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Polymer-supported reagents: O-alkylation of phenolic arylesters
Reactive Polymers, 6 (1987) 89-91
89
Elsevier Science Publishers B.V., Amsterdam - Printed in The Netherlands
POLYMER-SUPPORTED REAGENTS: O-ALKYLATION OF PHENOLIC ARYLESTERS * JAYSINGRAO G. DESHMUKH, RAMCHANDRA B. MANE, MANSINGRAO H. JAGDALE and MAN1KRAO M. SALUNKHE * *
Department of Chemistry, Shivaji University, Kolhapur 416 004, Maharashtra (India) (Received September 3, 1986; accepted in revised form December 12, 1986)
Phenoxides of aryl esters supported on Amberlyst A-26, on reaction with alkyl halide, gave the corresponding alkoxy aromatic esters in quantitative yield and purity. The preparation of this derivative by traditional methods is not possible due to hydrolysis of the ester group in the substrate. Interestingly, trans-esterification was observed when alcohol was used as solvent.
INTRODUCTION Reagents supported on insoluble polymers have found wide application in organic synthesis [1]. In view of the importance of O-alkylated phenolic aryl esters as basic compounds in the drug industry [2-6], a simple and efficient method is now reported for Oalkylation of phenolic aryl esters. In continuation of our previous work [7-10] on polymer-supported reactions we now report the use of anion exchange resins for O-alkylation of phenolic aryl esters. Alkyl halides in a suitable solvent were reacted with phenolic aryl ester anions bound to the ion exchange resin. This resulted in an ionic bond between a quaternary ammonium ion site on the resin and the phenoxy anion * Paper presented at the 3rd International Conference on Polymer-Supported Reactions in Organic Chemistry, Jerusalem, Israel, July 6-11, 1986 ** To whom correspondence should be addressed 0167-6989/87/$03.50
center. Alkylation was complete within 10 to 16 hours at room temperature, giving quantitative yields of products in essentially pure form.
EXPERIMENTAL In a typical reaction, 5 g of Amberlyst A-26 (C1-) was packed in a column which was eluted with 0.25 N aqueous sodium phenoxide (100 ml) until removal of chloride ion was complete. The resin was washed successively with water, acetone and ether, and dried in vacuo at 50 ° C over phosphorous oxide for 12 hours. The exchange capacity was determined by passing aqueous 1 M sodium chloride solution (100 ml) through the resin (0.3 g) in a column. The amount of phenoxide anion in the eluent was estimated by titration against 0.01 N hydrochloric acid using methyl orange as an indicator. To the above polymer-supported ion (5 g, 1
© 1987 Elsevier Science Publishers B.V.
90 TABLE I
R'=R"
R
COOCH3
~
Time(h)
Yield (%)
bp ( *C )
-CH 3
10
-C2H 5
12
95 98
2~8 230
-CH2CH2-CH3
10
90
210
0
_CH2CH=CH2
16
90
240
COOC2H5
-CH 3 .
I0
98
260
-C2H5
15
95
250
-CH2-CH2-CH 3
14
94
260
0
- C H 2 - C H = C2H
12
90
2~7
~00C2H5 .. O-
-CH3
16
85
250
-C2H 5
15
88
230
-CH 3
18
78
225
-C2H 5
20
75
237
~_
r.~C~
3
OC2H5 ~./'O
-C2H 5
12
90
270
-CH 3
15
92
237
-CH2-CH=CH 2
18
90
240
mmol of phenoxide ion per gram of dry resin) in 15 ml of the desired solvent (methanol for methyl ester and ethanol for ethyl ester) was added 5 mmol of alkyl halide. The resulting mixture was stirred (please refer to Table 1). The resin was filtered and the filtrate was slowly distilled under reduced pressure to remove the solvent. The products were characterised by IR, P M R and comparison with" authentic sampies.
R E S U L T S AND D I S C U S S I O N i CH2"NMe3
R" OH
(I)
RO
+
CH2-NMe 3
(II)
O-Alkylation of p-hydroxy ethyl benzoate with ethyl iodide was carried out at room temperature in benzene, chloroform and 1,2dirnethoxy ethane to yield the corresponding alkylated products in 70, 80 and 95 percent
yields, respectively. This is the most convenient and cheap method for preparation of alkyloxy phenyl esters, as the resin can be reused and quantitative yields of pure products were obtained. The preparation of these derivatives by the traditional solution method is not possible due to hydrolysis of the ester group in the substrate. Interestingly, transesterification was observed when alcohol was used as solvent. For example I, R ' = CH3, when stirred with methyl iodide in ethanol for 15 hours, afforded after work up the ethyl ester H 3 C O - C 6 H 4 - C O O C 2 H 5 in 90% yield. ACKNOWLEDGEMENT One of us (J.G.D.) is grateful to the U.G.C. New Delhi and Shri Swami Vivekanand Shikshan Sanstha, Kolhapur for financial support.
REFERENCES 1 A. McKillop and D.W. Young, Polymer supported reagents: Organic synthesis using supported reagents, Part I and Part II, Synthesis,(1979) 401 and (1979) 481. 2 J.F.J. Dippy and R.H. Lewis, Studies of the ortho effect. Part II. The dissociation constants of some o-substituted acids, J. Chem. Soc., (1937) 1426. 3 J.F.J. Dippy and R.H. Lewis, Chemical Constitution and the dissociation constants of monocarboxylic acids, J. Chem. Soc., (1936) 644, 4 J.J. Korst, J.D. Johnston, K. Butler, E.J. Bianco and L.H. Conover, The total synthesis of dl-6-demethyl6-deoxytetracycline,J. Amer. Chem. Soc., 90 (1968) 439. 5 H. Gilman, W. Longham and H.B. Willis, The twostage metalation of 2-bromodibenzofuran, J. Amer. Chem. Soc., 62 (1940) 346. 6 D.B. Denney, R. Melis and A.D. Pendse, Methylation of acids with pentamethoxy phosphorane, J. Org. Chem., 43 (1978) 4672. 7 J.G. Deshmukh, R.B. Mane, M.H. Jagdale and M.M. Selunkhe, Polymer supported reagents: Use of anion exchange resin in the synthesis of aryloxy acetic acid, Synth. Commun., 16 (1986) 479. 8 J.G. Deshmukh, R.B. Mane, M.H. Jagdale and M.M. Salunkhe, Polymer supported reagents: Synthesis of aryloxy acetic esters, Chem. Ind., (1986) 179.
91 9 M.T. Thorat, R.B. Mane, M.H. Jagdale and M.M. Salunkhe, Synthesis of phenacyl esters via polymer supported reagents, Org Prep. Proced. Int., 18 (1986) 203.
10 A.R. Sande, M.H. Jagdale, R.B. Mane and M.M. Salunkhe, Borohydride reducing agent derived from anion exchange resin, Tetrahedron Lett., 15 (1984) 3501.
89
Elsevier Science Publishers B.V., Amsterdam - Printed in The Netherlands
POLYMER-SUPPORTED REAGENTS: O-ALKYLATION OF PHENOLIC ARYLESTERS * JAYSINGRAO G. DESHMUKH, RAMCHANDRA B. MANE, MANSINGRAO H. JAGDALE and MAN1KRAO M. SALUNKHE * *
Department of Chemistry, Shivaji University, Kolhapur 416 004, Maharashtra (India) (Received September 3, 1986; accepted in revised form December 12, 1986)
Phenoxides of aryl esters supported on Amberlyst A-26, on reaction with alkyl halide, gave the corresponding alkoxy aromatic esters in quantitative yield and purity. The preparation of this derivative by traditional methods is not possible due to hydrolysis of the ester group in the substrate. Interestingly, trans-esterification was observed when alcohol was used as solvent.
INTRODUCTION Reagents supported on insoluble polymers have found wide application in organic synthesis [1]. In view of the importance of O-alkylated phenolic aryl esters as basic compounds in the drug industry [2-6], a simple and efficient method is now reported for Oalkylation of phenolic aryl esters. In continuation of our previous work [7-10] on polymer-supported reactions we now report the use of anion exchange resins for O-alkylation of phenolic aryl esters. Alkyl halides in a suitable solvent were reacted with phenolic aryl ester anions bound to the ion exchange resin. This resulted in an ionic bond between a quaternary ammonium ion site on the resin and the phenoxy anion * Paper presented at the 3rd International Conference on Polymer-Supported Reactions in Organic Chemistry, Jerusalem, Israel, July 6-11, 1986 ** To whom correspondence should be addressed 0167-6989/87/$03.50
center. Alkylation was complete within 10 to 16 hours at room temperature, giving quantitative yields of products in essentially pure form.
EXPERIMENTAL In a typical reaction, 5 g of Amberlyst A-26 (C1-) was packed in a column which was eluted with 0.25 N aqueous sodium phenoxide (100 ml) until removal of chloride ion was complete. The resin was washed successively with water, acetone and ether, and dried in vacuo at 50 ° C over phosphorous oxide for 12 hours. The exchange capacity was determined by passing aqueous 1 M sodium chloride solution (100 ml) through the resin (0.3 g) in a column. The amount of phenoxide anion in the eluent was estimated by titration against 0.01 N hydrochloric acid using methyl orange as an indicator. To the above polymer-supported ion (5 g, 1
© 1987 Elsevier Science Publishers B.V.
90 TABLE I
R'=R"
R
COOCH3
~
Time(h)
Yield (%)
bp ( *C )
-CH 3
10
-C2H 5
12
95 98
2~8 230
-CH2CH2-CH3
10
90
210
0
_CH2CH=CH2
16
90
240
COOC2H5
-CH 3 .
I0
98
260
-C2H5
15
95
250
-CH2-CH2-CH 3
14
94
260
0
- C H 2 - C H = C2H
12
90
2~7
~00C2H5 .. O-
-CH3
16
85
250
-C2H 5
15
88
230
-CH 3
18
78
225
-C2H 5
20
75
237
~_
r.~C~
3
OC2H5 ~./'O
-C2H 5
12
90
270
-CH 3
15
92
237
-CH2-CH=CH 2
18
90
240
mmol of phenoxide ion per gram of dry resin) in 15 ml of the desired solvent (methanol for methyl ester and ethanol for ethyl ester) was added 5 mmol of alkyl halide. The resulting mixture was stirred (please refer to Table 1). The resin was filtered and the filtrate was slowly distilled under reduced pressure to remove the solvent. The products were characterised by IR, P M R and comparison with" authentic sampies.
R E S U L T S AND D I S C U S S I O N i CH2"NMe3
R" OH
(I)
RO
+
CH2-NMe 3
(II)
O-Alkylation of p-hydroxy ethyl benzoate with ethyl iodide was carried out at room temperature in benzene, chloroform and 1,2dirnethoxy ethane to yield the corresponding alkylated products in 70, 80 and 95 percent
yields, respectively. This is the most convenient and cheap method for preparation of alkyloxy phenyl esters, as the resin can be reused and quantitative yields of pure products were obtained. The preparation of these derivatives by the traditional solution method is not possible due to hydrolysis of the ester group in the substrate. Interestingly, transesterification was observed when alcohol was used as solvent. For example I, R ' = CH3, when stirred with methyl iodide in ethanol for 15 hours, afforded after work up the ethyl ester H 3 C O - C 6 H 4 - C O O C 2 H 5 in 90% yield. ACKNOWLEDGEMENT One of us (J.G.D.) is grateful to the U.G.C. New Delhi and Shri Swami Vivekanand Shikshan Sanstha, Kolhapur for financial support.
REFERENCES 1 A. McKillop and D.W. Young, Polymer supported reagents: Organic synthesis using supported reagents, Part I and Part II, Synthesis,(1979) 401 and (1979) 481. 2 J.F.J. Dippy and R.H. Lewis, Studies of the ortho effect. Part II. The dissociation constants of some o-substituted acids, J. Chem. Soc., (1937) 1426. 3 J.F.J. Dippy and R.H. Lewis, Chemical Constitution and the dissociation constants of monocarboxylic acids, J. Chem. Soc., (1936) 644, 4 J.J. Korst, J.D. Johnston, K. Butler, E.J. Bianco and L.H. Conover, The total synthesis of dl-6-demethyl6-deoxytetracycline,J. Amer. Chem. Soc., 90 (1968) 439. 5 H. Gilman, W. Longham and H.B. Willis, The twostage metalation of 2-bromodibenzofuran, J. Amer. Chem. Soc., 62 (1940) 346. 6 D.B. Denney, R. Melis and A.D. Pendse, Methylation of acids with pentamethoxy phosphorane, J. Org. Chem., 43 (1978) 4672. 7 J.G. Deshmukh, R.B. Mane, M.H. Jagdale and M.M. Selunkhe, Polymer supported reagents: Use of anion exchange resin in the synthesis of aryloxy acetic acid, Synth. Commun., 16 (1986) 479. 8 J.G. Deshmukh, R.B. Mane, M.H. Jagdale and M.M. Salunkhe, Polymer supported reagents: Synthesis of aryloxy acetic esters, Chem. Ind., (1986) 179.
91 9 M.T. Thorat, R.B. Mane, M.H. Jagdale and M.M. Salunkhe, Synthesis of phenacyl esters via polymer supported reagents, Org Prep. Proced. Int., 18 (1986) 203.
10 A.R. Sande, M.H. Jagdale, R.B. Mane and M.M. Salunkhe, Borohydride reducing agent derived from anion exchange resin, Tetrahedron Lett., 15 (1984) 3501.