Nickel benzylation

P-Phenylethylamine is conveniently prepared by the hydrogenation under pressure of benzyl cyanide with Raney nickel catalyst (see Section VI,5) in the presence of either a saturated solution of dry ammonia in anhydrous methyl alcohol or of liquid ammonia the latter are added to suppress the formation of the secondary amine, di- P phenylethylamine ... 

Minute amounts of halide have a powerful poisoning effect upon the catalyst it is advisable to distil the benzyl cyanide from Raney nickel. 

An example of the application of the Raney nickel catalyst is given in Section IV,35 (p-phenylethylamine from benzyl cyanide). 

Catalytic hydrogenation is mostly used to convert C—C triple bonds into C C double bonds and alkenes into alkanes or to replace allylic or benzylic hetero atoms by hydrogen (H. Kropf, 1980). Simple theory postulates cis- or syn-addition of hydrogen to the C—C triple or double bond with heterogeneous (R. L. Augustine, 1965, 1968, 1976 P. N. Rylander, 1979) and homogeneous (A. J. Birch, 1976) catalysts. Sulfur functions can be removed with reducing metals, e. g. with Raney nickel (G. R. Pettit, 1962 A). Heteroaromatic systems may be reduced with the aid of ruthenium on carbon. 

Benzyl chloride is available in both anhydrous and stabilized forms. Both forms can be shipped in glass carboys, nickel and lined-steel dmms, and nickel tank tmcks and tank cars. Stabilized benzyl chloride can be shipped in unlined and lacquer-lined dmms, and tank tmcks or cars of constmction other than nickel. Glass-lined tanks are the first choice for bulk storage of anhydrous benzyl chloride lead-lined, nickel, or ceramic tanks can also be used. 

Benzyl chloride is classified by DOT as chemicals NOIBN, poisonous, corrosive and a hazardous substance (100 lbs-45.45 kg). Benzal chloride is classified as poisonous and a hazardous substance (5000 lbs-2270 kg). Benzotrichloride is classified under DOT regulation as a corrosive Hquid NOS and a hazardous substance (10 lbs-4.5 kg). The Freight Classification Chemical NOI appHes. It is shipped in lacquer-lined steel dmms and nickel-lined tank trailers. Benzal chloride is handled in a similar fashion. 

Esters and amides are quite resistant to hydrogenation under almost all conditions so their presence is not expected to cause difficulties. Alkyl ethers and ketals are generally resistant to hydrogenolysis but benzyl ethers are readily cleaved, particularly over palladium or Raney nickel catalysts. ... 

Raney Nickel W2 or W4, EtOH, 85-100% yield. Mono- and dimethoxy-substituted benzyl ethers and benzaldehyde acetals are not cleaved under these conditions, and trisubstituted alkenes are not reduced. 

ANILINES, BENZYL AMINES, AND ANALOGUES An orally active local anesthetic agent that can be used as an (intiarrhythmic agent is meobenti ne (57). Its patented synthesis starts with -hydroxyphenyl nitrile and proceeds by dimethyl sulfate etherification and Raney nickel reduction to Alkylation of -methyl-dimethylthiourea with completes l.he synthesis of meobenti ne (57). ... 

Nickel in the presence of ammonia is often used for reduction of nitriles to primary amines. The reaction is done at elevated temperatures and pressures ( 100 C, 1000 psig) unless massive amounts of nickel are used. Cobalt is used similarly but mainly under even more vigorous conditions. Nitriles containing a benzylamine can be reduced over Raney nickel to an amine without hydrogenolysis of the benzyl group (7). A solution of butoxycarbonyl)-3-aminopropyl]-N-<3-cyanopropyl)benzylamine (13.6 g) in 100 ml of ethanol containing 4 g. NaOH was reduced over 3.0 g Raney nickel at 40 psig for 28 h. The yield of A/ -benzyl-Air -(f-butoxycarbonyl)s >ermidine was 95% (7). 

Benzylamines tend to undergo hydrogenolysis with inversion over both Raney nickel and palladium, unlike benzyl-oxygen compounds I2Ia,I67o). 

Resistance to corrosion of electroless nickel, both as-deposited and, in most cases, after heating to 750°C, is listed by Metzger for about 80 chemicals and other products. Resistance was generally satisfactory, with attack at a rate below 13 /im/year. The only substances causing faster attack were acetic acid, ammonium hydroxide or phosphate, aerated ammonium sulphate, benzyl chloride, boric acid, fluorophosphoric acid, hydrochloric acid, aerated lactic acid, aerated lemon juice, sodium cyanide and sulphuric acid. 

Diastereoselective preparation of a-alkyl-a-amino acids is also possible using chiral Schiff base nickel(II) complexes of a-amino acids as Michael donors. The synthetic route to glutamic acid derivatives consists of the addition of the nickel(II) complex of the imine derived from (.S )-,V-[2-(phenylcarbonyl)phenyl]-l-benzyl-2-pyrrolidinecarboxamide and glycine to various activated olefins, i.e., 2-propenal, 3-phenyl-2-propenal and a,(f-unsaturated esters93- A... 

T-4)-J or Raney nickel and hydrogen.8 Alcohols of the benzylic type have also been reduced directly with hydrogen under pressure in the presence of various catalysts,9 and benzoic acids have been reduced to toluenes with rhenium-type catalysts and hydrogen at high temperatures and pressures.10... 

Although, as has already been mentioned, under matrix conditions between 10 and 77 K, there is no oxidative addition of a chloroolefin to nickel or palladium atoms (141), it is evident that this is simply a function of reaction and processing conditions, as it has been shown (68) that oxidative addition to C-C or C-H bonds by nickel atoms leads to pseudocomplexes having Ni C H ratios of 2-5 1 2. Klabunde and co-workers investigated the oxidative addition-reactions of palladium atoms with alkyl halides (73) and benzyl chlorides (74). 

Yet another approach uses electrolysis conditions with the alkyl chloride, Pe(CO)s and a nickel catalyst, and gives the ketone directly, in one step. In the first stage of methods 1, 2, and 3, primary bromides, iodides, and tosylates and secondary tosylates can be used. The second stage of the first four methods requires more active substrates, such as primary iodides or tosylates or benzylic halides. Method 5 has been applied to primary and secondary substrates. 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

---