Russian Chemical Reviews 68 (1) 55± 72 (1999) Reductive amination of oxygen-containing organic compounds VATarasevich,NGKozlov Contents I. Introduction 55 II. Reductive amination of carbonyl compounds with ammonia and amines 55 III. Reductive amination of alcohols with ammonia and amines 60 IV. Reductive amination of aldehydes and ketones with nitro compounds and pyridine bases 62 V. Reductive amination of aldehydes, ketones and alcohols with nitriles and oximes 63 VI. Conclusion 69 Abstract. The data dealing with reductive amination of oxygen- containing organic compounds of different classes are systema- tised. New data on the amination agents and the catalysts used are presented. The dependence of the reactivity of reagents on their structures is considered.The bibliography includes 249 references. I. Introduction Reductive amination or hydroamination is widely used for the synthesis of amines. This method is based on the reaction between oxygen- and nitrogen-containing compounds on the surface of a catalyst under a hydrogen atmosphere or in solution in the presence of hydrogen donors. In the literature, this reaction is often referred to as `reductive alkylation', which does not reflect exactly its chemical essence. It has beenshowninnumerous studies that during the reaction with oxygen-containing compounds in the presence of hydrogen donors, some nitrogen-containing compounds, namely, nitro and nitroso compounds, nitriles and oximes, are first reduced to amines, and then the latter react with oxygen-containing com- pounds.Thus, this reaction occurs successfully when an amino group is present; therefore, it is more correct to call this reaction `reductive amination' or `hydroamination' rather than `reductive alkylation'. This reviewdeals withreductive aminationreactions involving hydrogen or hydrogen donors; the reaction conditions and the catalysts used are discussed. II. Reductive amination of carbonyl compounds with ammonia and amines The ability of ammonia and amines to formimines with aldehydes and ketones and the fact that imines can be reduced relatively easily to the corresponding amines permitted the synthesis of amines by direct amination of carbonyl-containing compounds V A Tarasevich Centre for Chemical Technology, Belarus Academy of Sciences, ul.Zhodinskaya 16, 220141 Minsk, Republic of Belarus. Fax (7-017) 263 19 23. Tel. (7-017) 264 11 16 NGKozlov Institute of Physical Organic Chemistry, Belarus Academy of Sciences, ul. Surganova 13, 220072 Minsk, Republic of Belarus, Fax (7-017) 268 46 79. Tel. (7-017) 268 53 70 Received 2 July 1998 Uspekhi Khimii 68 (1) 61 ±79 (1999); translated by Z P Bobkova #1999 Russian Academy of Sciences and Turpion Ltd UDC 547.233 with ammonia or amines. Hydrogen (in the presence of a catalyst) or formic acid and its derivatives are used most often as the reducing agents in this process. This reaction is widely employed to prepare amines fromvarious aldehydes and ketones. Mignonac 1, 2 was the first tocarry out the reductive amination of aldehydes and ketones with ammonia.Mixtures of the corre- sponding primary, secondary and tertiary amines were obtained from aliphatic aldehydes and ammonia in the presence of nickel catalysts. Inthe first stage of the reaction, ammonia adds tothe carbonyl compound (Scheme 1, pathway a); this is followed by the reduction of either the product of nucleophilic addition itself, a-amino alcohol 1 (pathway d), or the product of its dehydration, imine 2 (pathways b and c).3 In some cases, the imines formed in the condensation of carbonyl compounds with ammonia can be isolated, whereas the a-amino alcohol 1 could not be isolated.4 As the primary amine is accumulated in the reaction mixture, it enters intoreactionwiththe initial carbonyl compoundsimilarly to ammonia (Scheme 1, pathway e).The imine 3, which is formed upon dehydration of the condensation product, is converted into secondary amine (pathways f and g). In addition, primary amine canreact withthe imine 2 to give addition product 4, the reduction of which also gives a secondary amine (pathways h± j). Secondary amines also can enter into this type of reactions (pathways k± n); this gives tertiary amines. Thus, the process occurs as a set of consecutive and parallel reactions yielding a mixture of primary, secondary and tertiary amines. To suppress the formation of secondary and tertiary amines, the reductive amination of carbonyl compounds is carried out in the presence of ammonium salts.5 Under these conditions, only primary amines are formed.Apparently, an excess of ammonium salts shifts equilibrium towards primary amines; in addition, the formation of secondary amines is suppressed because primary amines lose their nucleophilic properties upon transformation into alkylammoniumions + + H H H H Cl7 N H . Cl7+ H N H R N H R N + H H H H For example, the introduction of ammonium chloride into the reaction mixture during hydroamination of 1-(2,5-dimethoxyphe- nyl)propan-2-one 5 with ammonia in methanol in the presence of Raney nickel permitted the synthesis of 2-amino-1-(2,5-dimethox- yphenyl)propane 6 in 95%yield.656 MeO O CH2CMe OMe 5 Most often, hydroamination of carbonyl-containing com- pounds with ammonia is carried out in the presence of nickel catalysts.7 ± 9 When metallic rhenium and rhodium supported on alumina are used as the catalysts, the total yield of primary and secondary amines reaches 93%± 95%.10 In order to direct the process at the formation of secondary amines, catalysts are often modified by various oxides.Thus the reaction of cyclohexanone 7 with ammonia catalysed by the 0.35% PdO/SiO2 catalyst modi- fied by Ag, Mn, K, Na and Al oxides gives dicyclohexylamine 8 in 97% yield.11 NH3 O PdO/SiO2 7 Synthesis of 2,2-disubstituted 1,5-diaminopentane derivatives by the reaction of the corresponding aldehydes containing a terminal nitrile group with excess ammonia over acid catalysts has been reported.12, 13 The imino nitrile formed in the first stage is hydrogenated over catalysts based on Co, Ni, Ru and other noble metals at 60 ± 150 8C and 5 ± 15 MPa.The yields of diamines amount to 50% ± 72%. The use of reduced promoted fused iron catalysts (RPFIC) in various reactions, most of all, in reductive amination of carbonyl- containing compounds, has been described in a review.14 Among other reactions, the reductive amination of octan-2-one with ammonia has been studied in detail.15 ± 18 The kinetic isotope effect observed after replacement of H2 by D2 made it possible to propose a stepwise mechanism of reductive amination of carbonyl compounds, the addition of hydrogen to ketimine being the rate- determining step. Hydroamination of 3,5,5-trimethylcyclohex-2-enone (iso- phorone, 9) with ammonia in the presence of a copper ± zinc ± aluminium catalyst (SNM-1) and RPFIC at 160 ± 230 8C has been reported.19, 20 The yield of 3,3,5-trimethylcyclohexylamine 10 reaches 90%± 95%.RR0CHNH CR0R OH f 7H2O RR0CHN CR0R 3 g H2 RR0CHNH CHR0R RR0C O k (RR0CH)2N CR0R OH MeO NH3, H2 NH 8 RR0CHNH2 RR0C O NH3 a e H2 RR0CHN CR0R j 7NH3 i 2 (RR0CH)2N CR0R m H2 H2 NH2 7NH3 n (RR0CH)3N 7H2O l NH2 CH2CHMe OMe 6 3-Aminomethyl-3,5,5-trimethylcyclohexylamine 11 is pre- pared by reductive amination of 1,3,3-trimethyl-5-oxocyclohex- anecarbonitrile 12 with ammonia with simultaneous reduction of the cyano group at 50 ± 150 8C on Raney nickel or cobalt using anhydrous Ni, Co, Y, and La halides as co-catalysts.The yield of the amine 11 was 83%.21 Transformation of aldehydes and ammonia into secondary amines was attained 22 by using a three-component catalyst based on Cu, a metal of the series Cr, Mn, Fe and Zn and a platinum group metal (Pt, Pd, Ru, Rh). The predominant formation of either primary or secondary amines from ketones and ammonia can depend significantly on the procedure used to prepare the catalysts and on the catalyst composition, all other factors being the same. Study of hydroamination of cyclohexanone 7 with ammonia in the presence of various catalysts has demonstrated 23 that in the presence of a nickel catalyst, the primary amine, cyclohexylamine 13, is formed predominantly, whereas the use of colloidal platinum results in the secondary amine 8 being formed as the major product.However, later,24 it was found that in the presence of plati- nated silica gel, the ketone 7 is readily converted into the primary amine 13 rather than into the secondary amine 8, as noted in the study 23 cited above. Thus, depending on the method for the preparation of the platinum catalyst, either secondary or primary amines can be synthesised. Hydroamination of alicyclic ketones with aromatic amines in the presence of catalysts containing Ru, Rh, Pd or Ni supported on g-Al2O3 yields, depending on the temperature conditions, either cycloaliphatic or aromatic secon- V A Tarasevich, N G Kozlov Scheme 1 H2 RR0C OH RR0CHNH2 7H2O d NH2 1 H2O H2 7H2O b RR0C NH c 2 2 RR0CHNH CR0R h 4 NH2 Me Me NH3, H2 Me Me 7H2O O H2N Me Me 10 9 Me CN Me CH2NH2 NH3, H2 Me Me 7H2O O H2N Me Me 11 12 7, H2 NH3, H2 NH O NH2 Cat 7H2O 8 13 7Reductive amination of oxygen-containing organic compounds dary amines.For example, at 180 8C and pH2=5 MPa,25 dicy- clohexylamine was obtained from cyclohexanone 7 and aniline 14a over a nickel catalyst, whereas the reaction between the same compounds or their para-substituted derivatives at temperatures of dehydration of alicyclic compounds (above 300 8C) gives 26 only the corresponding diarylamines. R R0 O +H2N 14a ± c 180 8C, H2 NH 7H2O 8 (R=R0=H, 74%) 350 8C NH R R0 7H2,7H2O R, R 0 =H (a), Hal (b), Alk (c).The reductive amination of arylaliphatic aldehydes and ketones with ammonia results in the formation of primary aliphatic-aromatic amines. 9, 27, 28 The reaction is complicated by the reduction of the corresponding carbonyl compounds to hydrocarbons. The yield of the amination products is influenced by the location of the carbonyl group with respect to the aromatic ring of the initial aldehyde or ketone. The yields of amines produced from aromatic aldehydes or alkyl aryl ketones are much lower than the yields of amines formed upon hydroamina- tion of ketones in which the carbonyl group is removed from the aromatic nucleus. Thus over a nickel catalyst at 150 8C and 8 MPa, acetophenone is converted into 1-phenylethylamine 16 in 50% yield.28 O NH2 NH3, H2 CHMe CMe Cat 16 15 NH2 NH3, H2 CH2 CH2CHMe Cat Under the same conditions, benzylideneacetone 17 gives 2-amino-4-phenylbutane in 84% yield.29 O CH CHCMe 17 18 In this case, it should be borne in mind that the reaction starts with hydrogenation of the alkene double bond.This eliminates the conjugation between the carbonyl group and the aromatic nucleus. Thus it has been shown 30 that hydrogenation of 3-phe- nylacrolein 19 at 80 8C and pH2=2 MPa gives initially aldehyde 20 and then alcohol 21. OH O O 21 20 19 A method has been proposed 31, 32 for the synthesis of dia- mines 22 from aliphatic dialdehydes containing four to ten carbon atoms; according to this method, they are treated with excess ammonia and hydrogen in the presence of Ni, Co, Pd or Ru catalysts at 40 ± 1508 C and a pressure of 10 MPa.NH3, H2 H2NCH2(CH2)nCH2NH2 CHO(CH2)nCHO Cat 22 (78% ± 90%) n=4 ± 10. In order to prevent the formation of secondary amines and possible intramolecular cyclisation giving a heterocyclic deriva- 57 tive, excess ammonia is used (the ammonia : aldehyde molar ratio is 5 : 1). Conversely, an excess of the initial dicarbonyl compound is favourable for the formation of heterocyclic systems. Thus the reaction of acetonylacetone 23 with ammonia [the diketone : am- monia molar ratio is (2 ± 3) : 1] in the presence of Raney nickel at pH2=15 MPa resulted in the synthesis of a mixture of 2,5- dimethylpyrrole 24 and 2,5-dimethylpyrrolidine 25, i.e.amination and cyclisation were accompanied by hydrogenation of the pyrrole ring.33 Esters of 4-oxo acids behave in a similar way. O NH O O NH3 MeCCH2CH2CMe MeCCH2CH2CMe Cat 23 Me Me O NH2 NH + NH MeCH CHCH2CMe 7H2O Me Me 25 (28%) 24 (59%) Hydroamination with primary amines, like hydroamination with ammonia, involves evidently the intermediate formation of addition product 26, which is either hydrogenated to amine 27 or is converted initially into imine 28 and then into the amine.34 OH R00NH2 RR0C O RR0C NHR00 26 RR0C NR00 +H2O 28H2 H2 RR0CHNHR00 27 A kinetic study of the catalytic reductive amination of acetone 29 with isopropylamine 30 in aqueous alcohol over a platinum catalyst at 29 8C has demonstrated 35 that the reaction consists of two steps: the formation of imine 31 and its subsequent hydro- genation, giving rise to diisopropylamine 32.PriNH2 (30) H2 Pri2NH Cat Cat Me2C NPri 31 Me2CO 29 32 This pathway to secondary amines, which includes the for- mation of imines, has also been confirmed in studies dealing with hydroamination of furfural 33 with aromatic amines. It was shown that the reaction over palladium catalysts includes the initial formation of the corresponding imines, which are then hydrogenated, in particular, in the furan ring.36 ± 38 The yields of substituted N-(2-tetrahydrofurylmethyl)anilines 34 vary from 10% (for o-bromoaniline) to 85% (for aniline).When palladium immobilised in the polymeric matrix of the AB-17-8 or AN-1 anion exchanger is used, the yield of N-(2-tetrahydrofurylmethy- l)aniline reaches 100%. R H2, Cat CHO + H2N 7H2O O33 R R H2 NH CH N Cat O O CH234 R=H, m-Me, p-Me, o-Me, m-Hal, p-Hal, o-Hal. The reductive amination of furfural 33 with cyclohexylamine over the same catalysts at 20 ± 60 8C and pH2=0.98 ± 1.03 MPa in a solvent (an alcohol or a hydrocarbon) affords N-(2-tetrahydro- furylmethyl)cyclohexylamine 35 in a high yield.58 H2, Cat CHO + H2N 7H2O 13 O33 H2 NH CH N CH2 Cat O O 35 (99%) Palladium catalysts immobilised in an anion-exchanger poly- meric matrix are inferior to Pd/C regarding the rate of formation of the amine 35 but are superior regarding the selectivity and the service stability.The rate of reductive amination of the aldehyde 33 was found 39 to be directly proportional to the dielectric constant of the solvent. N,N-Diethylaminophenols are prepared 40 in high yields by reductive amination of acetaldehyde with o-, m- and p-amino- phenols at 150 8C and pH2=2 MPa in the presence of Pt, Pd or Ni catalysts in the medium of an aliphatic alcohol (MeOH, EtOH, PrnOH). For example, in the case of m-aminophenol, the yield of N,N-diethyl-m-aminophenol was 98.4%. In a study of reductive amination of aliphatic ketones with primary amines, it has been found 41 ± 43 that the product yield is substantially influenced by steric factors caused by the structures of both the ketone and the initial amine.Steric restrictions were considered 44 to be the only reason for the fact that the yields of amines upon the hydro- amination of ketones with cyclohexylamine 13 decrease in the sequence acetone>methyl ethyl ketone>diethyl ketone. When ethanolamine is used instead of cyclohexylamine, steric hindrance markedly diminishes, and the yields of hydroamination products obtained from acetone and diethyl ketone 36 become almost identical. Study of the influence of steric factors on the reductive amination of acetone with aniline and 2,4,6-trimethylaniline 37 45 has shown that the sterically hindered amine 37 is converted into secondary amine, N-isopropyl-2,4,6-trimethylaniline 38, in 36% yield (when aniline is used, the yield of the corresponding secondary amine increases to 98%).Me Me Me2CO, H2 Me NHPri Me NH2 Cat Me Me 38 37 The yield of the product of reductive amination of benzylide- neacetone 17 and benzylideneacetophenone 39 with toluidines 46 Me 300 8C 3 4 R R H2 H2 5 2 Me(CH2)2CCH2CHCHR0 CH2CHCHR0 Pt Pt O1O NHR00 46 NHR00 47 200 8C Me R=R0 =H, Me, Et; R00 =H, Me. V A Tarasevich, N G Kozlov varies as a function of the position of the methyl substituent in the aromatic amine. The yields of secondary amines 40 in the hydro- amination of the ketone 17 were 14.0, 35.0 and 52.4% for o-, m- and p-toluidine, respectively. Meanwhile, it was found that the yields of secondary amines formed from aliphatic amines increase with an increase in the basicity of the amine used. O Me H2 CH CHCR+H2N 7H2O 17, 39 R Me CH2 CH2CHNH 40 R=Me (17), Ph (39).Secondary amines of the aliphatic series have been prepared in two stages from primary amines and aldehydes.47 In the first stage, imines were synthesised; after isolation, they were hydrogenated over a platinum catalyst in anhydrous EtOH. The total yields of the imines 41 and the amines 42 were 40%± 63%.48 R0CHO H2 R NH2 Pt 7H2O RN CHR0 41 RNHCH2R0 42 R=R0 =Et, Prn, Pri, Bun, Bui. Reductive amination of carbonyl compounds of the furan series has been studied only occasionally. Reductive amination of unsaturated ketones 43 with ammonia has been reported.49 ± 51 The reaction was carried out in methanol saturated with ammonia over skeletal nickel ± aluminium catalyst and under a hydrogen pressure of 12 ± 14 MPa.52 O NH2 NH3, H2 Cat (CH CH)nCR (CH2 CH2)nCHR O O 43 n=1, 2; R=Alk.The synthesis of pyrrole (44) and pyrrolidine (45) homologues from furan derivatives 46, containing an amino group in the alkyl substituent, over platinum catalysts should be regarded as a peculiar intramolecular reductive amination reaction (Scheme 2). The reaction consists of two stages: hydrogenolysis of the furan ring at the O(1) ± C(5) bond to give amino ketones 47 and amino alcohols 48 and their intramolecular hydroamination leading to the formation of a heterocycle.53 ± 55 Selective hydrogenolysis at the O(1) ± C(5) bond is possible only with platinum catalysts R Scheme 2 R0 NR00 44 R Me(CH2)2CHCH2CHCHR0 OH NHR00 48 R R0 NR00 45Reductive amination of oxygen-containing organic compounds (Pt/C, Pt/asbestos); in this case, the mixture of reaction products contains pyrrolidines and pyrroles with a propyl radical at the 5-position.Pyrrolidine homologues are formed at 200 ± 220 8C, their yields being 85%± 90%, whereas pyrrole homologues are produced at 300 8C in *85% yield. The yields of N-methyl- substituted pyrrolidines and pyrroles are somewhat lower (70% and 73%± 75%). High-boiling nitrogen-containing compounds (2% ± 3%) and the recovered amine (*23%) were also detected in the product mixture.55 The structure of the pyrrolidines and pyrroles formed is determined by the structure of the aminoalkyl side chain.54, 55 The influence of the structure of alkyl and aminoalkyl groups in the molecules of the furan derivatives 49 on the course of hydro- genolysis and the formation of pyrrole and pyrrolidine trialkyl derivatives was studied.55 3 4 R 2 5 Me CH R00 C CH2 O1NH2 R0 49a ± c R=R0=R00=H (a); R=Me, R0=R00=H (b); R=R0=R00=Me (c).When the substituents R and R0 at the carbon atom attached directly to the furan ring in 49 are methyl groups, hydrogenolysis of the furan ring is more selective, due to the shielding effect, and involves the O(1) ± C(5) bond. In addition, in the presence of these substituents, the formation of the pyrrole ring is impossible. As a result, catalytic hydrogenation of 2-(3-amino-1,1-dimethylbutyl)- 5-methylfuran 49c over platinum catalysts at 250 8C resulted in the synthesis of 2-n-butyl-3,3,5-trimethylpyrrolidine 51.56 3 4 Me H2 2 5 Pt Me C CH2CHMe O1NH2 Me Me 49c 2 3 Me Me H2 Me(CH2)3C C CH2CHMe 4 NH 7H2O 5 O Me NH2 Me 50 51 Whereas the reaction on platinum catalysts gives only one series of pyrrolidine homologues owing to the selective rupture of the C(5) ± O(1) bond at 200 ± 220 8C, in the presence of skeletal nickel ± aluminium catalysts, three series of pyrrolidine homo- logues containing methyl, ethyl or n-propyl groups at the 2-posi- tion can be obtained (Scheme 3).57 Scheme 3 3 4 R 2 5 CH2 CH CH2 O1NH2 b c a R R R MeCCH2CHCH2 MeCH2CCH2CHCH2 Me(CH2)2CCH2CHCH2 O O NH2 NH2 NH2 O R R R NH NH HN (a) rupture of the O(1) ± C(5) bond; (b) rupture of the O(1) ± C(5) and C(4) ± C(5) bonds; (c) rupture of the O(1) ± C(5) and C(3) ± C(4) bonds.59 The yield of pyrrolidines in the hydrogenolysis products was, on the average, 70%± 75% based on the consumed amine. The pyrrolidines formed contained 35% of 2-methyl-4-R-pyrrolidines, 20% of 2-ethyl-4-R-pyrrolidines and 45% of 2-n-propyl-4-R- pyrrolidines. The formation of a particular pyrrolidine homo- logue depends substantially on the reaction temperature. For example, when the temperature is raised to 270 8C, the proportion of 2-methyl-4-R-pyrrolidines increases to approximately 50%± 60%; however, the overall content of pyrrolidines in the reaction products diminishes to 30%± 40%.The synthesis of pyrrole homologues over skeletal nickel ± aluminium catalyst is carried out at 300 8C;58 in this case, the mixture of pyrroles contains 30% of 2-methyl-5-R-pyrroles, 25% of 2-ethyl-5-R-pyrroles and 45% of 2-n-propyl-5-R-pyrroles (Scheme 4). 3 4 Scheme 4 2 5 CH R CH2 CH2 O1NH2 b c a R R R MeC(CH2)2CH MeCH2C(CH2)2CH MeCH2CH2C(CH2)2CH O O O H2N H2N H2N R R R HN NH HN (a) rupture of the O(1)7C(5) bonds; (b) rupture of the O(1)7C(5) and C(4)7C(5) bonds; (c) rupture of the O(1)7C(5) and C(3)7C(4) bonds. Hydroamination of cyclohexanone 7 and cyclopentanone 52 was performed 59 using azobenzene 53, 1,2-diphenylhydrazine 54 and cyclohexanone phenylhydrazone 55.It is known that hydra- zines are able to undergo hydrogenolysis over nickel ± alumina or copper ± alumina catalysts at 250 8C to give primary amines.60 It was found that in all cases, hydrogenolysis of the N±N bond and the formation of secondary cycloalkylamines (in 18% to 75% yields) is a typical reaction pathway. Since the N=N bond in azobenzene 53 is relatively stable, it can undergo hydrogenolyis only after saturation; therefore, the use of the hydrazine 54 results in higher yields of the reductive amination products; for example, the yields of N-cyclohexylaniline 56 obtained upon hydroamina- tion of cyclohexanone with azobenzene and 1,2-diphenylhydra- zine are 45% and 75%, respectively. H2 NH NH N N 54 53 7, H2 H2 N NH2 7H2O 14a NH 56 Several studies,14, 61 ± 70 `generically' related to hydroamina- tion, deserve special attention.They describe the synthesis of various amines in the presence of RPFIC in the Fischer ± Tropsch synthesis. These catalysts are used to prepare various hydro- carbons and oxygen-containing organic compounds from CO and H2.71, 72 The use of the modified Fischer ± Tropsch reaction for the synthesis of oxygen-containing compounds and their reductive amination with ammonia, alkylamines and piperidine 57 have led to the development of a number of one-step proce-60 dures for the synthesis of various amines. Thus hydrogenation of CO at 169 ± 195 8C, 10 ± 12 MPa and at an H2 :CO ratio of (2 ± 6) : 1 in the presence of HNMe2 (1 vol.%±10 vol.%) over RPFIC gives rise to dimethylalkylamines.70 The yield of liquid amines reaches 73%. The use of piperidine and RPFIC in the modified Fischer ± Tropsch synthesis permitted the preparation of N-alkyl- piperidines with alkyl substituents consisting of one to fifteen C atoms at the nitrogen atom (the selectivity of the reaction with respect to amines reaches 97%).64 ± 69 The highest activity was found for RPFIC containing V2O5, Al2O3 or Cr2O3 and CuO.68 Two pathways to N-alkyldimethylamines are possible: (1) hydro- amination of a surface oxygen-containing intermediate, precursor of an aldehyde, ketone or alcohol; (2) direct hydroamination of alkanals or alkyl methyl ketones, primary components of the Fischer ± Tropsch synthesis.Synthesis of alkylamines from CO, H2 and N2 in the presence of RPFIC has been carried out. The process included two alternating reactions performed in one catalytic area: first NH3 was obtained from H2 and N2 and then it was used to aminate the oxygen-containing or olefinic products of the Fischer ± Tropsch synthesis, formed after the introduction of CO. Primary terminal C4 ±C9 amines were the major reaction products.73, 74 Reductive amination of aldehydes and ketones is usually carried out at high (up to 50 MPa) pressures of hydrogen.75 Various solvents have been used in this process, MeOH, EtOH, PriOH, ButOH, THF and cyclohexanol.76 ± 78 Nickel or cobalt catalysts 34, 77,79 ± 81 and platinum group metals (Pt, Pd) supported on activated carbon 79, 82 ± 85 are used most often. Some metals (Ni, Pt, Ru, Rh) supported on an active material, for example, on alumina or kieselguhr, are also employed.77,86 ± 88 Catalysts based on copper and chromium oxide mixtures have been patented.89 Rhenium and palladium sulfides (Re2S7, PdS) as well as Fe, Co, Ni,Wand Mo sulfides supported on alumina proved to be highly active catalysts of reductive amination.90, 91 In some studies, catalysts modified with sulfur or other organic or inorganic sulfur-containing compounds have been considered.Thus reduc- tive amination of 4-methylpentan-2-one 58 with N-phenyl-1,4- phenylenediamine 59 over nickel supported on kieselguhr (63% Ni) at 165 8C and a hydrogen pressure of 5.2 ± 7.0 MPa gave N-phenyl-N0-(1,3-dimethylbutyl)-1,4-phenylenediamine 60 in 58% yield.The addition of But2S increased the yield of the diamine 60 to 97%.88 H2 MeCCH2CHMe2+H2N NH Ni 59 58 O NH NH MeCHCH2CHMe2 60 Sulfoxides, thiols and sulfur-containing heterocycles have also been used to modify the catalysts.92 The influence of the nature of the catalyst on the yield of the final product can be followed in relation to the reductive amination of camphor 61 with methyl- amine 62. Thus when Raney nickel is used as the catalyst, N- methylbornan-2-imine 63 (yield 82.8%) is formed predominantly, whereas the reaction over 5% Pd/C yields a mixture of the imine 63 and N-methylbornan-2-ylamine 64 (30.4% and 65.7%, respec- tively). H2 MeNH2 (62) 7H2O NHMe NMe O 64 61 63 H If platinum oxide is used as the catalyst, the yield of the amine 64 reaches 92.7%.82 High stereoselectivity of RPFIC, unusual for metallic heterogeneous catalysts, has been noted.93 ± 95 Thus the V A Tarasevich, N G Kozlov degree of transformation of d,l-camphor into endo- (65) and exo- bornan-2-ylamines (64) during hydroamination reaches 92%, the endo to exo ratio being (1.4 ± 1.8) : 1.Apparently, this stereo- selectivity is due to the `imine ± enamine' tautomerisation occur- ring on the acid ± base sites of the catalyst. RNH2, H2 + 7H2O H NHR O 65 64 61 H NHR R=H, Alk. Highly effective and selective catalysts for hydroamination of aldehydes and ketones with ammonia, amines and nitro com- pounds have been developed.These catalysts, which make it possible to conduct this reaction under mild conditions (20 ± 60 8C, and pH2=0.1 MPa), are Pd, Pt, Rh, Co, Fe, Ni and Cu complexes with dimethyl- and dibenzylglyoximes and with poly- meric macroligands such as polyacrylic acid, polyethyleneimine, copolymers, anion exchangers, cation exchangers, etc.96 ± 106 The rate of hydroamination in the presence of these catalysts depends appreciably on the nature of the polymeric matrix. The major contribution to the activity is made by the rigidity of those sections of the macromolecule which bear the active metal sites. The activity and selectivity of these catalysts can be controlled by changing the `local rigidity;' this can be attained by increasing the temperature, by using a different solvent or exchangeable ion, by varying the particle size of the support, by irradiating the polymeric matrix or by introducing microadditives of another solvent.99, 106 III.Reductive amination of alcohols with ammonia and amines The reaction of ammonia with alcohols results in the formation of mixtures of primary, secondary and tertiary amines. In the vast majority of cases, alcohols react with ammonia or amines only in the presence of catalysts. Heterogeneous acidic catalysts have found wide application in industry. In the presence of these catalysts, the process is carried out in the gas phase at 350 ± 450 8C. Their influence consists in the activation of the C±OH bond due to adsorption of the alcohol on the catalyst acid sites.The reactions between ammonia and alcohols are carried out using dehydrating catalysts (copper, nickel and cobalt on alumina, fused iron, copper chromites) 107 ± 111 and hydrogen. In this case, the reaction follows a mechanism other than the acid ± base one. First, the alcohol is dehydrogenated to give aldehyde, and then the aldehyde condenses with ammonia, and the imine thus formed undergoes hydrogenation coupled with dehydration. NH3 H2 RCHO RCH2OH 7H2 7H2O RCH NH Cat RCH NH RCH2NH2 (RCH2)2NH RCH NH (RCH2)3N 7NH3 7NH3 The mechanism of dehydration of alcohols followed by amination has been comprehensively studied by Bashkirov et al.112 ± 117 Secondary and tertiary amines are formed upon the reactions of primary and secondary amines with aldimines.RPFIC modified with various oxides have been successfully used in reactions with amines. For example, hydroamination of a number of alcohols (2-ethylhexan-1-ol, octan-1-ol, octan-2-ol, heptan-4-ol) with dimethylamine at 210 ± 240 8C gave the corre- sponding N,N-dimethylalkylamines in *80% yields. The highest yield of tertiary amine was observed in the presence of RPFIC promoted by 10% Al2O3+1% CuO.118 The same catalyst was used in the reductive amination of borneols 66 with ammonia, which afforded bornylamines 67 and 68, mostly as endo-iso- mers.119Reductive amination of oxygen-containing organic compounds NH3, H2 + 7H2O H NH2 OH 67 68 66 H NH2 Copper-containing catalysts exhibit high activity in the ami- nation of various alcohols with ammonia and amines. When bifunctional catalysts, Cu/Al2O3 or Ni/Al2O3, were used in hydro- amination of alicyclic alcohols, the yields of primary amines reached 80%. To suppress cyclisation and isomerisation, lithium and potassium hydroxides were introduced into the alumina.120 Hydroamination of cyclohex-2-enol 69 in the presence of Cu/ Al2O3, Ni/Al2O3 and Pt/Al2O3 has been studied.121 In the case of the copper catalysts, cyclohexylamine is mostly formed (yield 65%), whereas the reaction carried out at 310 8C over active dehydrating Pt and Ni catalysts containing 10%, 15% and 20% of the metal gives aniline.In the presence of copper and nickel catalysts at 310 8C, pyridine bases are formed, mostly 2-methyl- pyridine (60% ± 62% of the total amount of pyridine bases). Presumably, in the latter case, the reaction passes through the formation of an unstable bicyclic compound resulting from insertion of the nitrogen atom of the amino group into the ring with the simultaneous rupture of the carbon ± carbon bond.NH2 OH NH2 7H2 14a NH3 Cat HN NH3 69 7H2 Cat N When alkanols are hydroaminated with dimethylamine, 2-eth- ylhexylamine and cyclohexylamine over the industrial copper ± zinc ±aluminium oxide-type catalyst (SNM-1) and over RPFIC,122 ± 125 the highest yields of non-symmetrical secondary and tertiary amines (up to 90%) are attained at 175 ± 195 8C and at an amine : alcohol molar ratio of 0.2.Secondary amines con- taining an alkyl radical (C10 ±C22) are prepared by hydroamina- tion of alcohols with primary amines at pH2=0.3 ± 0.5 MPa in the presence of the Ni or Ni ± Cu catalyst containing someK2CO3; the yields of non-symmetrical secondary alkylamines can be as high as 85%. H2 RNHR0 +RNR0 RNH2+R0OH 2 Ni, K2CO3 R=C10H21 ±C22H45, R0 =CH3 ±C8H17. When K2CO3 is not added, the content of secondary amine in the amination products is 17%, and the content of tertiary amine is 45%.126 To increase the yield of amines, nickel catalysts are modified with various additives. Thus the activity of nickel oxides prepared by various methods and their mechanical mixtures with titanium dioxide, quartz and Aerosil has been studied in the vapour-phase amination of n-butanol in the presence of hydrogen under atmospheric pressure.127 Synergism of nickel ±titanium and nickel ± silicon binary oxide catalysts in this reaction was found.It is noteworthy that in some cases, in order to attain higher yields of amines, two-stage synthetic procedures are used, which include a separate a stage of dehydration of alcohols to aldehydes.111 Non-symmetrical dialkylamines are prepared in 75% ±90% yields 112 by the reaction of a primary amine with an alcohol in the presence of a catalyst containing copper chromite at 180 ± 210 8C and pH2=4.0 ± 12.0 MPa. When copper catalysts are used, the reaction between ethanol and ammonia at pH2=15.0 MPa affords triethylamine (yield 90%).128 Unlike hydroamination of primary and secondary aliphatic alcohols with ammonia, which mainly yields primary amines, hydroamination of tetrtahydrofurfuryl alcohol 70 gives rise to a 61 heterocyclic compound, piperidine 57.This reaction, which is of interest from the practical viewpoint, has been studied in detail.129 ± 135 Scheme 5 shows the possible pathways to the main products (57, 71 ± 74) formed from the alcohol 70, ammonia and hydrogen. It was found that, irrespective of the catalyst used, the reaction products contain piperidine, tetrahydrofurfurylamine 71, N-(n-pentyl)piperidine 72, N-(tetrahydrofurfuryl)piperidine 73 and bis(tetrahydrofurfuryl)amine 74. Scheme 5 NH3, H2 7H2O HN OH 57 O 70 NH3 NH2 7H2O O71 H2 H2 70 OH HO 7H2O 75 57 N OH 7H2O 72 76 70+57 N CH2 7H2O O 73 70+71 CH2NHCH2 7H2O O O 74 When this reaction is carried out in the presence of the SNM-1 catalyst, the yield of the amine 71 reaches 62% at a virtually complete conversion of tetrahydrofurfuryl alcohol. When Co- and Ni-based catalysts are used, the formation of piperidine is the predominant reaction route (its yield reaches 51%).The com- pounds 73 and 74 result from intermolecular amination of the alcohol 70 with piperidine and with the amine 71, respectively. The presence of N-(n-pentyl)piperidine 72 among the reaction prod- ucts was explained 135 by hydrogenolysis of the alcohol 70 at the intracyclic C±O bond with the intermediate formation of pen- tane-1,5-diol 75, its partial hydrodeoxygenation to n-pentan-1-ol 76 and subsequent interaction of the alcohol 76 with piperidine.Nitrogen-containing five-, six- and seven-membered hetero- cyclic compounds have been prepared by hydroamination of the corresponding diols with ammonia over the industrial SNM-1 catalysts and RPFIC.136 ± 139 The formation of the heterocycle in the reaction of butane-1,4-diol 77 with a mixture of NH3 and H2 (Scheme 6) occurs in two stages. First, the initial diol 77 is aminated to give 4-aminobutan-1-ol 78, and then this product undergoes intramolecular amination (cyclisation) to give pyrroli- dine 79. Scheme 6 NH3 OH O HO HO 7H2O 7H2 77 NH2 NH HO 7H2O 78 79 NH2 H2 78+79 N N 7NH3 81 80 N N N N 77+797H2O 7H2 82 8362 The yield of the compound 79 on the SNM-1 catalyst at 220 8C reaches 85.5%.139 The appearance of N-4-aminobutylpyr- rolidine 80 in the product mixture can be interpreted as being due to the reaction between 4-aminobutan-1-ol 78 and pyrrolidine.Partial hydrodeazotisation of the compound 80 affords N-(n- butyl)pyrrolidine 81. 1,4-Dipyrrolidinobutane 82 is formed upon exhaustive amination of butanediol with pyrrolidine. The highest yield of the compound 82 (22.5%) was attained with RPFIC. Dehydrogenation of one heterocycle in the molecule of 82 gives rise to N-(4-pyrrolidinobutyl)pyrrole 83. The reaction of hexane-2,5-diol 84 with a mixture of NH3 and H2 is highly selective. The yield of 2,5-dimethylpyrrolidine 25 over RPFIC at 200 8C amounts to 93%.139 The subsequent dehydro- genation of pyrrolidine 25 yields 2,5-dimethylpyrrole 24.OH NH3 72H2O 7H2 HN HN OH 84 24 25 Hydroamination of pentane-1,5-diol 75 and hexane-1,6-diol 85 with ammonia follows a similar route, resulting in the for- mation of piperidine 57 and perhydroazepine 86, respectively. (CH2)m NH3 HO(CH2)nNH2 HO(CH2)nOH 7H2O 7H2O 75, 85 NH 57, 86 n=5 (75), 6 (85); m=1 (57), 2 (86). The main pathways of the catalytic transformations of the diol 75 during its interaction with NH3 and H2 can be illustrated by Scheme 7. The presence of N-(n-pentyl)piperidine 72 in the reaction products is due to the alkylation of piperidine 57 with the diol 75 involving the intermediate formation of N-(5-hydrox- ypentyl)piperidine 87 and its subsequent hydrodeoxygenation. Hydrogenolysis of the C±C bond in the alkyl substituent of the compound 72 accompanied by elimination of an n-butane mole- cule gives rise to N-methylpiperidine 88.Scheme 7 H2 NH+HO(CH2)5OH N(CH2)5OH 7H2O 7H2O 75 87 57 H2 NMe N(CH2)4Me 7BunH 88 72 A typical feature of the transformation of the diol 85 139 (Scheme 8) is relatively high yields of N-alkyl-substituted perhy- droazepines 89 ± 91 and secondary and tertiary alkylamines 92 ± 94. For example, when the diol 85 is hydroaminated over the SNM-1 catalyst at 1808C, the total contents of perhydroazepines 89 and 91 in the reaction products reaches 22%. Piperazine and 1-alkyl- and 1,4-dialkyl-piperazines have been synthesised by hydroamination of diethanolamine or N-alkyldie- thanolamines in the presence of RPFIC.140 Cyclisation of ethyl- enediamine 95 with propane-1,2-diol 96 giving 2-methylpyrazine 97 over a catalyst containing 1% of Pd supported on a mixture of zinc and chromium oxides (Zn : Cr = 3 : 1) has been studied.141 The highest selectivity of this process is observed at 388C.N HNH2 H2N(CH2)2NH2+MeCHCH2OH Pd 7H2 Me Me 95 96 OH NH N97 V A Tarasevich, N G Kozlov Scheme 8 NH3 NH3 Me(CH2)5NH2 72H2O 72H2O HO(CH2)6OH 85 HN 86 H2 N(CH2)5Me 85+86 7MeH 89 H2 N Me N(CH2)4Me 7BunH 90 91 {Me(CH2)5}2NH Me(CH2)5NH2 7NH3 7H2 Me(CH2)5NH(CH2)4CH CH2 92 H2 Me(CH2)5 3N Me(CH2)5 2N(CH2)4Me 7NH3 7CH4 93 94 IV.Reductive amination of aldehydes and ketones with nitro compounds and pyridine bases Reduction of nitro compounds, which is carried out in a variety of ways (catalytic hydrogenation; reduction with iron in the presence of hydrochloric acid, with metal sulfides, zinc or iron in a strongly alkaline medium, lithium aluminium hydride and hydrazine; and electrochemical reduction) is among the methods used most widely for the synthesis of amines. These reactions occur via several intermediate stages; for most of the reducing agents listed above, they include the formation of nitroso compounds and hydroxylamines. H2 H2 H2 R2CHNO R2CHNO2 R2CHNHOH 7H2O 7H2O R2CHNH2 R2C NOH Catalytic hydrogenation has found wide application in indus- try. Most often, it is used to convert aromatic nitro compounds into the corresponding amines.142, 143 The ability of nitro compounds to be reduced to amines under the conditions of reductive amination has permitted the use of this ample class of nitrogen-containing organic compounds for direct amination of aldehydes and ketones.This reaction was first performed by Emerson.144 A mixture of acetone 29 and nitro- benzene 98 was reduced by hydrogen in an autoclave over platinum oxide; the yield of N-isopropylaniline 99 reached 59%.144±147 H2 NHPri NO2 PtO2 Me2CO+ 29 99 98 Subsequently this reaction has been widely used to synthesise secondary amines. Hydroamination by nitro compounds is nor- mally carried out in autoclaves over platinum catalysts under a pressure of hydrogen.86,148 Thus reductive amination of acetone by 4-nitrodiphenylamine at 120 8C and pH2=2.0 ±2.5 MPa on the Pt/C catalyst gave N-phenyl-N0-isopropyl-p-phenylenediamine in 95% yield.149 To increase the yield of secondary amines the catalysts are modified by various additives. For example, the reaction catalysed by platinum supported on carbon containing phosphorous acid gives amines in preparative yields.78 Other acids or acidic compounds�H3BO3, organic acids or anhydrides, CO2Reductive amination of oxygen-containing organic compounds � are also used as modifying agents.Acidic additives form salts with primary amines and thus prevent side reactions. Apart from platinum, nickel catalysts are also widely used in this reaction.The use of a catalyst containing 63% of Ni supported on kieselguhr permits preparation of secondary amines from nitro compounds and ketones in yields of up to 57%. Modification of this catalyst by sulfur-containing compounds (sulfides, disulfides, sulfoxides, thiols) made it possible to increase the yields of amines to 75%.87 Hydroamination carried out with aromatic nitro compounds is accompanied in some cases by hydrogenation of the aromatic ring.150,151 To prevent this process, mixtures otones with aromatic nitro compounds are reduced over various catalysts containing Pt, Pd, Ni, Rh, Os, Sr or Co on silica or alumina in the presence of SO2.150 The same can be attained by using metal sulfides.Amines can be obtained in preparative yields by conducting the reaction at 250 8C at a pressure of hydrogen of up to 10.0 MPa in the presence of cobalt, nickel or molybdenum selenide or telluride as the catalyst.152 Palladium-containing anion exchangers are efficient catalysts of hydroamination of aldehydes and ketones by nitro compounds (mostly, aromatic ones).99,106 A study of the influence of the substrate structure on the rates of hydroamination of oxygen- containing compounds by nitro compounds of the aromatic series has shown that the reaction rate decreases following an increase in the magnitude of the Hammett constant.153 Several studies 151, 154 ± 156 have been devoted to hydroamina- tion of alicyclic and heterocyclic ketones by nitro compounds of aliphatic and aromatic series over nickel± and copper ± alumina catalysts.It was found 151 that hydroamination of alicyclic ketones 99 with nitrobenzene at 250 8C and at pH2=2.0 MPa over nickel catalysts gives rise to N-cycloalkylcyclohexylamines in yields of up to 82%. In the presence of copper catalysts, N-cyclo- alkylanilines are formed in this reaction (yields 40%± 80%). H2 O NH (CH2)n Ni/Al2O3 (CH2)n NO2+ H2 NH 98 99 (CH2)n Cu/Al2O3 n=2 ± 4. The capability of pyridine and its alkyl-substituted derivatives to be reduced to piperidines permits the use of these nitrogen- containing heterocycles in the reductive amination of ketones. Thus reductive amination of aliphatic and alicyclic ketones with pyridine and its monomethyl derivatives over nickel catalysts under a pressure of hydrogen has been studied.157, 158 The reac- tions of pyridine 100 and a-, b- and g-picolines 101a ± c with ketones afford the corresponding N-substituted piperidines as the major products.R R0R00CO N CHR0R00 R H2 O N Ni/Al2O3 (CH2)n R N (CH2)n 100, 101a ± c R=H (100), 2-Me (101a), 3-Me (101b), 4-Me (101c); R0 =Me, Et, But; R00 =Me, Et; n=2, 3. It was assumed 157, 158 that this reaction can follow two path- ways. One of them includes simultaneous reduction of the ketone to the corresponding secondary alcohol and hydrogenation of pyridine 100 to piperidine 57. The subsequent interaction of the alcohol with piperidine accompanied by dehydration affords N- substituted piperidine derivatives.In the second pathway, pyr- idine is reduced to piperidine and the latter reacts directly with the ketone, without its intermediate transformation into the alcohol. This pathway, like the first one, affords N-substituted piperidine as the final product. 63 The use of a-picoline as the aminating agent demonstrated that the methyl group located in the vicinity of nitrogen has a substantial influence on the reaction route. For example, hydro- amination of methyl ethyl ketone 102 with this compound, in addition to the expected product 103 (yield 4%), gave the products resulting from elimination of the methyl group from the pyridine ring (104, 9%) and elimination of the methyl group from the N-substituent (105, 5%).Me CH Et N 103 Me Me H2 +O C Et N CH Et N Me 104 Me 102 101a Et N CH2 105 The course of hydroamination of aliphatic ketones with pyridine bases depends substantially on the ketone structure. Thus the highest yield of the final reaction products is achieved when pyridine is made to react with alkyl methyl ketones; for example, the yield of N-butan-2-ylpiperidine in the reaction with methyl ethyl ketone amounts to 50%. When pyridine reacts with diethyl ketone 36 and propyl ethyl ketone 106, the yields of the target reaction products sharply decrease (32%, for the ketone 36) due to the substantial steric hindrance created by the two alkyl radicals attached to the carbonyl group. tert-Butyl methyl ketone does not enter into hydroamination at all.158 The optimum conditions for the synthesis of N-alkylpiperidines are the follow- ing: temperature 220 ± 230 8C, pH2=2.0 MPa; v=0.3 h71, cata- lyst�20% Ni/Al2O3.158 V.Reductive amination of aldehydes, ketones and alcohols with nitriles and oximes 1. Nitriles and oximes as aminating agents Owing to the progress in the chemistry of nitrogen-containing organic compounds achieved in recent years, nitriles can be considered to be readily available starting compounds for the synthesis of diverse and valuable organic products. Methods of catalytic ammonolysis occupy a special place in the synthesis of nitriles. They include, first of all, oxidative ammonolysis of saturated and unsaturated hydrocarbons, meth- ylbenzenes, naphthalene and pyridine.Linear hydrocarbons, for example, butane and butenes, can be converted by ammonolysis into saturated and unsaturated mono- and dinitriles.159 ± 167 Thus oxidative ammonolysis of butadiene gives rise to a mixture of nitriles of fumaric and maleic acids (total yield 67%).168 Oxidative ammonolysis of toluene, xylenes, mesitylene or dimethylnaphtha- lenes can be used to synthesise nitriles of the corresponding mono- , di-, and tri-carboxylic acids, their yields being 70%± 95%.169, 170 Halotoluenes, toluidines and cresols can also be introduced into ammonolysis; this gives rise to the corresponding benzonitrile. Methylpyridines are converted into the nitriles of pyridinecarbox- ylic acids in 70%± 95% yields.171 ± 175 At present, ammonolysis is employed in industry to produce acrylonitrile, benzonitrile and nitriles of methacrylic, terephthalic, and nicotinic acids. These processes have been patented and considered in several reviews (see, for example, Refs 176 ±179).Thus, the development of this line of research has extended substantially the range of raw materials used for the production of diverse amines. Hydrogenation of carbonitriles has been studied in detail, because the products of their reduction are important for practical purposes. Nitriles are converted into primary amines upon the64 addition of two hydrogen molecules. However, the first molecule is added faster than the second one. Therefore, the reduction intermediately gives aldimines, which are converted into primary amines during subsequent hydrogenation.In some cases aldi- mines can be isolated in a pure state. The general pattern of hydrogenation of nitriles can be written as follows: H2 H2 RC N RCH NH RCH2NH2. Cat Cat Aldimines are highly reactive and are able to react with the resulting primary amines; this gives rise to secondary and tertiary amines. Therefore, hydrogenation of nitriles can yield different products, depending on the reaction conditions.180 Catalytic reduction of nitriles with molecular hydrogen is the most interesting process. A fairly broad range of catalysts have found practical application in the nitrile hydrogenation�mono- metallic (Pt, Pd, Ni, Co, etc.) and bimetallic (Ni ± Co, Co ± Cr, etc.) catalysts; bifunctional metallic catalysts supported on vari- ous materials (Al2O3, TiO2, SiO2, MgO) modified with various additives (acids, alkalis); and metals (Pt, Pd, Ni, Co) immobilised on polymers.For example, synthesis of 3-amino-5-aminomethyl- 2-methyl-4-methoxymethylpyridine by coupled hydrogenation and dehalogenation of 6-chloro-2-methyl-4-methoxymethyl-3- nitropyridine-5-carbonitrile over palladium-containing anion exchanger AB-17-8 has been described.181 The yield of the target product (20 ± 60 8C, pH2=0.98 ± 1.03 MPa, EtOH as the solvent) reaches 99%. The catalyst proposed for this reaction proved to be much more stable and active than Pd/C. Data on the liquid-phase hydrogenation of hexanenitrile to amines have been reported.182 Reduced metals (Ni, Co, Ru, Pd, Pt, Os, Cu) on g-Al2O3 were used as the catalysts in this reaction.In terms of their activity in hydrogenation, the studied catalysts can be arranged in the sequence Ru>Ni>Os>Co>Pd>Pt >Cu; the selectivities of these catalysts were also dissimilar. Thus the cobalt catalyst exhibited the highest selectivity (91%) with respect to primary amine (hexylamine). The highselectivity with respect to secondary amine was found for Ru and Pt catalysts (81% ± 89%). In the presence of the Pd catalyst, the yields of di- and tri-hexylamines are 65.4% and 34.6%, respectively. Hydro- genation of hexanenitrile over the industrial nickel ± chromium catalyst at 120 ± 140 8C and pH2=5.0 MPa gave a mixture of amines containing 64% of the secondary amine and 36% of the primary and tertiary amines (the total yield).By varying the reaction temperature, the pressure of hydrogen and the chemical composition of the catalyst, the ratio of the reaction products can be controlled. Thus at 145 8C and pH2=0.35 ± 0.50 MPa, 100% conversion of acetonitrile was attained; the reaction products were found to contain 3.1% of primary amines, 45.4% of secondary amines and 51.5% of tertiary amines. At higher temperatures, the yield of secondary amines increases.180 The use of Pd, Pt and Ru catalysts supported on lithium aluminium spinel in this reaction permits the preparation of an amine mixture containing 99.7% of tertiary amine.183 Numerous studies dealing with hydrogenation of acetonitrile 107 and acrylonitrile 108 over a series of copper and copper ± nickel catalysts with various metal contents (5% Cu; 8%Cu+2%Ni; 15%Cu+2%Ni, etc.) have been carried out.Gumbrin was used as the support. Some catalyst specimens were modified with NaOH (3%). Hydrogenation was carried out at 100 ± 200 8C under atmospheric pressure. The reduction of the nitriles 107 and 108 affords mixtures of the corresponding primary, secondary and tertiary amines. The copper ± nickel catalyst (8% Cu+2%Ni) annealed at 900 8C proved to be the most active towards hydrogenation of acrylonitrile; the total yield of amines on this catalyst was 69.7%. The modification of the Cu ± Ni catalyst with alkali increases its stability.184 The nitrile 108 was converted into dipropylamine in two stages with a high yield.185 In the first stage, acrylonitrile was hydrogenated to propionitrile 109 in the presence of a catalyst containing Pd, Bi and K on silica gel, and in the second stage, the resulting V A Tarasevich, N G Kozlov propionitrile was converted into dipropylamine using 50%± 56% Ni supported on kieselguhr at pH2=0.1 ± 2.0 MPa and 140 ± 200 8C.H2 H2 (CH3CH2CH2)2NH CHCN CH2CH2CN CH2 109 108 To increase the yield of primary amines, hydrogenation is carried out in the presence of ammonia. The role of ammonia or alkali is to retard the reaction of aldimines with amines and deamination.186 ± 188 The addition of ammonia markedly increases the yields of higher primary amines (C8 ±C24) produced in the hydrogenation of the corresponding individual nitriles or their mixtures.189 ± 191 The introduction of LiOH, NaOH, KOH or Na2CO3 (0.1 mass %± 2.0 mass % relative to the catalyst) leads to higher yields of primary amines.Thus hydrogenation of phenylacetonitrile 110 over Raney nickel gave 2-phenylethyl- amine 111 in 51.2% yield, the yield of the corresponding secon- dary amine 112 being 37.5%. When 2.0 mass % NaOH was introduced into the catalyst, the yield of the primary amine became 92.5% ±95.5%.192, 193 H2 CH2CN Cat 110 CH2CH2NH2+ CH2CH2 2NH 111 112 Since benzylamine 113 is a valuable compound for fine organic synthesis, a large number of studies dealing with catalytic hydrogenation of benzonitrile have been carried out.Hydrogena- tion of benzonitrile in dioxane in the presence of ammonia at 70 ± 80 8C has been studied.194 Nickel supported on kieselguhr was used as the catalyst. The benzene ring was not hydrogenated under these conditions; the yield of benzylamine was 76% ±79% and the selectivity was 82.5%. Interesting results have been obtained in a study of hydrogenation of benzonitrile on the Pt/C, Pd/C and Ru/ C catalysts.195 The reaction rate was found to increase on increasing the pressure of hydrogen; however, the yield of toluene also increased (from 0.3% ± 3.0% to 8%± 9%). Hydrogenation of nitriles and dinitriles in methanol or cyclo- hexane 196 is carried out on cobalt catalysts supported on Fe, Co, Mnor Cr metal powders at 80 ± 120 8C and pH2=25.0 ± 35.0 MPa in the presence of ammonia.The yields of the corresponding primary amines were 90%± 95%. It was noted that the service life of metal-supported catalysts is longer than those of catalysts supported on oxides. Dinitriles of the aliphatic and aromatic series are hydro- genated under the same conditions as mononitriles. For example, octamethylenediamine (yield 91%) is prepared by catalytic reduc- tion of the dinitrile of the corresponding acid in the presence of a ruthenium catalyst in an inert solvent containing an additive of NH3, at pH2=3.0 MPa.197 By varying the reaction conditions, the reduction of dinitriles can be terminated at the stage of formation of amino nitrile as the major reaction product.Thus the dinitriles CN(CH2)nCN (where n = 1 ± 10) can be converted on a rhodium catalyst into the corresponding amino nitriles, formed in high yields.198, 199 Data on the conditions and the mechanism of this reaction and various factors that influence its course have been described systematically.200 The mechanisms of the formation of primary, secondary and tertiary amines were described in detail. In terms of their activity in this reaction, known catalysts can be arranged in the following sequence: Pt>Pd>Ni>Co>Fe> Cu. The reduction of aliphatic dinitriles containing CN groups at the 1,2-, 1,3- and 1,4-positions, in addition to the corresponding diamines, yields five-, six- and seven-membered saturated hetero- cyclic compounds, resulting from intramolecular heterocyclisa-Reductive amination of oxygen-containing organic compounds tion.For example, succinodinitrile 115 is converted into pyrroli- dine 79. H2 H2N(CH2)4NH2 +NH3 NC(CH2)2CN 115 HN 79 Data on the hydrogenation of nitriles in the presence of homogeneous or heterogeneous catalysts in the liquid phase have been described systematically.201 The reaction mechanisms and the pathways to side products were considered. The effects of the solvent, temperature, the pressure of hydrogen and the nature of the catalyst on the course of this reaction carried out over heterogeneous catalysts were studied. Oximes are also hydrogenated using nickel catalysts.Thus hydrogenation of acetone oxime gives a mixture of amines in which the secondary amine predominates.202 H2 Me2CHNH2+(Me2CH)2NH Me2C NOH Hydrogenation of a number of alkylaromatic oximes has been studied.203 It was found that the formation of primary amines is preceded by the intermediate formation of imines 116; in some cases, they can be isolated from the reaction mixture (Scheme 9). The reaction products contain primary, secondary and tertiary amines.204 ± 207 Secondary amines result from interaction of the imine 116 with primary amines. They can also arise upon deamination of primary amines in the presence of a catalyst.208 Scheme 9 H2 H2 116 NH PhC PhC NOH PhCHNH2 Alk Alk 116 Alk NH2 H2 C N CHPh Ph NH CHPh PhC 7NH3 Alk Alk Alk Alk PhCH NH Alk 2 Rosenmund et al.209 were the first to use an oxime acetate for preventing the formation of a secondary amine.Hydrogenation of the benzaldehyde oxime acetate 117 gave a primary amine (formed as acetate 118) in 91% yield. + H2 CH NOAc AcO7 CH2NH3 117 118 Primary amines are also prepared by hydrogenation of oximes in acetic anhydride. Thus hydrogenation of benzaldehyde oxime under these conditions resulted in the synthesis of N-benzylaceta- mide; hydrogenation of acetone oxime gave N-(1-phenylethyl)a- cetamide.204 Free amines are obtained by hydrolysis of these amides. Good yields of primary amines, formed as hydrochlor- ides, are attained when oximes are hydrogenated on a palladium catalyst in anhydrous ethanol with three equivalents of HCl.210 Hydrogenation of oximes in the presence of ammonia,211 which increases the yield of primary amines, has found a wider practical application.In the case of catalytic hydrogenation of oximes, nickel, cobalt and rhodium supported on alumina are used most often as the catalysts.204 In the reduction of oximes of a,b-unsaturated ketones, platinum dioxide is used as the catalyst and MeOH is used as the solvent.205 The solvent has a substantial influence on the composition of the products of oxime reduction in the liquid phase. For example, when a more polar solvent was used, aziridine was obtained from benzylideneacetone oxime, in addition to the corresponding amine.212 Study of hydrogenation of cyclohexa- 65 none oxime in various solvents in the presence of Pt, Pd, Rh and Ru supported on finely dispersed carbon made it possible to elucidate the influence of the solvent and the catalyst on the reaction rate and the product composition.The reaction does not occur in dioxane; the reaction in methanol proceeds in the presence of the rhodium catalyst, while in acetic acid, it proceeds over a platinum catalyst. When the reaction is carried out in water, cyclohexanol is produced as the major product.212 Apart from the platinum Group metals listed above, cobalt is also used to catalyse hydrogenation of oximes. In some cases Raney cobalt is more active than the nickel catalyst.213 Alumina is usually employed as the support.204, 214 When oximes are reduced over copper catalysts, together with amines, side products are formed, in particular, the Beckmann rearrangement product, the corresponding ketones, aldehydes, nitriles and imines.215 Apart from molecular hydrogen, the hydrazine ± Raney nickel system is also widely used as the reducing agent in the hydro- genation of oximes.208, 216 This system permits easy and selective reduction of oximes to primary amines. 2.Reductive amination of oxygen-containing compounds with nitriles and oximes Significant progress in the development of new methods for the synthesis of amines was associated with the use in the reductive amination of nitriles and oximes, which had not been used previously as direct aminating agents. Hydroamination of oxy- gen-containing compounds with nitriles extends still further the potential of this reaction.The ability of nitriles to be reduced to amines under the conditions of catalytic hydrogenation made it possible to aminate various ketones and aldehydes in one stage.217 ± 221 The reaction is carried out in the vapour phase over a heterogeneous catalyst in a flow-type setup operating under a pressure of hydrogen. The process of hydroamination of oxygen-containing compounds with nitriles includes several successive coupled reactions resulting in the formation of secondary amines. In the carbonyl compound ± nitrile ±hydrogen system, this reactions occurs in accordance with the following scheme:218, 219 H2 RCN RCH2NH2, Cat R0 H2O RCH2NHCOH RCH2NH2+R0R00CO 7H2O R00 H2 RCH2NHCHR0R00 RCH2N CR0R00 R, R0 =H, Alk, Ar; R00 =Alk, Ar.Under the reaction conditions, carbonyl compounds are partly reduced to the corresponding alcohols. The possibility of hydroamination of alcohols with nitriles, as shown below, also cannot be ruled out. H2 RCN RCH2NH2, CatH2 R0R00CHOH, R0R00CO Cat RCH2NH2+R0R00CHOH RCH2NHCHR0R00 7H2O R=H, Alk, Ar; R0 =H, Alk, Ar; R00 =Alk, Ar. The reaction pathway depends on the structures of the reactants and on the rate of each particular stage. The above reactions might also occur simultaneously. Hydroamination of cyclic ketones by aliphatic nitriles under a pressure of hydrogen has been studied.218, 219 Nickel ± alumina and copper ± alumina catalysts with a metal content of 15%± 20%, both non-modified and modified by the addition of Li, Na66 and K, were used.The main reaction pathway is the formation of alicyclic secondary amines 119. O NHCH2R H2 +RCN (CH2)n (CH2)n Cat 107 ± 109, 120 7, 52 R=Me (107), CH=CH2 (108), Et (109), Prn (120); n=3 (7, 8), 2 (52, 121). The yields of the corresponding amines 119 with the 15% Cu/ Al2O3 catalyst at 240 8C and pH2=1.5 MPa reaches 75%. The introduction of alkaline additives (Li, Na, K) in the copper ± alumina catalyst increases the total yield of amines by 5%± 12%. The di(cycloalkyl)amines 8 and 121 are formed as side products. It was assumed 218 that the main reason for the formation of the amines 8 and 121 is the low stability of N-alkylcycloalkylamines 119 under the conditions employed.In fact, when N-ethylcyclo- hexylamine is passed over the catalyst under the conditions of hydroamination, it partly decomposes to give a mixture of cyclo- hexylamine 13 and dicyclohexylamine 8 (up to 30%). Study of the reductive amination of the alicyclic ketones 7 and 52 with aceto- (107), acrylo- (108), propio- (109) and butyro-nitriles (120) showed that the yield of N-alkylcycloalkylamines 119 decreases following an increase in the number of the carbon atoms in the nitrile molecule. N-Alkylcyclohexylamines 123 have been prepared in good yields (up to 73%) by hydroamination of phenols 122 with nitriles on nickel ± alumina catalysts. In this case, amination is accom- panied by hydrogenation of the aromatic ring.222 R0 R0 RCN, H2 OH Ni/Al2O3 122 R=Me, Et, Pr; R0 =H, o-Me, m-Me, p-Me.Table 1. Synthesis of aliphatic-aromatic secondary amines by hydroamination of ketones and aldehydes with nitriles Nitrile Ketone, aldehyde T=220 8C, pH2=1.5 MPa, v=0.25 h71 acetonitrile " Acetophenone Benzophenone Benzyl methyl ketone " Benzylidenacetone Acetone Methyl ethyl ketone Diethyl ketone Cyclopentanone Cyclohexanone "benzonitrile """" T=230 8C, pH2=1.5 MPa, v=0.20 h71 Benzylidenacetone acrylonitrile butyronitrile isobutyronitrile benzonitrile acetonitrile " p-Methoxybenzyl- idenacetone 1-Phenylpent- 1-en-3-one T=220 8C, pH2=1.0 MPa, v=0.30 h71 phenylacetonitrile " Acetone Diethyl ketone Methyl propyl ketone " Cyclohexanone " (CH2)n NH + (CH2)n 119 8, 121 NH CH2R 123 Catalyst 15% Cu/Al2O3+2% LiOH 15% Cu/Al2O3+2% LiOH 20% Cu/Al2O3 36% Cu/MgO 20% Cu/Al2O3 20% Cu/Al2O3 20% Cu/Al2O3 20% Cu/Al2O3 20% Cu/Al2O3 36% Cu/MgO 36% Cu/MgO 15% Cu/Al2O3+6% LiOH 36% Cu/MgO 15% Cu/Al2O3+6% LiOH 15% Cu/Al2O3+6% LiOH 20% Cu/MgO 20% Cu/Al2O3 20% Cu/MgO 20% Cu/MgO V A Tarasevich, N G Kozlov In order to synthesise aromatic amines which contain the amino group in the side chain and form a number of important biologically active compounds, hydroamination of acetophenone 15, benzophenone 124 and benzyl methyl ketone 125 with nitriles has been carried out.223 In the presence of copper ± alumina catalysts, the highest yields (31% ± 72%) of secondary amines were attained with 20%Cu/Al2O3 at 220 8C, pH2=1.5 ± 2.0 MPa.The reactivity of ketones in the amination by nitriles decreases in the order 125 > 15 > 124.223 The conjugated system of bonds present in acetophenone results in a lower positive charge on the carbonyl carbon atom; this accounts for the decrease in the reactivity of the ketone 15. In the case of hydroamination of benzophenone with acetonitrile, the yield of N-ethylbenzhydryl- amine is influenced not only by conjugation but also by steric factors. Ethylbenzene and diphenylmethane were isolated as side products upon hydroamination of aceto- and benzophenone. Virtually no propylbenzene is formed on hydroamination of benzyl methyl ketone.NHCH2R O R0CN, H2 CH R0 C R 15, 124 R=Me, Ph; R0 =Me, Et, Prn. O RCN, H2 C Me CH2125 R=Me, Et, Prn. Unsaturated ketones, aliphatic nitriles, phenylacetonitrile, aliphatic and alicyclic ketones, benzonitrile and aldehydes have been used successfully for the synthesis of aliphatic-aromatic amines 219, 223 ± 227 (Table 1). N-Alkylbornan-2-ylamines were synthesized in 45%± 55% yields by hydroamination of camphor 61 by aliphatic nitriles.228 The resulting amine N-ethyl-a-phenylethylamine N-ethylbenzhydrylamine N-ethyl-a-methyl-b-phenylethylamine N-ethyl-1-methyl-3-phenylpropylamine N-isopropylbenzylamine N-(butan-2-yl)benzylamine N-(pentan-3-yl)benzylamine N-cyclopentylbenzylamine N-cyclohexylbenzylamine N-propyl-1-methyl-3-phenylpropylamine N-butyl-1-methyl-3-phenylpropylamine N-isobutyl-1-methyl-3-phenylpropylamine N-benzyl-1-methyl-3-phenylpropylamine N-ethyl-1-methyl-3-(p-methoxyphenyl)- propylamine N-ethyl-3-phenyl-1-ethylpropylamine N-isopropyl-2-phenylethylamine N-(pentan-3-yl)-2-phenylethylamine N-(pentan-2-yl)-2-phenylethylamine N-cyclohexyl-2-phenylethylamine NHCH2R CH Me CH2 Yield (%) Ref.223 223 223 224 219 219 219 219 219 58 28 72 65 58 42 46 36 54 224, 225 224, 225 224, 225 224, 225 224 70 75 60 70 60 224 60 226 226 226 226 61 36 50 52Reductive amination of oxygen-containing organic compounds RCN, H2 7H2O O NHCH2R 61 R=Me, Et, Prn.Systematic study of the reductive amination of carbonyl- containing compounds and secondary alcohols of the terpene series resulted in the development of preparative and selective methods for the synthesis of both unsaturated and completely hydrogenated amines with diverse structures (aliphatic; mono- bi- and tricyclic; containing three-, four, five- and six-membered rings) 229 ± 239 (Table 2). A series of 3-(1-alkylaminoethyl)- and 3-(arylmethylami- noethyl)-pyridines have been synthesised in 50%± 65% yields by hydroamination of 3-acetylpyridine 126 with aliphatic and aro- matic nitriles.240O NHCH2R RCN, H2 C CH Cu/Al2O3 N N Me Me 126 R=Me, Et, Prn, Ar. Hydroamination of an a,b-unsaturated heterocyclic ketone� 4-(2-furyl)but-3-en-2-one 127�which has an additional reaction site, the oxygen atom of the furan ring, has been studied.This process can follow several alternative pathways depending on the catalyst used (Scheme 10). In the presence of a copper ± magne- sium catalyst, the reaction stops at the stage of formation of a Table 2. Reductive amination of carbonyl-containing compounds and alcohols of the terpene series. Nitrile, oxime Ketone, alcohol T=220 8C, pH2=1.5 MPa, v=0.25 h71 acetonitrile L-Camphor " 1,3,3-Trimethylbicyclo- [2.2.1]heptan-2-one (+)-S-Carvone " Acetone (+)-S-carvone oxime acetonitrile L-Menthol benzonitrile acetonitrile cis-3,7,7-Trimethylbicyclo- " [4.1.0]heptan-2-ol Hexahydropseudoionone 1-Ethylbicyclo[2.2.1]- heptan-2-one T=250 8C, pH2=1.5 MPa, v=0.25 h71 acetonitrile propionitrile acetonitrile Isocamphanone, isocamphanol Isofenchol 1-Ethyltricyclo- [2.2.1.02.6]heptan-3-one Citronellal propionitrile T=240 ± 260 8C, pH2=1.5 MPa, v=0.20 h71 acetonitrile 2-Acetylbicyclo- [2.2.1]hept-5-ene a The total yield is given.secondary amine of the furan series, namely, 2-(3-alkylaminobu- tyl)furan 128 (yield 45%± 48%); the use of copper ± alumina catalyst results in hydrogenolysis of the furan ring at the O(1) ± C(5) bond and cyclisation of the intermediate amino ketone. In this case, N-alkyl-2-methyl-5-propylpyrrolidine 129 is the main product (yield 42%± 46%).241 In addition, the reaction products contain a small amount of pyrrole derivatives 130 (5%), which result from the direct replacement of the oxygen atom of the furan ring by an amino group accompanied by hydrogenation of the carbonyl group and the double bond in the side chain.RCN 4 5 O1 Cu/MgO Cu/Al2O3 Catalyst 15% Cu/Al2O3+(2 ± 6)% LiOH 15% Cu/Al2O3+(2 ± 6)% LiOH 15% Cu/Al2O3+(2 ± 6)% LiOH 15% Cu/Al2O3+(2 ± 6)% LiOH 15% Cu/Al2O3+(2 ± 6)% LiOH; N-ethylmenthyl-, neomenthyl-, 36% Cu/MgO 15% Cu/Al2O3+(2 ± 6)% LiOH; N-ethyl-5-isopropyl-2-methylcyclo- 36% Cu/MgO 15% Cu/Al2O3+(2 ± 6)% LiOH 15% Cu/Al2O3+(2 ± 6)% LiOH 15% Cu/Al2O3+(2 ± 6)% LiOH 15% Cu/Al2O3+6% LiOH 15% Cu/Al2O3+(2 ± 6)% LiOH 15% Cu/Al2O3+(2 ± 6)% LiOH 36% Cu/MgO 67 Scheme 10 RCH2NH2, H2 Cat 3 O 2 CH CHCMe +RCH2NH2 127 NHCH2R + (CH2)2CHMe (CH2)3Me N O 128 130 CH2R Me Me(CH2)2C(CH2)2CHMe NCH2R+130 O NHCH2R (CH2)2Me 129 Ref.The resulting amine Yield (%) 229 60 a N-ethylbornylamines (exo- and endo-isomers) the same 230 80 60 ± 70 a 231 232 60 N-ethylcarvo-, isocarvo-, neocarvo- and neoisocarvomenthylamines N-isopropyl-5-isopropyl-2-methyl- cyclohexylamine 233, 234 70 a isomenthyl- and neoisomenthylamines 235 60 236 237 85 69 a hexylamine N-benzyl-1,5,9-trimethyldecylamine N-ethyl-1-ethylbicyclo[2.2.1]hept-2-yl- amines (exo- and endo-isomers) 238 80 N-ethylisocamphylamines 238 238 60 75 238 N-propylisofenchylamine N-ethyl-1-ethyltricyclo[2.2.1.02.6]- hept-3-ylamine N-propyl-3,7-dimethyloctylamine, N-propyl-3,7-dimethyloct-6-enylamine 35 30 239 70 2-(a-ethylaminoethyl)bicyclo- [2.2.1]heptane68 Several studies have been devoted to the interaction of nitriles with bifunctional oxygen-containing compounds in which both reaction sites can be involved in hydroamination. In particular, reactions of hydroxy ketones, diketones and diols were inves- tigated.242 ± 244 OH O RCCH2CHMe RCN Secondary amines, heterocyclic compounds O O RC(CH2)nCR or RCN Secondary amines, diamines, heterocyclic compounds RCH(OH)(CH2)nCH(OH)R a-Diketones and a-glycols react with nitriles according to similar patterns.Thus the reaction of diacetyl with nitriles yields the same products as the reaction of ethylene glycol, namely, mono- and diamines.243, 244 Acetylacetone (b-diketone) 131 is unstable under the reaction conditions, products of its decom- position being involved in reductive amination.The reaction of the diketone 131 and benzonitrile 114 over the 15% Cu/MgO catalyst at 240 8C and pH2=1.5 MPa gives rise to N-ethylbenzyl- amine 132 (yield 29%), N-isopropylbenzylamine 133 (yield 19%) and N,N-diethylbenzylamine (yield 18%) (Scheme 11). Scheme 11 O O 114, H2 Me2CO+MeCHO CMe MeCCH2 131 CH2NEt2 CH2NHEt CH2NHCHMe2 + + 134 133 132 Reactions of dinitriles with carbonyl compounds have been studied. It was found 221 that hydroamination of acetone and butanal with adiponitrile 135 can follow two pathways, one yielding a heterocycle and one yielding aliphatic amines.The nitrile groups in the adiponitrile molecule behave under the hydrogenation conditions as if they possessed different reactiv- ities. This fact has been explained by the formation of unstable cyclic systems.245 A pseudo-ring forms upon interaction of nitro- gen of one nitrile group with the hydrogen located at the a-position relative to the second nitrile group. Therefore, reduc- tive amination occurs as preferential reduction of one nitrile group rather than simultaneous reduction of both of them and yields 6-aminohexanenitrile 136. H2 CN CN NC (CH2)4 Cat H2N (CH2)5 136 135 The amino nitrile 136 can undergo two types of transforma- tion. The first of them is hydrogenation of the secondCNgroup to give hexamethylenediamine 137 and subsequent hydroamination of a carbonyl compound, for example, acetone 29.The second route includes hydrogenation of the amino nitrile 136 accompa- nied by cyclisation and gives rise to perhydroazepine 86. The crucial factor which determines the reaction route is temperature. Thus at 190 8C, the yields of N-isopropylperhydro- azepine 138 and N,N0-diisopropylhexamethylenediamine 139 are 25% and 84%, respectively, whereas at 240 8C they are 22% and 3%. H2 H2 H2N(CH2)5CH NH Cat Cat H2N(CH2)5CN 136 V A Tarasevich, N G Kozlov Me2CO, H2 NH NHCHMe2 Cat 86 138 Me2CO, H2 H2N(CH2)6NH2 Cat Me2CHNH(CH2)6NHCHMe2 139 137 The good results attained in hydroamination of oxygen- containing compounds, together with the theoretical fundamen- tals and the published data concerning reduction of oximes to primary amines under conditions similar to those used in hydro- amination, permitted oximes to be employed for the first time for reductive amination of various ketones and aldehydes.246 ± 249 Analysis of the ability of oximes to be reduced over heterogeneous catalysts led to the conclusion that, in addition to the traditional catalysts used to reduce oximes to primary amines (platinum Group metals and nickel), copper catalysts are also active in this process.Hydroamination of carbonyl compounds with various oximes includes several consecutive coupled reactions, resembling those involved in hydroamination of carbonyl compounds with nitriles.The necessity of a high degree of coupling between separate stages becomes evident if one examines the processes occurring in the `oxime ± carbonyl compound ± hydrogen' ternary systems over a heterogeneous catalyst. Initially, the oxime is reduced on the hydrogenating sites of the catalyst to give a primary amine (Scheme 12).247, 248 Scheme 12 H2 H2 RR0C NH RR0C NOH RR0CHNH2 Cat Cat R=Alk, Ar; R0 =H, Alk, Ar. The resultinimary amine can participate in many thermo- dynamically allowed reactions. Within the scope of our review, condensation of the primary amine with the carbonyl compound is of interest (Scheme 13).247, 248 Scheme 13 R00 H2 RR0CHNH C R000 RR0CHNH2+R00R000C O Cat 7H2O OH H2 RR0CHNHCHR00R000 RR0CHN CR00R000 Cat R, R00 =Alk, Ar; R0, R000 =H, Alk, Ar.The reaction of the primary amine with the imine, resulting from incomplete reduction of the oxime, is a competing process (Scheme 14).247, 248 Scheme 14 H2 RR0CH NHCHRR0 RR0C NH+RR0CHNH2 Cat 7NH3 NH2 H2 NHCHRR0 RR0C (RR0CH)2NH Cat Thus, when there is no coupling between the formation of primary amine and its condensation with the carbonyl compound (see Schemes 12 and 13), the overall process can be substantially influenced by the reaction of the primary amine with the nitrogen analogue of the carbonyl compound, i.e. imine (see Scheme 14). The formation of symmetrical secondary amines markedly decreases the selectivity of the main reaction.247, 248 The attainment of coupling depends appreciably on the catalyst. The carbonyl compound should be activated towards condensation (see Scheme 13) to an extent that its reactivity inReductive amination of oxygen-containing organic compounds Table 3.Reductive amination of ketones, aldehydes and alcohols with oximes. Oxime Ketone, aldehyde, alcohol T=210 8C, pH2=1.5 MPa, v=0.25 h71 Pentan-2-one Cyclohexanone Acetaldehyde Propanal Butanal 2-Methylpropanal cyclohexanone cyclopentanone cyclohexanone ""cyclopentanone " T=210 8C, pH2=1.0 MPa, v=0.30 h71 Acetaldehyde Propanal Pentanal 3-Methylbutanal benzaldehyde """ T=240 8C, pH2=1.5 MPa, v=0.25 h71 Cyclohexylmethanol 3-methylbutanal " relation to the nucleophile be higher than that of the imine.This activation occurs on the acid sites of the catalyst.248 The con- densation proceeds via intermediate formation of the addition product, which is converted into imine upon dehydration. This stage is followed by hydrogenation of the C=N double bond on the hydrogenating sites of the catalyst and by the formation of a secondary amine, which is the final reaction product. The data on the methods of synthesis of secondary amines from oximes, ketones, aldehydes and alcohols are presented in Table 3. VI. Conclusion The data considered in the review convincingly demonstrate the substantial progress achieved in the development of catalytic methods for the synthesis of amines based on reductive amination of various oxygen-containing organic compounds.The most significant achievements are the use of nitriles and oximes, which had not been used previously for these purposes, as aminating agents; elaboration and use of complex catalysts for reductive amination, which allow the processes to be conducted under mild conditions with high selectivity; and the use of reduced promoted fused iron catalysts in the synthesis of nitrogen-containing hetero- cycles. The assimilation of new reactions of oxidative ammonolysis and oxo synthesis made it possible to synthesise numerous nitriles, carbonyl compounds and oximes, needed for the production of amines of various structures and compositions. Thus, there are strong grounds for believing that in the near future, the reaction in question would become one of the most significant methods for the preparation of amines.References 1. G Mignonac, C Moureu C. R. Hebd. Seances Acad. Sci. 169 237 (1919) 2. G Mignonac C. R. Hebd. Seances Acad. Sci. 171 223 (1921) 3. M V Klyuev, M L Khidekel' Usp. Khim. 49 28 (1980) [Russ. Chem. Rev. 49 14 (1980)] 4. R Layer Chem. Rev. 63 489 (1963) 5. Jpn. P. 54-10 384; Ref. Zh. Khim. 12 N 69P (1980) 6. US P. 3 187 047; Chem. Abstr. 63 9873 (1965) 7. M A Popov, N I Shuikin Dokl. Akad. Nauk SSSR 101 273 (1955) a 8. M A Popov, N I Shuikin Izv. Akad. Nauk SSSR, Otd. Khim. Nauk 1082 (1962) b Catalyst 36% Cu/MgO 36% Cu/MgO 36% Cu/MgO N-(pentan-2-yl)cyclohexylamine N-(pental-2-yl)cyclopentylamine dicyclohexylamine 15% Cu/Al2O3+6% LiOH N-ethylcyclohexylamine N-propylcyclohexylamine N-butylcyclopentylamine N-isobutylcyclopentylamine 15% Cu/MgO 15% Cu/MgO 15% Cu/MgO 36% Cu/ZnO 15% Cu/Al2O3 36% Cu/MgO 36% Cu/MgO 15% Cu/Al2O3+6% LiOH N-(pentan-2-yl)cyclohexylmethylamine " 36% Cu/ZnO 69 Yield (%) Ref.The resulting amine 246 246 246 247 247 247 247 41 52 62 55 67 74 55 248 248 248 248 44 46 60 48 N-ethylbenzylamine N-propylbenzylamine N-pentylbenzylamine N-(pentan-2-yl)benzylamine 249 249 46 45 9. BRD P. 2 603 006; Chem. Abstr. 85 123 563 (1976) 10. US P. 3 597 438; Ref. Zh. Khim. 10 N 58P (1972) 11. Fr. P. 2 203 382; Ref. Zh. Khim. 19 N 60P (1975) 12. BRD P. 4 010 252; Ref. Zh. Khim.2 N 38P (1993) 13. BRD P. 4 016 340; Ref. Zh. Khim. 22 N 28P (1993) 14. L S Glebov,G A Kliger Usp. Khim. 58 1721 (1989) [Russ. Chem. Rev. 58 977 (1989)] 15. G A Kliger, L S Glebov, A N Bashkirov Neftekhimiya 17 599 (1977) 16. L S Glebov, G A Kliger, S M Loktev Neftekhimiya 30 631 (1990) 17. G A Kliger, L S Glebov, R A Fridman Kinet. Katal. 19 615 (1978) c 18. G A Kliger, L S Glebov, R A Fridman Kinet. Katal. 19 619 (1978) c 19. A N Shuikin, L S Glebov,G A Kliger, V G Zaikin Izv. Akad. Nauk, Ser. Khim. 2062 (1995) b 20. A N Shuikin, L S Glebov, E V Marchevskaya, G A Kliger, V G Zaikin Neftekhimiya 36 178 (1996) 21. BRD Appl. 410 688 2A1; Ref. Zh. Khim. 9 N 44P (1993) 22. Jpn. P. 2232; Ref. Zh. Khim. 2 N 36P (1991) 23. A Skita, F Keil Berichte 61 1682 (1928) 24.M A Popov, N I Shuikin Izv. Akad. Nauk SSSR, Otd. Khim. Nauk 140 (1951) b 25. BRD P. 4 116 117; Ref. Zh. Khim. 11 N 50P (1993) 26. V V Belov , L G Romanovskaya, V D Stytsenko, S B Kopeikina, L I Sula, in 15-i Mendeleevskii S'ezd po Obshchei i Prikladnoi Khimii (Tez. Dokl.), Minsk, 1993 [The 15th Mendeleev Congress on General and Applied Chemistry (Abstracts of Reports), Minsk, 1993] Vol. 1, p. 87 27. Fr. P. 1 468 354; Chem. Abstr. 67 81 798 (1967) 28. W S Emerson, J C Robinson Org. Synth. 23 68 (1943) 29. P Mastagli, M Metayer, A Bricard Bull. Soc. Chim. Fr. 1045 (1950) 30. J Sabadie, I Schifter, J-E Germain Bull. Soc. Chim. Fr. 616 (1977) 31. US P. 2 636 051; Ref. Zh. Khim. 7544 (1953) 32. Fr. P. 2 328 692; Ref.Zh. Khim. 14 N 89P (1978) 33. C Winans, H Adkins J. Am. Chem. Soc. 61 3499 (1939) 34. L Marko, J Bakos J. Organomet. Chem. 81 411 (1974) 35. A Le Bris, G Lefebvre, F Coussemant Bull. Soc. Chim. Fr. 1584 (1964) 36. M G Abdullaev, A A Nasibulin, M V Klyuev Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol. 37 55 (1994) 37. M G Abdullaev, A A Nasibulin, M V Klyuev Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol. 37 58 (1994) 38. M V Klyuev, A A Nasibulin, M G Abdulaev Neftekhimiya 34 413 (1994) 39. M V Klyuev, M G Abdulaev, A A Nasibulin Zh. Org. Khim. 31 416 (1995) d 40. US P. 4 967 004; Ref. Zh. Khim. 10 R 98P (1992)70 41. J R Corrigan, M-J Sullivan, H W Bishop J. Am. Chem. Soc. 75 6258 (1953) 42. J-P Charles, H Christol, G Solladie Bull.Soc. Chim. Fr. 4439 (1970) 43. T Kralt Rec. Trav. Chim. 77 990 (1958) 44. A Skita, F Kell Berichte 66 1400 (1933) 45. A Skita, F Kell Z. Allgem. Chem. 42 501 (1929) 46. M Murakami, K Suzuki,M Fujishige, J-W Kang Nippon Kagaku Zasshi 85 (3) 235 (1964); Chem. Abstr. 61 13 408 (1964) 47. E Woodruf, J Lambooy,W Burt J. Am. Chem. Soc. 62 922 (1940) 48. K Campbell, A Sommers, B Campbell J. Am. Chem. Soc. 66 82 (1944) 49. US P. 2 217 630; Chem. Abstr. 35 1065 (1941) 50. A A Ponomarev, N P Maslennikova, N V Alakina Dokl. Akad. Nauk SSSR 131 1355 (1960) a 51. J Kasiwagi Bull. Chem. Soc. Jpn. 2 310 (1927) 52. Z Zafiriadis, P Mastagli C. R. Hebd. Seances Acad. Sci. 236 295 (1953) 53. I F Bel'skii Izv. Akad. Nauk SSSR, Ser. Khim.1077 (1962) b 54. N I Shuikin, I F Bel'skii, G E Skobtsova Izv. Akad. Nauk SSSR, Ser. Khim. 1678 (1963) b 55. G E Abgaforova, N I Shuikin, I F Bel'skii Izv. Akad. Nauk SSSR, Ser. Khim. 734 (1965) b 56. N I Shuikin, A D Petrov, V G Glukhovtsev, I F Bel'skii, G E Skobtsova Izv. Akad. Nauk SSSR, Ser. Khim. 1682 (1964) b 57. I F Bel'skii, N I Shuikin, G E Skobtsova Izv. Akad. Nauk SSSR, Ser. Khim. 1675 (1963) b 58. N I Shuikin, I F Bel'skii, G E Abgaforova Izv. Akad. Nauk SSSR, Ser. Khim. 163 (1965) b 59. N S Kozlov, A V Kashinskii Dokl. Akad. Navuk BSSR 22 821 (1979) 60. N S Kozlov, A V Kashinskii Vestsi Akad. Navuk BSSR, Ser . Khim. Navuk (2) 121 (1979) 61. L S Glebov, G A Kliger, T P Popova, V E Shiryaeva, V P Ryznikov, E V Marchevskaya, O A Lesik, S M Loktev, V G Beryezkin J.Mol. Catal. 35 335 (1986) 62. G A Kliger, L S Glebov, V P Ryzhikov, V E Shiryaeva, T P Popova, S M Loktev Izv. Akad. Nauk SSSR, Ser. Khim. 1875 (1987) b 63. G A Kliger, L S Glebov, T P Popova, E V Marchevskaya, V G Beryezkin, S M Loktev J. Catal. 111 418 (1988) 64. L S Glebov, G A Kliger, S M Loktev Neftekhimiya 30 626 (1990) 65. G A Kliger, O A Lesik, E V Marchevskaya, A I Mikaya, V G Zaikin, L S Glebov, S M Loktev Neftekhimiya 31 503 (1991) 66. G A Kliger, O A Lesik, A I Mikaya, E V Marchevskaya, V G Zaikin, L S Glebov, S M Loktev Izv. Akad. Nauk SSSR, Ser. Khim. 503 (1991) b 67. G A Kliger, L S Glebov, S M Loktev,A N Shuikin, in Khimicheskie Sintezy na Osnove Odnouglerodnykh Molekul (Tez.Dokl. 3-i Vsesoyuz. Konf.), Moskva, 1991 [Chemical Syntheses Based on One- Carbon Molecules (Abstracts of Reports of the Third All-Union Conference), Moscow, 1991] p. 168 68. G A Kliger, L S Glebov, A N Shuikin, S M Loktev Khim. Tv. Topliva (4) 115 (1992) 69. L S Glebov, G A Kliger Khim. Tv. Topliva (6) 49 (1992) 70. USSR P. 1 528 771; Byull. Izobret. (46) 90 (1989) 71. L S Glebov, G A Kliger Usp. Khim. 63 192 (1994) [Russ. Chem. Rev. 63 185 (1994)] 72. L S Glebov, G A Kliger, A N Shuikin, S M Loktev Neftekhimiya 28 674 (1988) 73. G A Kliger, O A Lesik, L S Glebov, A I Mikaya, A V Ivanov, E V Marchevskaya, S M Loktev, V G Zaikin Dokl. Akad. Nauk SSSR 307 147 (1989) a 74. L S Glebov, G A Kliger, S M Loktev, in Khimicheskie Sintezy na Osnove Odnouglerodnykh Molekul (Tez.Dokl. 3-i Vsesoyuz. Konf.), Moskva, 1991 [Chemical Syntheses Based on One-Carbon Molecules (Abstracts of Reports of the Third All-Union Conference), Moscow, 1991] p. 166 75. US P. 3 707 563; Chem. Abstr. 78 58 996 (1973) 76. BRD P. 2 153 792; Chem. Abstr. 77 341 127 (1972) 77. P Acberli, J Gogerty, J Houlihen J. Med. Chem. 10 636 (1967) 78. US P. 3 522 309; Ref. Zh. Khim. 8 N 124P (1971) 79. US P. 2 424 063; Chem. Abstr. 41 7420 (1948) 80. G N Kao, B D Tilak, K Venkataraman J. Sci. Ind. Res. 14B 624 (1955) 81. Br. P. 602 332; Chem. Abstr. 43 253 (1949) V A Tarasevich, N G Kozlov 82. S Kiyooka, K Suruki Bull. Chem. Soc. Jpn. 47 2081 (1974) 83. US P. 3 860 651; Chem. Abstr. 82 170 330 (1975) 84.J Volf, J Pasek, P Kraus Sb. Yys. Sk. Chem.-Technol. Praze, Org. Chem. Technol. 27 C19 (1973); Chem. Abstr. 79 125 724 (1973) 85. Czech. P. 154 133; Chem. Abstr. 82 16 401 (1975) 86. US P. 3 209 030; Ref. Zh. Khim. 9 N 127P (1967) 87. US P. 3 366 684; Ref. Zh. Khim. 14 N 199P (1969) 88. US P. 3 739 026; Ref. Zh. Khim. 9 N 168P (1974) 89. Jpn. P. 15 601; Ref. Zh. Khim. 22 N 207P (1969) 90. M A Ryashentseva, Kh M Minachev, L S Geidnik Izv. Akad. Nauk SSSR, Ser. Khim. 1601 (1968) b 91. F S Dovell, H J Greenfield J. Org. Chem. 29 1265 (1964) 92. Swiss. P. 472 404 Ref. Zh. Khim. 5 N 49OP (1970) 93. USSR P. 956 004; Byull. Izobret. (33) 24 (1982) 94. USSR P. 810 671; Byull. Izobret. (9) 88 (1981) 95. L S Glebov, G A Kliger, V D Oppengeim, A N Shuikin, A N Yatsenko, V G Zaikin, S M Loktev Neftekhimiya 28 472 (1988) 96.M V Klyuev, M V Gapeeva, M L Khidekkel' Izv. Akad. Nauk SSSR, Ser. Khim. 2140 (1978) b 97. B G Rogachev,M L Khidekkel' Izv. Akad. Nauk SSSR, Ser. Khim. 141 (1969) b 98. M V Klyuev, A A Nasibulin, in 1-ya Rossiiskaya Konferentsiya po Klasternoi Khimii (Tez. Dokl.), S.-Peterburg, 1994 [The First Russian Conference on Cluster Chemistry (Abstracts of Reports), St.-Petersburg, 1994] p. 26 99. M V Klyuev, A A Nasibulin Kinet. Katal. 37 231 (1996) c 100. M V Klyuev, A A Nasibulin, E F Vainshtein, in Problemy Sol'va- tatsii i Kompleksoobrazovaniya v Rastvorakh (Tez. Dokl. 6-i Mezh- dunarod. Konf.), Ivanovo, 1995 [The Problems of Solvation and Complexing in Solutions (Abstracts of Reports of the Sixth Inter- national Conference), Ivanovo, 1995] p.147 101. E A Karakhanov, M V Klyuev, L V Tereshko, O V Kalinina, A G Dedov Neftekhimiya 31 312 (1991) 102. M V Klyuev, A D Pomogailo Gidrirovanie na Metallsoderzha- shchikh Polimerakh: Osobennosti, Problemy, Perspektivy (Hydro- genation on Metal-Containing Polymers: Features, Problems and Prospects) (Chernogolovka: Institute of Chemical Physics, Academy of Sciences of the USSR, 1988) p. 73 103. M V Klyuev Zh. Org. Khim. 20 1908 (1984) d 104. A A Nasibulin,M V Klyuev Zh. Prikl. Khim. 59 2712 (1986) e 105. M V Klyuev, L V Tereshko, N V Sidorova, E Yu Zhbanova Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol. 32 41 (1989) 106. M V Klyuev, V D Kopylova, T B Pogodina Zh.Fiz. Khim. 64 809 (1990) f 107. Br. P. 679 014; Chem. Abstr. 48 1416 (1954) 108. Swiss. P. 292 409; Chem. Abstr. 52 3224 (1958) 109. US P. 2 609 394; Chem. Abstr. 47 6436 (1953) 110. US P. 2 636 902; Chem. Abstr. 48 3991 (1954) 111. US P. 5 103 058; Ref. Zh. Khim. 3 N 35P (1994) 112. Yu B Kryukov, N S Zakirov, F I Novak, A N Bashkirov, E I Bogolepova Neftekhimiya 7 124 (1967). 113. A N Bashkirov, R A Fridman, E I Bogolepova, R M Smirnova, Yu B Kryukov Dokl. Akad. Nauk SSSR 201 847 (1972) a 114. R A Fridman, E I Bogolepova, R M Smirnova, Yu B Kryukov, G A Zhukova, A N Bashkirov Neftekhimiya 12 91 (1972) 115. R A Fridman, E I Bogolepova, Yu B Kryukov, A N Bashkirov Neftekhimiya 15 426 (1975) 116. G A Kliger, L F Lazutina, R A Fridman, Yu B Kryukov, A N Bashkirov Neftekhimiya 16 660 (1975) 117.G A Kliger, L F Lazutina, Yu B Kryukov, R A Fridman, A N Bashkirov Neftekhimiya 16 665 (1975) 118. A N Shuikin, G A Kliger, L S Glebov, E V Marchevskaya Neftekhimiya 31 507 (1991) 119. L S Glebov, A N Shuikin, G A Kliger, S M Loktev Izv. Akad. Nauk SSSR, Ser. Khim. 2176 (1990) b 120. N S Kozlov, G I Lomako, L T Gurskaya Vestsi Akad. Navuk BSSR, Ser. Khim. Navuk 68 (3) (1974) 121. N S Kozlov, G I Lomako, L T Gurskaya Dokl. Akad. Navuk BSSR 19 248 (1975) 122. A N Shuikin, L S Glebov, G A Kliger, V G Zaikin Neftekhimiya 33 321 (1993) 123. USSR P. 1 558 891; Byull. Izobret. (15) 134 (1990)Reductive amination of oxygen-containing organic compounds 124. G A Kliger, A N Shuikin, L S Glebov, A I Mikaya, S M Loktev, V G Zaikin Izv.Akad. Nauk SSSR, Ser. Khim. 1923 (1990) b 125. A N Shuikin, L S Glebov, G A Kliger, V G Zaikin Izv. Akad. Nauk, Ser. Khim. 799 (1993) b 126. Fr. P. 2 679 901; Ref. Zh. Khim. 2 N 44P (1994) 127. V V Belov, O V Isaev, L G Romanovskaya, E V Belyaeva, L I Sula, P P Voronin Neftekhimiya 31 642 (1991) 128. BRD P. 3 627 592; Ref. Zh. Khim. 4 N 27P (1989) 129. USSR P. 715 576; Byull. Izobret. (6) 114 (1980) 130. A N Bashkirov, G A Kliger, O A Lesik, E V Marchevskaya, L S Glebov Kinet. Katal. 24 392 (1983) c 131. G A Kliger, O A Lesik, V P Ryzhikov, L S Glebov, S M Loktev Izv. Akad. Nauk SSSR, Ser. Khim. 2847 (1987) b 132. G A Kliger, L S Glebov, O A Lesik, S M Loktev, in 5-ya Vsesoyuz.Konf. po Mekhanizmu Kataliticheskikh Reaktsii (Tez. Dokl.), Moskva, 1990 [The Fifth All-Union Conference on the Mechanism of Catalytic Reactions (Abstracts of Reports), Moscow, 1990] p. 171 133. G A Kliger, L S Glebov, O A Lesik, S M Loktev Neftekhimiya 31 221 (1991) 134. G A Kliger, L S Glebov, O A Lesik, S M Loktev in 7-i Neftekhi- micheskii Simpozium (Tez. Dokl.), Kiev, 1990 [The Seventh Petro- chemical Symposium (Abstracts of Reports), Kiev, 1990] p. 171 135. L S Glebov, G A Kliger, A N Shuikin, V G Zaikin Neftekhimiya 36 344 (1996) 136. USSR P. 1 567 581; Byull. Izobret. (20) 99 (1990) 137. USSR P. 1 404 507; Byull. Izobret. (23) 106 (1988) 138. A N Shuikin, G A Kliger, V G Zaikin, L S Glebov Izv. Akad. Nauk, Ser. Khim. 2046 (1995) b 139.A N Shuikin, L S Glebov, G A Kliger, V G Zaikin Neftekhimiya 36 65 (1996) 140. G A Kliger, Kh Fidler, L S Glebov, V G Zaikin, K Khaage, S M Loktev Neftekhimiya 28 684 (1988) 141. L Forni, P Pollesel J. Catal. 130 403 (1991) 142. A A Tokar', Yu T Nikolaev, S L Kiperman, in Anilinokrasoch- naya Promyshlennost' (Aniline-Dye Industry) (Moscow: NIITEKhIM, 1979) No. 6, p. 1 143. J Pasek, J Cerny Chem. Prum. 22 (9) 436 (1972); Chem. Abstr. 78 86 359 (1973) 144. W S Emerson, H W Mohrman J. Am. Chem. Soc. 62 69 (1940) 145. W S Emerson, C A Uraneck, J. Am. Chem. Soc. 63 749 (1941) 146. US P. 23 880 420; Chem. Abstr. 40 94 (1946) 147. US P. 23 886 067; Chem. Abstr. 40 1879 (1946) 148. Br. P. 1 117 332; Ref. Zh. Khim. 8 N 155P (1969) 149.B R Aleksic, B D Aleksic, M Velickovic, Z S Lubarda, B Z Markovic, V N Kosanic, S S Bogdanov Hem. Ind. 42 387 (1988); Chem. Abstr. 111 23128 (1989) 150. Br. P. 1 098 236; Ref. Zh. Khim. 5 N 133P (1969) 151. N S Kozlov, S I Kozintsev Vestsi Akad. Navuk BSSR, Ser. Khim. Navuk 108 (3) (1975) 152. US P. 3 538 162; Ref. Zh. Khim. 15 N 215 (1971) 153. M V Klyuev Zh. Org. Khim. 23 581 (1987) d 154. N S Kozlov, S I Kozintsev, L V Naumova, in 6-e Vsesoyuz. Soveshch. po Khimii Nitrosoedinenii (Tez. Dokl.), Moskva, 1977 [The Sixth All-Union Meeting on the Chemistry of Nitro Compounds (Abstracts of Reports), Moscow, 1977] p. 112. 155. N S Kozlov, S I Kozintsev, in 6-e Vsesoyuz. Soveshch. po Khimii Nitrosoedinenii (Tez. Dokl.), Moskva, 1977 [The Sixth All-Union Meeting on the Chemistry of Nitro Compounds (Abstracts of Reports), Moscow, 1977] p.113 156. N S Kozlov, A V Kashinskii Dokl. Akad. Navuk BSSR 23 150 (1979) 157. N S Kozlov, S I Kozintsev Vestsi Akad Navuk BSSR, Ser. Khim. Navuk 119 (5) (1974) 158. N S Kozlov, S I Kozintsev, D I Burakova Vestsi Akad Navuk BSSR, Ser. Khim. Navuk 70 (6) (1974) 159. Jpn. P. 57-62 247; Ref. Zh. Khim. 8 N 72P (1983) 160. Jpn. P. 54-32 766; Ref. Zh. Khim. 19 N 61P (1980) 161. Jpn. P. 57-134 454; Ref. Zh. Khim. 3 N 77P (1984) 162. Avstral. P. 352 096; Ref. Zh. Khim. 8 N 77P (1980) 163. US P. 4 327 037; Ref. Zh. Khim. 3 N 63P (1983) 164. Jpn. P. 58-118 551; Ref. Zh. Khim. 14 N 65P (1984) 165. GDR P. 298 455; Ref. Zh. Khim. 3 N 31P (1993) 166.GDR P. 300 018; Ref. Zh. Khim. 19 N 34P (1993) 71 167. W S Chen, M D Lee React. Kinet. Catal. Lett. 47 187 (1992) 168. US P. 4 433 671; Ref. Zh. Khim. 24 N 69P (1984) 169. US P. 4 336 205; Ref. Zh. Khim. 9 N 205P (1983) 170. T Kudo Chem. Econ. Eng. Rev. 2 (7) 43 (1970) 171. B V Suvorov Geterogennyi Kataliz v Khimii Geterotsiklicheskikh Soedinenii (Heterogeneous Catalysis in the Chemistry of Hetero- cyclic Compounds) (Riga: Zinatne, 1981) p. 20 172. S Kumer, S Z Hissain Chem. Age India 30 727 (1979) 173. A Andersson, S T Lundin J. Catal. 65 9 (1980) 174. B V Suvorov, P B Vorob'ev, T P Mikhailovskaya Kinet. Katal. 34 301 (1993) c 175. B V Suvorov, N A Belova, V I Gostev Kinet. Katal. 34 296 (1993) c 176. A Das, A Kar Indian J. Technol.18 267 (1980) 177. B V Suvorov, N R Bukeikhanov Okislitel'nye Reaktsii v Organi- cheskom Sinteze (Oxidation Reactions in Organic Synthesis) (Moscow: Khimiya, 1978) p. 123 178. M A Dalin, I K Kolchin, B R Serebryakov Nitril Akrilovoi Kisloty (Nitrile of Acrylic Acid) (Baku: Izd. Akad. Nauk Azerb. SSR, 1968) p. 227 179. JKStille, TWCampbell (Eds) Condensation Monomers (New York: Wiley-Interscience, 1972) 180. BRD P. 2 839 134; Ref. Zh. Khim. 21 N 8OP (1980) 181. A A Nasibulin,M V Klyuev Zh. Org. Khim. 31 1068 (1995) d 182. M I Yakushkin, O Sh Gorbatyi-Kalika Kataliticheskie Reaktsii v Zhidkoi Faze (Catalytic Reactions in the Liquid Phase) (Alma-Ata: Nauka, 1978) Vol. 2, p. 32 183. BRD P. 2 839 135; Ref. Zh. Khim. 21 N 81P (1980) 184.Kh I Areshidze, G O Chevadze, G L Dvali Soobshch. Akad. Nauk Gruz. SSR 83 373 (1976) 185. Russ. P. 2 024 491; Byull. Izobret. (23) (1994) 186. R A Searles Chem. Age India 35 303 (1984) 187. US P. 5 130 491; Ref. Zh. Khim. 18 N 42P (1994) 188. US P. 5 254 737; Ref. Zh. Khim. 24 N 37P (1994) 189. Nether. P. 186 511; Ref. Zh. Khim. 8 N 31P (1992) 190. Jpn. P. 2 157 251; Ref. Zh. Khim. 9 N 36P (1992) 191. BRD P. 4 039 936; Ref. Zh. Khim. 9 N 33P (1993) 192. F Fluchaire, F Cambret Bull. Soc. Chim. Fr. 22 (1944) 193. GDR P. 156 178; Ref. Zh. Khim. 15 N 71P (1983) 194. G K Suleimanov, Ya G Abdulaeva, A Sh Novruzova Azerb. Khim. Zh. 66 (1980) 195. E N Zil'berman Reaktsii Nitrilov (Reactions of Nitriles) (Moscow: Khimiya, 1972) 196. BRD P.1 911 830; Ref. Zh. Khim. 24 N 70P (1979) 197. Jpn. P. 41 158; Ref. Zh. Khim. 6 N 37P (1995) 198. US P. 4 389 348; Ref. Zh. Khim. 5 N 75P (1984) 199. F Mares, J E Galle, S E Diamond, F J Regina, in The National Meeting of American Chemical Society (Abstracts of Reports), New Orleans, Washington, DC, 1987 p. 289 200. L Kh Freidlin, T A Sladkova Usp. Khim. 33 664 (1964) [Russ. Chem. Rev. 33 (1964)] 201. C De Bellefon, P Fonilloux Catal. Rev. Sci. Eng. 36 459 (1994) 202. A Mailhe, M Murat Bull. Soc. Chim. Fr. 9 464 (1911) 203. R Guy Bull. Soc. Chim. Fr. 615 (1974) 204. Fr. P. 647 090; Chem. Abstr. 23 2446 (1929) 205. A Dornow, A Frese Arch. Pharm. 285 463 (1952) 206. R Guy, D Couturier, Ch Glacet C. R. Hebd. Seances Acad. Sci., Ser. C 277 519 (1973) 207. L Beregi Magy. Kem. Foly. 56 257 (1950) 208. D Lloyd, R H McDougall, F J Wasson J. Chem. Soc. Jpn. 822 (1965) 209. K W Rosenmund, E Pfankuch Berichte 56 2258 (1923) 210. W H Hartung J. Am. Chem. Soc. 50 3370 (1928) 211. BRD P. 2 460 311; Chem. Abstr. 83 147 116 (1975) 212. E Breitner, E Roginski, P Rylander J. Chem. Soc. 2918 (1959) 213. W Reewe, J Christian J. Am. Chem. Soc. 78 860 (1956) 214. US P. 139 454; Chem. Abstr. 61 5534 (1964) 215. S Yamaguchi Bull. Chem. Soc. Jpn. 1 35 (1927) 216. US P. 3 959 379; Chem. Abstr. 85 93 788 (1977) 217. USSR P. 455 944; Byull. Izobret. (1) 51 (1975) 218. N S Kozlov, S I Kozintsev, L V Naumova Dokl. Akad. Nauk SSSR 226 1341 (1976) a 219. N S Kozlov, S I Kozintsev, L V Naumova, T K Efimova Vestsi Akad Navuk BSSR, Ser. Khim. Navuk 50 (5) (1976)V A Tarasevich, N G Kozlov 72 220. N S Kozlov, V I Cherepok Vestsi Akad Navuk BSSR, Ser. Khim. Navuk 55 (2) (1977) 221. N S Kozlov, V A Tarasevich, S I Kozintsev Dokl. Akad. Navuk BSSR 28 37 (1984) 222. USSR P. 747 852; Byull. Izobret. (26) 99 (1980) 223. N S Kozlov, S I Kozintsev, L V Naumova, T K Efimova Dokl. Akad. Navuk BSSR 21 326 (1977) 224. N S Kozlov, L I Moiseenok, S I Kozintsev Dokl. Akad. Nauk SSSR 241 1345 (1978) a 225. USSR P. 620 477; Byull. Izobret. (31) 57 (1978). 226. N S Kozlov, L V Gladkikh, S I Kozintsev, T K Efimova Dokl. Akad. Navuk BSSR 23 713 (1979) 227. N S Kozlov, L I Moiseenok, N N Gladkikh, S I Kozintsev, L V Gladkikh Dokl. Akad. Navuk BSSR 27 532 (1983) 228. USSR P. 517580; Byull. Izobret. (22) 72 (1976) 229. I I Bardyshev, N G Kozlov, T I Pekhk, T K Vyalimyae Vestsi Akad. Navuk BSSR, Ser. Khim. Navuk (4) 71 (1980) 230. N G Kozlov, G V Kalechits, T K Vyalimyae Khim. Prir. Soedin. 480 (1983) g 231. USSR P. 765 257; Byull. Izobret. (35) 141 (1980) 232. I I Bardyshev, N G Kozlov, T K Vyalimyae, T I Pekhk Khim. Prir. Soedin. 546 (1980) g 233. USSR P. 825 504; Byull. Izobret. (16) 95 (1981) 234. N G Kozlov, T I Pekhk, T K Vyalimyae Khim. Prir. Soedin. 312 (1981) g 235. G V Kalechits, N G Kozlov, T I Pekhk, T K Vyalimyae Zh. Obshch. Khim. 53 203 (1983) h 236. N G Kozlov, T K Vyalimyae, L A Popova, S A Makhnach, T E Kozlova Zh. Obshch. Khim. 57 2739 (1987) h 237. N G Kozlov, G V Kalechits, N A Belikova, M D Ordubadi, T K Vyalimyae Zh. Org. Khim. 21 535 (1985) d 238. N G Kozlov, Doctoral Thesis in Chemical Sciences, Institute of Physical Organic Chemistry, Academy of Sciences of Bel. SSR, Minsk, 1990 239. T S Raikova,N G Kozlov, T K Vyalimyae Zh. Org. Khim. 17 1468 (1981) d 240. USSR P. 535 298; Byull. Izobret. (42) 69 (1976) 241. N S Kozlov, L I Moiseenok, S I Kozintsev Dokl. Akad. Nauk SSSR 252 1132 (1980) a 242. N S Kozlov, L I Moiseenok, S I Kozintsev Dokl. Akad. Navuk BSSR 28 1002 (1984) 243. N S Kozlov, L I Moiseenok, S I Kozintsev Dokl. Akad. Navuk BSSR 24 917 (1980) 244. N S Kozlov, L I Moiseenok, S I Kozintsev Vestsi Akad. Navuk BSSR, Ser. Khim. Navuk (6) 25 (1980) 245. A P Tomilov, S K Smirnov Adiponitril i Geksametilendiamin (Adi- ponitrile and Hexamethylenediamine) (Moscow: Khimiya, 1974) 246. USSR P. 650 994; Byull. Izobret. (9) 119 (1979) 247. N S Kozlov, V A Tarasevich, S I Kozintsev, L V Gladkikh Dokl. Akad. Nauk SSSR 244 1130 (1979) a 248. N S Kozlov, V A Tarasevich, S I Kozintsev Dokl. Akad. Navuk BSSR 23 910 (1979) 249. N S Kozlov, A S Zhavrid, L V Gladkikh, S I Kozintsev, V A Tarasevich Vestsi Akad. Navuk BSSR, Ser. Khim. Navuk (3) 57 (1983) a�Dokl. Chem. Technol., Dokl. Chem. (Engl. Transl.) b�Russ. Chem. Bull. (Engl. Transl.) c� Catal. (Engl. Transl.) d�Russ. J. Org. Chem. (Engl. Transl.) e�Russ. J. Appl. Chem. (Engl. Transl.) f�Russ. J. Phys. Chem. (Engl. Transl.) g�Chem. Nat. Compd. (Engl. Transl.) h�Russ. J. Gen. Chem. (Engl