Thionyl chloride nitriles

Further, d-citronellal, the corresponding aldehyde, may be converted into citronellic acid through its oxime and nitrile. Citronellic acid, when treated with thionyl chloride in benzene solution, yields a chloride of a chlorinated acid which is converted by the action of alcohol into the hydrochloride of ethyl citronellate, or hydrochloride of ethyl rhodinate,... 

Phenylacetonitrile is alkylated with secondary butyl bromide and the resultant nitrile is hydrolyzed to 3-methyl-2-phenylvaleric acid. The acid is converted to the acid chioride with thionyl chloride and the acid chloride is in turn reacted with 1-methyl-4-piperidinol. Finally dimethyl sulfate is reacted with the ester. 

The simplest method of nitrile preparation is the Sj 2 reaction of CN with a primary or secondary alkyl halide, as discussed in Section 20.5. Another method for preparing nitriles is by dehydration of a primary amide, RCONH2. Thionyl chloride is often used for the reaction, although other dehydrating agents such as POCI3 also work. 

By the action of thionyl chloride Steinkopf prepared from this substance the long-sought nitroacetonitrile 2 N02.CH2.CN, and by the hydrolysis of this nitrile, nitroacetic acid.3... 

The above hydrochloride is treated with thionyl chloride in liquid sulfur dioxide, to produce an amorphous chloride hydro chloride, which is converted to the nitrile with sodium cyanide in liquid hydrogen cyanide, Methanolysis then gives the ester of the nitrile. Alkaline hydrolysis of this last compound, followed by catalytic dehydrogenation in water using a deactivated Raney Nickle catalyst (see JOC, 13, 455 1948) gives dl-lysergic acid. 

This method has been used extensively for the generation of diene- and triene-conjugated nitrile ylides (see Section 7.4.1.2) using strong bases. Potasium tert-butoxide (58) was used for the most part but in recent work (59,60) it was reported that lithium bisftrimethylsilyl)amide is both more effective and more convenient. It has also been shown that thermally unstable imidoyl chlorides for use in these reactions can be prepared by reaction of the corresponding amides with chlorodi-methylformiminium chloride at 0 °C, a reaction that is more effective than using either thionyl chloride or phosphoms pentachloride at higher temperatures (61). 

Racemic 2-ethylhexanonitrile has been obtained only by the action of phosphorus pentachloride on 2-ethylhexanaldoxime 4 the levorotatory form has been prepared from the active amide by the method described.6 Other amides have been converted to nitriles by dehydration with thionyl chloride.6-6... 

An unusual rearrangement provides the key to the preparation of a highly substituted pyrrolidone, doxapram (26-7), that is used as a respiratory stimulant. The synthesis starts with the displacement of chlorine on pyrrolidine (26-1) by the carbanion from diphenylacetonitrile (26-2) to give (26-3) as the product. The quite hindered nitrile is then hydrolyzed to the corresponding carboxylic acid (26-4) by basic hydrolysis. The reaction of acid with thionyl chloride presumably proceeds initially to form the corresponding acid chloride. The close proximity of that group to basic... 

Nitration of hydroxypropiophenone (7-1) followed by conversion of the phenol to its methyl ether by means of methyl iodide provides the intermediate (7-2) the nitro group is then reduced to the corresponding amine (7-3) by catalytic reduction. The newly introduced amine is then replaced by a nitrile group by successive conversion to the diazonium salt by means of nitrous acid followed by treatment with cuprous cyanide (7-4). Reaction with aluminum chloride removes the methyl ether to afford the ortho acylphenol (7-5). This is converted to the chromone (7-6) as above by reaction with benzoyl chloride and sodium benzoate. The nitrile is next hydrolyzed to the carboxylic acid (7-7) by means of sulfuric acid. The acid is then converted to its acid chloride by means of thionyl chloride and that treated with 2-(A -piperidyl)ethanol (7-8). There is thus obtained flavoxate (7-9) [8], a muscle relaxant whose name reflects its flavone nucleus. 

Acyl chlorides Thionyl chloride, 297 Acyl nitriles... 

A key step in the synthesis of the /3-lactamase inhibitor cilastatin (Bayer, Leverkusen, Germany) is the preparation of (S)-2,2-dimethylcyclopropane carboxamide. The chemically synthesized corresponding nitrile, l-cyano-2,2-dimethylcyclopropane, is hydrolyzed by a highly active but enanhounspecific nitrile hydratase to the racemic carboxamides. An amidase from Comomonas acidovorans overexpressed in E. coli selectively hydrolyzes the undesired (R)-isomer to the acid. The remaining (S) enantiomer is obtained with > 99% e.e. and 48% conversion (the resulting E value thus exceeds 100). The (R)-acid is recycled by chemical amidation with thionyl chloride and ammonia. The process has been developed by Lonza (Visp, Switzerland) and runs on a 15 m3 scale (Rasor, 2001). 

Wear nitrile rubber gloves, laboratory coat, eye protection, and, if necessary, a self-contained breathing apparatus. Cover the spill with a 1 1 1 mixture by weight of sodium carbonate or calcium carbonate, clay cat litter (bentonite), and sand. When the thionyl chloride has been absorbed, scoop the mixture into a plastic pail, and in the fume hood, very slowly add the mixture to a pail of cold water. Allow to stand 24 hours. Test the pH of the solution and neutralize if necessary with sodium carbonate. Decant the solution to the drain. Treat the solid residue as normal refuse.11... 

Nitriles can be prepared by the SN2 reaction of a cyanide ion with a primary alkyl halide. However, this limits the nitriles that can be synthesised to those having the following general formula RCH2CN. A more general synthesis of nitriles involves the dehydration of primary-amides with reagents such as thionyl chloride or phosphorus pentoxide ... 

Primary amides are dehydrated to nitriles using a dehydrating agent like thionyl chloride (SOCl3), phosphorus pentoxide (P2Os), phosphoryl trichloride (POCl3), or acetic anhydride o... 

Benzylidenehydrazinouracils (514), derived from 6-hydrazinouracils (513) and aldehydes, are cyclized upon UV irradiation and treatment with thionyl chloride or NBS, to afford pyrazolo[3,4-rf]pyrimidines (516), depending on the presence of protons at R2 and/or R3 (Scheme 51) fully methylated hydrazones are decomposed into 6-methylaminouracils (515) and nitriles <73S300, 74H(2)153, 75BCJ1484, 84JHC969, 92AHC(55)129>. 

---