Zinc(0)/dimethylformamide-mediated synthesis of symmetrical carboxylic anhydrides from acid chlorides

Article abstract of DOI:10.1016/j.tetlet.2008.06.073

The high yielding synthesis of symmetrical carboxylic anhydrides from acid chlorides mediated by zinc dust in the presence of dimethylformamide is presented. A mechanism involving the reductive insertion of zinc(0) into the C-Cl bond of a Vilsmeier-type iminium intermediate as the crucial step is also proposed.

Full text of DOI:10.1016/j.tetlet.2008.06.073

Tetrahedron Letters 49 (2008) 5322–5323
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Zinc(0)/dimethylformamide-mediated synthesis of symmetrical carboxylic
anhydrides from acid chlorides
a,b,
a,b
Audrey Serieys a, Candice Botuha a,b, Fabrice Chemla a,b, , Franck Ferreira
, Alejandro Pérez-Luna
*
*
a UPMC Univ Paris 06, UMR 7611, Laboratoire de Chimie Organique, Institut de Chimie Moléculaire (FR 2769), case 183, 4 place Jussieu, F–75005 Paris, France
b CNRS, UMR 7611, Laboratoire de Chimie Organique, Institut de Chimie Moléculaire (FR 2769), case 183, 4 place Jussieu, F–75005 Paris, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The high yielding synthesis of symmetrical carboxylic anhydrides from acid chlorides mediated by zinc
dust in the presence of dimethylformamide is presented. A mechanism involving the reductive insertion
of zinc(0) into the C–Cl bond of a Vilsmeier-type iminium intermediate as the crucial step is also
proposed.
Received 4 June 2008
Accepted 16 June 2008
Available online 19 June 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Carbenoids
Carboxylic anhydrides
Reductive insertion
Vilsmeier iminiums
Zinc
A panoply of methods has been reported in the literature for the
synthesis of carboxylic anhydrides.1 Generally, these are prepared
by dehydration of carboxylic acids with powerful acylating or
dehydrating agents. For instance, among the very recent
publications thionyl chloride,2 sulfonyl chlorides,3 phosgene equiv-
alents,4 phophoranes,5 pyridazin-3(2H)-ones,6 imidazolinium chlo-
rides,7 dinitrogen tetroxide,8 1,3,5-triazines,9 trichloroacetonitrile/
triphenylphosphine,10 and carbodiimides11 have been used. Alter-
natively, carboxylic anhydrides can be prepared by the reaction
of acid chlorides with carboxylates,12 or by the direct reaction of
Table 1
Zinc(0)/dimethylformamide-mediated conversion of acid chlorides 1a–j into carbox-
ylic anhydrides 2a–j
Zn(0) (0.55 equiv.)
DMF (2 equiv.)
O
O
O
R
Cl
R
O
R
pentane
0 ºC to 20 ºC
1a–j
2a–j
Entry
R
Anhydridea
t (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
Pent
i-Bu
t-Bu
Cyclopropyl
Cyclobutyl
Cyclopentyl
Cyclohexyl
C6H5
2a
2b
2c
2d
2e
2f
2g
2h
2i
20
20
16
3
2
2
2
2
2
2
71
69
89
77
84
66
92
75
67
95
acid chlorides with carboxylic acids in the presence of a base,13
a
solid-phase 4-vinylpyridine co-polymer,13c a polymer-supported
cobalt phosphine complex,13d and palladium(II) or cobalt(II) chlo-
rides.14 Carboxylic anhydrides have also been recently prepared
from acid chlorides by reaction with a base and water,13c,15 under
ultrasound basic media,16 and under basic phase-transfer condi-
tions using ammonium chlorides.17
4-MeOC6H4
4-ClC6H4
10
2j
In this Letter, we would like to report the zinc(0)/dimethylform-
amide-triggered preparation of various symmetrical carboxylic
anhydrides from the corresponding acid chlorides. Under the opti-
mized conditions, acid chlorides 1a–j (1 equiv) were added drop-
wise at 0°C to a stirred suspension of zinc dust (0.55 equiv) in a
mixture of anhydrous dimethylformamide (2 equiv) and pentane
(Table 1).18,19 The resulting suspension, with a clear colorless super-
natant, was allowed to warm to 20 °C. It was then maintained under
a
All new compounds were fully characterized by IR, 1H, and 13C NMR.
Yields in pure symmetrical carboxylic anhydrides.
b
vigorous stirring at this temperature until the disappearance of all
the zinc (2–20 h) and the formation of a dark orange gummy mix-
ture. In all the cases, symmetrical carboxylic anhydrides 2a–j were
obtained in good to excellent yields (66–95%) as analytically pure
products after trituration of the dark orange gum with 3% Et2O in
pentaneandfiltrationof thereactionmixturethroughflashsilicagel.
Interestingly, both zinc and dimethylformamide were demon-
strated to play a crucial role in this reaction, since no reaction
* Corresponding authors. Tel.: +33 1 44 27 55 71; fax: +33 1 44 27 75 67 (F.F.).
E-mail addresses: fabrice.chemla@upmc.fr (F. Chemla), franck.ferreira@upmc.fr
(F. Ferreira).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.06.073

A. Serieys et al. / Tetrahedron Letters 49 (2008) 5322–5323
5323
mechanism, further studies will be undertaken to prove the forma-
tion of carbenoid 4. The extension of this method to the synthesis
of unsymmetrical carboxylic anhydrides is currently under investi-
gations in our group and will be reported in due course.
N
N
R
Cl
R
O
H
O
O
H
1
O
O
Cl
Cl
References and notes
1. Ogliaruso, M. A.; Wolfe, J. F. Synthesis of Carboxylic Acids, Esters and Their
Derivatives; John Wiley & Sons: New York, 1991; pp 198.
O
O
Zn(0)
Cl
N
2. Kazemi, F.; Kiasat, R. Phosphorous, Sulfur, and Silicon 2003, 178, 2287.
3. Kazemi, F.; Sharghi, H.; Nasseri, M. A. Synthesis 2004, 205.
4. Kocz, R.; Roestamadji, J.; Mobashery, S. J. Org. Chem 1994, 59, 2913.
5. Kawamura, Y.; Sato, Y.; Horie, T.; Tsukayama, M. Tetrahedron Lett. 1997, 38,
7893.
6. (a) Park, Y.-D.; Kim, J.-J.; Kim, H.-K.; Cho, S.-D.; Kang, Y.-J.; Park, K. H.; Lee, S.-G.;
Yoon, Y.-J. Synth. Commun. 2005, 35, 371; (b) Kim, J.; Park, Y.-D. ; Lee, W. S.;
Cho, S.-D. ; Yoon, Y.-J. Synthesis 2003, 1517.
N
O
O
R
R
H
ClZn
H
3
4
O
R
O
1
carbenoidic
decomposition
7. Isobe, T.; Ishikawa, T. J. Org. Chem. 1999, 64, 6984.
8. Kim, Y. H.; Kim, K.; Park, Y. J. Tetrahedron Lett. 1990, 31, 3893.
9. Kamiñski, Z. J.; Kolesiñska, B.; Malgorzata, M. Synth. Commun. 2004, 34, 3349.
10. Kim, J.; Jang, D. O. Synth. Commun. 2001, 31, 395.
11. Clarke, P. A.; Kayaleh, N. E.; Smith, M. A.; Baker, J. R.; Bird, S. J.; Chan, C. J. Org.
Chem. 2002, 67, 5226.
12. (a) Hajipour, A. R.; Mazloumi, Gh. Synth. Commun. 2002, 32, 23; (b) Liang, Y.;
Jwo, J.-J. J. Mol. Catal. A 2001, 170, 57; (c) Ferris, A. F.; Emmons, W. D. J. Am.
Chem. Soc. 1953, 75, 232; (d) Pasha, M. A.; Rizwana, S. Indian J. Chem. Sect. B
2005, 44, 420.
O
2
R
R
Scheme 1. Postulated mechanism for the zinc(0)/dimethylformamide-mediated
formation of carboxylic anhydrides from acid chlorides.
13. (a) Fukuoka, S.; Takimoto, S.; Katsuki, T.; Yamaguchi, M. Tetrahedron Lett. 1987,
28, 4711; (b) Rambacher, P.; Mäke, S. Angew. Chem. 1968, 80, 487; (c) Fife, W.
K.; Zhang, Z. Tetrahedron Lett. 1986, 27, 4933; (d) Leadbeater, N. E.; Scott, K. A. J.
Org. Chem. 2000, 65, 4770.
14. (a) Wang, J.-X.; Hu, Y.; Cui, W.-F. Synth. Commun. 1994, 24, 3261; (b) Srivastava,
R. R.; Kabalba, G. W. Tetrahedron Lett. 1992, 33, 593.
occurs without one of these two reagents. In order to explain this,
we have envisioned that the reaction is driven by the zinc(0)-
mediated reduction of a Vilsmeier-type species generated in situ
from acid chlorides 1 and dimethylformamide.20 We have then
postulated that the initial steps of the mechanism might corres-
pond to the activation of 1 equiv of acid chloride 1 through the
nucleophilic attack of dimethylformamide leading to the revers-
ible21 formation of the Vilsmeier-type iminium salt 3 with a
carboxylate anion as the counter ion (Scheme 1).
The fact that no reaction occurs without zinc(0) suggests that
these initial steps are equilibria which are very little displaced
in the sense of the formation of 3. In the following step, the irre-
versible zinc(0)-mediated reduction of iminium salt 3,22,23 result-
ing in the observed disappearance of zinc(0), might give
carbenoid 4 with a carboxylate counter ion. Carbenoid 4 might
then undergo carbenoidic reactions24 resulting in the formation
of the dark orange gum. This reduction, which might drive all
the initial equilibria in the sense of the formation of 4, could be
a zinc insertion analogous to those previously described by one
of us for the preparations of enol esters25 and thiosulfonic
S-esters,26 the key steps of which involve, respectively, the inser-
tion of zinc(0) into the C–Cl bond of acid chlorides and the S–Cl
bond of thiosulfonic acid chlorides. Finally, the corresponding
symmetrical carboxylic anhydride 2 is obtained by the condensa-
tion of the carboxylate counter ion of carbenoid 4 with another
equivalent of acid chloride 1.
15. Dhimitruka, I.; SantaLucia, J., Jr. Org. Lett. 2006, 8, 47.
16. Hu, Y.; Wang, J.-X.; Li, S. Synth. Commun. 1997, 27, 243.
17. (a) Jászay, Z.; Petneházy, I.; Toke, L. Heteroat. Chem. 2004, 15, 447; (b)
Wang, J.-X.; Hu, Y.-L.; Cui, W.-F. J. Chem. Res. (S) 1990, 84; (c) Plusquellec,
D.; Roulleau, F.; Lefeuvre, M.; Brown, E. Tetrahedron 1988, 44, 2471.
18. Typical procedure: Under argon, to
a suspension of zinc dust (360 mg,
5.50 mmol) in pentane (10 mL) and anhydrous DMF (1.55 mL, 20.00 mmol)
was added dropwise at 0 °C the acid chlorides 1a–j (10 mmol). The resulting
mixture was warmed to room temperature and stirred between 2 and 20 h
depending on the acid chloride (see Table 1). The mixture was then filtered
over a pad of flash silica gel (5 Â 3 cm) eluting with 3% Et2O in pentane (500–
700 mL). Removal of the solvents in vacuo furnished the corresponding pure
symmetrical carboxylic anhydrides 2a–j.
19. Data for cyclopentanecarboxylic anhydride 2f: 1H NMR (400 MHz, C6D6) d 1.20–
1.27 (m, 4H), 1.41–1.48 (m, 4H), 1.53–1.60 (m, 4H), 1.77–1.86 (m, 4H), 1.49–
2.57 (m, 2H); 13C NMR (50.3 MHz, C6D6) d 26.5, 30.1, 45.5, 172.8; IR (ATR
diamond) 1740 (s), 1807 (s), 2872 (m), 2956 cmÀ1 (m).
20. For early work concerning the formation of acid halides from carboxylic acids
and imidoyl halides, see: (a) Bosshard, H. H.; Mory, R.; Schmid, M.; Zollinger,
Hch. Helv. Chim. Acta 1959, 42, 1653; (b) Colson, A. Bull. Soc. Chim. Fr. 1897, 17,
59.
21. Barrett, A. G. M.; Braddock, D. C.; James, R. A.; Koike, N.; Procopiu, P. A. J. Org.
Chem. 1998, 63, 6273.
22. For the titanium(0)-mediated reduction of an iminium chloride, see: Betschart,
C.; Seebach, D. Helv. Chim. Acta 1987, 70, 2215.
23. For related reductions of acid cyanides, see: (a) Baek, H. S.; Lee, S. J.; Yoo, B. W.;
Ko, J. J.; Kim, S. H.; Kim, J. H. Tetrahedron Lett. 2000, 41, 8097; (b) Baruah, B.;
Boruah, A.; Prajapati, D.; Sandhu, J. S. Tetrahedron Lett. 1997, 38, 7603.
24. For carbenoids derived from Vilsmeier reagents, see: (a) Cheng, Y.; Goon, S.;
Meth-Cohn, O. J. Chem. Soc., Perkin Trans. 1 1998, 1619; (b) Böhme, H.; Sutoyo,
P. Tetrahedron Lett. 1981, 22, 1671.
25. Chemla, F.; Normant, J. F. Tetrahedron 1997, 53, 17265.
26. (a) Chemla, F.; Karoyan, P. Org. Synth. 2002, 78, 99; (b) Chemla, F. Synlett 1998,
894.
In conclusion, we have disclosed an easy and straightforward
high yielding preparation of various symmetrical carboxylic
anhydrides by reaction of acid chlorides with zinc dust in the pres-
ence of dimethylformamide. In order to confirm the postulated