jr-allyl(trimethylsilyl)palladium intermediates are proposed. ... 

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