Indium(I) bromide-mediated dichlorocyanomethylation of carbonyl compounds. The preparation of 2,2-dichloro-3-hydroxynitriles

Article abstract of DOI:10.1016/S0040-4039(01)00833-4

Carbonyl compounds were efficiently transformed into their corresponding 2,2-dichloro-3-hydroxynitrile derivatives by the action of trichloroacetonitrile and indium(I) bromide.

Full text of DOI:10.1016/S0040-4039(01)00833-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4745–4746
Indium(I) bromide-mediated dichlorocyanomethylation of
carbonyl compounds. The preparation of
2,2-dichloro-3-hydroxynitriles
J. A. No´brega,a Simone M. C. Gonc¸alvesa and C. Peppeb,*
aDepartamento de Qu´ımica Fundamental, Universidade Federal de Pernambuco, Recife-PE 50.670-901, Brazil
bLaborato´rio de Materiais Inorgaˆnicos, Departamento de Qu´ımica, Universidade Federal de Santa Maria-RS 97105-900, Brazil
Received 7 May 2001; accepted 16 May 2001
Abstract—Carbonyl compounds were efficiently transformed into their corresponding 2,2-dichloro-3-hydroxynitrile derivatives by
the action of trichloroacetonitrile and indium(I) bromide. © 2001 Elsevier Science Ltd. All rights reserved.
Although indium metal has been employed for CꢀC
bond formation,1 the use of indium(I) compounds, such
as indium(I) halides, remains virtually unexplored. We
have observed the InBr-mediated chemoselective pro-
duction of 2-bromo-3-hydroxynitriles from dibro-
moacetonitrile and carbonyl compounds,2 while the
In-mediated reaction gave low yields of a complex
mixture of products.3 This encouraged us to investigate
indium(I) halides-mediated reactions as an alternative
when the metal-mediated process is not efficient.
Table 1 shows that a variety of carbonyl compounds
were successfully transformed into 2 in good to excel-
lent yields, revealing the generality of the reaction. The
literature registers one attempt to couple carbonyl com-
−
pounds with the CCl2CN nucleophile generated under
the Darzens conditions (sodium methoxide/methanol);
the result is the production of a complex mixture; the
desired products 2 were isolated in low yields for very
few cases.5 We conclude that generation of the
−CCl2CN nucleophile from 1 allows a novel and highly
efficient protocol for the preparation of 2,2-dichloro-3-
hydroxy-acetonitriles, with significant improvements
over previous methodologies.
We report here the dichlorocyanomethylation of car-
bonyl compounds to the corresponding 2,2-dichloro-3-
hydroxynitriles, 2 promoted by InBr (Eq. (1)).4 The
proposed active organoindium species is the intermedi-
ate 1, formed by the oxidative insertion of the mono-
bromide into one of the carbonꢀchlorine bonds of
Cl3CCN. Coupling between 1 and the carbonyl com-
pound, followed by hydrolysis of the indium alcoxide,
leads to 2 (Eq. (1)).
Acknowledgements
J.A.N. would like to thank CNPq for the award of a
scholarship.
(1)
* Corresponding author. E-mail: peppe@quimica.ufsm.br
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00833-4

4746
J. A. No´brega et al. / Tetrahedron Letters 42 (2001) 4745–4746
Table 1. InBr-mediated preparation of 2,2-dichloro-3-hydroxynitriles
Entry
R
R%
Product
Time (h)
Yield (%)
a
b
c
d
e
f
g
h
i
(CH3)2CH
(CH3)3C
(C6H5)2CH
H
H
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
2
2
1.5
2.5
1
1
1
1
1
3
2
2
3
70
68
76
65
90
93
86
85
88
75
73
64
60
(CH2)5
4-Cl-C6H4
H
H
H
H
H
4-O2N-C6H4
4-CH3O-C6H4
C4H3Oa
C6H5CHꢁCH
j
k
l
2-Cyclohexen
2j
2k
2l
C6H5
CH3
C6H5
CH3
COOC2H5
COC6H5
m
2m
a 2-Furaldehyde.
References
tially washed with a saturated solution of NaHCO3 and
brine, dried (Na2SO4), filtered, and evaporated to dryness.
The reaction product 2g was separated by column chro-
matography on silica gel (hexane/ethyl acetate=5/1),
analysed: calcd (%) for C10H9Cl2NO2: C, 48.82; H, 3.66;
N, 5.69. Found: C, 48.80; H, 3.66; N, 5.71 and character-
1. (a) Cintas, P. Synlett 1995, 1087–1096; (b) Li, C. J.; Chan,
T. H. Tetrahedron 1999, 11149–11176.
2. No´brega, J. A.; Gonc¸alves, S. M. C.; Peppe, C. Tetra-
hedron Lett. 2000, 41, 5779–5782.
3. Araki, S.; Hirashita, T.; Shimizu, K.; Ikeda, T.; Butsugan,
Y. Tetrahedron 1996, 52, 2803–2816.
4. A typical procedure involves the addition of CCl3CN (111
mg, 0.76 mmol) to a stirred and cooled (−5°C) suspension
of InBr (150 mg, 0.76 mmol) and p-methoxybenzaldehyde
(0.76 mmol) in tetrahydrofuran (5 mL) under nitrogen.
After the complete consumption of the insoluble InBr, the
reaction was monitored by TLC until complete consump-
tion of the carbonyl compound (see Table 1 for the time
required). The solution obtained was then acidified with
HCl (0.1 M, 5 mL) and the aqueous solution extracted
twice with ethyl acetate (60 mL); the extract was sequen-
1
ised by H NMR (in CDCl3, ppm from TMS): 3.65 (s, 1H,
OH), 3.80 (s, 3H, OCH3), 5.03 (s, 1H, CHOH), 6.90 (d,
2H, J=8.8 Hz, CHar. meta), 7.46 (d, J=8.8 Hz, CHar.
ortho). 13C NMR (in CDCl3, ppm from TMS): 55.29
(OCH3), 73.10 (CCl2CN), 80.68 (CHOH), 113.72 (CHar.
meta), 114.16 (CN), 125.93 (HO(CCl2CN)H-Car ipso),
129.63 (CHar. ortho), 160.77 (CH3O-Car ipso); infrared
spectroscopy (cm−1): 3480 (w OH), 2255 (w CN); and mass
+
’
spectrometry (M =245/247/249 m/e). Yields and other
reaction conditions are given in Table 1. Analytical and
spectroscopic data for 2a–i is available upon request.
5. Coutrot, P. Bull. Soc. Chim. Fr. 1965, 1965–1970.
.