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O2 System
L.I. Simandi (Editor),Dioxygen Activation and Homogeneous Catalytic Oxidation 0 1991 Elsevier Science Publishers B.V.. Amsterdam
279
Novel Oxidation of Phenols by a Copper(I1) Complex Catalyst / 0 2 System K. Takehira, M. Shimizu, Y. Watanabe, T. Hayakawa, and H. Orita National Chemical Laboratory for Industry, Tsukuba Research Center, Higashi 1-1, Tsukuba, Ibaraki 305, Japan Abstract 2,4,6-Trimethylphenol was efficiently oxidized to the corresponding p-hydroxybenzaldehyde by a cupric chloride-acetone oxime catalyst / 0 2 system in alcoholic solvents. It is likely that the reaction proceeds via a quinone methide intermediate, followed by 1.6addition of an alcohol to form acetal, which is then hydrolyzed to the aldehyde. When acids were present, preferable formation of 2,6-dimethyl-p-benzoquinoneby the oxidative demethylation was observed. 2,6-Dimethylphenol was also oxygenated to the corresponding p-benzoquinone by the same system with acids. Thus, acids play an important role in the 1.7-oxygenation of aromatic ring of 2,6-dimethylphenols by dioxygen.
1. I n t r o d u c t i o n We have recently reported that copper(I1) chloride coupled with amine, hydroxylamine, or oxime catalyzes the oxidation of 2,3,6-trimethylpheno1(2,3,6-TMP) to trimethyl-pbenzoquinone (TMQ) with dioxygen in alcoholic so1vents.l) It is well known that phenol oxidations catalyzed by copper produce dimers or polymers as well known in the production of poly(pheny1ene oxide) from 2,6-dimethylphenol (2,6-DMP) industrialyzed by GE company. However, our copper(I1) system catalyst accelerated the selective oxidation of phenols to p-benzoquinones in the presence of acids.1) It is likely that acids play an important role in the selective p-oxidation of phenols. How does the oxidation proceed in the case of p-methyl substituted phenols by using our catalyst system? We have studied the oxidation of 2,4,6-trimethylphenoI (2,4,6-TMP) and 2,6-DMP; the former and the latter afforded 3,5-dimethyl-4-hydroxybenzaldehyde(DMHBA) and 2,6-dimethyl-p-benzoquinone (2,6-DMQ), respectively. Aromatic aldehydes are important intermediates in industrial production of a wide variety of speciality chemicals, such as pharmaceuticals, flavour chemicals, dyes, and agrochemicals. Several methods for the aromatic aldehyde syntheses from toluenes have been developed;2) chlorination followed by hydrolysis, stoichiometric oxidation with inorganic oxydants, electric/electrocatalytic oxidation, and catalytic oxygen transfer with some oxygen donors. The most attractive method seems a catalytic oxidation with molecular oxygen. For examples, p-cresols are oxidized with molecular oxygen to the corresponding p-hydroxybenzaldehydes in the presence of a catalytic amount of cobalt Shiff base (yields 45%)3) or cobaltous oxide (yields 78%)2*4)in methanol. The latter process seems promising but requires long reaction time and strongly basic conditions in the presence of a large amount of sodium hydroxide.
280
Here, we report the selective and efficient oxidation of 2,4,6-TMP to DMHBA with a copper(I1) system catalyst and discuss on its reaction mechanism. 2.
Ex pe ri me nt al
A typical run of phenol oxidation was carried out as follows: 2 mmol of 2,4,6-TMP was dissolved in 2 ml of an alcoholic solvent together with 0.1 mmol of CuCl2.2H20 and 0.2 mmol of acetone oxime, and the reaction was carried out for several hours at 60°C under atmospheric pressure of oxygen. A time course of the oxidation was monitored by measuring the amount of consumed oxygen with a gas burette. The reaction products, DMHBA, 2.6-DMQ. 2,6-dimethyl-4-alkoxymethylphenol(l),and dialkyl formal(2) were chromatographed on silica gel, identified by IH-NMR and IR. Yield were determined by GLC using Silicone DCQF 1 as a column.
3. Results and Discussion
3.1. 2 , 6 - D M P Oxidation The results of the oxidation of 2,6-DMP are shown in Table 1. The activity of copper (11) chloride alone was very low and, even when coupled with LiCI. the activity did not increase enough . While use of diethylamine alone as an additive resulted in the production of a large amount of polymer, use of diethylamine hydrochloride caused an increase in the activity for p-oxygenation. A choice of the additive is likely important; the addition of hydroxylaniine combined with an acid, especially with sulfuric acid, caused a great increase i n the activity. Thus, the presence of acids promoted the formation of 2,6DMQ. In addition, the activities are dependent on a type of solvents; use of a branched Table 1 Copper(I1) catalyzed oxidation of 2,6-DMP to 2,6-DMQ CuC12-2H20 (mmol)
Additive (mmol)
Solvent (mu ~~~
0.2 0.2 LiCl(O.2) 0.1 LiCl(O.2) 0.2 Et2NH-HC1(0.2) 0.2 NH20H*HC1(0.4) 0.1 NH20H*HCI(0.2) 0.1 (NH20H)2*H2S04(0.1)
Conv. (%)
2,6-DMP, 2 mmol; Oxygen pressure, 114.7 kPa.
-~~~
~
n-HeOH(2) n-HeOH(2) f-B uOH( 2) n-HeOH( 2) ti-HeOH(2) t - B UOH( 2) t-BuOH(2) O.lMe2C=NOH(O.2)+HCI(0.2) t-BuOH(2) 0.1 (NH20H)2*H2S04(0.1) i-PrOH(2) 0.1 (NH20H)2*H2S04(0.1) r-AmOH(2) 0.1 (NH20H)2*H2S04(0.1) Tol( I.S)+i-PrOH(O.S) 0.1 (NH20H)2*H2S04(0.1) Tol(O.S)+i-PrOH( 1.5)
Yield Temp. React. (%) ("C) timc(1i)
30.1 61.5 10.1 98.0 98.1 100 100 78.7 100 100 100 100
7.9 39.9 70.5
45.8 73.2 82.5 32.3 77.4 85.8 88.2 86.3
60 60 40 60 60 40 40 40 40 40 40 40
5 5 5 S
3 3 2 5
2.5 2 2 2
281
alcohol or its mixing with aromatic solvent resulted in the high yield of 2,6-DMQ production. In the latter case, only a small amount of alcohol was enough to get the highest yield of 2,6-DMQ. It implies that alcohol works not only as the solvent but also as a crucial component for this phenol oxidation. The results thus obtained are very similar to those obtained in the 2,3,6-TMP oxidation,l) and therefore it is most likely that the both oxidations proceed by the same mechanism.
3.2. 2 , 4 , 6 - T M P Oxidation The results of the 2,4,6-TMP oxidations with several copper(I1) system catalysts in 11hexanol are shown in Table 2. The maximum rate of oxygen consumption was calculated from the oxygen uptake during the reaction and is shown as d02(rnax)/dt in Table 2. Copper(I1) choride alone or even coupled with LiCl showed a very low activity. The addition of diethylamine caused a large increase in the activity for the DMHBA production, while its coupling with hydrochloric acid resulted in a decrease in the activity. As recently reported by US,^) copper(I1)-amine( 1: 1) complexes were active, where the most effective amine was diethylamine, and the presence of an excess amount of amine caused a rapid formation of polymer. In the case of acetone oxime, the highest yield of DMHBA was obtained, and the unfavourable effect of hydrochloric acid was also observed in this case. Interestingly, hydroxylamine hydrochloride or sulfate gave high rate of oxygen consumption, but afforded the low yield of DMHBA. The presence of an acid accelerated formations of both 2,6-DMQ and dihexyl formal as by-products, resulting in a lowering in the selectivity of DMHBA production. When the ratio of acetone oxime to copper(I1) chloride was increased, both the high activity in the rate of 0 2 consumption and the high yield of DMHBA were obtained(Tab1e 3). The addition of hydrochloric acid clearly caused an increase in the yield of 2.6-DMQ with decreases in both the reaction rate and the yield of DMHBA. A time course of the oxidation revealed that DMHBA formed was successively oxidized to 2.6-DMQ. In the presence of acetone oxime, a half amount(O.l mmol) of CuC12.2H20 was enough for the substantial conversion of 2,4,6-TMP to DMHBA . The results of the 2,4,6-TMP oxidations in several alcohols are shown in Table 4. Table 2 Copper(I1) catalyzed oxidation of 2,4,6-TMP to DMHBA Additive (mmol)
d02(max)/dt (mmol/h)
Conv.
0.144 0.155 0.815 0.497 2.92 1.70 3.40 2.81
40.0 45.6 97.6 95.0 98.7 93.6 94.5 96.5
LiCl(O.2) E t 2NH( 0.2) Et2NH-HC1(0.2) Me2C=NOH(0.2) Me2C=NOH(0.2)+HCI(O.2) NH20H-HC1(0.2) (NH20H)2*H2S04(0.1 )
(%)
Yield(%) of DMHBA 2,6-DMQ
2.7 3.5 77.7 44.5 85.6 52.1 47.9 61.6
2.7 1.8 3.7 4.2 6.1 21.9 27.4 15.9
React. time(min) 3 00 300 240 300 54 120 54 54
2.4,6-TMP, 2 mmol; CuCl2*2H20,0.2 mmol; n-hexanol, 2 ml; Temp., 60°C; Oxygen pressure, 114.7 kPa.
282
Table 3 Copper(I1)-acetone oxime catalyzed oxidation of 2,4,6-TMP ___
CuC12.2H20 Me2C=NOH HCI d02(max)dt Conv. Yield(%) of React. (mmol) (nimol) (mmol) (mmol/h) (%) DMHBA 2,6-DMQ time(min) 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.1
0.2 0.4 0.6 0.4 0.4 0.4 0.4 0.2 0.4
0.2 0.4
2.92 3.75 4.46 2.99 2.01 3.55 3.62 2.54 3.66
98.7 97.5 100 96.1 93.0 100 100 100 100
85.6 91.7 89.9 56.2 43.0 94.8 76.5 91.3 92.2
6.1 5.0 6.5 19.1 20.9 4.0 16.8 4.3 4.3
54 45 37 60 110 90 180 90 60
2,4,6-TMP, 2 niniol; ti-hexanol, 2 nil; Temp., 60°C; Oxygen pressure, 114.7 kPa. While a very low yield of DMHBA was obtained in methanol, ethanol afforded a preferable result than methanol, though the yield was still not so high. Use of primary alcohols possessing long alkyl chains as the solvent resulted in a good yield production of DMHBA. t-Butanol oppositely afforded a very low yield of DMHBA. The higher temperature of the reaction gave the higher rate of the oxidation. Thus, the effects of the alcohol solvent or the reaction temperature in the 2,4,6-TMP oxidation with the copper(I1) chloride-acetone oxime catalyst are clearly different from those obtained in the 2,3,6Table 4 Copper(I1)-acetone oxime catalyzed oxidation of 2,4,6-TMP in various alcohols ~~
S o 1veil t MeOH EtOH n-PrOH n- Bu OH t-BuOH n-HeOH II-BUOH~)
i-BuOHa) t-BuOHa) I I - H e 0H a
d02(max)/dt (mniol/h) 0.695 0.965 1.24 0.196 0.955 2.60 2.77 0.212 1.82
Conv. (%)
43.6 97.3 100 100 40.3 97.6 100 100
62.3 100
Yield(%) of DMHBA 2,6-DMQ 8.1 55.4 78.4 77.2 21.9 73.0 81.7 83.0 42.2 82.5
3.1 4.3 3.5 2.7 3.3 5.8 2.9
React. time(min) 300 3 00 248 195 300 195 86 86 300 120
2,4,6-TMP, 2 mmol; CuCI2*2H20,0.1 mmol; Me2C=NOH, 0.2 mmol; Solvent, 2 ml; Temp., 40"C(a)600C), Oxygen pressure, 1 14.7 kPa.
283
31
I
0 2,4,6-TMP
2
0 DMHBA A 2,6-DMQ
A 2a
1
0
0
100
200
300
0
la
0
02 consumed
400
Reaction time (hr) Fig. 1 Time course of the 2,4,6-TMP oxidation with a copper(I1) chloride-acetone oxime catalyst. 2,4,6-TMP, 2 mniol; CuC12.2H20, 0.1 mmol; Me2C=NOH, 0.2 mmol; ti-HeOH, 2 ml; Temp., 40°C; p02, 114.7 kPa. TMPl) or 2,6-DMP oxidation with a copper(I1) chloride-hydroxylamine hydrochloride catalyst, where the branched alcohol such as t-butanol afforded rather preferable results under the room temperature. A time course of the oxidation of 2,4,6-TMP with the copper(I1) chloride-acetone oxime catalyst in rz-hexanol were followed by analysing the reaction products(Fig. I). At the beginning of the oxidation, a substantial production of 3,5-dimethyl-4-hexyloxymethylphenol( 1 a ) was observed and then replaced by the DMHBA production as the reaction proceeded. Small quantities of 2,6-DMQ and dihexyl formal(2a) were detected during the reaction. When the other alcohol was used as the solvent, the corresponding 1 and 2 were also observed. The yield of 1 at the early stage of the oxidation largely depended on the nature of alcohol. Primary alcohols afforded good yields of 1, but r-butanol showed the low value. These results clearly suggest that 1 is an intermediate in the 2,4,6-TMP oxidation to DMHBA with the copper(I1) chloride-acetone oxime catalyst. When 2.4.6-TMP was oxidized in the presence of acids, i.e., with the copper(I1) chloride-hydroxylamine hydrochloride catalyst in n-hexanol, l a was not produced and the amounts of both 2,6DMQ and 2a substantially increased with decreasing in the yield of DMHBA still as the main product. When the reaction was carried out by using 2 mmol of 2,4,6-TMP, 0.1 mmol of CuC12*21320,0.2mmol of NH20HoHCI in 2 ml of n-hexanol at 40°C for 3 hours, all 2,4,6TMP was consumed together with 2.3 mmol of oxygen uptake, and 1.02 mmol of DMHBA, 0.23 mmol of 2,6-DMQ, and 0.26 mmol of 2a were produced. A plausible mechanism of the oxidation of 2,4,6-trimethylphenol is shown in Fig. 2. 2,4,6-TMP can be converted to the phenoxy radical in the resonance state with I via one
284
Fig. 2 A plausible mechanism of 2,4,6-TMP oxidation electron transfer to Cu(II), and Cu(1) thus formed in turn activates dioxygen. I reacts with the activated dioxygen to form I1 as a key intermediate. In the absence of acids, I 1 can be selectively converted to quinone methide(II1) which undergoes 1.6-addition of alcohol to form 1. These steps are repeated once more upon 1 to form acetal(1V) , which is rapidly hydrolyzed to DMHBA. A small part of I V can be oxidatively decomposed to 2.6-DMQ and 2. In the presence of acids, a part of I1 can be protonated to its hydroperoxide, which is converted to 2,6-DMQ. Thus, the presence of acids is favourable to the p-benzoquinone formation also in the present 2,4,6-TMP oxidation, as observed in the oxidation of 2,6DMP or 2,3,6-TMP previously reported.1)
References K. Takehira, M. Shimizu, Y. Watanabe, H. Orita, and T. Hayakawa, Tetrcrhedron Lett., 30,6691(1989); J. Clietn. Soc., Chem. Commun., 1989, 1705. R. A. Sheldon and N. de Heij, "The Role of Oxygen in Chemistry and Biochemistry," Studies in Organic Chemistry, Vol. 33, Ed., W. Ando and Y. Moro-oka, Elsevier, Amsterdam, 1988, p243. T. Shimizu, A. Nishinaga, and T. Matsuura, Preprint of the 12th Oxidation Symposium, Synth. Org. Chem. SOC.Jpn., Tokyo, 1978, p74. K. Nishizawa, K. Hamada, and T. Aratani, Eur. Pat, Appl., 0,012,939( 1979) to Sumitomo. K. Takehira, M. Shimizu, Y. Watanabe, H. Orita, and T. Hayakawa, Tetrahedron Lett., 31, 2607(1990).
279
Novel Oxidation of Phenols by a Copper(I1) Complex Catalyst / 0 2 System K. Takehira, M. Shimizu, Y. Watanabe, T. Hayakawa, and H. Orita National Chemical Laboratory for Industry, Tsukuba Research Center, Higashi 1-1, Tsukuba, Ibaraki 305, Japan Abstract 2,4,6-Trimethylphenol was efficiently oxidized to the corresponding p-hydroxybenzaldehyde by a cupric chloride-acetone oxime catalyst / 0 2 system in alcoholic solvents. It is likely that the reaction proceeds via a quinone methide intermediate, followed by 1.6addition of an alcohol to form acetal, which is then hydrolyzed to the aldehyde. When acids were present, preferable formation of 2,6-dimethyl-p-benzoquinoneby the oxidative demethylation was observed. 2,6-Dimethylphenol was also oxygenated to the corresponding p-benzoquinone by the same system with acids. Thus, acids play an important role in the 1.7-oxygenation of aromatic ring of 2,6-dimethylphenols by dioxygen.
1. I n t r o d u c t i o n We have recently reported that copper(I1) chloride coupled with amine, hydroxylamine, or oxime catalyzes the oxidation of 2,3,6-trimethylpheno1(2,3,6-TMP) to trimethyl-pbenzoquinone (TMQ) with dioxygen in alcoholic so1vents.l) It is well known that phenol oxidations catalyzed by copper produce dimers or polymers as well known in the production of poly(pheny1ene oxide) from 2,6-dimethylphenol (2,6-DMP) industrialyzed by GE company. However, our copper(I1) system catalyst accelerated the selective oxidation of phenols to p-benzoquinones in the presence of acids.1) It is likely that acids play an important role in the selective p-oxidation of phenols. How does the oxidation proceed in the case of p-methyl substituted phenols by using our catalyst system? We have studied the oxidation of 2,4,6-trimethylphenoI (2,4,6-TMP) and 2,6-DMP; the former and the latter afforded 3,5-dimethyl-4-hydroxybenzaldehyde(DMHBA) and 2,6-dimethyl-p-benzoquinone (2,6-DMQ), respectively. Aromatic aldehydes are important intermediates in industrial production of a wide variety of speciality chemicals, such as pharmaceuticals, flavour chemicals, dyes, and agrochemicals. Several methods for the aromatic aldehyde syntheses from toluenes have been developed;2) chlorination followed by hydrolysis, stoichiometric oxidation with inorganic oxydants, electric/electrocatalytic oxidation, and catalytic oxygen transfer with some oxygen donors. The most attractive method seems a catalytic oxidation with molecular oxygen. For examples, p-cresols are oxidized with molecular oxygen to the corresponding p-hydroxybenzaldehydes in the presence of a catalytic amount of cobalt Shiff base (yields 45%)3) or cobaltous oxide (yields 78%)2*4)in methanol. The latter process seems promising but requires long reaction time and strongly basic conditions in the presence of a large amount of sodium hydroxide.
280
Here, we report the selective and efficient oxidation of 2,4,6-TMP to DMHBA with a copper(I1) system catalyst and discuss on its reaction mechanism. 2.
Ex pe ri me nt al
A typical run of phenol oxidation was carried out as follows: 2 mmol of 2,4,6-TMP was dissolved in 2 ml of an alcoholic solvent together with 0.1 mmol of CuCl2.2H20 and 0.2 mmol of acetone oxime, and the reaction was carried out for several hours at 60°C under atmospheric pressure of oxygen. A time course of the oxidation was monitored by measuring the amount of consumed oxygen with a gas burette. The reaction products, DMHBA, 2.6-DMQ. 2,6-dimethyl-4-alkoxymethylphenol(l),and dialkyl formal(2) were chromatographed on silica gel, identified by IH-NMR and IR. Yield were determined by GLC using Silicone DCQF 1 as a column.
3. Results and Discussion
3.1. 2 , 6 - D M P Oxidation The results of the oxidation of 2,6-DMP are shown in Table 1. The activity of copper (11) chloride alone was very low and, even when coupled with LiCI. the activity did not increase enough . While use of diethylamine alone as an additive resulted in the production of a large amount of polymer, use of diethylamine hydrochloride caused an increase in the activity for p-oxygenation. A choice of the additive is likely important; the addition of hydroxylaniine combined with an acid, especially with sulfuric acid, caused a great increase i n the activity. Thus, the presence of acids promoted the formation of 2,6DMQ. In addition, the activities are dependent on a type of solvents; use of a branched Table 1 Copper(I1) catalyzed oxidation of 2,6-DMP to 2,6-DMQ CuC12-2H20 (mmol)
Additive (mmol)
Solvent (mu ~~~
0.2 0.2 LiCl(O.2) 0.1 LiCl(O.2) 0.2 Et2NH-HC1(0.2) 0.2 NH20H*HC1(0.4) 0.1 NH20H*HCI(0.2) 0.1 (NH20H)2*H2S04(0.1)
Conv. (%)
2,6-DMP, 2 mmol; Oxygen pressure, 114.7 kPa.
-~~~
~
n-HeOH(2) n-HeOH(2) f-B uOH( 2) n-HeOH( 2) ti-HeOH(2) t - B UOH( 2) t-BuOH(2) O.lMe2C=NOH(O.2)+HCI(0.2) t-BuOH(2) 0.1 (NH20H)2*H2S04(0.1) i-PrOH(2) 0.1 (NH20H)2*H2S04(0.1) r-AmOH(2) 0.1 (NH20H)2*H2S04(0.1) Tol( I.S)+i-PrOH(O.S) 0.1 (NH20H)2*H2S04(0.1) Tol(O.S)+i-PrOH( 1.5)
Yield Temp. React. (%) ("C) timc(1i)
30.1 61.5 10.1 98.0 98.1 100 100 78.7 100 100 100 100
7.9 39.9 70.5
45.8 73.2 82.5 32.3 77.4 85.8 88.2 86.3
60 60 40 60 60 40 40 40 40 40 40 40
5 5 5 S
3 3 2 5
2.5 2 2 2
281
alcohol or its mixing with aromatic solvent resulted in the high yield of 2,6-DMQ production. In the latter case, only a small amount of alcohol was enough to get the highest yield of 2,6-DMQ. It implies that alcohol works not only as the solvent but also as a crucial component for this phenol oxidation. The results thus obtained are very similar to those obtained in the 2,3,6-TMP oxidation,l) and therefore it is most likely that the both oxidations proceed by the same mechanism.
3.2. 2 , 4 , 6 - T M P Oxidation The results of the 2,4,6-TMP oxidations with several copper(I1) system catalysts in 11hexanol are shown in Table 2. The maximum rate of oxygen consumption was calculated from the oxygen uptake during the reaction and is shown as d02(rnax)/dt in Table 2. Copper(I1) choride alone or even coupled with LiCl showed a very low activity. The addition of diethylamine caused a large increase in the activity for the DMHBA production, while its coupling with hydrochloric acid resulted in a decrease in the activity. As recently reported by US,^) copper(I1)-amine( 1: 1) complexes were active, where the most effective amine was diethylamine, and the presence of an excess amount of amine caused a rapid formation of polymer. In the case of acetone oxime, the highest yield of DMHBA was obtained, and the unfavourable effect of hydrochloric acid was also observed in this case. Interestingly, hydroxylamine hydrochloride or sulfate gave high rate of oxygen consumption, but afforded the low yield of DMHBA. The presence of an acid accelerated formations of both 2,6-DMQ and dihexyl formal as by-products, resulting in a lowering in the selectivity of DMHBA production. When the ratio of acetone oxime to copper(I1) chloride was increased, both the high activity in the rate of 0 2 consumption and the high yield of DMHBA were obtained(Tab1e 3). The addition of hydrochloric acid clearly caused an increase in the yield of 2.6-DMQ with decreases in both the reaction rate and the yield of DMHBA. A time course of the oxidation revealed that DMHBA formed was successively oxidized to 2.6-DMQ. In the presence of acetone oxime, a half amount(O.l mmol) of CuC12.2H20 was enough for the substantial conversion of 2,4,6-TMP to DMHBA . The results of the 2,4,6-TMP oxidations in several alcohols are shown in Table 4. Table 2 Copper(I1) catalyzed oxidation of 2,4,6-TMP to DMHBA Additive (mmol)
d02(max)/dt (mmol/h)
Conv.
0.144 0.155 0.815 0.497 2.92 1.70 3.40 2.81
40.0 45.6 97.6 95.0 98.7 93.6 94.5 96.5
LiCl(O.2) E t 2NH( 0.2) Et2NH-HC1(0.2) Me2C=NOH(0.2) Me2C=NOH(0.2)+HCI(O.2) NH20H-HC1(0.2) (NH20H)2*H2S04(0.1 )
(%)
Yield(%) of DMHBA 2,6-DMQ
2.7 3.5 77.7 44.5 85.6 52.1 47.9 61.6
2.7 1.8 3.7 4.2 6.1 21.9 27.4 15.9
React. time(min) 3 00 300 240 300 54 120 54 54
2.4,6-TMP, 2 mmol; CuCl2*2H20,0.2 mmol; n-hexanol, 2 ml; Temp., 60°C; Oxygen pressure, 114.7 kPa.
282
Table 3 Copper(I1)-acetone oxime catalyzed oxidation of 2,4,6-TMP ___
CuC12.2H20 Me2C=NOH HCI d02(max)dt Conv. Yield(%) of React. (mmol) (nimol) (mmol) (mmol/h) (%) DMHBA 2,6-DMQ time(min) 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.1
0.2 0.4 0.6 0.4 0.4 0.4 0.4 0.2 0.4
0.2 0.4
2.92 3.75 4.46 2.99 2.01 3.55 3.62 2.54 3.66
98.7 97.5 100 96.1 93.0 100 100 100 100
85.6 91.7 89.9 56.2 43.0 94.8 76.5 91.3 92.2
6.1 5.0 6.5 19.1 20.9 4.0 16.8 4.3 4.3
54 45 37 60 110 90 180 90 60
2,4,6-TMP, 2 niniol; ti-hexanol, 2 nil; Temp., 60°C; Oxygen pressure, 114.7 kPa. While a very low yield of DMHBA was obtained in methanol, ethanol afforded a preferable result than methanol, though the yield was still not so high. Use of primary alcohols possessing long alkyl chains as the solvent resulted in a good yield production of DMHBA. t-Butanol oppositely afforded a very low yield of DMHBA. The higher temperature of the reaction gave the higher rate of the oxidation. Thus, the effects of the alcohol solvent or the reaction temperature in the 2,4,6-TMP oxidation with the copper(I1) chloride-acetone oxime catalyst are clearly different from those obtained in the 2,3,6Table 4 Copper(I1)-acetone oxime catalyzed oxidation of 2,4,6-TMP in various alcohols ~~
S o 1veil t MeOH EtOH n-PrOH n- Bu OH t-BuOH n-HeOH II-BUOH~)
i-BuOHa) t-BuOHa) I I - H e 0H a
d02(max)/dt (mniol/h) 0.695 0.965 1.24 0.196 0.955 2.60 2.77 0.212 1.82
Conv. (%)
43.6 97.3 100 100 40.3 97.6 100 100
62.3 100
Yield(%) of DMHBA 2,6-DMQ 8.1 55.4 78.4 77.2 21.9 73.0 81.7 83.0 42.2 82.5
3.1 4.3 3.5 2.7 3.3 5.8 2.9
React. time(min) 300 3 00 248 195 300 195 86 86 300 120
2,4,6-TMP, 2 mmol; CuCI2*2H20,0.1 mmol; Me2C=NOH, 0.2 mmol; Solvent, 2 ml; Temp., 40"C(a)600C), Oxygen pressure, 1 14.7 kPa.
283
31
I
0 2,4,6-TMP
2
0 DMHBA A 2,6-DMQ
A 2a
1
0
0
100
200
300
0
la
0
02 consumed
400
Reaction time (hr) Fig. 1 Time course of the 2,4,6-TMP oxidation with a copper(I1) chloride-acetone oxime catalyst. 2,4,6-TMP, 2 mniol; CuC12.2H20, 0.1 mmol; Me2C=NOH, 0.2 mmol; ti-HeOH, 2 ml; Temp., 40°C; p02, 114.7 kPa. TMPl) or 2,6-DMP oxidation with a copper(I1) chloride-hydroxylamine hydrochloride catalyst, where the branched alcohol such as t-butanol afforded rather preferable results under the room temperature. A time course of the oxidation of 2,4,6-TMP with the copper(I1) chloride-acetone oxime catalyst in rz-hexanol were followed by analysing the reaction products(Fig. I). At the beginning of the oxidation, a substantial production of 3,5-dimethyl-4-hexyloxymethylphenol( 1 a ) was observed and then replaced by the DMHBA production as the reaction proceeded. Small quantities of 2,6-DMQ and dihexyl formal(2a) were detected during the reaction. When the other alcohol was used as the solvent, the corresponding 1 and 2 were also observed. The yield of 1 at the early stage of the oxidation largely depended on the nature of alcohol. Primary alcohols afforded good yields of 1, but r-butanol showed the low value. These results clearly suggest that 1 is an intermediate in the 2,4,6-TMP oxidation to DMHBA with the copper(I1) chloride-acetone oxime catalyst. When 2.4.6-TMP was oxidized in the presence of acids, i.e., with the copper(I1) chloride-hydroxylamine hydrochloride catalyst in n-hexanol, l a was not produced and the amounts of both 2,6DMQ and 2a substantially increased with decreasing in the yield of DMHBA still as the main product. When the reaction was carried out by using 2 mmol of 2,4,6-TMP, 0.1 mmol of CuC12*21320,0.2mmol of NH20HoHCI in 2 ml of n-hexanol at 40°C for 3 hours, all 2,4,6TMP was consumed together with 2.3 mmol of oxygen uptake, and 1.02 mmol of DMHBA, 0.23 mmol of 2,6-DMQ, and 0.26 mmol of 2a were produced. A plausible mechanism of the oxidation of 2,4,6-trimethylphenol is shown in Fig. 2. 2,4,6-TMP can be converted to the phenoxy radical in the resonance state with I via one
284
Fig. 2 A plausible mechanism of 2,4,6-TMP oxidation electron transfer to Cu(II), and Cu(1) thus formed in turn activates dioxygen. I reacts with the activated dioxygen to form I1 as a key intermediate. In the absence of acids, I 1 can be selectively converted to quinone methide(II1) which undergoes 1.6-addition of alcohol to form 1. These steps are repeated once more upon 1 to form acetal(1V) , which is rapidly hydrolyzed to DMHBA. A small part of I V can be oxidatively decomposed to 2.6-DMQ and 2. In the presence of acids, a part of I1 can be protonated to its hydroperoxide, which is converted to 2,6-DMQ. Thus, the presence of acids is favourable to the p-benzoquinone formation also in the present 2,4,6-TMP oxidation, as observed in the oxidation of 2,6DMP or 2,3,6-TMP previously reported.1)
References K. Takehira, M. Shimizu, Y. Watanabe, H. Orita, and T. Hayakawa, Tetrcrhedron Lett., 30,6691(1989); J. Clietn. Soc., Chem. Commun., 1989, 1705. R. A. Sheldon and N. de Heij, "The Role of Oxygen in Chemistry and Biochemistry," Studies in Organic Chemistry, Vol. 33, Ed., W. Ando and Y. Moro-oka, Elsevier, Amsterdam, 1988, p243. T. Shimizu, A. Nishinaga, and T. Matsuura, Preprint of the 12th Oxidation Symposium, Synth. Org. Chem. SOC.Jpn., Tokyo, 1978, p74. K. Nishizawa, K. Hamada, and T. Aratani, Eur. Pat, Appl., 0,012,939( 1979) to Sumitomo. K. Takehira, M. Shimizu, Y. Watanabe, H. Orita, and T. Hayakawa, Tetrahedron Lett., 31, 2607(1990).