p-METHOXYBENZALDEHYDE 1
p-Methoxybenzaldehyde age at the less-hindered side of the acetal, whereas NaBH3CN/
HCl,4 or NaBH3CN/TFA/DMF11 result in formation of an MPM
ether at the less-hindered alcohol.
CHO
OBn
MeO
BnO O Mp
O
[123-11-5] C8H8O2 (MW 136.16)
MeO O
InChI = 1/C8H8O2/c1-10-8-4-2-7(6-9)3-5-8/h2-6H,1H3 NaBH3CN
NaBH3CN
TMSCl (2)
InChIKey = ZRSNZINYAWTAHE-UHFFFAOYAA
TFA, DMF
MeCN
OBn OBn
(protection of diols as the versatile p-methoxybenzylidene acetal;
BnO OH BnO OMPM
protection of dithiols,1 amines, hydroxy amines,2 and diamines3)
OMPM OH
MeO O MeO O
Alternate Name: p-anisaldehyde.
ć%
Physical Data: bp 248 C; d 1.119 g cm-3.
Form Supplied in: clear liquid; widely available.
Protection of Amines. p-Methoxybenzaldehyde has been
used to protect an amine as the MPM derivative by reductive
amination with Sodium Borohydride.21 It is also used to prepare
Protection of Diols. p-Methoxybenzylidene acetals are
imine derivatives of glucosamines which are used in glycoside
easily prepared from diols by reaction of the aldehyde
couplings.22
in the presence of an acid catalyst such as Hydrogen
Chloride4,5 or Zinc Chloride6. They can also be prepared
from the diol and p-MeOC6H4CH2OMe by oxidation with 2,3-
Dichloro-5,6-dicyano-1,4-benzoquinone (CH2Cl2, rt, 30 min,
1. Kishi, Y.; Fukuyama, T.; Nakatusuka, S., J. Am. Chem. Soc. 1973, 95,
49 82% yield)7 or by acid-catalyzed acetal exchange with p-
6490.
MeOC6H4CH(OMe)2.8 The p-methoxybenzylidene acetal can be
2. Witkop, B.; Patrick, J. P.; Kissman, H. M., Chem. Ber. 1952, 85,
prepared by DDQ oxidation of a p-methoxybenzyl group that has a
949.
neighboring hydroxy function.9 This methodology has been used
3. Weidenhagen, R.; Train, G.; Wegner, H.; Nordstrom, L., Chem. Ber.
to advantage in a number of syntheses.10 12 Reaction of an epox- 1936, 75, 1936.
ide with p-methoxybenzaldehyde in the presence of Tin(IV) Chlo- 4. Serfontain, W. J.; Lourens, G. J.; De Waal, H. L., J. Med. Chem. 1965,
8, 889.
ride results in the formation of the acetal without prior conversion
5. Smith, M.; Rammler, D. H.; Goldberg, I. H.; Khorana, H. G., J. Am.
to the diol (eq 1).13
Chem. Soc. 1962, 84, 430.
6. Hanessian, S.; Kloss, J.; Sugawara, T. In Trends in Synthetic
CHO
Carbohydrate Chemistry; Horton, D.; Hawkins, L. D.; McGarvey, G.
3A MS, SnCl4
+
J., Eds.; ACS Symposium Series 386; American Chemical Society;
CHO
CH2Cl2,  78 °C
O Washington, 1989; p 64.
MeO
7. Oikawa, Y.; Nishi, T.; Yonemitsu, O., Tetrahedron Lett. 1983, 24,
4037.
O
(1)
8. Kloosterman, M.; Slaghek, T.; Hermans, J. P. G.; Van Boom, J. H., Recl.
CHO Trav. Chim. Pays-Bas 1984, 103, 335.
O
9. Oikawa, Y.; Yoshioka, T.; Yonemitsu, O., Tetrahedron Lett. 1982, 23,
MeO
889.
10. Sviridov, A. F.; Ermolenko, M. S.; Yaskunsky, D. V.; Borodkin, V. S.;
Kochetkov, N. K., Tetrahedron Lett. 1987, 28, 3835.
The advantages of the p-methoxybenzylidene acetal are that
11. Yadav, J. S.; Chander, M. C.; Joshi, B. V., Tetrahedron Lett. 1988, 29,
ć%
acid-catalyzed hydrolysis (80% AcOH, 25 C, 10 h, 100% yield) is 2737.
10 times faster than that of the benzylidene group;5 it is cleaved ox- 12. (a) Jones, A. B.; Yamaguchi, M.; Patten, A.; Danishefsky, S. J.; Ragan, J.
A.; Smith, D. B.; Schreiber, S. L., J. Org. Chem. 1989, 54, 17. (b) Smith,
idatively with Cerium(IV) Ammonium Nitrate (MeCN, H2O)14
A. B., III; Hale, K. J.; Laakso, L. M.; Chen, K.; Riera, A., Tetrahedron
and it is relatively stable to Na/NH3.15
Lett. 1989, 30, 6963.
As with the benzylidene group, a variety of methods have been
13. Sturmer, R., Liebigs Ann. Chem. 1991, 311.
developed to effect cleavage of one of the two C O bonds in this
14. Johansson, R.; Samuelsson, B., J. Chem. Soc., Chem. Commun. 1984,
acetal. Cleavage with Diisobutylaluminum Hydride10,16,17 has
201.
proven to be quite selective and is controlled by both electronic
15. Tone, H.; Hikota, M.; Hamada, T.; Nishi, T.; Oikawa, Y.; Yonemitsu, O.,
and steric factors. Oxidative cleavage with DDQ7 results in the
Chem. Pharm. Bull. 1989, 37, 1155.
formation of a mixture of the two possible monobenzoates. In the
16. Evans, D. A.; Kalder, S. W.; Jones, T. K.; Clardy, J.; Stout, T. S., J. Am.
carbohydrate field, selective cleavage to give either the more- or
Chem. Soc. 1990, 112, 7001.
less-substituted derivative is possible with the proper choice of
17. Aicher, T. O.; Buszck, K. R.; Fang, F. G.; Forsyth, C. J.;
reagents (eq 2).4 19 Use of LiAlH4/AlCl3,12 BH3·NMe3/AlCl3,4
Jung, S. H.; Kishi, Y.; Scola, P. M., Tetrahedron Lett. 1992, 33,
BH3·THF, heat,20 or NaBH3CN/TMSCl/MeCN11 results in cleav- 1549.
Avoid Skin Contact with All Reagents
2 p-METHOXYBENZALDEHYDE
18. (a) Johansson, R.; Samuelsson, B., J. Chem. Soc., Perkin Trans. 1 1984, 22. (a) Lucas, R. A.; Dickel, D. F.; Dziemian, R. L.; Ceglowski, M. J.; Hensle,
2371. (b) Garegg, P. J.; Hultberg, H.; Wallin, S., Carbohydr. Res. 1982, B. L.; MacPhillamy, H. B., J. Am. Chem. Soc. 1960, 82, 5688. (b) Mootoo,
108, 97. D. R.; Fraser-Reid, B., Tetrahedron Lett. 1989, 30, 2579. (c) Bergmann,
M.; Zervas, L., Chem. Ber. 1931, 64, 975.
19. Joniak, D.; Kôsíková, B.; Kosáková, L., Collect. Czech. Chem. Commun.
1978, 43, 769.
20. Tsuri, T.; Kamata, S., Tetrahedron Lett. 1985, 26, 5195.
Peter G. M. Wuts
21. Smith, A. B.; III, Rano, T. A.; Chida, N.; Sulikowski, G. A., J. Org.
The Upjohn Company, Kalamazoo, MI, USA
Chem. 1990, 55, 1136.
A list of General Abbreviations appears on the front Endpapers