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Ruthenium complex catalyzed dehydration of carboxamides to nitriles in the presence of urea derivatives
87
Journal of Molecular Catalysis, 58 (1990) 87-94
RUTHENIUM COMPLEX CATALYZED DEHYDRATION OF CARBOXAMIDES TO NITRILES IN THE I’RESENCE OF UREA DERIVATIVES YOSHIHISA
WATANABE*,
FUMIO
OKUDA,
and YASUSHI
TSUJI
Department of Hydrocarbon Chemistry, Faculty of Engineering, Kyoto University, Sakyoku, Kyoto 606 (Japan) (Received January 10,1989;
accepted March 3,1989)
The dehydration of carboxamides to nitriles was effectively catalyzed by dichlorotris(triphenylphosphine)ruthenium (RuCl,(PPh,)J in the presence of urea derivatives. Thus, benzamide gave benzonitrile in 84% yield with high selectivity at 140 “C in 24 h in the presence of 1,3_diphenylurea, whereas in the absence of ureas the conversion of benzamide and selectivity to the product are low. The addition of urea derivatives was essential in the present reaction in order to improve the selectivities to nitriles. The ureas are believed to decompose to isocyanates which scavenge the water formed. Several carboxamides, including aromatic and aliphatic, were readily dehydrated to give the corresponding nitriles in 87-94% yields with high selectivity.
Introduction Organic nitriles have been widely utilized as solvents and organic intermediates for the production of synthetic resins, dyes and medicines. Although there are many methods for preparing nitriles, one of the most common is the dehydration of carboxamides. Generally, the dehydration of carboxamides to nitriles is carried out in the presence of an equimolar amount of dehydrating agent, such as phosphorus pentoxide [la]. This method, however, requires temperatures near 200 “C and tedious work-up procedures [lb]. A variety of other dehydrating agents, including phosphoryl chloride, phosphorus chloride, thionyl chloride [21, triphenylphosphine/CC1, [3], trisubstituted phosphine dichloride supported on polystyrene [41 and hexamethylcyclotrisiazane [51, have also been used. However, most of these reagents require hazardous or drastic conditions. As for homogeneous transition-metal catalyzed reactions, Blum and co-workers reported that carboxamides readily gave nitriles in the presence of a catalytic amount of chlorotris(triphenylphoshine)rhodium *Author to whom correspondence 0304-5102/90/$3.50
should be addressed. 0 Elsevier Sequoia/Printed
in The Netherlands
88
(RhCl(PPh,),), and benzamide was dehydrated to benzonitrile in 70% yield [61. To our knowledge, this is the only example of homogeneous metal complex-catalyzed dehydration of a carboxamide to a nitrile. In this method, however, the catalyst and carboxamide must be pretreated for 2 min at 285 “C, followed by heating the mixture for 6 h at 250 “C. We have investigated the effective utilization of C, compounds and carbon monoxide by homogeneous metal-catalyzed reactions, and recently reported the ruthenium-catalyzed addition of formamide derivatives to olefins [7] and platinum-catalyzed carbonylations [8,91. In the course of these studies, we found that a homogeneous ruthenium catalyst is highly active in dehydration of carboxamides when used with urea derivatives. The reaction gives the corresponding nitriles in good yields with high selectivities. The present reaction seems to be more attractive, since urea derivatives are very easy to handle and readily obtained from carbon dioxide or carbon monoxide [9,101. ResuIts
The dehydration of carboxamides to nitriles was effectively catalyzed by RuCLJPPh& in the presence of an equimolar amount of urea derivatives with high selectivity (eqn. 1): Ru’&( PPh3 I3
R-CONH;!
>
R-CN
(1)
1 eq. urea derivatives - H20
Table 1 shows the effect of the nature of the urea derivative using benzamide as the substrate. In the absence of the urea derivative, conversion of
TABLE 1 Effect of various urea derivatives on the dehydration of benaamidea Selectivityb (% )
Run
Urea derivative
C0nv.b (%I
1
none
30
65
2’
(-JN”CONHC)
85
100
3” 4 5 6
CsHsNHCONHCsH, NH,CONH, CHsNHCONHCH, C,H,NHCONHC,H, (CH,),NCON(CH&
87 56 57 43 37
91 92 100 100 76
7
“Benzamide (10 mmol), urea derivatives (10 mmol), RuCl,(PPh& (5.0 ml), for 24 h at 180 “C. b Determined by GLC based on the amount of bensamide charged. ’ Diglyme (8.0 ml) was used.
(0.10 mmol), diglyme
89
g
- 100
-
0:’ 0
0.5
LO [urea]/[
1.5
75
2.0
amide]
1. Effect of molar ratio of urea to amide. Benzamide (10 mmol), RuCl,(PPh,), 1,3-dimethylurea, diglyme (5.0 ml), at 180 “C for 24 h.
Fig.
(0.10 mmol),
benzamide was low (run 1). Upon the addition of urea derivatives, however, the conversion of benzamide and selectivity to benzonitrile improved considerably (runs 2-6). In particular, with l,&dicyclohexylurea and 1,3diphenylurea, benzonitrile was obtained in 100 and 91% selectivity with 85 and 87% conversion, respectively. During the reaction, carbon dioxide was evolved into the gas phase. Other urea derivatives such as urea, 1,3dimethylurea and 1,3-diethylurea also realized high selectivities, although amide conversions were moderate (runs 4-6). 1,1,3,3-Tetramethyl urea, a tetrasubstituted urea, was not effective, and the reaction (run 7) was practically the same as without added urea (run 1). Figure 1 shows the effect of the molar ratio of urea to amide using 1,3-dimethylurea and benzamide as substrates. The addition of an equimolar amount of 1,3-dimethylurea to benzamide gave the best result. On the other hand, with a decrease in the urea, both the selectivity and the yield of TABLE 2 Effect of various solvents on the dehydration of benzamide with 1,3-dimethylurea” Run
Solvent
Conv.b (95)
Selectivityb (96)
5 8 9 10 11’ 12
diglyme THF hexane ethanol ethanol acetonitrile
57 48 8 75 18 0
100 99 100 11 -
“Benzamide (10 mmol), 1,3-dimethylurea (10 mmol), RuCl,(PPhs), (5.0 ml), for 24 h at 180 “C. b Determined by GLC based on the amount of benzamide charged. ‘Urea itself was used as the urea derivative.
(0.10 mmol),
solvent
90
TABLE 3 Effect of reaction conditions on the dehydration of benzamide in the presence of an equimolar amount of 1,3-diphenylureaa Run
Time (h)
Temp (“C)
Conv.b (o/o)
Selectivityb ( % )
13 14 15 16 3
24 6 24 6 24
100 140 140 180 180
0 54 91 94 87
93 92 85 91
a Benzamide (10 mmol), 1,3-diphenylurea (10 mmol), RuCl,(PPh,), (8.0 ml). b Determined by GLC based on the amount of benzamide charged.
(0.10 mmol),
diglyme
benzonitrile were lowered. The selectivity to benzonitrile reached almost 100% as the amount of 1,3-dimethylurea increased, while conversion (yield) of the amide was suppressed in the presence of excess 1,3-dimethylurea. The reaction was carried out in various solvents (Table 2). The choice of solvent affected the reaction markedly. Ethers such as diglyme or THF gave good results among the solvents used (runs 5, 8). In hexane and ethanol conversions to the nitrile were low (runs 9-11). In ethanol, selectivity to the nitrile was especially low, owing to formation of N-alkylated amides as by-products (runs 10, 11). The catalyst, RuC12(PPh&, is a good catalyst for TABLE 4 Catalyst precursors for the dehydration of benzamide with 1,3-dimethylureae Run
Catalyst
17c 18 5 19 20 21 22 23 24f 25 26 27 28
none none RuCl, (PPh,), RuH, (PPh,), RuCl,UYOC,H,),), RuCl,.nH,O-BP(OBu RuCl,.nH,O-3PBue” RuCl,nH,O Ru(COD)(COT) RuJCO),, RhCl(PPh,), PdCl,(PPh& PPhog
Conv.b (%) 0 0
)Sd
57 48 19 35 21 2 13 0 4 31 0
Selectivityb ( %) -
100 100 100 100 100 100 100 -
* Bensamide (10 mmol), catalyst (0.10 mmol; 1 mol%), 1,3-dimethylurea (10 mmol), diglyme (5.0 ml), for 24 h at 180 “C. b Determined by GLC based on the amount of benzamide charged. ‘Without the addition of the ureas. d RuCl,.nH,O (0.10 mmol) and P(OBu), (0.30 mmol) as catalyst. e RuCl,.nH,O (0.10 mmol) and PBu, (0.30 mmol) as catalyst. f Diglyme (8.0 ml) was used. g Only triphenylphosphine (0.30 mmol) was used without metal catalyst.
91
N-alkylation of amides with alcohols [ 11 I. The reaction did not proceed at all in acetonitrile, presumably due to the strong coordinating ability of this solvent (run 12). In diglyme, the effects of reaction time and temperature are examined with 1,3-dimethylurea as the urea derivative (Table 3). The dehydration did not occur at 100 “C, and both benzamide and 1,3-diphenylurea were recovered (run 13). Considerable formation of benzonitrile was observed at 140°C (runs 14, 15) and 180°C (runs 3, 16). Catalytic activities of various ruthenium complexes are shown in Table 4. The presence of a catalyst is essential in this reaction (runs 17, 18). RuClz(PPh& was the most effective catalyst precursor (run 3). RuH,(PPh,), also showed good catalytic activity in the present reaction (run 19>, while other ruthenium catalysts gave unsatisfactory results (runs 20-25). However, it should be noted that selectivities to the product are always 100% in these cases. Although an excess triphenylphosphine is reported to convert benzamide to benzonitrile 131, no reaction occurred in the presence of triphenylphosphine alone under our conditions (run 28). RhCl(PPh&, which shows a high activity at high temperature (viu!c supru) [63 showed almost no catalytic activity under the present reaction conditions (run 26). PdCLJPPh& was not an effective catalyst (run 27). The present method was applied to various carboxamides using 1,3diphenyl- and 1,3-dimethylureas (Table 5). l,&Diphenylurea was always more effective than 1,3dimethylurea. Thus 4-methylbenzamide, caprylamide, phenylacetamide and cyclohexanecarboxamide are converted into the TABLE 5 Ruthenium-catalyzed dehydration of various carboxamides” Run
Carboxamide
(R.NH),CO; R=
Conv.b (8)
Select.b (8)
Yieldb (%)
5 3 29 30 31 32 33 34 35 36 37 38 39 40 41
benzamide benzamide Q-methylbenxamide 4-methylbensamide 4-methoxybenzamide 4-methoxybenzamide 4-chlorobenzamide I-chlorobenzamide nicotinamide caprylamide caprylamide phenylacetamide phenylacetamide cyclohexanecarboxamide cyclohexanecarboxamide
CHsCeHsCH,CsHsCH,CsHr.CHsCsHsCH,CH,-C,HSCH,C,H,CH,CeH,--
57 a7 40 99 48 98 26 99 0 75 96 32 98 62 98
100 91 100 94 31 40 62 66 -
57 79 40 93 (68) 15 39 16 65 75 (63) 37 (60) 31 92 (64) 62 94
100 91 97 94 100 96
“Carboxamide (10 mmol), urea derivatives (10 mmol), RuCl,(PPh& (0.10 mmol), for 24 h at 180 “C; diglyme, 5.0 ml with 1,3-dimethylurea and 8.0 ml with 1,3_diphenylurea. b Determined by GLC based on the amount of carboxamide charged; figures in parentheses are isolated yields.
92
corresponding nitriles in 93, 87, 92 and 94% yields, respectively. However, methoxy and chloro substituents in benzamide derivatives reduced the yields and selectivities considerably.
Discussion The dehydration reaction was carried out in the presence of water (5.6 mmol) in order to investigate the role of urea derivatives. In the absence of 1,3-dimethylurea, selectivity to benzonitrile was low and benzoic acid was the main product (eqn. 2). On .the other hand, the addition of 1,3dimethylurea led to selective formation of benzonitrile (eqn. 3). This fact may indicate that urea derivatives function as scavengers of water generated in the reaction, thereby keeping the selectivities to nitriles high. Hz0
+
RuCI2(PPt+ conv.
selectivity
54% H20,
Q-CCOH 48 “la
29%
CH3NHCONHCH3
(3)
CN
RuCl2( PPh& selectivity
conv. 32% benzamide
conditions:
1Ommol
CH3NHCONHCH3 diglyme
5 ml
100%
, Hz0 0.1 ml (5.6mmol
1Ommol
, RuCl~(PPh313
) at 180%
for
(2)
), 0.1 mmol
,
24h
It has been revealed that on heating, disubstituted urea derivatives are dissociated to isocyanates and primary amines, whereas tetrasubstituted urea derivatives, such as 1,1,3,3_tetramethylurea, are not (eqn. 4) 1121. Therefore, in the present reaction, the isocyanates may be able to scavenge water to give amines and carbon dioxide (eqn. 5): A RNH-C-NHR
.
N
RNH2
(4)
RN=C=O
+
;; R = H , CH3 RN=C=O
+
, C&&H2
Hz0
-
,
C6H5
etc. RNH2
+
CO2
(5)
Indeed, in the reaction using l,Bdiphenylurea, 2.4 equivalent of aniline based on benzonitrile was detected after the reaction. This shows that the urea was converted to the corresponding amine and carbon dioxide (eqn. 6). Furthermore, benzamide can be similarly dehydrated to benzonitrile in the presence of an equimolar amount of ethyl isocyanate, instead of 1,3-
93
diethylurea, with high selectivity (eqn. 7). This result clearly shows that the isocyanate does not interfere the reaction and effectively scavenges water. In the reaction, 1,1,3,3-tetramethylurea was not effective (vi& supru). This may be due to the fact that tetrasubstituted ureas do not liberate isocyanates.
c”-
GjH5NHCONHCrjH5
CONH2 RuCl2(PPh&,
- CO2 Q3
“CN -
l
7.9mmol
I_\ u
NH2
(6)
19. Ommol
1 eq. C~HF;N=C=O RuClz(PPh3 conv.
39 %
13
selectivity
98 %
Finally, the reaction was carried out with other dehydrating reagents in place of urea derivatives. Under the same reaction conditions (180 “C for 24 h) using benzamide, trimethyl orthoformate gave benzonitrile in only 15% selectivity with 61% conversion. An acetal, 2,2-dimethoxypropane, was also not effective, giving the nitrile in only 59% selectivity and 66% conversion. Experimental section Material All organic chemicals employed in this study were commercially available. 1,3-Dimethylurea was dried under reduced pressure at room temperature over night. The solvents were dried over suitable reagents 1131 and were stored under argon. RuCMPPh,), 1141, RuH,(PPh,), 1151, RuCl,(P(OC,H,),), [161, Ru(COD)(COT) 1171, RhCl(PPh& 1181 and PdCl,(PPh,), [191 were prepared according to procedures in the literature. General procedure A typical reaction of 4-methylbenzamide with 1,3-diphenylurea is described here to exemplify the general procedure. A 50ml stainless steel reactor (Taiatsu Scientific Glass Co. Ltd., TVS-1 type) containing a glass liner was used in the reaction. A mixture of diglyme (8.0 ml), 4-methylbenzamide (1.35 g, 10 mmol), 1,3-diphenylurea (2.12 g, 10 mmol) and RuClz(PPh& (96 mg, 0.1 mmol) was placed in the glass liner. After sealing the reactor, Ar was introduced with three 10 kg cm-’ pressurization-depressurization cycles. The reactor was heated to 180 “C in 1 h with magnetic stirring and kept at this temperature for 24 h. The reaction was terminated by rapidly cooling. The resulting dark brown solution was subject to GLC analysis. Vacuum distillation afforded 0.66 g of 4-methylbenzonitrile in pure form (68% yield). Analytical procedure The products were identified by lH NMR, 13C NMR, IR spectra and elemental analysis. These identifications were confirmed by comparison with
94
authentic samples. ‘H NMR spectra were obtained at 99.6 MHz on a JEOL JNM IX-90 spectrometer and 13C NMR spectra at 22.05 MHz on a JEOL JNM FK-100 spectrometer, using tetramethylsilane as internal standard and CDC13 as solvent. IR spectra were recorded on a Nicolet 54X Fourier transform IR spectrophotometer. GLC analyses were carried out on a Shimadzu GC 8APF apparatus with Nz carrier gas, using a glass column (2.6 0 x 3 m) packed with Poly I 110 (5% on supported Chromosorb W AW DMCS, SO/SOmesh). Conversions of substrates and selectivities to products were determined by the GLC internal standard method. Elemental analyses were performed at the Microanalytical Center of Kyoto University.
References 1 (a) J. Zabicky, The Chemistry of Amides, Inter-science,New York, 1970, p. 274; (b) R. E. Kent and S. M. McElvain, Org. Synth., 3 (1955) 493. 2 J. A. Krynitsky and H. W. Carhart, Org. Synth., 4 (1963) 463. 3 E. Yamato and S. Sugasawa, Tetrahedron L&t., 50 (1970) 4383. 4 H. M. Relles and R. W. Schluenz, J. Am. Chem. Sot., 96 (1974) 6469. 5 W. E. Dermis, J. Org. Chem., 35 (1970) 3253. 6 (a) J. Bhuu and A. Fisher, Tetrahedron L&t., 23 (1970) 1963; (b) J. Blum, A. Fisher and E. Greener, Tetrahedron, 29 (1973) 1073. 7 Y. Tsuji, S. Yoshii, T. Ohsumi, T. Kondo and Y. Watanabe, J. Orgarwmetall. Chem., 331 (1987) 379. 8 (a) R. Takeuchi, Y. Tsuji and Y. Watanabe, J. Chem. Sot, Chem. Commun., (1986) 351; (b) T. Kondo, Y. Tsuji and Y. Watanabe, Tetrahedron L&t., 29 (1988) 3833. 9 Y. Tsuji, R. Takeuchi and Y. Watanabe, J. Orgarwmetall. Chem., 290 (1985) 249. 10 M. M. Taqui Khan, S. B. Halligudi, S. H. R. Abdi and S. Shukla, J. Mol. Catal., 48 (1988) 25. 11 Y. Watanabe, T. Ohta and Y. Tsuji, Bull. Chem. Sot. Jpn., 56 (1983) 2647. 12 (a) T. Hoshino, T. Mukaiyama and H. Hoshino, J. Am. Chem. Sot., 74 (1952) 3097; (b) T. Hoshino, T. Mukaiyama and H. Hoshino, Bull. Chem. Sot. Jpn., 25 (19521 392; (cl T. Mukaiyama, S. Ozaki and Y. Kobayashi, op. cit., 29 (1956) 51. 13 D. D. Pen-in, W. L. F. Armarego and D. R. Pen-in, Purification of Laboratory Chemicals, 2nd edn., Pergamon, Oxford, 1980. 14 P. S. Hallman, T. A. Stephenson and G. Wilkinson, Znorg. Synth., 12 (1972) 238. 15 R. Young and G. Wilkinson, Znorg. Synth., 17 (1977) 75. 16 W. G. Peet and D. H. Gerlach, Znorg. Synth., 15 (1974) 40. 17 K. Itoh, H. Nagashima, T. Ohshima, N. Ohshima and H. Nishiyama, J. Organometall. C?u.zm.,272 (1984) 179. 18 J. A. Osbom and G. Wilkinson, Znorg. Synth., 10 (1967) 67. 19 F. G. Mann and D. Pm-die, J. Chem. Sot., (1935) 1549.
Journal of Molecular Catalysis, 58 (1990) 87-94
RUTHENIUM COMPLEX CATALYZED DEHYDRATION OF CARBOXAMIDES TO NITRILES IN THE I’RESENCE OF UREA DERIVATIVES YOSHIHISA
WATANABE*,
FUMIO
OKUDA,
and YASUSHI
TSUJI
Department of Hydrocarbon Chemistry, Faculty of Engineering, Kyoto University, Sakyoku, Kyoto 606 (Japan) (Received January 10,1989;
accepted March 3,1989)
The dehydration of carboxamides to nitriles was effectively catalyzed by dichlorotris(triphenylphosphine)ruthenium (RuCl,(PPh,)J in the presence of urea derivatives. Thus, benzamide gave benzonitrile in 84% yield with high selectivity at 140 “C in 24 h in the presence of 1,3_diphenylurea, whereas in the absence of ureas the conversion of benzamide and selectivity to the product are low. The addition of urea derivatives was essential in the present reaction in order to improve the selectivities to nitriles. The ureas are believed to decompose to isocyanates which scavenge the water formed. Several carboxamides, including aromatic and aliphatic, were readily dehydrated to give the corresponding nitriles in 87-94% yields with high selectivity.
Introduction Organic nitriles have been widely utilized as solvents and organic intermediates for the production of synthetic resins, dyes and medicines. Although there are many methods for preparing nitriles, one of the most common is the dehydration of carboxamides. Generally, the dehydration of carboxamides to nitriles is carried out in the presence of an equimolar amount of dehydrating agent, such as phosphorus pentoxide [la]. This method, however, requires temperatures near 200 “C and tedious work-up procedures [lb]. A variety of other dehydrating agents, including phosphoryl chloride, phosphorus chloride, thionyl chloride [21, triphenylphosphine/CC1, [3], trisubstituted phosphine dichloride supported on polystyrene [41 and hexamethylcyclotrisiazane [51, have also been used. However, most of these reagents require hazardous or drastic conditions. As for homogeneous transition-metal catalyzed reactions, Blum and co-workers reported that carboxamides readily gave nitriles in the presence of a catalytic amount of chlorotris(triphenylphoshine)rhodium *Author to whom correspondence 0304-5102/90/$3.50
should be addressed. 0 Elsevier Sequoia/Printed
in The Netherlands
88
(RhCl(PPh,),), and benzamide was dehydrated to benzonitrile in 70% yield [61. To our knowledge, this is the only example of homogeneous metal complex-catalyzed dehydration of a carboxamide to a nitrile. In this method, however, the catalyst and carboxamide must be pretreated for 2 min at 285 “C, followed by heating the mixture for 6 h at 250 “C. We have investigated the effective utilization of C, compounds and carbon monoxide by homogeneous metal-catalyzed reactions, and recently reported the ruthenium-catalyzed addition of formamide derivatives to olefins [7] and platinum-catalyzed carbonylations [8,91. In the course of these studies, we found that a homogeneous ruthenium catalyst is highly active in dehydration of carboxamides when used with urea derivatives. The reaction gives the corresponding nitriles in good yields with high selectivities. The present reaction seems to be more attractive, since urea derivatives are very easy to handle and readily obtained from carbon dioxide or carbon monoxide [9,101. ResuIts
The dehydration of carboxamides to nitriles was effectively catalyzed by RuCLJPPh& in the presence of an equimolar amount of urea derivatives with high selectivity (eqn. 1): Ru’&( PPh3 I3
R-CONH;!
>
R-CN
(1)
1 eq. urea derivatives - H20
Table 1 shows the effect of the nature of the urea derivative using benzamide as the substrate. In the absence of the urea derivative, conversion of
TABLE 1 Effect of various urea derivatives on the dehydration of benaamidea Selectivityb (% )
Run
Urea derivative
C0nv.b (%I
1
none
30
65
2’
(-JN”CONHC)
85
100
3” 4 5 6
CsHsNHCONHCsH, NH,CONH, CHsNHCONHCH, C,H,NHCONHC,H, (CH,),NCON(CH&
87 56 57 43 37
91 92 100 100 76
7
“Benzamide (10 mmol), urea derivatives (10 mmol), RuCl,(PPh& (5.0 ml), for 24 h at 180 “C. b Determined by GLC based on the amount of bensamide charged. ’ Diglyme (8.0 ml) was used.
(0.10 mmol), diglyme
89
g
- 100
-
0:’ 0
0.5
LO [urea]/[
1.5
75
2.0
amide]
1. Effect of molar ratio of urea to amide. Benzamide (10 mmol), RuCl,(PPh,), 1,3-dimethylurea, diglyme (5.0 ml), at 180 “C for 24 h.
Fig.
(0.10 mmol),
benzamide was low (run 1). Upon the addition of urea derivatives, however, the conversion of benzamide and selectivity to benzonitrile improved considerably (runs 2-6). In particular, with l,&dicyclohexylurea and 1,3diphenylurea, benzonitrile was obtained in 100 and 91% selectivity with 85 and 87% conversion, respectively. During the reaction, carbon dioxide was evolved into the gas phase. Other urea derivatives such as urea, 1,3dimethylurea and 1,3-diethylurea also realized high selectivities, although amide conversions were moderate (runs 4-6). 1,1,3,3-Tetramethyl urea, a tetrasubstituted urea, was not effective, and the reaction (run 7) was practically the same as without added urea (run 1). Figure 1 shows the effect of the molar ratio of urea to amide using 1,3-dimethylurea and benzamide as substrates. The addition of an equimolar amount of 1,3-dimethylurea to benzamide gave the best result. On the other hand, with a decrease in the urea, both the selectivity and the yield of TABLE 2 Effect of various solvents on the dehydration of benzamide with 1,3-dimethylurea” Run
Solvent
Conv.b (95)
Selectivityb (96)
5 8 9 10 11’ 12
diglyme THF hexane ethanol ethanol acetonitrile
57 48 8 75 18 0
100 99 100 11 -
“Benzamide (10 mmol), 1,3-dimethylurea (10 mmol), RuCl,(PPhs), (5.0 ml), for 24 h at 180 “C. b Determined by GLC based on the amount of benzamide charged. ‘Urea itself was used as the urea derivative.
(0.10 mmol),
solvent
90
TABLE 3 Effect of reaction conditions on the dehydration of benzamide in the presence of an equimolar amount of 1,3-diphenylureaa Run
Time (h)
Temp (“C)
Conv.b (o/o)
Selectivityb ( % )
13 14 15 16 3
24 6 24 6 24
100 140 140 180 180
0 54 91 94 87
93 92 85 91
a Benzamide (10 mmol), 1,3-diphenylurea (10 mmol), RuCl,(PPh,), (8.0 ml). b Determined by GLC based on the amount of benzamide charged.
(0.10 mmol),
diglyme
benzonitrile were lowered. The selectivity to benzonitrile reached almost 100% as the amount of 1,3-dimethylurea increased, while conversion (yield) of the amide was suppressed in the presence of excess 1,3-dimethylurea. The reaction was carried out in various solvents (Table 2). The choice of solvent affected the reaction markedly. Ethers such as diglyme or THF gave good results among the solvents used (runs 5, 8). In hexane and ethanol conversions to the nitrile were low (runs 9-11). In ethanol, selectivity to the nitrile was especially low, owing to formation of N-alkylated amides as by-products (runs 10, 11). The catalyst, RuC12(PPh&, is a good catalyst for TABLE 4 Catalyst precursors for the dehydration of benzamide with 1,3-dimethylureae Run
Catalyst
17c 18 5 19 20 21 22 23 24f 25 26 27 28
none none RuCl, (PPh,), RuH, (PPh,), RuCl,UYOC,H,),), RuCl,.nH,O-BP(OBu RuCl,.nH,O-3PBue” RuCl,nH,O Ru(COD)(COT) RuJCO),, RhCl(PPh,), PdCl,(PPh& PPhog
Conv.b (%) 0 0
)Sd
57 48 19 35 21 2 13 0 4 31 0
Selectivityb ( %) -
100 100 100 100 100 100 100 -
* Bensamide (10 mmol), catalyst (0.10 mmol; 1 mol%), 1,3-dimethylurea (10 mmol), diglyme (5.0 ml), for 24 h at 180 “C. b Determined by GLC based on the amount of benzamide charged. ‘Without the addition of the ureas. d RuCl,.nH,O (0.10 mmol) and P(OBu), (0.30 mmol) as catalyst. e RuCl,.nH,O (0.10 mmol) and PBu, (0.30 mmol) as catalyst. f Diglyme (8.0 ml) was used. g Only triphenylphosphine (0.30 mmol) was used without metal catalyst.
91
N-alkylation of amides with alcohols [ 11 I. The reaction did not proceed at all in acetonitrile, presumably due to the strong coordinating ability of this solvent (run 12). In diglyme, the effects of reaction time and temperature are examined with 1,3-dimethylurea as the urea derivative (Table 3). The dehydration did not occur at 100 “C, and both benzamide and 1,3-diphenylurea were recovered (run 13). Considerable formation of benzonitrile was observed at 140°C (runs 14, 15) and 180°C (runs 3, 16). Catalytic activities of various ruthenium complexes are shown in Table 4. The presence of a catalyst is essential in this reaction (runs 17, 18). RuClz(PPh& was the most effective catalyst precursor (run 3). RuH,(PPh,), also showed good catalytic activity in the present reaction (run 19>, while other ruthenium catalysts gave unsatisfactory results (runs 20-25). However, it should be noted that selectivities to the product are always 100% in these cases. Although an excess triphenylphosphine is reported to convert benzamide to benzonitrile 131, no reaction occurred in the presence of triphenylphosphine alone under our conditions (run 28). RhCl(PPh&, which shows a high activity at high temperature (viu!c supru) [63 showed almost no catalytic activity under the present reaction conditions (run 26). PdCLJPPh& was not an effective catalyst (run 27). The present method was applied to various carboxamides using 1,3diphenyl- and 1,3-dimethylureas (Table 5). l,&Diphenylurea was always more effective than 1,3dimethylurea. Thus 4-methylbenzamide, caprylamide, phenylacetamide and cyclohexanecarboxamide are converted into the TABLE 5 Ruthenium-catalyzed dehydration of various carboxamides” Run
Carboxamide
(R.NH),CO; R=
Conv.b (8)
Select.b (8)
Yieldb (%)
5 3 29 30 31 32 33 34 35 36 37 38 39 40 41
benzamide benzamide Q-methylbenxamide 4-methylbensamide 4-methoxybenzamide 4-methoxybenzamide 4-chlorobenzamide I-chlorobenzamide nicotinamide caprylamide caprylamide phenylacetamide phenylacetamide cyclohexanecarboxamide cyclohexanecarboxamide
CHsCeHsCH,CsHsCH,CsHr.CHsCsHsCH,CH,-C,HSCH,C,H,CH,CeH,--
57 a7 40 99 48 98 26 99 0 75 96 32 98 62 98
100 91 100 94 31 40 62 66 -
57 79 40 93 (68) 15 39 16 65 75 (63) 37 (60) 31 92 (64) 62 94
100 91 97 94 100 96
“Carboxamide (10 mmol), urea derivatives (10 mmol), RuCl,(PPh& (0.10 mmol), for 24 h at 180 “C; diglyme, 5.0 ml with 1,3-dimethylurea and 8.0 ml with 1,3_diphenylurea. b Determined by GLC based on the amount of carboxamide charged; figures in parentheses are isolated yields.
92
corresponding nitriles in 93, 87, 92 and 94% yields, respectively. However, methoxy and chloro substituents in benzamide derivatives reduced the yields and selectivities considerably.
Discussion The dehydration reaction was carried out in the presence of water (5.6 mmol) in order to investigate the role of urea derivatives. In the absence of 1,3-dimethylurea, selectivity to benzonitrile was low and benzoic acid was the main product (eqn. 2). On .the other hand, the addition of 1,3dimethylurea led to selective formation of benzonitrile (eqn. 3). This fact may indicate that urea derivatives function as scavengers of water generated in the reaction, thereby keeping the selectivities to nitriles high. Hz0
+
RuCI2(PPt+ conv.
selectivity
54% H20,
Q-CCOH 48 “la
29%
CH3NHCONHCH3
(3)
CN
RuCl2( PPh& selectivity
conv. 32% benzamide
conditions:
1Ommol
CH3NHCONHCH3 diglyme
5 ml
100%
, Hz0 0.1 ml (5.6mmol
1Ommol
, RuCl~(PPh313
) at 180%
for
(2)
), 0.1 mmol
,
24h
It has been revealed that on heating, disubstituted urea derivatives are dissociated to isocyanates and primary amines, whereas tetrasubstituted urea derivatives, such as 1,1,3,3_tetramethylurea, are not (eqn. 4) 1121. Therefore, in the present reaction, the isocyanates may be able to scavenge water to give amines and carbon dioxide (eqn. 5): A RNH-C-NHR
.
N
RNH2
(4)
RN=C=O
+
;; R = H , CH3 RN=C=O
+
, C&&H2
Hz0
-
,
C6H5
etc. RNH2
+
CO2
(5)
Indeed, in the reaction using l,Bdiphenylurea, 2.4 equivalent of aniline based on benzonitrile was detected after the reaction. This shows that the urea was converted to the corresponding amine and carbon dioxide (eqn. 6). Furthermore, benzamide can be similarly dehydrated to benzonitrile in the presence of an equimolar amount of ethyl isocyanate, instead of 1,3-
93
diethylurea, with high selectivity (eqn. 7). This result clearly shows that the isocyanate does not interfere the reaction and effectively scavenges water. In the reaction, 1,1,3,3-tetramethylurea was not effective (vi& supru). This may be due to the fact that tetrasubstituted ureas do not liberate isocyanates.
c”-
GjH5NHCONHCrjH5
CONH2 RuCl2(PPh&,
- CO2 Q3
“CN -
l
7.9mmol
I_\ u
NH2
(6)
19. Ommol
1 eq. C~HF;N=C=O RuClz(PPh3 conv.
39 %
13
selectivity
98 %
Finally, the reaction was carried out with other dehydrating reagents in place of urea derivatives. Under the same reaction conditions (180 “C for 24 h) using benzamide, trimethyl orthoformate gave benzonitrile in only 15% selectivity with 61% conversion. An acetal, 2,2-dimethoxypropane, was also not effective, giving the nitrile in only 59% selectivity and 66% conversion. Experimental section Material All organic chemicals employed in this study were commercially available. 1,3-Dimethylurea was dried under reduced pressure at room temperature over night. The solvents were dried over suitable reagents 1131 and were stored under argon. RuCMPPh,), 1141, RuH,(PPh,), 1151, RuCl,(P(OC,H,),), [161, Ru(COD)(COT) 1171, RhCl(PPh& 1181 and PdCl,(PPh,), [191 were prepared according to procedures in the literature. General procedure A typical reaction of 4-methylbenzamide with 1,3-diphenylurea is described here to exemplify the general procedure. A 50ml stainless steel reactor (Taiatsu Scientific Glass Co. Ltd., TVS-1 type) containing a glass liner was used in the reaction. A mixture of diglyme (8.0 ml), 4-methylbenzamide (1.35 g, 10 mmol), 1,3-diphenylurea (2.12 g, 10 mmol) and RuClz(PPh& (96 mg, 0.1 mmol) was placed in the glass liner. After sealing the reactor, Ar was introduced with three 10 kg cm-’ pressurization-depressurization cycles. The reactor was heated to 180 “C in 1 h with magnetic stirring and kept at this temperature for 24 h. The reaction was terminated by rapidly cooling. The resulting dark brown solution was subject to GLC analysis. Vacuum distillation afforded 0.66 g of 4-methylbenzonitrile in pure form (68% yield). Analytical procedure The products were identified by lH NMR, 13C NMR, IR spectra and elemental analysis. These identifications were confirmed by comparison with
94
authentic samples. ‘H NMR spectra were obtained at 99.6 MHz on a JEOL JNM IX-90 spectrometer and 13C NMR spectra at 22.05 MHz on a JEOL JNM FK-100 spectrometer, using tetramethylsilane as internal standard and CDC13 as solvent. IR spectra were recorded on a Nicolet 54X Fourier transform IR spectrophotometer. GLC analyses were carried out on a Shimadzu GC 8APF apparatus with Nz carrier gas, using a glass column (2.6 0 x 3 m) packed with Poly I 110 (5% on supported Chromosorb W AW DMCS, SO/SOmesh). Conversions of substrates and selectivities to products were determined by the GLC internal standard method. Elemental analyses were performed at the Microanalytical Center of Kyoto University.
References 1 (a) J. Zabicky, The Chemistry of Amides, Inter-science,New York, 1970, p. 274; (b) R. E. Kent and S. M. McElvain, Org. Synth., 3 (1955) 493. 2 J. A. Krynitsky and H. W. Carhart, Org. Synth., 4 (1963) 463. 3 E. Yamato and S. Sugasawa, Tetrahedron L&t., 50 (1970) 4383. 4 H. M. Relles and R. W. Schluenz, J. Am. Chem. Sot., 96 (1974) 6469. 5 W. E. Dermis, J. Org. Chem., 35 (1970) 3253. 6 (a) J. Bhuu and A. Fisher, Tetrahedron L&t., 23 (1970) 1963; (b) J. Blum, A. Fisher and E. Greener, Tetrahedron, 29 (1973) 1073. 7 Y. Tsuji, S. Yoshii, T. Ohsumi, T. Kondo and Y. Watanabe, J. Orgarwmetall. Chem., 331 (1987) 379. 8 (a) R. Takeuchi, Y. Tsuji and Y. Watanabe, J. Chem. Sot, Chem. Commun., (1986) 351; (b) T. Kondo, Y. Tsuji and Y. Watanabe, Tetrahedron L&t., 29 (1988) 3833. 9 Y. Tsuji, R. Takeuchi and Y. Watanabe, J. Orgarwmetall. Chem., 290 (1985) 249. 10 M. M. Taqui Khan, S. B. Halligudi, S. H. R. Abdi and S. Shukla, J. Mol. Catal., 48 (1988) 25. 11 Y. Watanabe, T. Ohta and Y. Tsuji, Bull. Chem. Sot. Jpn., 56 (1983) 2647. 12 (a) T. Hoshino, T. Mukaiyama and H. Hoshino, J. Am. Chem. Sot., 74 (1952) 3097; (b) T. Hoshino, T. Mukaiyama and H. Hoshino, Bull. Chem. Sot. Jpn., 25 (19521 392; (cl T. Mukaiyama, S. Ozaki and Y. Kobayashi, op. cit., 29 (1956) 51. 13 D. D. Pen-in, W. L. F. Armarego and D. R. Pen-in, Purification of Laboratory Chemicals, 2nd edn., Pergamon, Oxford, 1980. 14 P. S. Hallman, T. A. Stephenson and G. Wilkinson, Znorg. Synth., 12 (1972) 238. 15 R. Young and G. Wilkinson, Znorg. Synth., 17 (1977) 75. 16 W. G. Peet and D. H. Gerlach, Znorg. Synth., 15 (1974) 40. 17 K. Itoh, H. Nagashima, T. Ohshima, N. Ohshima and H. Nishiyama, J. Organometall. C?u.zm.,272 (1984) 179. 18 J. A. Osbom and G. Wilkinson, Znorg. Synth., 10 (1967) 67. 19 F. G. Mann and D. Pm-die, J. Chem. Sot., (1935) 1549.