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Synthesis of cyclic amines and their alkyl derivatives from amino alcohols over supported copper catalysts
Applied Catalysis, 53 (1989) 107-115 Elsevier Science Publishers B.V., Amsterdam - Printed in The Netherlands
107
Synthesis of Cyclic Amines and Their Alkyl Derivatives from Amino Alcohols Over Supported Copper Catalysts J. KIJENSKI and P.J. NIEDZIELSKI
Laboratory of Catalytic Synthesis, Institute of Organic Technology, Warsaw Technical University (Politechnika), Koszykowa 75, 00662 Warsaw (Poland) and A.BAIKER*
Department of Industrial and Engineering Chemistry, Swiss Federal Institute of Technology, ETH-Zentrum, CH-Zilrich (Switzerland) (Received 24 February 1989, revised manuscript received 10 April 1989 )
ABSTRACT Cyclization of amino alcohols over copper supported on y-alumina and magnesia was found to be an efficient method for the synthesis of cyclic amines, their alkyl derivatives and in some instances also their dehydro derivatives. Reactions were carried out in the temperature range 200300 C using a continuous fixed-bed reactor and methanol or ethanol as solvent. The selectivities with respect to the different products depended markedly on the reaction temperature and the catalyst used. The amino alcohols used as reactants were 3-amino-l-propanol, 4-amino-l-butanol, 5-amino-l-pentanol and 6-amino-l-hexanol. The reaction of 3-amino-l-propanol was unspecific and led to various fragmentation products. In contrast, the reaction of 4-amino-l-butanol yielded either pyrrolidine (selectivity 62% ), N -methylpyrrolidine (71%) or L/l-dehydropyrrolidine (47%), depending on the conditions. The reaction of 5-amino-l-pentanolled either to piperidine (99%) or N-methylpiperidine (93%). Hexahydro-1H-azepine (95%) was the main product of the cyclization of6-amino-l-hexanol. 0
INTRODUCTION
Cyclic amines are of importance in the chemical industry as components and intermediates for pharmaceuticals, detergents, additives, etc. [1]. Although attractive, little has been reported on the synthesis of cyclic amines by heterogeneous catalytic routes [2-10]. This work is a continuation of our previous efforts at studying catalytic amination and cycloamination of alcohols over supported copper catalysts [9,10]. We report the cyclization of some amino alcohols in alcoholic solution over copper supported on y-alumina and magnesia. The aim of this work was to 0166-9834/89/$03.50
© 1989 Elsevier Science Publishers B.V.
108
investigate the influence of important reaction conditions, such as temperature, presence of solvent and nature of catalyst carrier, on the selectivity with respect to the desired products. Further, we wanted to probe the range of applicability of this process for the synthesis of cyclic amines and their alkyl derivatives. EXPERIMENTAL
Apparatus and procedure Reactions were carried out in a continous fixed-bed reactor in the temperature range 200-300°C and at atmospheric pressure. The quartz reactor tube (0.22 m~0.02 m I.D.) was filled with 10 cm3 of catalyst. Solutions of amino alcohols (16 mol-% ) in methanol or ethanol were dosed into the reactor using an infusion pump (Medipan ). The dosing rate (HLSV) was 1 cm3 of reactant solution per 1 cm3 of catalyst per hour. The flow-rate of carrier gas (nitrogen or hydrogen ) was 7.2 1(STP ) /h. Materials The supported copper catalyst were prepared by impregnation of the support materials with aqueous solution of copper (II) nitrate. y-Alumina (Degussa) and magnesia (precipitated from magnesium nitrate hexahydrate according to a previously described procedure [ 111) were used as carriers. After impregnation, the catalysts were dried at 60 ’ C for 48 h and subsequently calcined at 500°C for 6 h. Before use the catalysts were reduced with hydrogen-nitrogen as described previously [ 12). The copper content of the catalysts was 17% (w/w). Grains of size 0.5-1.0 mm were used in the catalytic experiments. BET surface areas of the catalysts were Cu/Al,O, 155 m2/g and Cu/MgO 18 m’/g. Amino alcohols ( > 97% pure) were supplied by Fluka. Analysis The liquid product mixtures were analysed by gas chromatography (GC) (Varian Aerograph 2868) using a 1.5-m glass column filled with 4% Carbowax 20M-8% KOH on Carbopack B 60 ( Supelco ) or a 25-m capillary column filled with SE-54. Products were identified by mass spectrometry using a Finnigan 4000 mass spectrometer. For quantitative GC analysis, calibration factors were determined. When not all the reaction products could be identified, the unknown molar calibration factors were replaced by those of known reaction products with similar retention times. Product distributions calculated with this assumption should be considered to be approximate.
109
Yields of products ( Yi) were defined as
where, Pi is the number of moles of product (i) and C (P,) is the sum of the number of moles of reactant and products at the reactor outlet. Note that in all results reported the conversion of the reactant was 100% and that in this instance the yield also corresponds to the product selectivity. RESULTS AND DISCUSSION
4-Amino-1-butanol Important reaction products observed with 4-amino-1-butanol over Cu/A1203 were pyrrolidine (I), N-methylpyrrolidine (II), d ‘-dehydropyrrolidine (III) and, at higher temperatures, also 1,2_dimethylpyrrolidine (IV). Fig. 1 shows the relevant reactions leading to these products. Note that the methanol used as the solvent acted as an alkylating agent (products II and IV). The product distributions obtained over Cu/A1203 and Cu/MgO are listed in Table 1 and depended strongly on the catalyst used and on temperature. In contrast to the reaction over Cu/A1203, where all reactions shown in Fig. 1 occurred, formation of III and IV was not observed over Cu/MgO. It is also interesting that at higher temperatures ( > 250°C) the ratio of N-methylpyrrolidine to pyrrolidine was hardly influenced by temperature increase when Cu/MgO was used.
HO-NH*
“0-Q I: (I)
\
-2
0N' (111)
Fig. 1. Reactions of 4-amino-1-butanol. Corresponding product distributions are listed in Table 1.
110 TABLE 1
Reaction products of 4-amino-1-butanol with complete conversion Catalyst
Cu/Al 2 0 3
Cu/MgO
Yields of products? (mol-%)
Reaction temperature ( DC)
I
II
III
IV
200 225 250 275 300
20 45 20 9 3
33 13 55 55
47 42 42 10 6
0 0 0 10 24
200 225 250 275 300
42 62 45 45 44
58 38 55 55 56
0 0 0 0 0
0 0 0 0 0
71
"Products are shown in Fig. 1. (VI)
0
(IX)
OCH 3
~
N
-3H,
OCH 3
I
H
tH 3
.&
(X)
N
CH30H! -H2O
CH,oH
-H2O HO~NH2-
r
0
H
(V)
1 [ OOH]
1. -H2O 2. CH,OH
-H2O
CH'OCH 3
-H2O
I
-H,
(XI)
.&
N
0 (VII)
00 tH 3
(VIU)
Fig. 2. Reactions of 5-amino-1-pentanol. Corresponding product distributions are listed in Table 2.
5-Amino-I-pentanol Depending on the temperature and the catalyst used, the products observed in the reaction of 5-amino-l-pentanol were piperidine (V), I-methylpiperidine (VI), Lt1-dehydropiperidine (VII), I-methylpiperidone (VIII), 3-meth-
111
TABLE 2 Reaction products of 5-amino-l-pentanol Catalyst
Cu/Al,O,: Without hydrogen
With hydrogen
Cu/MgO: Without hydrogen
With hydrogen
with complete conversion
Reaction temperature (“C)
Yields of products” (mol-%)
200 225 250 300 200 225 250 300
99 89 80
225 250 300 225 250 300
62 23
V
83 70 16
60
VI
VII
VIII
IX
x
XI
40
11
9
6
1 10b 20 28 6 20 50 75 37 73 93 20 14 60
11 10 22
1 2 5 5 5
“Products are shown in Fig. 2. ‘Completion to 100% is represented by many non-identified substances (probably fragmentation products) which appeared in small amounts. TABLE 3 Reaction products of 5-amino-1-pentanol reaction in ethanolic solution in the presence of hydrogen with complete conversion Reaction temperature (“C)
Yields of products” (mol-%) Piperidine
1-Ethylpiperidine
A ‘-Dehydropiperidine
200 225 250 275
94 4 0 0
0 70 74 80
1 7 7 10
“Completion to 100% is represented by non-identified substances appearing in small amounts.
ylpiperidine (IX), 3-methylpyridine (X ) and 3,5-lutidine (XI ). The relevant reactions leading to these products are presented in Fig. 2. The catalysts differed markedly in their alkylation activity. Cyclization to piperidine (V) was prevalent over Cu/A1203 up to 250 aC, whereas at 300’ C no more V was found
112
in the product mixture. At this temperature the major products were l-methylpiperidone (VIII) and 1-methylpiperidine (VI), indicating that both dehydrogenation and alkylation were favoured by higher temperature. Under these conditions, two isomeric methylpiperidines (VI and IX) and also methyl derivatives of pyridine (X and XI) were detected in the product mixture. It is interesting that these compounds were not formed when Cu/MgO was used as the catalyst. In this case, piperidine (V) and l-methylpiperidine (VI) were the major products. The latter was obtained with a 93% yield at 300°C. In order to investigate the influence of hydrogen on the product distribution, experiments were performed with hydrogen in the feed. The product distributions obtained under these conditions are listed in Table 2. The presence of hydrogen in the feed has a marked influence on the product distribution. Similar behaviour has also been observed with other amination reactions [ 7,8,13151. In the presence of hydrogen, the alkylation activity of Cu/A1203 increased and became important at lower temperatures already. In contrast, the alkylation activity of Cu/MgO decreased in the presence of hydrogen. Hydrogenolysis of the reactant amino alcohol and also of the products led to several unidentified fragmentation products and thereby to considerably poorer selectivities. Cyclization of 5-amino-1-pentanol in the presence of hydrogen was also carried out in ethanolic solution. In this instance, 1-ethylpiperidine was the main product (Table 3). No traces of the methyl derivatives were detected in the product mixture under these conditions, indicating that the solvent was the only alkylating agent in the reaction system. Comparison of the yields of corresponding alkyl derivatives formed in reactions carried out in methanol (Table 2) and ethanol (Table 3) reveals that the alkylation activity was markedly higher for ethanol than for methanol. 6-Amino-I-hexanol
Hexahydro-lH-azepine (XII) and 1,2-lupetidine (XIII) products of the reaction of 6-amino-l-hexanol (Scheme 1).
were the main
-Hz0 HOWNH2
-
(1) H CH,
Scheme 1.
(XII)
(XIII)
The product distributions of this reaction are listed in Table 4. Note that even at 250’ C many unidentified side-products appeared in the product mixture in small amounts. This behaviour is accounted for by the number of unidentified peaks which appeared in the gas chromatogram: for the product mixture obtained over Cu/A1203 this number increased from 3 (225°C) to 25 (3OO”C),
113 TABLE 4 Reaction products of 6-amino-l-hexanol Catalyst
Reaction temperature (“Cl
reaction with complete conversion
Yields of products (mol-% ) XII”
XIII
Unidentified by-products
Cu/A&O,
225 250 275 300
95 86 67 27
1 2 1 2
4 12 32 71
Cu/MgO
200 225 250 275 300
89 84 77 75 55
10 13 20 24 38
1 3 3 1 7
-
(3Jb (14) (14) (25) (2) (7) (7) (7) (10)
“products are shown in Scheme 1. bNumbers in parentheses correspond to the number of unidentified peaks in the gas chromatogram.
corresponding to 4% and 71%, respectively, of the total peak areas of the gas chromatogram. The reaction over Cu/MgO was much more selective (with a maximum of seven peaks not exceeding 7% of the total peak area). Also, Cu/MgO was more active in the alkylation of the primarily formed hexahydro-lH-azepine to 1,2lupetidine. It should be emphasized that no monoalkyl derivatives were detected in the reaction products of 6-amino-l-hexanol over either catalyst. 3-Aminopropanol 3-Aminopropanol did not undergo cyclization to the expected four-membered ring under the conditions used. Only fragmentation of the reactant and the formation of tar-like products were observed. The light fraction of the products contained various propylamines and several low-boiling substances which were not identified. CONCLUSIONS
Cyclization of amino alcohols in alcoholic solution has been shown to be an interesting route for the synthesis of cyclic amines and their alkyl derivatives. The selectivity with respect to the cyclic amine depends on various factors, such as the starting amino alcohol, the nature of the catalyst support, temperature and the presence of hydrogen. Under suitable conditions, 4-amino-lbutanol is converted with a selectivity of 62% to the cyclic amine (pyrrolidine) or with 71% selectivity to the alkyl derivative (N-methylpyrrolidine). The corresponding selectivities with 5-amino-1-pentanol are much higher, being 99% to the cyclic amine (piperidine) and 95% to the alkyl derivative (l-meth-
114
ylpiperidine). 6-Amino-1-hexanol is converted with a yield of 95% to the corresponding cyclic amine (hexahydro- lH-azepine), whereas monoalkyl derivatives are not obtained with this reactant. 3-Amino-l-propanol does not undergo cyclization under the conditions used. Depending on the carrier, copper catalysts show markedly different selectivity behaviour. Cu/MgO exhibits much higher activity than Cu/Al,O, for alkylation. An exception is the reaction of 4-amino-1-butanol, where this tendency is not evident. However, this reaction shows another peculiarity: dehydrogenation to d l-dehydropyrrolidine is an important side-reaction over Cu/A1203, but does not occur over Cu/MgO. The reason for this complex behaviour is not understood. As regards the influence of hydrogen on the catalyst selectivity, our studies indicate that the presence of hydrogen in the reaction mixture has a marked effect on the product distribution of the reaction. It enhances significantly the alkylation activity of alumina-supported copper, whereas for magnesia-supported copper a decrease in the alkylation activity is observed in the presence of hydrogen. Another factor influencing the selectivity of the cycloamination in the presence of hydrogen, namely hydrogenolysis of the reactant and products becomes important at higher temperatures, leading to lower selectivities with respect to the desired cyclic amine. The use of an alcohol as solvent was found to be an interesting possibility for the efficient synthesis of alkyl derivatives of the cyclic amines. Replacement of methanol by ethanol led to the formation of ethyl derivatives as the only alkylation product. This reaction may offer interesting prospects for the direct synthesis of various alkyl derivatives of cyclic amines. ACKNOWLEDGEMENT
Thanks are due to Fluka (Buchs, Switzerland) for providing the amino alcohols.
REFERENCES 1 2 3 4 5 6 7 8
Ullman’s Enzyklopiidie der Technischen Chemie, Vol. 7, Verlag Chemie, Weinheim, 4th ed., 1975, p. 374. E.I. Karpeiskaya, Yu. N. Kukushin, V.A. Trefimov, I.D. Ratner and D.P. Shaskin, Bull. Acad. Sci. USSR, 23 (1974) 307. E.I. Karpeiskaya and I.P. Yukolev, Bull. Acad. Sci. USSR, 23 (1974) 313. A. Venot, Bull. Sot. Chim. Fr., 12 (1972) 4736. A. Venot, Bull. Sot. Chim. Fr., 12 (1972) 4744. I. Scriabin, Bull. Sot. Chim. Fr., 5 (1947) 454. H. Uffer and W. Breuer, in P. Friedlander (Editor), Fortschritte der Teerfabrikation und verwandter Industriezweige, Vol. 12, Springer, Berlin, 1937, p. 360. Ger. Offen., DE 3125662 Al, 1983.
115 9 10 11 12 13 14 15
A. Baiker and J. Kijeriski, Catal. Rev. Sci. Eng., 27 (1985) 653. W. Hammerschmidt, A. Baiker, A. Wokaun and W. Fluhr, Appl. Catal., 20 (1986) 305. J. Kijeriski and S. Malinowski, J. Chem. Soc., Faraday Trans. I, 74 (1978) 250. A. Baiker and W. Richarz, Synth. Commun., 8 (1978) 27. A. Baiker, W. Caprez and W.L. Holstein, Ind. Eng. Chem., Prod. Res. Dev., 22 (1983) 217. J. Runeberg, A. Baiker and J. Kijenski, Appl. Catal., 17 (1985) 309. A. Baiker, Stud. Surf. Sci. Catal., 41 (1988) 283.
107
Synthesis of Cyclic Amines and Their Alkyl Derivatives from Amino Alcohols Over Supported Copper Catalysts J. KIJENSKI and P.J. NIEDZIELSKI
Laboratory of Catalytic Synthesis, Institute of Organic Technology, Warsaw Technical University (Politechnika), Koszykowa 75, 00662 Warsaw (Poland) and A.BAIKER*
Department of Industrial and Engineering Chemistry, Swiss Federal Institute of Technology, ETH-Zentrum, CH-Zilrich (Switzerland) (Received 24 February 1989, revised manuscript received 10 April 1989 )
ABSTRACT Cyclization of amino alcohols over copper supported on y-alumina and magnesia was found to be an efficient method for the synthesis of cyclic amines, their alkyl derivatives and in some instances also their dehydro derivatives. Reactions were carried out in the temperature range 200300 C using a continuous fixed-bed reactor and methanol or ethanol as solvent. The selectivities with respect to the different products depended markedly on the reaction temperature and the catalyst used. The amino alcohols used as reactants were 3-amino-l-propanol, 4-amino-l-butanol, 5-amino-l-pentanol and 6-amino-l-hexanol. The reaction of 3-amino-l-propanol was unspecific and led to various fragmentation products. In contrast, the reaction of 4-amino-l-butanol yielded either pyrrolidine (selectivity 62% ), N -methylpyrrolidine (71%) or L/l-dehydropyrrolidine (47%), depending on the conditions. The reaction of 5-amino-l-pentanolled either to piperidine (99%) or N-methylpiperidine (93%). Hexahydro-1H-azepine (95%) was the main product of the cyclization of6-amino-l-hexanol. 0
INTRODUCTION
Cyclic amines are of importance in the chemical industry as components and intermediates for pharmaceuticals, detergents, additives, etc. [1]. Although attractive, little has been reported on the synthesis of cyclic amines by heterogeneous catalytic routes [2-10]. This work is a continuation of our previous efforts at studying catalytic amination and cycloamination of alcohols over supported copper catalysts [9,10]. We report the cyclization of some amino alcohols in alcoholic solution over copper supported on y-alumina and magnesia. The aim of this work was to 0166-9834/89/$03.50
© 1989 Elsevier Science Publishers B.V.
108
investigate the influence of important reaction conditions, such as temperature, presence of solvent and nature of catalyst carrier, on the selectivity with respect to the desired products. Further, we wanted to probe the range of applicability of this process for the synthesis of cyclic amines and their alkyl derivatives. EXPERIMENTAL
Apparatus and procedure Reactions were carried out in a continous fixed-bed reactor in the temperature range 200-300°C and at atmospheric pressure. The quartz reactor tube (0.22 m~0.02 m I.D.) was filled with 10 cm3 of catalyst. Solutions of amino alcohols (16 mol-% ) in methanol or ethanol were dosed into the reactor using an infusion pump (Medipan ). The dosing rate (HLSV) was 1 cm3 of reactant solution per 1 cm3 of catalyst per hour. The flow-rate of carrier gas (nitrogen or hydrogen ) was 7.2 1(STP ) /h. Materials The supported copper catalyst were prepared by impregnation of the support materials with aqueous solution of copper (II) nitrate. y-Alumina (Degussa) and magnesia (precipitated from magnesium nitrate hexahydrate according to a previously described procedure [ 111) were used as carriers. After impregnation, the catalysts were dried at 60 ’ C for 48 h and subsequently calcined at 500°C for 6 h. Before use the catalysts were reduced with hydrogen-nitrogen as described previously [ 12). The copper content of the catalysts was 17% (w/w). Grains of size 0.5-1.0 mm were used in the catalytic experiments. BET surface areas of the catalysts were Cu/Al,O, 155 m2/g and Cu/MgO 18 m’/g. Amino alcohols ( > 97% pure) were supplied by Fluka. Analysis The liquid product mixtures were analysed by gas chromatography (GC) (Varian Aerograph 2868) using a 1.5-m glass column filled with 4% Carbowax 20M-8% KOH on Carbopack B 60 ( Supelco ) or a 25-m capillary column filled with SE-54. Products were identified by mass spectrometry using a Finnigan 4000 mass spectrometer. For quantitative GC analysis, calibration factors were determined. When not all the reaction products could be identified, the unknown molar calibration factors were replaced by those of known reaction products with similar retention times. Product distributions calculated with this assumption should be considered to be approximate.
109
Yields of products ( Yi) were defined as
where, Pi is the number of moles of product (i) and C (P,) is the sum of the number of moles of reactant and products at the reactor outlet. Note that in all results reported the conversion of the reactant was 100% and that in this instance the yield also corresponds to the product selectivity. RESULTS AND DISCUSSION
4-Amino-1-butanol Important reaction products observed with 4-amino-1-butanol over Cu/A1203 were pyrrolidine (I), N-methylpyrrolidine (II), d ‘-dehydropyrrolidine (III) and, at higher temperatures, also 1,2_dimethylpyrrolidine (IV). Fig. 1 shows the relevant reactions leading to these products. Note that the methanol used as the solvent acted as an alkylating agent (products II and IV). The product distributions obtained over Cu/A1203 and Cu/MgO are listed in Table 1 and depended strongly on the catalyst used and on temperature. In contrast to the reaction over Cu/A1203, where all reactions shown in Fig. 1 occurred, formation of III and IV was not observed over Cu/MgO. It is also interesting that at higher temperatures ( > 250°C) the ratio of N-methylpyrrolidine to pyrrolidine was hardly influenced by temperature increase when Cu/MgO was used.
HO-NH*
“0-Q I: (I)
\
-2
0N' (111)
Fig. 1. Reactions of 4-amino-1-butanol. Corresponding product distributions are listed in Table 1.
110 TABLE 1
Reaction products of 4-amino-1-butanol with complete conversion Catalyst
Cu/Al 2 0 3
Cu/MgO
Yields of products? (mol-%)
Reaction temperature ( DC)
I
II
III
IV
200 225 250 275 300
20 45 20 9 3
33 13 55 55
47 42 42 10 6
0 0 0 10 24
200 225 250 275 300
42 62 45 45 44
58 38 55 55 56
0 0 0 0 0
0 0 0 0 0
71
"Products are shown in Fig. 1. (VI)
0
(IX)
OCH 3
~
N
-3H,
OCH 3
I
H
tH 3
.&
(X)
N
CH30H! -H2O
CH,oH
-H2O HO~NH2-
r
0
H
(V)
1 [ OOH]
1. -H2O 2. CH,OH
-H2O
CH'OCH 3
-H2O
I
-H,
(XI)
.&
N
0 (VII)
00 tH 3
(VIU)
Fig. 2. Reactions of 5-amino-1-pentanol. Corresponding product distributions are listed in Table 2.
5-Amino-I-pentanol Depending on the temperature and the catalyst used, the products observed in the reaction of 5-amino-l-pentanol were piperidine (V), I-methylpiperidine (VI), Lt1-dehydropiperidine (VII), I-methylpiperidone (VIII), 3-meth-
111
TABLE 2 Reaction products of 5-amino-l-pentanol Catalyst
Cu/Al,O,: Without hydrogen
With hydrogen
Cu/MgO: Without hydrogen
With hydrogen
with complete conversion
Reaction temperature (“C)
Yields of products” (mol-%)
200 225 250 300 200 225 250 300
99 89 80
225 250 300 225 250 300
62 23
V
83 70 16
60
VI
VII
VIII
IX
x
XI
40
11
9
6
1 10b 20 28 6 20 50 75 37 73 93 20 14 60
11 10 22
1 2 5 5 5
“Products are shown in Fig. 2. ‘Completion to 100% is represented by many non-identified substances (probably fragmentation products) which appeared in small amounts. TABLE 3 Reaction products of 5-amino-1-pentanol reaction in ethanolic solution in the presence of hydrogen with complete conversion Reaction temperature (“C)
Yields of products” (mol-%) Piperidine
1-Ethylpiperidine
A ‘-Dehydropiperidine
200 225 250 275
94 4 0 0
0 70 74 80
1 7 7 10
“Completion to 100% is represented by non-identified substances appearing in small amounts.
ylpiperidine (IX), 3-methylpyridine (X ) and 3,5-lutidine (XI ). The relevant reactions leading to these products are presented in Fig. 2. The catalysts differed markedly in their alkylation activity. Cyclization to piperidine (V) was prevalent over Cu/A1203 up to 250 aC, whereas at 300’ C no more V was found
112
in the product mixture. At this temperature the major products were l-methylpiperidone (VIII) and 1-methylpiperidine (VI), indicating that both dehydrogenation and alkylation were favoured by higher temperature. Under these conditions, two isomeric methylpiperidines (VI and IX) and also methyl derivatives of pyridine (X and XI) were detected in the product mixture. It is interesting that these compounds were not formed when Cu/MgO was used as the catalyst. In this case, piperidine (V) and l-methylpiperidine (VI) were the major products. The latter was obtained with a 93% yield at 300°C. In order to investigate the influence of hydrogen on the product distribution, experiments were performed with hydrogen in the feed. The product distributions obtained under these conditions are listed in Table 2. The presence of hydrogen in the feed has a marked influence on the product distribution. Similar behaviour has also been observed with other amination reactions [ 7,8,13151. In the presence of hydrogen, the alkylation activity of Cu/A1203 increased and became important at lower temperatures already. In contrast, the alkylation activity of Cu/MgO decreased in the presence of hydrogen. Hydrogenolysis of the reactant amino alcohol and also of the products led to several unidentified fragmentation products and thereby to considerably poorer selectivities. Cyclization of 5-amino-1-pentanol in the presence of hydrogen was also carried out in ethanolic solution. In this instance, 1-ethylpiperidine was the main product (Table 3). No traces of the methyl derivatives were detected in the product mixture under these conditions, indicating that the solvent was the only alkylating agent in the reaction system. Comparison of the yields of corresponding alkyl derivatives formed in reactions carried out in methanol (Table 2) and ethanol (Table 3) reveals that the alkylation activity was markedly higher for ethanol than for methanol. 6-Amino-I-hexanol
Hexahydro-lH-azepine (XII) and 1,2-lupetidine (XIII) products of the reaction of 6-amino-l-hexanol (Scheme 1).
were the main
-Hz0 HOWNH2
-
(1) H CH,
Scheme 1.
(XII)
(XIII)
The product distributions of this reaction are listed in Table 4. Note that even at 250’ C many unidentified side-products appeared in the product mixture in small amounts. This behaviour is accounted for by the number of unidentified peaks which appeared in the gas chromatogram: for the product mixture obtained over Cu/A1203 this number increased from 3 (225°C) to 25 (3OO”C),
113 TABLE 4 Reaction products of 6-amino-l-hexanol Catalyst
Reaction temperature (“Cl
reaction with complete conversion
Yields of products (mol-% ) XII”
XIII
Unidentified by-products
Cu/A&O,
225 250 275 300
95 86 67 27
1 2 1 2
4 12 32 71
Cu/MgO
200 225 250 275 300
89 84 77 75 55
10 13 20 24 38
1 3 3 1 7
-
(3Jb (14) (14) (25) (2) (7) (7) (7) (10)
“products are shown in Scheme 1. bNumbers in parentheses correspond to the number of unidentified peaks in the gas chromatogram.
corresponding to 4% and 71%, respectively, of the total peak areas of the gas chromatogram. The reaction over Cu/MgO was much more selective (with a maximum of seven peaks not exceeding 7% of the total peak area). Also, Cu/MgO was more active in the alkylation of the primarily formed hexahydro-lH-azepine to 1,2lupetidine. It should be emphasized that no monoalkyl derivatives were detected in the reaction products of 6-amino-l-hexanol over either catalyst. 3-Aminopropanol 3-Aminopropanol did not undergo cyclization to the expected four-membered ring under the conditions used. Only fragmentation of the reactant and the formation of tar-like products were observed. The light fraction of the products contained various propylamines and several low-boiling substances which were not identified. CONCLUSIONS
Cyclization of amino alcohols in alcoholic solution has been shown to be an interesting route for the synthesis of cyclic amines and their alkyl derivatives. The selectivity with respect to the cyclic amine depends on various factors, such as the starting amino alcohol, the nature of the catalyst support, temperature and the presence of hydrogen. Under suitable conditions, 4-amino-lbutanol is converted with a selectivity of 62% to the cyclic amine (pyrrolidine) or with 71% selectivity to the alkyl derivative (N-methylpyrrolidine). The corresponding selectivities with 5-amino-1-pentanol are much higher, being 99% to the cyclic amine (piperidine) and 95% to the alkyl derivative (l-meth-
114
ylpiperidine). 6-Amino-1-hexanol is converted with a yield of 95% to the corresponding cyclic amine (hexahydro- lH-azepine), whereas monoalkyl derivatives are not obtained with this reactant. 3-Amino-l-propanol does not undergo cyclization under the conditions used. Depending on the carrier, copper catalysts show markedly different selectivity behaviour. Cu/MgO exhibits much higher activity than Cu/Al,O, for alkylation. An exception is the reaction of 4-amino-1-butanol, where this tendency is not evident. However, this reaction shows another peculiarity: dehydrogenation to d l-dehydropyrrolidine is an important side-reaction over Cu/A1203, but does not occur over Cu/MgO. The reason for this complex behaviour is not understood. As regards the influence of hydrogen on the catalyst selectivity, our studies indicate that the presence of hydrogen in the reaction mixture has a marked effect on the product distribution of the reaction. It enhances significantly the alkylation activity of alumina-supported copper, whereas for magnesia-supported copper a decrease in the alkylation activity is observed in the presence of hydrogen. Another factor influencing the selectivity of the cycloamination in the presence of hydrogen, namely hydrogenolysis of the reactant and products becomes important at higher temperatures, leading to lower selectivities with respect to the desired cyclic amine. The use of an alcohol as solvent was found to be an interesting possibility for the efficient synthesis of alkyl derivatives of the cyclic amines. Replacement of methanol by ethanol led to the formation of ethyl derivatives as the only alkylation product. This reaction may offer interesting prospects for the direct synthesis of various alkyl derivatives of cyclic amines. ACKNOWLEDGEMENT
Thanks are due to Fluka (Buchs, Switzerland) for providing the amino alcohols.
REFERENCES 1 2 3 4 5 6 7 8
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