9

Albright-Goldman Oxidation

A. GENERAL DESCRIPTION OF THE REACTION

This reaction was first reported by Albright and Goldman from the American Cyanamid
Company in 1965.1 It is a mild conversion of primary and secondary alcohols into cor-
responding aldehydes and ketones using the mixture of dimethyl sulfoxide and acetic
anhydride as the oxidant. This reaction is particularly useful for the oxidation of the steri-
cally hindered hydroxyl groups. In general, the oxidation is carried out by allowing a mixture
of 1 mmol primary or secondary alcohol, 3 mL DMSO, and 2 mL (20 mmol excess) acetic
anhydride to stand at room temperature for 18–24 h.2

B. GENERAL REACTION SCHEME

OH O
DMSO/Ac2O

R R′ R R′
(R′ = H, alkyl or aryl)

Comprehensive Organic Name Reactions and Reagents, by Zerong Wang

Copyright © 2010 John Wiley & Sons, Inc.

33
34 ALBRIGHT-GOLDMAN OXIDATION

C. PROPOSED MECHANISMS

Displayed here is a simple illustration of this reaction.

O
O O
O O
O
O
Ac2O
O
RR′CHOH AcO–
O O S
S O
–
AcO R
S S
H O
R´ H

O O

O O O
S S AcO + S + + AcOH
R O
R R′
H O O O

R′ H O
R H O
R′

D. MODIFICATION

This reaction has been modified using the mixture of DMSO and one of the following
reagents: benzoic anhydride, polyphosphoric acid, and phosphorus pentoxide. However, it
seems that the mixture of acetic anhydride and DMSO is still the best combination for this
reaction.3

E. APPLICATIONS

This reaction has been used to convert primary and secondary alcohols into corresponding
aldehydes and ketones, especially for the sterically hindered alcohols. This reaction has been
commonly used in carbohydrate transformation. However, for the oxidation of phenols with
DMSO/Ac2 O, the thiomethoxymethylation of the corresponding phenols occurs.4

F. RELATED REACTIONS

Other oxidation reactions using DMSO as an oxidant include the Pfitzner-Moffatt

Oxidation (DMSO/dicyclohexylcarbodiimide), Swern oxidation (DMSO/oxalyl chloride
or trifluoroacetic anhydride), Onodera oxidation (DMSO/phosphorus pentoxide), Parikh-
Doering Oxidation (DMSO/pyridine-sulfur trioxide), Corey-Kim Oxidation (dimethyl
sulfide/N-chlorosuccinimide), and Liu oxidation (DMSO/phenyl dichlorophosphate).
 CITED EXPERIMENTAL EXAMPLES 35

G. CITED EXPERIMENTAL EXAMPLES

N
H H DMSO/Ac2O
H

MeO2C

1 OH

N N
H H H H
H + H

H H

MeO2C MeO2C

O O CH2SCH3
2 3
84% 0.7%
Reference 3.

To a mixture of 886 g yohimbine (1) and 7.55 L dry dimethyl sulfoxide was added
5.05 L acetic anhydride. The mixture was stirred at room temperature for 18 h, then diluted
with 16.8 L ethanol, stirred for 1 h, and mixed with 4.2 L water. Concentrated ammonium
hydroxide (11 L) was added while maintaining the temperature at 15–30◦ C by cooling. The
mixture was then diluted with 16.8 L water. Filtration gave a solid that was washed with
water and dried to give 818 g (93%) of tan crystals, with a m.p. of 248–250◦ C (dec.). A
slurry of this tan crystal was formed twice with 4 L ethanol, and 742 g methyl yohimban-
17-one 16α-carboxylate (2) was obtained by filtration, in a yield of 84%, m.p. 253–254◦ C
(dec.).
The filtrate from the first slurry with 4 L ethanol was concentrated to give a dark colored
gum. The gum was dissolved in chloroform-acetone-ethanol (6:3:1) and filtered through
synthetic magnesia silica gel. The filter cake was washed with acetone, and the combined
filtrates were concentrated to give 40 g of dark gum. The gum (20 g) was chromatographed
on a column of 300 g silica gel using chloroform-ethanol (99.3:0.7) as the eluting solvent
and 250-mL cuts were collected. Evaporation of cuts 5–11 gave the product as a glass.
The combined glass from two column purifications was crystallized from methanol to
give 6.95 g (0.7%) methyl 17α-[(methylthio)methoxy]yohimban-l6α-carboxylate (3) as tan
crystals, m.p. 195–198◦ C.
36 ALBRIGHT-GOLDMAN OXIDATION

OBn OBn OBn OBn

O O
DMSO/Ac 2O
HO O O
OBn OBn
O

OMe OMe

Reference 5.

To a mixture of 18 mL anhydrous DMSO and 15 mL acetic anhydride was added 2.93 g

p-methoxyphenyl-2,4,6-tri-O-benzyl-β-d-galactopyranoside. The solution was stirred
under nitrogen for 12 h at room temperature, then acetic anhydride was evaporated and
the remaining solution was diluted with water and extracted with chloroform. The com-
bined organic layers were washed with H2 O, dried over anhydrous Na2 SO4 , filtered, and
concentrated under reduced pressure. The residue was purified by chromatography on silica
gel using EtOAc/petroleum ether (1:3) as the eluent to give 2.45 g p-methoxyphenyl-2,4,6-
tri-O-benzyl-β-d-xylo-hex-3-ulopyranoside as a light yellow solid, in a yield of 84%, m.p.
85–87◦ C; α23 ◦
D = −52 (c = 1, CHCl3 ).

Other references related to the Albright-Goldman oxidation are cited in the literature.6

H. REFERENCES

1. Albright, J. D. and Goldman, L., J. Org. Chem., 1965, 30, 1107.

2. Albright, J. D. and Goldman, L., J. Am. Chem. Soc., 1965, 87, 4214.
3. Albright, J. D. and Goldman, L., J. Am. Chem. Soc., 1967, 89, 2416.
4. Hayashi, Y. and Oda, R., J. Org. Chem., 1967, 32, 457.
5. Bazin, H. G.; Du, Y. G.; Polat, T. and Linhardt, R., J. Org. Chem., 1999, 64,7254.
6. (a) Dodd, D. S. and Oehlschlager, A. C., J. Org. Chem., 1992, 57, 2794. (b) Tadanier, J.; Martin,
J, R.; Goldstein, A. W. and Hirner, E. A., J. Org. Chem., 1978, 43, 2351. (c) Wikholm, R. J. and
Moore, H. W., J. Am. Chem. Soc., 1972, 94, 6152. (d) Dmitriev, B. A.; Kost, A. A. and Kochetkov,
N. K., Izv. Akad. Nauk SSSR, Ser. Khim., 1969, 903. (e) Gabriel, T.; Chen, W. Y. and Nussbaum,
A. L., J. Am. Chem. Soc., 1968, 90, 6833. (f) Sweat, F. W. and Epstein, W. W., J. Org. Chem.,
1967, 32, 835. (g) Torssell, K., Tetrahedron Lett., 1966, 4445.