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Influence of the cation in condensation of glyoxylic acid on phenols in aqueous hydroxide solution
INFLUENCE OF THE CATION IN CONDENSATION OF GLYOXYLIC ACID ON PHENOLS IN AQUEOUS HYDROXIDE SOLUTION
MARIE-FRANCE WUTHRICK AND CHRISTIAN MALIVERNEY Rh6ne-Poulenc Industrialisation, Centre de Recherche, d'Ing6nierie et de Technologie - 85 avenue des Fr~res Perret- BP 62 - 69192 Saint-Fons Cedex France.
INTRODUCTION Hydroxy and alkoxy aromatic aldehydes are very important products, used primarily as flavors and fragrances, secondly as intermediates in the manufacture of agrochemicals, pharmaceuticals, cosmetics and in the electroplating industry, etc (ref. 1). Ortho and para hydroxybenzaldehydes, vanillin, ethyl vanillin, protocatechualdehyde, veratraldehyde and piperonal are the most important products. Different processes are proposed for the synthesis of aromatic aldehydes but only very few are satisfactory for industrial applications. The main processes for the manufacture of hydroxybenzaldehydes are based on the functionalisation of phenol, catechol and catechol derivatives (guaiacol, guetol .... ). Ortho substitutions can be specific, as in the condensation of phenyl metaborate with formaldehyde to give salicylaldehyde after catalytic oxidation of intermediate saligenin (ref. 2), but generally, condensations with carbon electrophilic reagents give mixtures of ortho and para isomers (ref. 3). The more interesting challenge is the regiospecific preparation of para substitution products for the manufacture of 4-hydroxybenzaldehyde, vanillin and ethyl vanillin. One of the classical methods is the condensation of a phenol with glyoxylic acid in basic media to give substituted mandelic acids as intermediates. The corresponding 343
aromatic aldehydes are obtained decarboxylation (ref. 4) (Fig. 1).
after
OH
homogeneous
catalytic
ONa
OH 02,
COOH
oxidative
cata
H20, OH"
NaOH OH
CHO
R = H, OMe, OEt COONa
Fig. 1.
Preparationof hydroxybenzaldehydesfrom phenols and glyoxylic acid.
The base usually used for the condensation between phenols and glyoxylic acid is sodium hydroxide. The reaction is selective for the para position, but the 2- and 4-hydroxymandelic acids produced are more reactive than the phenols, and the consecutive reaction is the formation of dimandelic acid (Fig. 2). OH
R O ~
+
CHOI
NaOH
COOH
H20
R = Me, Et
OH
OH
I
COOH
OH
I R O ~ o H
RO, +
RO
~
COOH OH
+
OOH "para . Fig. 2 .
.
.
.
ortho .
.
.
.
di"
Condensationbetween phenols and glyoxylic acid in basic media
To minimize dimandelic acid formation, the phenol is used in excess, generally two or more equivalents. Results are listed in Table 1 (ref. 5).
344
Table 1. Results for the condensation between 2-alkoxyphenols and glyoxylic acid (GA) in aqueous sodium hydroxide.
ArOH
molar ratio
Conv.
NaOH/(ArOH +GA) ArOH % guaiacol
0.95
47.5
Yield (/GA) %
Selectivity (/ArOH) %
para
ortho
di
para
ortho
di
84.2
5.2
8.7
86.5
5.3
9.5
molar ratio ArOH/glyoxylic acid (GA) = 2 9 [H20 ] p/p = 82 % 9 35~ - 4 hours
Our goal was to increase the chemical yield and selectivity into the para mandelic acid.
T H E P A R A S E L E C T I V I T Y O F THE CONDENSATION Different parameters such as temperature, pH and the conversion of guaiacol have no effect upon paraselectivity. We thought that changing
the nature of the
base, in particular the steric hindrance generated by the cation around the phenol function, could increase the paraselectivity, even in aqueous solution, as proposed by the Japanese company UBE, with cyclodextrins (ref. 6). Unfortunately, no increase of paraselectivity has been observed ! In the same way, the replacement of sodium hydroxide by potassium hydroxide leads to bad results (ref. 7), especially because consumption of glyoxylic acid by the Cannizzaro dismutation (ref. 8). Normally, however, we can expect the paraselectivity to be improved when the size of the cation is increased. The literature mentions at least three cases 9 the Kolbe reaction (ref. 9), the Reimer-Tiemann reaction (ref. 10) and the hydroxymethylation of phenols in alcoholic media (ref. 11), where with hydroxide anion the para/ortho ratio is increased following the series of the cations N a + K + < Cs + < R4 N + .
345
<
Finally, we have discovered that the use of a tetra-alkylammonium hydroxide dramatically increases the paraselectivity of the reaction in aqueous media. Our initial results are listed in Table 2 (ref. 12).
Table 2. Increase of paraselectivity by the use of tetra-alkylammonium hydroxides. a)
conversion
cation (M +)
guaiacol %
para
ortho
di
47.5
86.5
5.3
4.5
NMe 4
38.5
96.0
2.7
1.0
NEt4
49.0
95.4
2.5
1.2
NPr4
40.0
95.6
3.3
1.1
NBu 4
21.3
95.9
3.0
1.1
NMe3Bz
33.0
95.0
3.9
1.0
Na b)
selectivity
(/guaiacol) %
a) MOH/(guaiacol +GA) = 1 , except for b) 9 0.95 " guaiacol/GA = 2 9 35 ~ 9 3 h (except for b) " 4 h).
Differences in conversion are explained in certain cases by the heterogeneity of the mixture. Tetraethylammonium hydroxide was used for all of the following experiments. To have the best process using tetraethylammonium hydroxide, we have searched for those parameters giving the best yield and lowest price combined " influence of the quantity of base, guaiacol/glyoxylic acid ratio, concentration ....
INFLUENCE OF RATIO OF TETRAETHYLAMMONIUM HYDROXIDE Firstly, the amount of hydroxide (molar ratio Et4NOH/(guaiacol + G A ) ) has an influence on the rate of reaction : after four hours at 35~
conversion is at a
maximum for ratios between 0.75 and 0.9. To either side of this range (0.7 and 0.96), some glyoxylic acid remains and the corresponding yields are lower. If the reaction is continued, these increase negligably. 346
The yields increase regularly from ratio 0.7 to ratio 0.855 decreasing thereafter. The paraselectivity increases in the same way, from ratio 0.7 (93 %) to ratio 0.96 (97.2 %). T h e results of these experiments are listed in Table 3 and Figure 3. Table 3. Influence of molar ratio of tetraethylammonium hydroxide
Yield (/GA) %
Selectivity (/guaiacol) %
Et4NOH/
conv. %
guaia +GA
guaiacol
para
ortho
di
E
para
ortho
di
E
0.7
47.4
88.2
4.8
3.4
96.4
93.0
5.1
1.8
99.9
0.75
49.3
92.5
4.4
3.2
100.0
93.8
4.5
1.6
99.9
0.8
49.5
94.0
4.0
3.2
101.2
95.0
4.0
1.6
100.6
0.855
50.0
96.0
3.6
2.8
102.4
96.0
3.6
1.4
101.0
0.9
49.0
94.5
3.1
2.5
100.1
96.4
3.2
1.3
100.9
0.96
48.2
93.7
2.7
2.1
98.5
97.2
2.8
1.1
101.1
molar ratio guaiacol/glyoxylic acid = 2 9 35 ~ 9 4 hours
95
85 --
Conversion
A
yield of para
of guaiacol
-
selectivity of para
75
65
55
§
45 0.7
0.75
0.8
0.86
0.9
0.96
ratio Et4NOH
Fig. 3. Conversion, yield and selectivity functions of molar ratio of hydroxide
347
INFLUENCE OF CONCENTRATION GLYOXYLIC ACID
AND M O L A R R A T I O G U A I A C O L /
Neutralisation of guaiacol with sodium hydroxide results in a guaiacol-sodium guaiacolate complex of which the solubility depends on temperature and dilution. To carry out the condensation with glyoxylic acid, it is necessary to have an homogeneous mixture. The temperature can be raised, but due to the Cannizzaro reaction of glyoxylic acid, it is economically decreases with dilution.
uninteresting, and productivity
If the analogous complex with tetraethylammonium hydroxide exists, it is completely soluble in all cases, and it is possible to increase productivity by increasing the concentration. Glyoxylic acid and quaternary ammonium hydroxide are sold in aqueous solution, at 50 % and 40 % weight respectively. To increase the concentration, the only possibility is to reduce the quantity of water initially mixed with guaiacol. Usually, for the process using sodium hydroxide, the initial mixture is composed of 1.25 mole of guaiacol per litre of distilled water (,~ Co >, = 1.25 mol/1). If the initial volume of water is divised by four (--> ,, Co ~> = 5 tool/l), the volume of the final mixture is reduced by one third. In
the
Table
4
are
listed
results
obtained
with
a
molar
ratio
Et4NOH/(guaiacol + G A ) = 0.855 after four hours at 35~
Table 4 . Influence of excess of guaiacol and concentration
guaiacol
yield (/GA) %
,, Co ,, conv.* %
/ GA
Selectivity (/guaiacol) %
guaiacol
para
ortho
di
E
para
ortho
di
E
2.5
5
98.2
96.0
3.6
2.4
102
97.7
3.7
1.2
102.6
2
1.25
100.0
96.0
3.9
3.0
103
96.0
3.9
1.5
101.0
1.75
5
98.1
93.0
3.2
3.5
99.7
95.4
3.2
1.8
100.0
1.5
2.5
96.8
91.3
3.2
4.4
98.9
94.4
3.2
2.3
99.9
,, Co ,, = number of moles of guaiacol / volume of water conv.* = observed conversion of guaiacol/theoretical maximum conversion and theoretical maximum conversion = 100 x molar ratio GA/guaiacol 348
CONCLUSION We have discovered that the use of tetra-alkylammonium hydroxide in place of sodium hydroxide increases dramatically the paraselectivity of the condensation between guaiacol and glyoxylic acid in aqueous media. The other advantages are the possibility to increase the productivity, increasing initial concentration, with a lower ratio of base. The new conditions for condensation can be used for other 2 alloxyphenols for example 2 ethoxyphenol.
References C. Maliverney, M. Mulhauser, "Hydroxybenzaldehydes" in Encyclopedia of Chemical Technology 4th ed., Vol.13, pp.1030-1042, John Wiley, New-York, (1994). 2. a) J. Le Ludec, DE 2,612,844, (1976), (to Rhbne-Poulenc). b) P.A.R. Marchand, J.B. Grenet, US 3,321,526, (1967), (to Rh6ne-Poulenc). 3. H. Wynberg, Chem. Rev., 60, 169 (1960). 4. P. Maggioni, F. Minisci, BE 85,993, (1979), (to Brichima S.P.A.). 5. I. Jouve, Internal Report. 6. T. Huemura, JP 54,061,142, (1979), (to UBE). 7. D. Nobel, Internal Report. 8. E.R. Alexander, J. Am. Chem. Soc., 69, 289 (1947). 9. A.S. Lindsey and H. Jeskey, Chem. Rev., 57,588 (1957). 10. H. Wynberg, Org. React. 28, 1-36 (1982). 11. H. Iwane, T. Sugawara, EP 485,613, (1990), (to Mitsubishi Petrochem)~ 12. a) D. Nobel, FR 92-08,578, (1992), (to Rhbne-Poulenc Chimie). b) C. Malivemey, Internal Report. 1.
349
MARIE-FRANCE WUTHRICK AND CHRISTIAN MALIVERNEY Rh6ne-Poulenc Industrialisation, Centre de Recherche, d'Ing6nierie et de Technologie - 85 avenue des Fr~res Perret- BP 62 - 69192 Saint-Fons Cedex France.
INTRODUCTION Hydroxy and alkoxy aromatic aldehydes are very important products, used primarily as flavors and fragrances, secondly as intermediates in the manufacture of agrochemicals, pharmaceuticals, cosmetics and in the electroplating industry, etc (ref. 1). Ortho and para hydroxybenzaldehydes, vanillin, ethyl vanillin, protocatechualdehyde, veratraldehyde and piperonal are the most important products. Different processes are proposed for the synthesis of aromatic aldehydes but only very few are satisfactory for industrial applications. The main processes for the manufacture of hydroxybenzaldehydes are based on the functionalisation of phenol, catechol and catechol derivatives (guaiacol, guetol .... ). Ortho substitutions can be specific, as in the condensation of phenyl metaborate with formaldehyde to give salicylaldehyde after catalytic oxidation of intermediate saligenin (ref. 2), but generally, condensations with carbon electrophilic reagents give mixtures of ortho and para isomers (ref. 3). The more interesting challenge is the regiospecific preparation of para substitution products for the manufacture of 4-hydroxybenzaldehyde, vanillin and ethyl vanillin. One of the classical methods is the condensation of a phenol with glyoxylic acid in basic media to give substituted mandelic acids as intermediates. The corresponding 343
aromatic aldehydes are obtained decarboxylation (ref. 4) (Fig. 1).
after
OH
homogeneous
catalytic
ONa
OH 02,
COOH
oxidative
cata
H20, OH"
NaOH OH
CHO
R = H, OMe, OEt COONa
Fig. 1.
Preparationof hydroxybenzaldehydesfrom phenols and glyoxylic acid.
The base usually used for the condensation between phenols and glyoxylic acid is sodium hydroxide. The reaction is selective for the para position, but the 2- and 4-hydroxymandelic acids produced are more reactive than the phenols, and the consecutive reaction is the formation of dimandelic acid (Fig. 2). OH
R O ~
+
CHOI
NaOH
COOH
H20
R = Me, Et
OH
OH
I
COOH
OH
I R O ~ o H
RO, +
RO
~
COOH OH
+
OOH "para . Fig. 2 .
.
.
.
ortho .
.
.
.
di"
Condensationbetween phenols and glyoxylic acid in basic media
To minimize dimandelic acid formation, the phenol is used in excess, generally two or more equivalents. Results are listed in Table 1 (ref. 5).
344
Table 1. Results for the condensation between 2-alkoxyphenols and glyoxylic acid (GA) in aqueous sodium hydroxide.
ArOH
molar ratio
Conv.
NaOH/(ArOH +GA) ArOH % guaiacol
0.95
47.5
Yield (/GA) %
Selectivity (/ArOH) %
para
ortho
di
para
ortho
di
84.2
5.2
8.7
86.5
5.3
9.5
molar ratio ArOH/glyoxylic acid (GA) = 2 9 [H20 ] p/p = 82 % 9 35~ - 4 hours
Our goal was to increase the chemical yield and selectivity into the para mandelic acid.
T H E P A R A S E L E C T I V I T Y O F THE CONDENSATION Different parameters such as temperature, pH and the conversion of guaiacol have no effect upon paraselectivity. We thought that changing
the nature of the
base, in particular the steric hindrance generated by the cation around the phenol function, could increase the paraselectivity, even in aqueous solution, as proposed by the Japanese company UBE, with cyclodextrins (ref. 6). Unfortunately, no increase of paraselectivity has been observed ! In the same way, the replacement of sodium hydroxide by potassium hydroxide leads to bad results (ref. 7), especially because consumption of glyoxylic acid by the Cannizzaro dismutation (ref. 8). Normally, however, we can expect the paraselectivity to be improved when the size of the cation is increased. The literature mentions at least three cases 9 the Kolbe reaction (ref. 9), the Reimer-Tiemann reaction (ref. 10) and the hydroxymethylation of phenols in alcoholic media (ref. 11), where with hydroxide anion the para/ortho ratio is increased following the series of the cations N a + K + < Cs + < R4 N + .
345
<
Finally, we have discovered that the use of a tetra-alkylammonium hydroxide dramatically increases the paraselectivity of the reaction in aqueous media. Our initial results are listed in Table 2 (ref. 12).
Table 2. Increase of paraselectivity by the use of tetra-alkylammonium hydroxides. a)
conversion
cation (M +)
guaiacol %
para
ortho
di
47.5
86.5
5.3
4.5
NMe 4
38.5
96.0
2.7
1.0
NEt4
49.0
95.4
2.5
1.2
NPr4
40.0
95.6
3.3
1.1
NBu 4
21.3
95.9
3.0
1.1
NMe3Bz
33.0
95.0
3.9
1.0
Na b)
selectivity
(/guaiacol) %
a) MOH/(guaiacol +GA) = 1 , except for b) 9 0.95 " guaiacol/GA = 2 9 35 ~ 9 3 h (except for b) " 4 h).
Differences in conversion are explained in certain cases by the heterogeneity of the mixture. Tetraethylammonium hydroxide was used for all of the following experiments. To have the best process using tetraethylammonium hydroxide, we have searched for those parameters giving the best yield and lowest price combined " influence of the quantity of base, guaiacol/glyoxylic acid ratio, concentration ....
INFLUENCE OF RATIO OF TETRAETHYLAMMONIUM HYDROXIDE Firstly, the amount of hydroxide (molar ratio Et4NOH/(guaiacol + G A ) ) has an influence on the rate of reaction : after four hours at 35~
conversion is at a
maximum for ratios between 0.75 and 0.9. To either side of this range (0.7 and 0.96), some glyoxylic acid remains and the corresponding yields are lower. If the reaction is continued, these increase negligably. 346
The yields increase regularly from ratio 0.7 to ratio 0.855 decreasing thereafter. The paraselectivity increases in the same way, from ratio 0.7 (93 %) to ratio 0.96 (97.2 %). T h e results of these experiments are listed in Table 3 and Figure 3. Table 3. Influence of molar ratio of tetraethylammonium hydroxide
Yield (/GA) %
Selectivity (/guaiacol) %
Et4NOH/
conv. %
guaia +GA
guaiacol
para
ortho
di
E
para
ortho
di
E
0.7
47.4
88.2
4.8
3.4
96.4
93.0
5.1
1.8
99.9
0.75
49.3
92.5
4.4
3.2
100.0
93.8
4.5
1.6
99.9
0.8
49.5
94.0
4.0
3.2
101.2
95.0
4.0
1.6
100.6
0.855
50.0
96.0
3.6
2.8
102.4
96.0
3.6
1.4
101.0
0.9
49.0
94.5
3.1
2.5
100.1
96.4
3.2
1.3
100.9
0.96
48.2
93.7
2.7
2.1
98.5
97.2
2.8
1.1
101.1
molar ratio guaiacol/glyoxylic acid = 2 9 35 ~ 9 4 hours
95
85 --
Conversion
A
yield of para
of guaiacol
-
selectivity of para
75
65
55
§
45 0.7
0.75
0.8
0.86
0.9
0.96
ratio Et4NOH
Fig. 3. Conversion, yield and selectivity functions of molar ratio of hydroxide
347
INFLUENCE OF CONCENTRATION GLYOXYLIC ACID
AND M O L A R R A T I O G U A I A C O L /
Neutralisation of guaiacol with sodium hydroxide results in a guaiacol-sodium guaiacolate complex of which the solubility depends on temperature and dilution. To carry out the condensation with glyoxylic acid, it is necessary to have an homogeneous mixture. The temperature can be raised, but due to the Cannizzaro reaction of glyoxylic acid, it is economically decreases with dilution.
uninteresting, and productivity
If the analogous complex with tetraethylammonium hydroxide exists, it is completely soluble in all cases, and it is possible to increase productivity by increasing the concentration. Glyoxylic acid and quaternary ammonium hydroxide are sold in aqueous solution, at 50 % and 40 % weight respectively. To increase the concentration, the only possibility is to reduce the quantity of water initially mixed with guaiacol. Usually, for the process using sodium hydroxide, the initial mixture is composed of 1.25 mole of guaiacol per litre of distilled water (,~ Co >, = 1.25 mol/1). If the initial volume of water is divised by four (--> ,, Co ~> = 5 tool/l), the volume of the final mixture is reduced by one third. In
the
Table
4
are
listed
results
obtained
with
a
molar
ratio
Et4NOH/(guaiacol + G A ) = 0.855 after four hours at 35~
Table 4 . Influence of excess of guaiacol and concentration
guaiacol
yield (/GA) %
,, Co ,, conv.* %
/ GA
Selectivity (/guaiacol) %
guaiacol
para
ortho
di
E
para
ortho
di
E
2.5
5
98.2
96.0
3.6
2.4
102
97.7
3.7
1.2
102.6
2
1.25
100.0
96.0
3.9
3.0
103
96.0
3.9
1.5
101.0
1.75
5
98.1
93.0
3.2
3.5
99.7
95.4
3.2
1.8
100.0
1.5
2.5
96.8
91.3
3.2
4.4
98.9
94.4
3.2
2.3
99.9
,, Co ,, = number of moles of guaiacol / volume of water conv.* = observed conversion of guaiacol/theoretical maximum conversion and theoretical maximum conversion = 100 x molar ratio GA/guaiacol 348
CONCLUSION We have discovered that the use of tetra-alkylammonium hydroxide in place of sodium hydroxide increases dramatically the paraselectivity of the condensation between guaiacol and glyoxylic acid in aqueous media. The other advantages are the possibility to increase the productivity, increasing initial concentration, with a lower ratio of base. The new conditions for condensation can be used for other 2 alloxyphenols for example 2 ethoxyphenol.
References C. Maliverney, M. Mulhauser, "Hydroxybenzaldehydes" in Encyclopedia of Chemical Technology 4th ed., Vol.13, pp.1030-1042, John Wiley, New-York, (1994). 2. a) J. Le Ludec, DE 2,612,844, (1976), (to Rhbne-Poulenc). b) P.A.R. Marchand, J.B. Grenet, US 3,321,526, (1967), (to Rh6ne-Poulenc). 3. H. Wynberg, Chem. Rev., 60, 169 (1960). 4. P. Maggioni, F. Minisci, BE 85,993, (1979), (to Brichima S.P.A.). 5. I. Jouve, Internal Report. 6. T. Huemura, JP 54,061,142, (1979), (to UBE). 7. D. Nobel, Internal Report. 8. E.R. Alexander, J. Am. Chem. Soc., 69, 289 (1947). 9. A.S. Lindsey and H. Jeskey, Chem. Rev., 57,588 (1957). 10. H. Wynberg, Org. React. 28, 1-36 (1982). 11. H. Iwane, T. Sugawara, EP 485,613, (1990), (to Mitsubishi Petrochem)~ 12. a) D. Nobel, FR 92-08,578, (1992), (to Rhbne-Poulenc Chimie). b) C. Malivemey, Internal Report. 1.
349