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Acetic anhydride (Ac2O)

Article in Synlett September 2009

DOI: 10.1055/s-0029-1217816

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SPOTLIGHT 2547

SYNLETT Acetic Anhydride (Ac2O)

Spotlight 291 Compiled by Lucas Villas Bas Hoelz
Lucas V. B. Hoelz was born in Bom Jardim (Brazil), in 1980. He
graduated in Pharmacy (2005) and received his M.Sc. degree in Or-
This feature focuses on a re- ganic Chemistry (2007) from Universidade Federal do Rio de Jan-
agent chosen by a postgradu- eiro (UFRJ). Currently, he is working toward his D.Sc. in
ate, highlighting the uses and Chemistry at the same university under the supervision of Joaquim
preparation of the reagent in F. M. da Silva, Magaly G. Albuquerque and Ricardo B. de Alen-
current research castro. His research focus on the b1-adrenergic receptor, including
the design and synthesis of new selective b-blockers.
LAB 609, Centro de Tecnologia, Bloco A, Instituto de Qumica,
Universidade Federal do Rio de Janeiro, C.P. 68563, CEP 21945-
970, Rio de Janeiro, Brazil
E-mail: lucashoelz@iq.ufrj.br
Introduction Preparation
Acetic anhydride (Ac2O) is a very refractive liquid smell- Ac2O (1) was formerly produced starting from sodium ac-
ing strongly of acetic acid with a boiling point at 139 C.1 etate and acetyl chloride (A). However, nowadays it is
It is a cheap and commercialized reagent widely used in usually prepared from acetic acid dehydration (B,
the synthesis of oxazolones,2 thiohydantoins,3 thioace- Scheme 1).13
tates,4 enamides,5 geminal diacetates,6 thiadiazoles,7 as O O O O
well as in the preparation of carbonyl compounds from + + NaCl
A
imines.8 Further, it is used in acetylations,9 bromina- Cl ONa+ O
tions,10 Grignard reactions,11 and reductive acylations of 1

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nitropyrroles.12 O
800 C
O O
B + H2O
OH O
1

Scheme 1
Abstracts
(A) Sun and Cui described the synthesis of oxazolones from a mix- O
H O
ture of aryl or heteroaryl aldehydes, hippuric acid (2) and anhydrous O N
OH
sodium acetate in Ac2O under microwave irradiation. All reactions O
2
were carried out in a few seconds and provided good yields (49 Ar
N
56%).2 ArCHO
, NaOAc, Ac2O
MW
4956%

(B) According to Reyes and Burgess, the reaction of some amino ac- R O
O
ids (e.g., glycine, alanine, and phenylalanine) with Ac2O and ammo- a R = H, 51%
H2N Ac2O, NH4SCN
nium thiocyanate gave the 1-acetyl-2-thiohydantoins in good yields OH AcN NH b R = Me, 68%
(5171%), respectively.3 100 C, 30 min c R = Bn, 71%
R
S

(C) Nasir Baig and co-workers reported a simple and efficient meth- O
odology to synthesize thioacetates from alkyl halides in good yields [BnEt3N]2MoS4
(8097%). [BnEt3N]2MoS4 and Ac2O are key reagents in this multi- R X + Ac2O MeCN, 27 h, r.t. R S
step tandem reaction process.4 8097%

(D) Benzylic and non-benzylic ketoximes can be successfully con- NOH NHAc
verted into enamides using a mixture of Ac2O and Et3P in toluene.5
Et3P, Ac2O
74%
PhMe, reflux

NOH NHAc

Et3P, Ac2O
54%
PhMe, reflux

SYNLETT 2009, No. 15, pp 25472548xx. 209

Advanced online publication: 27.08.2009
DOI: 10.1055/s-0029-1217816; Art ID: V29709ST
Georg Thieme Verlag Stuttgart New York
2548 SPOTLIGHT

(E) Geminal diacetates can be prepared from aliphatic and aromatic O H

aldehydes in moderate to excellent yields (3693%) by a simple Ac2O, InCl3/Al2O3
OAc
treatment with Ac2O in the presence of InCl3/Al2O3.6 R H 8 min, r.t. R
OAc
3693%

(F) Thiosemicarbazones react with Ac2O under mild conditions to O Me

give thiadiazole compounds in moderate to high yields (4095%).7 H S 4095%
Ar N H N
H N O
N N N + Ac O 6075 C Ar
2
+
N 727 h +N
S
H R N Me
O O N
R = H, Ph O O R

(G) The SDS (sodium dodecyl sulphate) surfactant mediated cleav- R1 N

N R1 O
age of imines to the corresponding carbonyls (aldehydes and ke- R1NHCOMe + O
tones) and acetanilides can be achieved with Ac2O in water in very 8589%
good to excellent yields (8591%).8 9094%
R2
N R3
Ac2O, SDS, H2O R2NHCOMe + R3CHO
9095% 8691%
R4
N Ph OHC
R4NHCOMe + Ph
8693% 8791%

(H) Various alcohols and phenols can be acetylated under solvent-

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free conditions using Ac2O as acylating agent and a catalytic amount catalyst A
of heterogeneous cobalt(II) Salen complex (catalyst A). The prod- ROH + Ac2O ROAc + AcOH
30120 min, 50 C
ucts were prepared under mild conditions, short reaction times, and 9599%
R = Alk, Ar
in high yields (9599%).9

(I) An efficient procedure for the monobromination of activated ar- R1 R1

omatic compounds can be achieved by treatment with KBr in Ac2O
followed by a dropwise addition of nitric acid in Ac2O.10 1) KBr, Ac2O Br
3695%
2) HNO3, Ac2O
R4 R2 R4 R2
R3 R3

(J) 3,5-Bis(trifluoromethyl)phenylmagnesium chloride reacts with CF3

CF3
Ac2O to produce 3,5-bis(trifluoromethyl)acetophenone. The product
is formed within one hour in high yields (8687%).11 Ac2O, THF
8687%
0 C, 1 h
F3C MgCl F3C
O

(K) The reductive acylation of nitropyrroles using a mixture of NO2

Ac2O, acetic acid, and indium powder provided pyrrolylamides in In, AcOH, 60 C
moderate to good yields (4186%).12 N Ac2O, MeOH N O
R R
4186%

References
(1) The Merck Index 14th Ed.; ONeil M. J., Heckelman P. E.,
Koch C. B., Roman K. J., Kenny C. M., DArecca M. R;
Merck Research Laboratories: New York, 2006, 11.
(2) Sun, Y.-F.; Cui, Y.-P. Dyes Pigments 2009, 81, 27.
(3) Reyes, S.; Burgess, K. J. Org. Chem. 2006, 71, 2507.
(4) Baig Nasir, R. B.; Sai Sudhir, V.; Chandrasekaran, S. Synlett
2008, 2684.
(5) Zhao, H.; Vandenbossche, C. P.; Knig, S. G.; Singh, S. P.;
Bakale, R. P. Org. Lett. 2008, 10, 505.
(6) Salavati-Niasari, M.; Hydarzadeh, S. J. Mol. Catal. A:
Chem. 2005, 237, 259??.
(7) Shih, M.-H.; Wu, C.-L. Tetrahedron 2005, 61, 10917.
(8) Das Sharma, S.; Gogoi, P.; Baruah, M.; Konwar, D. Synth.
Commun. 2007, 37, 2473.
(9) Rajabi, F. Tetrahedron Lett. 2009, 50, 395.
(10) Tsoukala, A.; Liguori, L.; Occhipinti, G.; Bjrsvik, H.-R.
Tetrahedron Lett. 2009, 50, 831.
(11) Leazer, J. L. Jr.; Cvetovich, R. Org. Synth. 2005, 82, 115.
(12) Fu, L.; Gribble, G. W. Synthesis 2008, 788.
(13) Faith, Keyes, and Clark's Industrial Chemicals 4th Ed.;
Lowenheim, F. A.; Moran, M. K.; Wiley-Interscience: New
York, 1975, 16.

Synlett 2009, No. 15, 25472548 Thieme Stuttgart New York

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