0-Cyano ethers

Platinum, palladium, and rhodium will function well under milder conditions and are especially useful when other reducible functions are present. Freifelder (23) considers rhodium-ammonia the system of choice when reducing -amino nitriles and certain )5-cyano ethers, compounds that undergo extensive hydrogenolysis under conditions necessary for base-metal catalysis. 

The most popular and versatile bonded phase is octadecylsilane (ODS), n-C18H37, a grouping that is non-polar and used for reverse phase separations. Octylsilane, with its shorter chain length, permits faster diffusion of solutes and this results in improved peak symmetry. Other groups are attached to provide polar phases and hence perform normal phase separations. These include cyano, ether, amine and diol groups, which offer a wide range of polarities. When bonded stationary phases are used, the clear distinction between adsorption and partition chromatography is lost and the principles of separation are far more complex. 

Vinyl ethyl Methyl l-cthoxy-l-methoxy-3-cyano-ether propane-3-carboxylate (19%)... 

The nature of nitrooleflns has little influence on the efficiency of this one-pot process, and other functionalities snch as cyano, ether, and chlorine can be preserved. The role of the nitro gronp is crncial in the reported process since its electron-withdrawing effect firstly helps the nncleophilic attack of the amino or hydroxyl fnnctionality to the alkene, then it allows a stabilized carbanion with the consequent formation of an intramolecnlar C-C bond (nitroaldol reaction) and, finally, favors the elimination of water (ElcB). Moreover, the nse of solvent-free conditions (SFC) in combination with heterogeneons catalyst represents one of the more powerful green chemical technology procednres. 

Aromatic and aliphatic amino ethers have been synthesized by this method. An example of the formation of a cyano ether is the preparation of p-cyano benzyl methyl ether from the substituted benzyl bromide and sodium methoxide (84%). Also, certain aryloxyacetonitriles, AtOCHjCN, are made by the condensation of chloroacetonitrile with sodium phenoxides in a solution of methyl ethyl ketone containing a small amount of sodium iodide (70-80%). Aromatic nitro ethers, like o- and p-nitrodiphenyl ether, have been prepared by the Ullmann procedure (84%). The synthesis of alkyl p-nitrophenyl ethers has also been accomplished with good yields (55-92%). ... 

An important method for the preparation of keto ethers is the reaction of cyano ethers with Grignard reagents. In this manner, a large number of a-alkojty aliphatic ketones have been made (30-70%). ° Likewise, phenoxymethyl alkyl ketones have been prepared (20-64%).When the Grignard reagent contains an i)-alkoxy group, 0)-alkoxy ketones are formed, ... 

Treatment of a-halo ethers with metallic cyanides such as cuprous, mercuric, or silver cyanides gives the corresponding cyano ethers the alkali cyanides are without effect. Very little of the corresponding isonitriles are encountered despite the fact that these compounds often result from the interaction of heavy-metal cyanides and alkyl halides. Generally, cuprous cyanide, the most commonly used reagent, is suspended in dry anhydrous ether or dry benzene and treated with the halo ether under gentle reflux (55-80%). 

An elegant procedure for generating ct-cyano ethers from acyclic or cyclic acetals and ketals is their reaction with r-alkyl isocyanides in the presence of an equimolar amount of TiCU (Scheme 18). 72 7]je exchange of alkoxy groups against cyanide functions proved to be very important for the preparation of cyanoquinones. ... 

Starting with, -famesol, a Sharpless asymmetric epoxidation [16] followed by four convenient functional group transformations afforded aldehyde 73 (Scheme 14). Reaction of 73 with 2 equivalents of sodium cyanide gave a mixture of cyanohydrins (1 1) which upon treatment with 5 mol % of tosic acid underwent cyclization to give cyano ether 74 (40%) and the Ci4-epimer (39%). The epimer could be treated with potassium hexamethyldisilazane to afford more of the desired product (74) [46]. 

A promising preparation of 4-aryloxy-l,2,3-triazoles (8.1-6) involves aryl cyano ethers and diazomethane (Eq. 11). ... 

Oishi, T., Watanabe, K., and Murata, M., Convergent synthesis of trans-fused 6/n/6/6 ( = 7, 8) tetracyclic ether system via (X-cyano ethers, Tetrahedron Lett., 44, 7315, 2003. 

A review of diastereoselective additions of organometallics to chiral oxazolidines has appeared (94MI99). The Diels-Alder reaction of (R)-2-phenyl-4-methyleneoxazolidin-5-one 59 with 2,3-dimethylbutadiene proceeds with exo-diastereoselectivity to yield the adduct 60 (94T941). The action of sodium cyanide on the chiral oxazolidinium salt 61 leads to the cyano ether 62 stereoselectively (93TL8325). 

Miscellaneous Transformations. Cyanotrimethylsilane effects the transformation of acyl chlorides to acyl cyanides, a-chloro ethers and a-chloro thioethers to a-cyano ethers and a-cyano thioethers (eq 19), t-butyl chlorides to nitriles (eqs 20 and 21), 1,3,5-trisubstituted hexahydro-l,3,5-triazines to amino-acetonitriles, the cyanation of allylic carbonates and acetates (eqs 22 and 23), and the formation of aryl thiocyanates from aryl sulfonyl chlorides and sulfinates. The reagent has been used effectively in peptide synthesis and in a range of other synthetic applications. " ... 

The reaction can also be carried out on trimethylsilyl ethers of cyanohydrins, which can be obtained from the ketone and trimethylsilyl cyanide. The cyano ether is reduced to the aminomethylcarbinol by LiAlH4 ... 

Into a 500 nil. round-bottomed flask, provided with a double surface condenser, place 50 g. (63 ml.) of pure, dry acetone, 50 g. (47 ml.) of ethyl cyanoacetate (Section 111,131) and 0 -5 g. of piperidine. Allow to stand for 60 hours and heat on a water bath for 2 hours. Treat the cold reaction mixture with 100 ml. of ether, wash with dilute hydrochloric acid, then with water, and dry over anhydrous sodium or magnesium sulphate. Distil under diminished pressure and collect the ethyl fsopropylidene cyanoacetate (ethyl a-cyano-pp-dimethylacrylate) at 114-116°/14mm.(l). The yield is 39 g. 

Di lve 20 g. of the cyano ester in 100 ml. of rectified spirit and add a solution of 19 2 g. of pure potassium cyanide in 40 ml. of water. Allow to stand for 48 hours, then distil oflF the alcohol on a water bath. Add a large excess of concentrated hydrochloric acid and heat under reflux for 3 hours. Dilute with water, saturate the solution with ammonium sulphate, and extract with four 75 ml. portions of ether. Dry the combined ethereal extracts with anhydrous sodium or magnesium sulphate, and distil off the ether. RecrystaUise the residual acid from excess concentrated hydrochloric acid, and dry in the air. The yield of pure ew-dimethyl-succinic acid, m.p. 141-142°, is 12 g. 

Olah s original preparative nitrations were carried out with mixtures of the aromatic compound and nitronium salt alone or in ether, and later with sulpholan as the solvent. High yields of nitro-compounds were obtained from a wide range of aromatic compounds, and the anhydrous conditions have obvious advantages when functional groups such as cyano, alkoxycarbonyl, or halogenocarbonyl are present. The presence of basic fimctions raises difficulties with pyridine no C-nitration occurs, i-nitropyridinium being formed. ... 

Aryl, heteroaryl, and alkenyl cyanides are prepared by the reaction of halides[656-658] or triflates[659,660] with KCN or LiCN in DMF, HMPA, and THF. Addition of crown ethers[661] and alumina[662] promotes efficient aryl and alkenyl cyanation. lodobenzene is converted into benzonitrile (794) by the reaction of trimethylsiiyl cyanide in EtiN as a solvent. No reaction takes place with aryl bromides and chlorides[663]. The reaction was employed in an estradiol synthesis. The 3-hydroxy group in 796 was derived from the iodide 795 by converting it into a cyano group[664]. 

Diphenoxylate Hydrochloride. l-(3-Cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxyhc acidmonohydrochlorhydrate [3810-80-8] (Lomotil) (13) is a white, odorless, crystalline powder that melts at 220—226°C. It is soluble ia methanol, spariagly soluble ia ethanol and acetone, slightly soluble ia water and isopropyl alcohol, freely soluble ia chloroform, and practically iasoluble ia ether and hexane. The method of preparation for diphenoxylate hydrochloride is available (11). Diphenoxylate hydrochloride [3810-80-8] (13) is an antidiarrheal that acts through an opiate receptor. It has effects both on propulsive motility and intestinal secretion. Commercial forms are mixed with atropiae to discourage abuse. 

An unusual method for the preparation of syndiotactic polybutadiene was reported by The Goodyear Tire Rubber Co. (43) a preformed cobalt-type catalyst prepared under anhydrous conditions was found to polymerize 1,3-butadiene in an emulsion-type recipe to give syndiotactic polybutadienes of various melting points (120—190°C). These polymers were characterized by infrared spectroscopy and nuclear magnetic resonance (44—46). Both the Ube Industries catalyst mentioned previously and the Goodyear catalyst were further modified to control the molecular weight and melting point of syndio-polybutadiene by the addition of various modifiers such as alcohols, nitriles, aldehydes, ketones, ethers, and cyano compounds. 

The mechanism of thermolysis and photolysis of ethers of 3-hydroxy-1,2-benzisoxazole has also been studied. Heating of the allyl ether (43) gave minor amounts of (44) and two benzoxazoles. Photolysis of (45) in methanol gave a benzisoxazole and an iminoester, via intermediate (46). Thermolysis at 600 °C gave a benzoxazole, a benzoxazolone and cyano-phenol (Scheme 16) (71DIS(D)4483). 

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