Ind. Eng. Chern. Process Des. Dev., Vol. 17, No. 1, 1978
9
Kinetics of Caprolactam Formation from 6-Aminocaproic Acid, Ester, and Amide Frank Mares and Desmond Sheehan' Chemical Research Center, Allied Chemical Corporation, Morristown, New Jersey 07960
The kinetics of cyclization of 6-aminocaproic acid, ethyl 6-aminocaproate, and 6-aminocaproamide to caprolactam in ethanol and water were determined over the temperature range 150-280 OC.The reaction rate constants and the activation energies of individual steps were calculated. The most efficient process is the cyclization of 6-aminocaproic acid in ethanol at 200 O C , which yields at least 98 % of caprolactam. No oligomers were detected and the half-life of the reaction is less than 10 min. The second best procedure, given the limitation that only water and ethanol were examined as solvents, is cyclization of 6-aminocaproic acid in water at -300 O C . However, in this process oligomers are formed and the molecular weight and quantity of the oligomers increase with increasing concentration of 6-aminocaproic acid.
Introduction Cyclizations of 6-aminocaproic acid, alkyl 6-aminocaproates, and 6-aminocaproamide are well documented in the literature (Berther and Giesen, 1959; Fisher and Oberrauch, 1960; Kobayshi and Hattori, 1957; Kunichika and Kashiwabara, 1963; Sheehan, 1969; Tanaka et al., 1971). However, the efficiency of published procedures is difficult to compare due to the lack of quantitative data. This paper fills the gap in part by describing the kinetics of cyclization of 6-aminocaproic acid, ethyl 6-aminocaproate, and 6-aminocaproamide in water and ethanol. These two solvents were chosen as representatives of polar (water) and relatively nonpolar (ethanol) media. Solvents less polar than ethanol were not considered because of the low solubility of 6-aminocaproic acid in such solvents. Experimental Section Gas-Liquid Chromatography. Samples were treated first with Regisil and trimethylchlorosilane in order to exchange the protons of either NHz or COzH groups for trimethylsilyl groups. The required sample aliquots containing tetraglyme as internal standard (-100 pL) were transferred into a vial and freed from the solvent in a vacuum oven at 30-40 "C and -200 mmHg. T o the dry samples, a few drops of pyridine, 150 pL of Regisil, and 150 pL of trimethylchlorosilane were added. The vials were sealed with Teflon screw caps and warmed to 80 "C for 0.5 h. Aliquots (-5 pL) of the samples were then injected into a 2 f t X '14 in. column filled with 10% SE-30 on Diatoport a t temperatures programmed from 100 to 250 "C at a rate of 20 "Clmin. This method was suitable for the analysis of ethyl 6-aminocaproate, 6-aminocaproic acid, caprolactam, and 6-aminocaproamide. Even after silylation, the oligomers were insufficiently volatile to pass through the column. Potentiometric Titration. A formal method was used for the carboxyl group determinations. The sample (-1 g aliquot) was mixed with 37% formal solution (-1 mL) adjusted to pH 6.0. Using a glass electrode as the indicator, $he sample was then titrated with 0.1 M KOH standardized by potassium hydrogen phthalate. The amino groups were determined by potentiometric titration in acetic acid using a glass electrode indicator. Perchloric acid (70??,8.5 mL) was dissolved in 1L of acetic acid followed by addition of 15 mL of acetic anhydride. The mixture was allowed to stand overnight and then standardized with potassium hydrogen phthalate. The samples (-1 g aliquots) were freed of solvent in a vacuum oven at 30-40 "C/200
mmHg. The dry samples were dissolved in glacial acetic acid and then titrated with 0.1 M HC104. 6-Aminocaproic acid was crystallized from water and dried in vacuo over PzO5. Titration showed 7.63 mequiv of -COzH/g and 7.62 mequiv of -NHz/g. Ethyl 6-Aminocaproate, Pure hydrochloride of ethyl 6aminocaproate was prepared from 6-aminocaproic acid and absolute ethanol. Ethyl 6-aminocaproate was freed from the hydrochloride form on Ion Exchanger Bio-Rad AG 1-X8 which was converted into the basic form by aqueous NaOH solution. Water was then exchanged for dry methanol, and washing with methanol was continued until no water was found in the eluent. A solution of ethyl 6-aminocaproate hydrochloride in methanol was then passed through the column. Methanol was evaporated in vacuo a t room temperature and the residue stored in a refrigerator under Nz; NMR 6 4.15 (2 H,q), 6 2.7 (2 H,t), 6 2.3 (2 H,t), 6 1.45 (6 H,m), 6 1.27 (2 H,s), 6 1.26 (3 H,t). The content of ethyl 6-aminocaproate was monitored by potentiometric titration in acetic acid. The sample did not contain any C1-. Any sample older than 1week was discarded. 6-Aminocaproamide. A solution of 5-cyanovaleroamide (10 g) in ethanol saturated with ammonia was hydrogenated over Raney Ni at 70 "C and 700 psi initial H2 pressure. When the required amount of hydrogen was consumed, the reaction was stopped, the solvent evaporated, and the product treated with HC1. The 6-aminocaproamide hydrochloride obtained was crystallized from ethanol to constant melting point, 149 "C. The hydrochloride (20.47 g) was suspended in methanol (100 mL) and an ion exchanger (150mL) Bio-Rad AG 1-XP (activity 1.5 mequiv/mL) was added. The ion exchanger was first converted into its basic form in water and then washed with methanol until all the water was removed. The mixture was stirred under Nz until no C1- was detected (-l/z h). The ion exchanger was filtered off and washed three times with methanol. The solvent was evaporated at room temperature, affording 16.6 g (99%) of 6-aminocaproamide. This product was dissolved in either water or ethanol and the required amount of internal standard (triglyme or tetraglyme) was added for subsequent gas chromatographic analyses. The content of 6-aminocaproamide was monitored by potentiometric titration in acetic acid. This stock solution was refrigerated and stored under Nz. Kinetics Measurement. The required amount of 6-aminocaproic acid or its derivatives was weighed together with
0019-788217811117-0009$01.00/0 0 1978 American Chemical Society
10
Ind. Eng. Chem. Process Des. Dev., Vol. 17, No. 1, 1978
IC.
I0C
800
600
400 Y8"
Figure 1. Cyclization of ethyl 6-aminocaproate in ethanol at 200 "C. The meaning of the symbols A, B, and C is the same as in Scheme I. The points represent the experimental data; the curves are theoretical functions as calculated by analog computer using differential equations (4) through (6). the solvent and the internal standard in an autoclave (-40 mL content) equipped with a sampling device. The air was replaced by Nz and the autoclave was immersed in a constanttemperature bath. The temperature was kept constant with a precision of f0.2 "C. About seven samples per run were withdrawn at appropriate intervals. The samples were analyzed and the data obtained were processed on an analog computer. Each run was repeated three times. The tabulated reaction rate constants are averages of the three runs; the maximum deviation observed for the rate constants of repeated runs was fs%. Results a n d Discussion Ethyl 6-Aminocaproate in Ethanol. Conversion of ethyl 6-aminocaproate to caprolactam was followed at a concentration of 0.9 mol/kg (all concentrations so expressed refer to moles of aminocaproic substrate per kilogram of solution) and at temperatures from 150 to 250 OC. Reactant and product concentrations in a typical run a t 200 OC plotted as a function of time are shown in Figure 1. The conversion to caprolactam never reached loo%, possibly due to the reverse reaction (eq 1)and/or formation of by-products. Since ethyl 6-aminocaproate always disappeared from the reaction mixture completely, the reversibility indicated in eq 1 could be discounted. To confirm this conclusion, H,&(CHJ,CO,Et
0
0
+
= '/'z([A]o - [ B l t - m )
2 3
? I
I / T 103
Figure 2. Activation energies for cyclization ( E l )and dimerization (E21 of ethyl 6-aminocaproate in ethanol.
Table I. Reaction Rate Constants for Cyclization of Ethyl 6-Aminocaproate in Ethanol k2 X lo3, t,"C
T,K
150
423 473 493 523
200 220 250
( 1 / T )X lo3
k l X lo3, min-l
kg-mol-l
1.14 7.62
2.355 2.114
2.028 1.912
12.1
42.9
min-'
0.713 8.45 19.4 65.3
Scheme I. Ethyl 6-Aminocaproate in Ethanol H,N(CHJ5COLEt
G
O
+
\
K
EtOH
H,N(CH,),COSH(CH,),CO-Et
+
EtOH
C B
(Figure 1).The results and Scheme I agree with the known fact that amines react faster with esters (eq 2 ) than with amides (eq 3). 2HZN(CH2)5C02Et
EtOH
(11
a mixture of caprolactam and ethanol was held at 200 "C for 26 h. As expected, no change in the caprolactam concentration was observed. In order to determine the probable structures of the byproducts the concentration of -NHz was determined a t the end of every run. It was found that the final concentration of -NH1 always corresponded to one-half of the difference between the initial concentration of ethyl 6-aminocaproate and the final concentration of caprolactam (eq la). (The symbols in eq l a through 7 are explained in Scheme I.) This datum strongly suggests that the by-product is a linear dimer (Scheme I).
[-"z]
I 9
(la)
The dimer could be formed in two ways as shown by eq 2 and 3. In order to distinguish between several possible reaction schemes the runs were analyzed on an analog computer. It was established that Scheme I, which leads to the differential equations (4)-(6) gives the best fit between the experimental data and the theoretical curves plotted by the computer
-+
G
O
H~N(CHZ)~CONH(CH~)+ ~ CEtOH O ~ E ~(2)
+
-
H,N(CH,),CO,Et
H,N(CH-),COKH(CH,),CO.Et (3)
+
dA - klA kzA2 (4) dt dB = klA (5) dt dC - = kzA2 (6) dt The resulting reaction rate constants at different temperatures are summarized in Table I and Figure 2. (Only Tables I, V, X, XI, XII, and XI11 giving rate constant data are included in this text. Tables 11, 111, IV, VI, VII, VIII, and IX containing detailed analytical data for various runs are provided in the supplementary microfilm edition. See the paragraph at the end of the paper regarding the supplementary material.) The activation energy (Figure 2 ) for the cyclization of the ester to caprolactam is appreciably lower than that for
Ind. Eng. Chem. Process Des. Dev., Vol. 17, No. 1, 1978
11
21
IO
mole, kg
Ye
log
__
Ye - Y
A 05
Mll.
Figure 3. Cyclization of ethyl 6-aminocaproate in water a t 200 "C; A = ethyl 6-aminocaproate;A' = [-COzH]; B = caprolactam.
dimerization. Therefore, the amount of caprolactam formed decreases and the final concentration of the dimer increases with increasing temperature. At 200 "C (Figure 1) the time required to reach the maximum caprolactam concentration is at least 600 min and only 90% of caprolactam is formed. In order to increase the caprolactam yield, it is necessary to lower the temperature substantially, but even at 150 "C the amount of dimer formed is still about 5%, and the time required to reach maximum caprolactam concentration is a t least 33 h. The conclusions above are valid only for a relatively dilute solution (-1 mol/kg) of ethyl 6-aminocaproate in ethanol. The dimerization of ethyl 6-aminocaproate follows second-order kinetics (eq 6) and the reaction rate should then be proportional to the square of the amino ester concentration. The rate of dimerization relative to cyclization increases as a function of the amino ester concentration (eq 7). Therefore, ethyl 6aminocaproate can be quantitatively cyclized to caprolactam only if the reaction is run at a low temperature and high dilution.
MI"
Figure 4. Graphical representation of eq 8a.
9
M,"
Figure 5. Cyclization of 6-aminocaproamide in ethanol at 250 "C. The meaning of the symbols A, B, and C is the same as in Scheme 11. The points represent the experimental data. The curves are theoretical functions as calculated by analog computer using differential equations (10) through (12).
Ethyl 6-Aminocaproate in Water. The cyclization of ethyl 6-aminocaproate was studied at a concentration of about 0.8 mol/kg and temperatures of 100 and 200 "C. After 4.5 h at 100 "C no ester remained in the reaction mixture, and after 6 h the reaction mixture was analyzed. Only 19%of caprolactam was formed. Potentiometric titration of the -C02H groups showed that 77.7% of the original ester is present as 6-aminocaproic acid, indicating that the hydrolysis of the ester function is much faster than any reaction in the system. In order to understand the exact course of the reaction, the cyclization was studied in detail at 200 "C. The results (Figure 3) further establish that the hydrolysis of ethyl 6-aminocaproate is the fastest reaction in the system and that 6-aminocaproic acid is formed. The cyclization of ethyl 6-aminocaproate to caprolactam is a slower competitive reaction. From the time that ethyl 6-aminocaproate vanishes, the system can be described as a first-order reversible reaction (8) by eq 8a where a represents the concentration of ethyl 6-aminocaproate a t t = 0 and Y and Ye represent the concentration
of caprolactam at any time during the reaction and at equilibrium, respectively. Expression 8a is fulfilled as follows from Figure 4 and the final result is similar to the cyclization of 6-aminocaproic acid in water which is described subsequently. 6-Aminocaproamide i n Ethanol. Formation of caprolactam from 6-aminocaproamide was studied at a concentration of about 1 mol/kg and temperatures from 170 to 250 "C. The analytical data are summarized in Tables I1 to IV and for a representative run at 250 "C are plotted as a function of time in Figure 5 . In all of the runs, the conversion of 6-aminocaproamide to caprolactam was much less than 100%. Since the concentration of 6-aminocaproamide approaches zero, oligomer formation must be competitive with lactam formation. At the end of the reaction, the -NH2 concentration is about half of the difference between the initial concentration of 6-aminocaproamide and the final concentration of caprolactam (see eq 9, where the symbols are the same as in Scheme 11,and Figure 5 ) . This finding indicates that a linear dimer is the major oligomeric component (Scheme 11).The dimer can be formed by two reactions (Scheme 11,reactions 2 and 3). The system was analyzed on an analog computer and dif-
(8a)
ferential equations (10)-(12) gave the best fit between the calculated theoretical curves and the experimental data
12
Ind. Eng. Chem. Process Des. Dev., Vol. 17, No. 1,'1978
log k + 3
El
16.5 KCdlImOle
i2
18.8 K c a I I n o l e
E3
11.8 K c a 1 i n o l e
100
200
300
MI"
I/T l o 3
Figure 6. The activation energies for cyclization ( E l )and dimerization (Ea and E B )of 6-aminocaproamidein ethanol.
Table V. Reaction Rate Constants for Cyclization of 6-Aminocaproamide in Ethanol k z x 103, k 3 x 103, k l X lo3, kg-mol-' kg-mol-' t , "C
T,K
(UT) x IO3
171 200 250
444 473 523
2.255 2.115 1.915
min-l 1.73 5.28 28.9
min-1 4.35 15.6 100.8
Scheme 11.6-Aminocaproamide in Ethanol H,N(CHJ,CONHz A ~ A +
$
min-l 4.33 12.1
33.7
A
n LN.0 + 3"
Figure 7.6-Aminocaproamide in water at 200 O C . The symbols are the same as in Scheme 111. The points represent experimentaldata. The curves are theoretical as calculated by the analog computer using the differential equations (21a)to (21d). There are minor details which were omitted from the discussion above, not taken into account in the computer analysis, and are summarized below. The concentration of 6-aminocaproamide never reached zero as required by Scheme 11. Even a t 250 "C after 250 min 1%of the original 6-aminocaproamide was present in the reaction mixture. However, the equilibrium must be shifted heavily to the side of caprolactam and for practical purposes the low concentration of aminocaproamide is unimportant and can be eliminated completely if ammonia is removed from the reaction mixture as it is formed. In the reactor used in this work ammonia is primarily in the gas phase so that true equilibrium could not be established and was neglected in our calculations. Ethyl 6-aminocaproate was also found in the reaction mixture. The fact that the concentration of ethyl 6-aminocaproate as a function of time (Tables I11 and IV)follows a typical curve for an intermediate, would strongly suggest that reactions 13 and 14 are occurring. At equilibrium, the concentration of ethyl 6-aminocaproate is -1.5%. This can be explained only by the reversible reaction 14.
+
H ~ N ( C H ~ ) & O N H ZEtOH (Figure 5). Dimer formation as described in reaction 3 (Scheme 11) plays only a minor role because at no stage of the reaction are the concentrations of both 6-aminocaproamide and caprolactam high a t the same time. (10)
dB _ KIA - k3AB dt
+
dC - ksA k3AB _ dt Using Scheme 11, all of the runs were analyzed by computer, and kl, kz, and k3 were calculated for different temperatures. The results are listed in Table V.The activation energies were computed from the slopes of the log k vs. 1/T plots (Figure 6). The highest yield of caprolactam at 250 OC (Figure 5) was -70%. The activation energy for caprolactam formation lies between the activation energies for reactions 2 and 3 which are responsible for dimer formation. Consequently, we can expect that temperature change will have very limited influence on the final relative concentrations of caprolactam and dimer. This is clearly demonstrated by the data in Tables I1 through IV.
EtO(-) 7
H,N(CHJsCO,Et
e
+ 3"
(13)
+ EtOH
(14)
HzN(CH2)5COzEt
-
Earlier it was shown that alcoholysis of caprolactam and, therefore, even of 6-aminocaproamide does not occur. However, in this case the ammonia formed in the course of the reaction causes formation of alkoxide ion which is known to catalyze the alcoholysis of amides. The minor extent of ethyl 6-aminocaproate formation can be avoided by removal of ammonia from the reaction mixture. Again, for practical purposes, this complication is unimportant. 6-Aminocaproamide in Water. Conversion of 6-aminocaproamide to caprolactam in water was studied at a concentration of -1 mol/kg and at temperatures ranging from 180 to 250 OC. The data listed in Tables VI through IX and represented in Figure 7 show that 6-aminocaproamide is cyclized to caprolactam in competition with hydrolysis to 6-aminocaproic acid. The concentration of 6-aminocaproamide never reaches zero; e.g., a t 200 OC -2.5% remains in the reaction mixture. This residual concentration may be due to equilibrium 15. This equilibrium was not studied in detail because it contributes very little to the total kinetic picture.
Ind. Eng. Chem. Process Des. Dev., Vol. 17, No. 1, 1978
13
3 1
log k+3
E3
25
E:
16 6 X c a ’ Y r ~ l e
Eo
12 I YcaI,-Ole
Ee
22
20
24
9 2
