Synthesis Nitrile

1 synthesis

1.1 ammoxidation
1.2 hydrocyanation
1.3 organic halides , cyanide salts
1.4 cyanohydrins
1.5 dehydration of amides , oximes
1.6 sandmeyer reaction
1.7 other methods

synthesis

industrially, main methods producing nitriles ammoxidation , hydrocyanation. both routes green in sense not generate stoichiometric amounts of salts.

ammoxidation

in ammoxidation, hydrocarbon partially oxidized in presence of ammonia. conversion practiced on large scale acrylonitrile:

ch3ch=ch2 +  ⁄2 o2 + nh3 → ncch=ch2 + 3 h2o

in production of acrylonitrile, side product acetonitrile. on industrial scale, several derivatives of benzonitrile, phthalonitrile, isobutyronitrile prepared ammoxidation. process catalysed metal oxides , assumed proceed via imine.

hydrocyanation

hydrocyanation industrial method producing nitriles hydrogen cyanide , alkenes. process requires homogeneous catalysts. example of hydrocyanation production of adiponitrile, precursor nylon-6,6 1,3-butadiene:

ch2=ch−ch=ch2 + 2 hcn → nc(ch2)4cn

from organic halides , cyanide salts

two salt metathesis reactions popular laboratory scale reactions. in kolbe nitrile synthesis, alkyl halides undergo nucleophilic aliphatic substitution alkali metal cyanides . aryl nitriles prepared in rosenmund-von braun synthesis.

cyanohydrins

synthesis of aromatic nitriles via silylated cyanohydrins

the cyanohydrins special class of nitriles. classically result addition of alkali metal cyanides aldehydes in cyanohydrin reaction. because of polarity of organic carbonyl, reaction requires no catalyst, unlike hydrocyanation of alkenes. o-silyl cyanohydrins generated addition trimethylsilyl cyanide in presence of catalyst (silylcyanation). cyanohydrins prepared transcyanohydrin reactions starting, example, acetone cyanohydrin source of hcn.

dehydration of amides , oximes

nitriles can prepared dehydration of primary amides. in presence of ethyl dichlorophosphate , dbu benzamide converts benzonitrile:

two intermediates in reaction amide tautomer , phosphate adduct b.

in related dehydration, secondary amides give nitriles von braun amide degradation. in case, 1 c-n bond cleaved. dehydration of aldoximes (rch=noh) affords nitriles. typical reagents transformation triethylamine/sulfur dioxide, zeolites, or sulfuryl chloride. exploiting approach one-pot synthesis of nitriles aldehyde hydroxylamine in presence of sodium sulfate.

from aryl carboxylic acids (letts nitrile synthesis)

sandmeyer reaction

aromatic nitriles prepared in laboratory aniline via diazonium compounds. sandmeyer reaction. requires transition metal cyanides.

arn+

2 + cucn → arcn + n2 + cu

other methods

a commercial source cyanide group diethylaluminum cyanide et2alcn can prepared triethylaluminium , hcn. has been used in nucleophilic addition ketones. example of use see: kuwajima taxol total synthesis
cyanide ions facilitate coupling of dibromides. reaction of α,α′-dibromoadipic acid sodium cyanide in ethanol yields cyano cyclobutane:



in so-called franchimont reaction (which developed belgian doctoral student antoine paul nicolas franchimont (1844-1919) in 1872) α-bromocarboxylic acid dimerized after hydrolysis of cyanogroup , decarboxylation


aromatic nitriles can prepared base hydrolysis of trichloromethyl aryl ketimines (rc(ccl3)=nh) in houben-fischer synthesis
nitriles can obtained primary amines via oxidation. common methods include use of potassium persulfate, trichloroisocyanuric acid, or anodic electrosynthesis.
α-amino acids form nitriles , carbon dioxide via various means of oxidative decarboxylation. henry drysdale dakin discovered oxidation in 1916.




^ peter pollak, gérard romeder, ferdinand hagedorn, heinz-peter gelbke nitriles ullmann s encyclopedia of industrial chemistry 2002, wiley-vch, weinheim. doi:10.1002/14356007.a17_363
^ gregory, robert j. h. (1999). cyanohydrins in nature , laboratory: biology, preparations, , synthetic applications . chemical reviews. 99: 3649–3682. doi:10.1021/cr9902906. 
^ chun-wei kuo; jia-liang zhu; jen-dar wu; cheng-ming chu; ching-fa yao; kak-shan shia (2007). convenient new procedure converting primary amides nitriles . chem. commun. 2007 (3): 301–303. doi:10.1039/b614061k. pmid 17299646. 
^ sharwan k, dewan, ravinder singh, , anil kumar (2006). 1 pot synthesis of nitriles aldehydes , hydroxylamine hydrochloride using sodium sulfate (anhyd) , sodium bicarbonate in dry media under microwave irradiation (open access). arkivoc: (ii) 41–44. cs1 maint: multiple names: authors list (link)
^ o-tolunitrile , p-tolunitrile h. t. clarke , r. r. read org. synth. 1941, coll. vol. 1, 514.
^ w. nagata , m. yoshioka (1988). diethylaluminum cyanide . organic syntheses. ; collective volume, 6, p. 436 
^ w. nagata, m. yoshioka, , m. murakami (1988). preparation of cyano compounds using alkylaluminum intermediates: 1-cyano-6-methoxy-3,4-dihydronaphthalene . organic syntheses. cs1 maint: multiple names: authors list (link) ; collective volume, 6, p. 307 
^ reynold c. fuson; oscar r. kreimeier & gilbert l. nimmo (1930). ring closures in cyclobutane series. ii. cyclization of α,α′-dibromo-adipic esters . j. am. chem. soc. 52 (10): 4074–4076. doi:10.1021/ja01373a046. 
^ a. p. n. franchimont (1872). ueber die dibenzyldicarbonsäure [on 2,3-diphenylsuccinic acid]. berichte der deutschen chemischen gesellschaft. 5: 1048–1050. doi:10.1002/cber.187200502138. 
^ j. houben, walter fischer (1930) Über eine neue methode zur darstellung cyclischer nitrile durch katalytischen abbau (i. mitteil.), berichte der deutschen chemischen gesellschaft (a , b series) 63 (9): 2464 – 2472. doi:10.1002/cber.19300630920
^ yamazaki, shigekazu; yamazaki, yasuyuki (1990). nickel-catalyzed dehydrogenation of amines nitriles . bulletin of chemical society of japan. 63 (1): 301–303. doi:10.1246/bcsj.63.301. 
^ chen, fen-er; kuang, yun-yan; hui-fang, dai; lu, liang (2003). selective , mild oxidation of primary amines nitriles trichloroisocyanuric acid . synthesis. 17: 2629–2631. doi:10.1055/s-2003-42431. 
^ schäfer, h. j.; feldhues, u. (1982). oxidation of primary aliphatic amines nitriles @ nickel hydroxide electrode . synthesis. 2: 145–146. doi:10.1055/s-1982-29721. 
^ hiegel, gene; lewis, justin; bae, jason (2004). conversion of α‐amino acids nitriles oxidative decarboxylation trichloroisocyanuric acid . synthetic communications. 34 (19): 3449–3453. doi:10.1081/scc-200030958. 
^ hampson, n; lee, j; macdonald, k (1972). oxidation of amino compounds @ anodic silver . electrochimica acta. 17 (5): 921–955. doi:10.1016/0013-4686(72)90014-x. 
^ dakin, henry drysdale (1916). oxidation of amino-acids cyanides . biochemical journal. 10 (2): 319–323. doi:10.1042/bj0100319. pmc 1258710 . pmid 16742643.