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Alumina-mediated deacetylation of benzaldehyde diacetates. A simple deprotection method
00404039193 56.00 + .@I Pcrgamml RB?ssLid
Teaahedrm~Lam, Vol. 34. No. 20, Pp. 3207-3210s 1993 Printedin Gnu BriIain
ALUMINA-MEDIATED DEACETYLATION OF BENZALDEHYDE DIACETATES. A SIMPLE DEPROTECTION METHOD Rajender
Arnab
S. Varma*,
K. Chatterjee
and Manju
Varma
The Center for Biotechnology, Baylor College of Medicine, 4OtXl Research Forest Drive, The Woodlands, TX 77381, U. S. A.
Key Words:
A
Abstract: deprotection conditions
simple, of
extremely
benzaldehyde
on neutral
conventional
Deprotection; arylaldehyde diacetates; Solid surface; Selectivity; Microwave irradiation
alumina
methods facilitates
fast,
and
diacetates surface.
high is
Gentle
yielding
described heating,
method which
using
for occurs
microwave
Alumina;
the
selective
under
mild
irradiation
or
the procedure.
The formation of diacetyl acetals constitutes one of the simplest methods to derivatize the aldehyde moiety.1 The direct and easy accessibility of these l,ldiacetates from toluenes has been the basis of the preparation of aldehydes from the corresponding toluenes.2 The salient feature of such geminal diacetates as protecting groups is their moderate stability towards acids.3 In view of their facile cleavage under basic conditions, they complement the use of acetal aldehyde as protecting groups.4 However, there are few convenient methods known for the deprotection of geminal acetates3 and hence the limited popularity of such aceta1s.t The conventional deprotection is achieved using either sodium hydroxide or potassium carbonate in aqueous tetrahydrofuran solutions left overnight.3 Also, the regeneration of pnitrobenzaldehyde from the p-nitrobenzaldiacetate has been accomplished in refluxing alcoholic sulfuric acid.* Two novel approaches have appeared for the deprotection of benzaldehyde diacetates. One procedure utilizes boron triiodide-N,N-diethylaniline complex, generated in situ from borane: N,N-diethylaniline and iodine; the reaction in benzene under inert atmosphere provides moderate yield of aldehydes.5 More recently, the selective deprotection of benzaldehyde diacetates has also been accomplished using an oxidant, ceric ammonium nitrate (CAN) coated on silica gel, in dichloromethane.6
Dedicated
to Dr. George
Kabalha on the occasion of his 50th birthday 3207
3208
During the course of an improved synthesis of aurones on alumina surface,7 we noticed an interesting deacetylation reaction. s Consequently, we decided to carry out the reaction of benzaldehyde diacetates under similar conditions using neutral alumina.9 We wish to report that the deactylation reaction results in the rapid formation of arylaldehydes in high yields (2 minutes or less) under mild conditions on ordinary adsorption grade neutral alumina9 at room temperature. When subjected to microwave irradiation (35’C). we observed that the reaction is further accelerated and is completed in seconds (-30-40 seconds). However, the effect is purely thermal 10 for these acetal derivatives and is borne out by the fact that similar reaction rates and yields are observed by alternative heating modes at 35°C. Although, the reaction rates are similar for the above deactylation reaction irrespective of the mode of heating,10 we recommend the use of microwave oven for warming of adsorbed material on solid surfaces as it is convenient and cleaner when compared to other means of heating (conventional ovens, oil baths or heating mantles). Microwave heating has been used for a wide variety of applications including the rapid synthesis of organic compounds. 11-12 Of special interest are the reactions that can be accomplished under “dry” conditions using microwaves.t3-14 Since the reactants adsorbed on the surface of alumina and silica gel only absorb the microwaves, a variety of reagents supported on solid surfaces15 can also be utilized for organic reactions under very safe conditions using domestic microwave ovens; specialized commercial systems require sealed teflon bombs for solution chemistry. We are currently investigating the use of such methodology for a wide variety of organic reactions. We explored various reaction conditions for this conversion and found that a ratio of 10-l lg of alumina/mmol of the diacetate is required for optimum yield. The reaction on alumina is unique in that a variety of functional groups (see table) are tolerated and high yields are readily obtained which may not be attainable using conventional procedures.*-6 Further, selective deacetylation to p-acetoxybenzaldehyde (entry 3) could be achieved in 30 seconds with out affecting the acetoxy group. Also, the reaction is fast enough that no undesirable byproducts originating from arylaldehyde via a concomitant Cannizzaro reaction16 are observed in the reaction product. Our results are summarized in the table with corresponding yields reported for microwave assisted reactions conducted at -35°C. The deprotection of benzaldehyde diacetate (entry 1) is representative of the Neutral alumina9 (3.6g) is added to a solution of general procedure employed. benzaldehyde diacetate (0.054g. 0.284mmol) dissolved in a minimum amount of dichloromethane (1-2ml) at room temperature and the reaction mixture was thoroughly mixed using a vortex mixer. The adsorbed material is dried in air (beaker) and placed in an alumina bath inside the microwave oven.10 Upon completion of the
3209
Table: Entry
Deprotection
of
benzaldebyde
diacetates
Geminal diacetate
Aryldehyde@)
FH(OCOCH&
CHO
0 ’
1
0
0
2
on c
neutral Time
alumina Yield (%$‘)
40 sec.
98 (65>5
40 Sec.
89(a>1
30 sec. (2Min.Y
97 (98f WC
30 Sec.
94 (92f
30 sec.
88 (85$
0
CH3
C%
$HO
yH(OCOCH&
0
3
0
4 Me0
iKOCH,
OCOCH,
qH(OCOCH&
CHO
0
OMe
0%
0
Me0 CHO
5
NO2
NO2
CHO
40
6
CN
CN
CH=CH-CH(OCOCH3)2
yH=CH-CHO
0
7
Sec.
95
40 Sec.
92
0
~~mduc~ yhibii tuqbmud for
hysical ad spectralproperties inaccord with the assigoedstn~ctures; b) Isolated
y-k&, figuxes ioparenthesesreferto knownyields by other mthods;
deplotectiooof both, the acetoxy1 and acetal gnlup
c) l-ii
and yield
3210
reaction as followed by TLC examination (40 Seconds), the product is extracted into dichloromethane (4x5ml). Removal of the solvent, under reduced pressure afforded essentially quantitative yield of benzaldehyde. In conclusion, we have developed a simple method for the selective deacetylation of geminal diacetate derivatives of arylaldehydes that occurs under mild conditions using inexpensive aluminum oxide. The study also points out the unstable nature of arylaldehyde 1,l -diacetates on common chromatography alumina. REFERENCES AND NOTES 1.
:: 4. 2: :: 9. 10.
11. 12.
13. 14.
15.
16.
Greene,T. W.; Wuts.P. G. M. Protective Groups in Organic Synrhesis, Wiley, New York, 2nd Edn., 1991, ~~185-186 and references cited therein. Liebermann. S. V.; Connor, R. Org. Synrh. CON. Vol., 1943, II. 441. Kochhar. K. S.; Bal, B. S.; Deshpande, R. P.; Rajadhyaksha. S. N.; Pinnick, H. W. J. Org. Chem. 1983.48. 1765. Greene, T. W.; Wuts, P. G. M. Prorective Groups in Organic Synrhesis, Wiley, New York, 2nd Edn., 1991. ~~175-222. Narayan, C.; Padmanabhan, S.; Kabalka, G. W. Tetrahedron Lerr.. 1990.31, 6977. Coteile. P.; Catteau, J. -P. Tetrahedron Lett., 1992,33, 3855. Varma. R. S.: Vanna. M. Tetrahedron Lett.. 1992.33. 5937. Varma; R. S:; Varma, M.; Chatterjee, A. i. Unpublished observations. Aluminum oxide [80-200 mesh, for chromatographic analysis (Fisher, Cat. No. A 540-500)) was used as received. For a critical evaluation of activation process by microwaves see: Laurent, R.; Laporterie, A.; Dubac. J.; Berlan, J.; Lefeuvre, Is.; Audhuy. M. J. Org. Chem. 1992,57. 7099. The temperature of the alumina supporting the benzaldehyde diacetates was found to be -35OC after 30 seconds of irradiation in an alumina bath (heat sink) inside a Sears Kenmore microwave Similar yields of the products are oven equipped with a turntable at full power (800Watts). obtained using alternate mode of heating (conventional oven or oil bath at 35OC). For recent reviews on Microwave Assisted Chemical Reactions see Abramovich. R. A. Org. Prep. Proced. Ink, 1991.23, 683; Mingos. D. M. P.; Baghurst, D.R. Chem. Sot. Rev..1991.20, 1. a) Gedye. R.; Smith, F.; Westaway, K.; Ali. H.; Baldisera, L.; Laberge, L.; Rousell, J. Tetrahedron Lett.. 1986.27. 279. b) Giguerc, R. J.; Bray, T. L.; Duncan, S. M.; Majetich, G. Tetrahedron Lerr.. 1986,27, 4945. c) Giguere, R. J.; Namen. A. M.; Lopez, B. 0.; Arepally. A.; Ramos, D. E.; Majetich, G.; 6553. Defrauw, J. Terruhedron Lett., 1987.28, d) Bose, A. K.; Manhas, M. S.; Ghosh, M.; Raju, V. S.; Tabei. K.; Urbanczyk-Lipkowska, 2. Heterocycles. 1990.30, 741. e) Bose, A. K.; Manhas, M. S.; Ghosh. M.; Shah, M.; Raju, V. S.; Bari. S. S.; Nawaz, S. N.; Banik, B. K.; Chaudhary, A. G.; Barakat. K. J. 1. Org. Chem. 1991,56, 6968. f) Banik, B. K.; Manhas, M. S.; Kaluza. Z.; Barakat. K. J.; Bose, A. K. Tetrahedron Left.. 1992,33, 3603. Bram, G.; Loupy, A.; Majdoub, M.; Gutierrez, E.; Ruiz-Hitzky. E. Tetrahedron, 1990,46, 5167. a) Benalloum. A.; Labiad, B.; Villemin. D. J. Chem. Sot. Chem. Commun.. 1989, 386. b) Villemin, D.; Labiad, B.; Guhilal. Y. Chem. Ind. (London) 1989, 607. c) Villemin, D.; Labiad, B. Synth. Commun., 1990,20, 3333 and 3325. d) Villemin. D.; Benalloum, A. Synch. Commun., 1991,21, I and 63. e) Villemin. D.; Lalaoui. M.; Benalloum, A. Chem. Ind. (London) 1991, 176. gor leading reviews pertinent to organic reactions on solid supports see: a) Posner. G. H. Anaew. Chem. Inr. Ed. Enal.. 1978,17. 487. bj McKillop, A.; Young. D.W. Synthesis, lg79, 401; and 481. c) Cornellis, A.; Laszlo. P. Synthesis, 1985, 909. d) Laszlo. P. Act. Chem. Res., 1986,19, 121. e) Laszlo, P.; Cornellis. A. Aldrichimica Acta, 1988,21, 97. Varma. R. S.; Vanna, M. Unpublished observations.
(Received in
USA 16 February 1993)
Teaahedrm~Lam, Vol. 34. No. 20, Pp. 3207-3210s 1993 Printedin Gnu BriIain
ALUMINA-MEDIATED DEACETYLATION OF BENZALDEHYDE DIACETATES. A SIMPLE DEPROTECTION METHOD Rajender
Arnab
S. Varma*,
K. Chatterjee
and Manju
Varma
The Center for Biotechnology, Baylor College of Medicine, 4OtXl Research Forest Drive, The Woodlands, TX 77381, U. S. A.
Key Words:
A
Abstract: deprotection conditions
simple, of
extremely
benzaldehyde
on neutral
conventional
Deprotection; arylaldehyde diacetates; Solid surface; Selectivity; Microwave irradiation
alumina
methods facilitates
fast,
and
diacetates surface.
high is
Gentle
yielding
described heating,
method which
using
for occurs
microwave
Alumina;
the
selective
under
mild
irradiation
or
the procedure.
The formation of diacetyl acetals constitutes one of the simplest methods to derivatize the aldehyde moiety.1 The direct and easy accessibility of these l,ldiacetates from toluenes has been the basis of the preparation of aldehydes from the corresponding toluenes.2 The salient feature of such geminal diacetates as protecting groups is their moderate stability towards acids.3 In view of their facile cleavage under basic conditions, they complement the use of acetal aldehyde as protecting groups.4 However, there are few convenient methods known for the deprotection of geminal acetates3 and hence the limited popularity of such aceta1s.t The conventional deprotection is achieved using either sodium hydroxide or potassium carbonate in aqueous tetrahydrofuran solutions left overnight.3 Also, the regeneration of pnitrobenzaldehyde from the p-nitrobenzaldiacetate has been accomplished in refluxing alcoholic sulfuric acid.* Two novel approaches have appeared for the deprotection of benzaldehyde diacetates. One procedure utilizes boron triiodide-N,N-diethylaniline complex, generated in situ from borane: N,N-diethylaniline and iodine; the reaction in benzene under inert atmosphere provides moderate yield of aldehydes.5 More recently, the selective deprotection of benzaldehyde diacetates has also been accomplished using an oxidant, ceric ammonium nitrate (CAN) coated on silica gel, in dichloromethane.6
Dedicated
to Dr. George
Kabalha on the occasion of his 50th birthday 3207
3208
During the course of an improved synthesis of aurones on alumina surface,7 we noticed an interesting deacetylation reaction. s Consequently, we decided to carry out the reaction of benzaldehyde diacetates under similar conditions using neutral alumina.9 We wish to report that the deactylation reaction results in the rapid formation of arylaldehydes in high yields (2 minutes or less) under mild conditions on ordinary adsorption grade neutral alumina9 at room temperature. When subjected to microwave irradiation (35’C). we observed that the reaction is further accelerated and is completed in seconds (-30-40 seconds). However, the effect is purely thermal 10 for these acetal derivatives and is borne out by the fact that similar reaction rates and yields are observed by alternative heating modes at 35°C. Although, the reaction rates are similar for the above deactylation reaction irrespective of the mode of heating,10 we recommend the use of microwave oven for warming of adsorbed material on solid surfaces as it is convenient and cleaner when compared to other means of heating (conventional ovens, oil baths or heating mantles). Microwave heating has been used for a wide variety of applications including the rapid synthesis of organic compounds. 11-12 Of special interest are the reactions that can be accomplished under “dry” conditions using microwaves.t3-14 Since the reactants adsorbed on the surface of alumina and silica gel only absorb the microwaves, a variety of reagents supported on solid surfaces15 can also be utilized for organic reactions under very safe conditions using domestic microwave ovens; specialized commercial systems require sealed teflon bombs for solution chemistry. We are currently investigating the use of such methodology for a wide variety of organic reactions. We explored various reaction conditions for this conversion and found that a ratio of 10-l lg of alumina/mmol of the diacetate is required for optimum yield. The reaction on alumina is unique in that a variety of functional groups (see table) are tolerated and high yields are readily obtained which may not be attainable using conventional procedures.*-6 Further, selective deacetylation to p-acetoxybenzaldehyde (entry 3) could be achieved in 30 seconds with out affecting the acetoxy group. Also, the reaction is fast enough that no undesirable byproducts originating from arylaldehyde via a concomitant Cannizzaro reaction16 are observed in the reaction product. Our results are summarized in the table with corresponding yields reported for microwave assisted reactions conducted at -35°C. The deprotection of benzaldehyde diacetate (entry 1) is representative of the Neutral alumina9 (3.6g) is added to a solution of general procedure employed. benzaldehyde diacetate (0.054g. 0.284mmol) dissolved in a minimum amount of dichloromethane (1-2ml) at room temperature and the reaction mixture was thoroughly mixed using a vortex mixer. The adsorbed material is dried in air (beaker) and placed in an alumina bath inside the microwave oven.10 Upon completion of the
3209
Table: Entry
Deprotection
of
benzaldebyde
diacetates
Geminal diacetate
Aryldehyde@)
FH(OCOCH&
CHO
0 ’
1
0
0
2
on c
neutral Time
alumina Yield (%$‘)
40 sec.
98 (65>5
40 Sec.
89(a>1
30 sec. (2Min.Y
97 (98f WC
30 Sec.
94 (92f
30 sec.
88 (85$
0
CH3
C%
$HO
yH(OCOCH&
0
3
0
4 Me0
iKOCH,
OCOCH,
qH(OCOCH&
CHO
0
OMe
0%
0
Me0 CHO
5
NO2
NO2
CHO
40
6
CN
CN
CH=CH-CH(OCOCH3)2
yH=CH-CHO
0
7
Sec.
95
40 Sec.
92
0
~~mduc~ yhibii tuqbmud for
hysical ad spectralproperties inaccord with the assigoedstn~ctures; b) Isolated
y-k&, figuxes ioparenthesesreferto knownyields by other mthods;
deplotectiooof both, the acetoxy1 and acetal gnlup
c) l-ii
and yield
3210
reaction as followed by TLC examination (40 Seconds), the product is extracted into dichloromethane (4x5ml). Removal of the solvent, under reduced pressure afforded essentially quantitative yield of benzaldehyde. In conclusion, we have developed a simple method for the selective deacetylation of geminal diacetate derivatives of arylaldehydes that occurs under mild conditions using inexpensive aluminum oxide. The study also points out the unstable nature of arylaldehyde 1,l -diacetates on common chromatography alumina. REFERENCES AND NOTES 1.
:: 4. 2: :: 9. 10.
11. 12.
13. 14.
15.
16.
Greene,T. W.; Wuts.P. G. M. Protective Groups in Organic Synrhesis, Wiley, New York, 2nd Edn., 1991, ~~185-186 and references cited therein. Liebermann. S. V.; Connor, R. Org. Synrh. CON. Vol., 1943, II. 441. Kochhar. K. S.; Bal, B. S.; Deshpande, R. P.; Rajadhyaksha. S. N.; Pinnick, H. W. J. Org. Chem. 1983.48. 1765. Greene, T. W.; Wuts, P. G. M. Prorective Groups in Organic Synrhesis, Wiley, New York, 2nd Edn., 1991. ~~175-222. Narayan, C.; Padmanabhan, S.; Kabalka, G. W. Tetrahedron Lerr.. 1990.31, 6977. Coteile. P.; Catteau, J. -P. Tetrahedron Lett., 1992,33, 3855. Varma. R. S.: Vanna. M. Tetrahedron Lett.. 1992.33. 5937. Varma; R. S:; Varma, M.; Chatterjee, A. i. Unpublished observations. Aluminum oxide [80-200 mesh, for chromatographic analysis (Fisher, Cat. No. A 540-500)) was used as received. For a critical evaluation of activation process by microwaves see: Laurent, R.; Laporterie, A.; Dubac. J.; Berlan, J.; Lefeuvre, Is.; Audhuy. M. J. Org. Chem. 1992,57. 7099. The temperature of the alumina supporting the benzaldehyde diacetates was found to be -35OC after 30 seconds of irradiation in an alumina bath (heat sink) inside a Sears Kenmore microwave Similar yields of the products are oven equipped with a turntable at full power (800Watts). obtained using alternate mode of heating (conventional oven or oil bath at 35OC). For recent reviews on Microwave Assisted Chemical Reactions see Abramovich. R. A. Org. Prep. Proced. Ink, 1991.23, 683; Mingos. D. M. P.; Baghurst, D.R. Chem. Sot. Rev..1991.20, 1. a) Gedye. R.; Smith, F.; Westaway, K.; Ali. H.; Baldisera, L.; Laberge, L.; Rousell, J. Tetrahedron Lett.. 1986.27. 279. b) Giguerc, R. J.; Bray, T. L.; Duncan, S. M.; Majetich, G. Tetrahedron Lerr.. 1986,27, 4945. c) Giguere, R. J.; Namen. A. M.; Lopez, B. 0.; Arepally. A.; Ramos, D. E.; Majetich, G.; 6553. Defrauw, J. Terruhedron Lett., 1987.28, d) Bose, A. K.; Manhas, M. S.; Ghosh, M.; Raju, V. S.; Tabei. K.; Urbanczyk-Lipkowska, 2. Heterocycles. 1990.30, 741. e) Bose, A. K.; Manhas, M. S.; Ghosh. M.; Shah, M.; Raju, V. S.; Bari. S. S.; Nawaz, S. N.; Banik, B. K.; Chaudhary, A. G.; Barakat. K. J. 1. Org. Chem. 1991,56, 6968. f) Banik, B. K.; Manhas, M. S.; Kaluza. Z.; Barakat. K. J.; Bose, A. K. Tetrahedron Left.. 1992,33, 3603. Bram, G.; Loupy, A.; Majdoub, M.; Gutierrez, E.; Ruiz-Hitzky. E. Tetrahedron, 1990,46, 5167. a) Benalloum. A.; Labiad, B.; Villemin. D. J. Chem. Sot. Chem. Commun.. 1989, 386. b) Villemin, D.; Labiad, B.; Guhilal. Y. Chem. Ind. (London) 1989, 607. c) Villemin, D.; Labiad, B. Synth. Commun., 1990,20, 3333 and 3325. d) Villemin. D.; Benalloum, A. Synch. Commun., 1991,21, I and 63. e) Villemin. D.; Lalaoui. M.; Benalloum, A. Chem. Ind. (London) 1991, 176. gor leading reviews pertinent to organic reactions on solid supports see: a) Posner. G. H. Anaew. Chem. Inr. Ed. Enal.. 1978,17. 487. bj McKillop, A.; Young. D.W. Synthesis, lg79, 401; and 481. c) Cornellis, A.; Laszlo. P. Synthesis, 1985, 909. d) Laszlo. P. Act. Chem. Res., 1986,19, 121. e) Laszlo, P.; Cornellis. A. Aldrichimica Acta, 1988,21, 97. Varma. R. S.; Vanna, M. Unpublished observations.
(Received in
USA 16 February 1993)