Y. Kimura et al. / Tetrahedron Letters 53 (2012) 1116–1118
1117
Table 1
Synthetic examples using isolated VR
Entry
1
Materials
Temp (°C)
Time (h)
1
Products
Isolated yield % (GC area %)
HOOC
COOH
COOH
ClOC
COCl
COCl
60
82
84
2
3
60
60
1
3
HOOC
HOOC
ClOC
ClOC
O
O
87a
COOH
COCl
OH
Cl
4
5
rt
rt
1
1
(90)
O
O
OH
Cl
(95.5)
a
After concentration and cooling to 15 °C of 1,4-dioxane to one-quarter volume.
Table 2
Reactions by VR prepared in situ from OPC with DMF
Entry
Materials
F
DMF (equiv)
Temp (°C)
Time (h)
Product
F
Isolated yield % (GC area %)
1
2
CHO
CHO
0.3
9.0
50
50
3
3
CHCl2
(95)
(98)
H5C2
H5C2
CHCl2
OH
Cl
3
4
1.0
9.0
rt
rt
1
(quant)
92
OH
Cl
0.5
H3CO
H3CO
H3C
N
H3C
N
CHO
5
3.0
70
1
84
H3C
H3C
The filtrate containing PA was evaporated in vacuo to precipi-
tate almost pure PA detected by GC–MS,7 which could be reused
as a material for OPC by our method.4
Similarly, 2-chloro-1,3-dimethylimidazolium chloride (DMC)
and N,N,N,N-tetramethylchloroformamidinium chloride (TMC)
were obtained by the reaction of 1,3-dimethyl-2-imidazolidinone
(DMI) and N,N,N,N-tetramethylurea (TMU) with OPC at
100–140 °C, respectively.8 DMC and TMC are efficient dehydrat-
ing reagents9,10 and useful intermediates for powerful fluorinat-
ing reagents11 (Scheme 3).
We next attempted some synthetic transformations by the
above isolated VR or VR prepared in situ as shown in Tables 1
and 2.14 Thus, [1,10-biphenyl]-4,40-dicarboxylic acid, napthalene-
2,6-dicarboxylic acid, and 4,40-oxydibenzoic acid were found to
undergo rapid and efficient conversion to the corresponding acid
chlorides by treatment with the isolated VR in dioxane at 60 °C
(Table 1 entries 1–3). Aliphatic carboxylic acid such as octanoic
acid could be converted to octanoyl chloride in DMF (entry 4).
Benzyl chloride could be produced from benzyl alcohol in high
yield (entry 5).15
The synthetic utility of VR was further demonstrated (Table 2)
by the successful deoxychlorination of 4-fluorobenzaldehyde (en-
try 1), 4-ethylbenzaldehyde (entry 2) and alcohols (entries 3–4),
and the formylation of 4-dimethylaminobenzene (entry 5) using
VR prepared in situ.16
Acknowledgments
We are grateful to Messrs. Yuji Kaneko, and Etsushi Nishikawa
(Research Institute, Ihara Chemical Industry Co., Ltd.) for NMR
analysis.
References and notes
1. (a) Vilsmeier, A.; Haack, A. Ber. Dtsch. Chem. Ges. 1927, 60B, 119–122; (b)
Marson, C. M. Tetrahedron 1992, 48, 3659–3726.
2. Fieser and Fieser’s, Reagents for Organic Synthesis; John Wiley and Sons, New
Jersey. 1,284 286 2,154 3,116 4,186 5,251 6,220 7,422 8,186 9,514 12,564,
13,341 16,144 20,153 21,131 22,188 250 23,168.
3. Reaction of DMF with pivaloyl chloride was recently reported whereby
(Chloromethylene)dimethyliminium chloride may be formed in situ Dubey,
A.; Upadhyay, A. K.; Kumar, P. Tetrahedron Lett. 2010, 51, 744–746.
4. Kimura, Y et al. W.O. Patent 2010/013684, 2010; Chem. Abstr. 2010, 152, 214950.
5. Solubility of phthalic anhydride in 1,4-dioxane, tetrahydrofuran, or 1,2-
dimethoxyethane at room temperature was about 1 g PA/5 mL solvent, while
solubility of VR was 1 g VR/350–450 mL solvent. t-butylmethyl ether,
cyclopentylmethyl ether, and toluene need more than 10 times volume to
dissolve PA at room temperature.
6. (Chloromethylene)dimethyliminium chloride (VR) is very hygroscopic, so it
could not be handled in moist air.
7. Preparation of VR: To a mixture of N,N-dimethylformamide 30 g (0.41 mol) in
1,4-dioxane (330 mL) was added OPC 90 g (0.44 mol) at room temperature, and
then the whole mixture was stirred at 40 °C for 3 h. The white precipitates of
(chloromethylene)dimethyliminium chloride (VR) that formed were collected
by filtration under
(100 mL ꢀ 2) and hexane (100 mL), and dried under reduced pressure [41 g
(78% yield), mp 126 °C (decomp) (lit. 12 132 °C); IR (CHCl3); 1699 (C@N+) cmꢁ1
1H NMR (300 MHz, CDCl3) d 11.00 (s, 1H, CH), 3.98 (s, 6H, CH3)]. The spectrum
data were identical with those of the commercial
a nitrogen atmosphere, washed with 1,4-dioxane
;
The ready availability, low cost, and high activity of VR pre-
pared from OPC with DMF, and the operation of the overall pro-
cess hold promise for the industrial scale preparation of acid
chlorides, alkyl chlorides, and some aromatic aldehydes.
(chloromethylene)dimethyliminium chloride supplied by Aldrich Chemical
Co. N,N-dimethylformamide was also detected in the both the NMR spectra,