Electrochemical oxidation of 2,2,2-trifluoroethanol to trifluoroacetaldehyde 2,2,2-trifluoroethyl hemiacetal

Article abstract of DOI:10.1016/S0040-4039(00)00880-7

Electrochemical oxidation of 2,2,2-trifluoroethanol (1) gave trifluoroacetaldehyde 2,2,2-trifluoroethyl hemiacetal (2b), which was more reactive than commercially available trifluoroacetaldehyde ethyl hemi-acetal (2a). The high reactivity of 2b was utiliz

Full text of DOI:10.1016/S0040-4039(00)00880-7

Tetrahedron Letters 41 (2000) 5873±5876
Electrochemical oxidation of 2,2,2-tri¯uoroethanol to
tri¯uoroacetaldehyde 2,2,2-tri¯uoroethyl hemiacetal
Kimihiro Shirai, Osamu Onomura, Toshihide Maki and Yoshihiro Matsumura*
Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
Received 5 April 2000; revised 15 May 2000; accepted 26 May 2000
Abstract
Electrochemical oxidation of 2,2,2-tri¯uoroethanol (1) gave tri¯uoroacetaldehyde 2,2,2-tri¯uoroethyl
hemiacetal (2b), which was more reactive than commercially available tri¯uoroacetaldehyde ethyl hemi-
acetal (2a). The high reactivity of 2b was utilized, for example, for the facile synthesis of 1-furyl-2,2,2-tri-
¯
uoroethanol (4) from furan. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: electrochemistry; oxidation; alcohols; ¯uorine and compounds.
Tri¯uoroacetaldehyde (1) is an important source material to prepare compounds having a tri-
1
¯uoromethyl group, while commercially available tri¯uoroacetaldehyde ethyl hemiacetal (2a)
has often been used as an equivalent of 1 because of the troublesome handling of 1 due to its low
2
3
boiling point. The preparation methods of 1 so far reported, however, have been rather limited:
4
2
(
(
i) Sn/Ru-catalyzed hydrogenation of tri¯uoroacetic acid; (ii) reduction of tri¯uoroacetic acid;
5
6
iii) reduction of tri¯uoroacetic acid esters; (iv) reduction of tri¯uoroacetonitrile; (v) oxidation
7
8
of tri¯uoropropane; and (vi) ¯uorination of chloral with hydrogen ¯uoride. Although all of
these methods consist of a number of simple steps, most of them are not always appropriate for
large-scale production, except method (i); furthermore, some starting compounds are not easily
ꢀ
4
available. Also, method (i) must be carried out under severe reaction conditions (400±450 C).
We report herein a new facile method for the preparation of tri¯uoroacetaldehyde 2,2,2-tri-
uoroethyl hemiacetal (2b) starting from 2,2,2-tri¯uoroethanol (3) (Eq. (1)) and also present data
¯
that shows that 2b is superior to 2a as an equivalent of 1.
*
Corresponding author.
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00880-7

5
874
ꢁ1†
Our method uses an electrochemical oxidation of 3 for the preparation of 2b. Thus, into a cell
equipped with platinum plate electrodes (1Â2 cm) without a diaphragm was charged a solution of
(10 g, 0.1 mol) containing Et NBF (1.08 g, 5.0 mmol) as a supporting electrolyte. The solution
3
4
4
ꢀ
was electrolyzed with a constant current (0.2 A) at ^10 C. The terminal voltage was 25±30 V
through the electrolysis. After 1.5 F/mol of electricity was passed, the solution was poured onto
pentane:ether (1:1 (v/v), 100 mL) and then the organic portion was washed with water three
times. The yield of 2b was more than 70%.9
2
,2,2-Tri¯uoroethyl hemiacetal 2b seemed to be producible from ethyl hemiacetal 2a. However,
the transformation of 2a to 2b proved dicult. Namely, an addition of 2a to a solution of an
excess amount (10 equiv.) of 2,2,2-tri¯uoroethanol (3) containing a catalytic amount of p-TsOH
or sodium hydride resulted in the 72% recovery of 2a with 28% formation of 2b (Eq. (2)). On the
other hand, the transformation of 2b to 2a was easily achieved (Eq. (3)).
ꢁ
2†
3†
ꢁ
With 2b in hand using the electrochemical method, we developed its utilization in organic
synthesis. It was used as an equivalent of 1 as described in Eqs. (4) and (5), in which 2b showed
a reactivity similar to 2a.
10
ꢁ
4†
5†
ꢁ
The synthetic advantage of 2b over 2a was shown by an acid-catalyzed a-hydroxy-tri¯uoro-
ethylation of furan leading to 1-furyl-2,2,2-tri¯uoroethanol (4)11 (Eq. (6)).
ꢁ6†
This type of reaction was ®rst presumed to be achievable by using 2a, but the reaction of 2a
with furan in the presence of p-TsOH resulted in the formation of many unidenti®ed products

5
875
together with a trace amount of 4. Fortunately, on the other hand, the reaction of 2b with furan
in the presence of p-TsOH a€orded 4 in 60% yield. A similar satisfactory result was also obtained
by using an electrolyzed solution of 3 without isolation of 2b.
The unsuccessful result in the case of 2a can be explained as follows. It has been known that an
ethoxyl group is less reactive than a tri¯uoroethoxyl group as a leaving group. Thus, an acid
12
0
treatment of 2a may give two kinds of cationic intermediates 5 and 5 which lead to the formation
of complex products (Scheme 1). In contrast with 2a, an acid-catalyzed reaction of 2b might
a€ord mainly 4 because of the feasibility of the tri¯uoroethoxyl group leaving from 2b.
Another example indicating a di€erence in the reactivity between 2a and 2b was the reaction
with ethyl 3-aminocrotonate (6) to give hydroxy-tri¯uoromethylated product 713 (Eq. (7)). The
reaction of 2b with 6 proceeded faster than that of 2a with 6 as shown in Fig. 1.
ꢁ7†
Figure 1. Reaction of 2a,b with 6

5
876
The high reactivity of 2b in comparison with 2a in this type of reaction can also be explained in
terms of the ability of the tri¯uoroethoxyl group as a leaving group.
In summary, we have found a new preparation method of 2b using an electrochemical oxidation
of 3. The method is very convenient not only for large-scale production but also for laboratory-
scale experimentation since the starting compound 3 is easily available and the electrochemical
method allows us to achieve the aimed oxidation without any oxidizing reagent. Also, we have
demonstrated the novel reactivity of 2b which could be utilized as an equivalent of 1 in a di€erent
way from the corresponding ethyl derivative 2a. Further utilization of 2b for the synthesis of tri-
¯uoromethyl-containing compounds is now under investigation.
References
1
. (a) Patel, D. V.; Rielly-Gauvin, K.; Ryono, D. Tetrahedron Lett. 1988, 29, 4665±4668. (b) Iseki, K.; Oishi, S.;
Kobayashi, Y. Tetrahedron 1996, 52, 71±84. (c) Mikami, K.; Yajima, T.; Takasaki, T.; Matsukawa, S.; Terada,
M.; Uchimaru, T.; Maruta, M. Tetrahedron 1996, 52, 85±98. (d) Iseki, K.; Oishi, S.; Kobayashi, Y. Chem. Pharm.
Bull. 1996, 44, 2003±2008. (e) Abouabdellah, A.; Begre, J.-P.; Bonnet-Delpon, D.; Nga, T. T. T. J. Org. Chem.
 Â
1
997, 62, 8826±8833.
. Husted, D. H.; Ahlbrecht, A. H. J. Am. Chem. Soc. 1952, 74, 5422±5426.
. Ishii, A.; Takeda, Y. J. Synth. Org. Chem., Jpn. 1999, 57, 898±899.
. Ferreo, R. M.; Jacquot, R. Eur. Pat. EP 539274, 1993 (Chem. Abstr. 1993, 119, 138494).
. (a) Pierce, O. R.; Kane, T. G. J. Am. Chem. Soc. 1954, 76, 300±301. (b) Lee, S. A. Eur. Pat. EP 516311, 1992
2
3
4
5
(Chem. Abstr. 1993, 118, 80496).
6
7
8
9
. Henne, A. L.; Pelley, R. L.; Alm, R. M. J. Am. Chem. Soc. 1950, 72, 3370±3371.
. Shechter, H.; Conrad, F. J. Am. Chem. Soc. 1950, 72, 3371±3373.
. Siegemung, G. Ger. Pat. DE 2139211, 1973 (Chem. Abstr. 1973, 78, 110577m).
. The product 2b contaminated with a small amount of 3 (ꢂ5%) was obtained. The obtained 2b could be utilized
without puri®cation for further synthetic use. The NMR and IR spectra of the obtained 2b are as follows: IR ꢀmax
:
^
1 1
3
400, 1287, 1125, 1173, 1121, 841 cm ; H NMR (300 MHz, CDCl ): ꢁ 4.01 (q, 2H, J=5.5 Hz), 4.99 (q, 1H,
3
J=3.4 Hz). The identi®cation of 2b was achieved by its conversion to the benzoylated compound: IR ꢀmax: 3069,
^1 1
2
967, 1752, 1603, 1455, 1402, 1362, 1302, 1219, 1136, 1082, 1069, 1030, 1001, 963, 918, 716, 687, 664, 613 cm ; H
NMR (300 MHz, CDCl ): ꢁ 4.18±4.41 (m, 2H), 6.26 (q, 1H, J=3.6 Hz), 7.46±7.58 (m, 2H), 7.62±7.74 (m, 1H),
3
1
3
8
3
.06±8.16 (m, 2H). C NMR (75 MHz, CDCl ): ꢁ 67.1 (q, J=35.7 Hz), 91.4 (q, J=37.6 Hz), 120.6 (q, J=279.2
8 6 3
Hz), 122.9 (q, J=276.6 Hz), 127.6, 128.9, 130.5, 134.7, 165.2. Anal. calcd for C11H F O : C, 43.72; H, 2.67. Found
C, 43.50; H, 2.73.
0. Gong, Y.; Kato, K.; Kimoto, H. Synlett 1999, 1403±1404.
1. Tri¯uoromethylation of furfural has been known for the synthesis of 4. (a) Watanabe, S.; Fujita, T.; Sakamoto, M.;
Mino, Y.; Kitazume, T. J. Fluorine Chem. 1995, 73, 21±26. (b) Yokoyama, Y.; Mochida, K. Synlett 1996, 1191±
1
1
1
2. Matsumura, Y.; Satoh, Y.; Onomura, O.; Maki, T. J. Org. Chem. 2000, 65, 1549±1551.
192.
1
1
^1 1
3. Compound 7: IR ꢀmax: 3420, 2986, 1721, 1613, 1518, 1269, 1240, 1161, 1127 cm ; H NMR (300 MHz, CDCl
3
): ꢁ
.32 (t, 3H, J=7.1 Hz), 2.06 (s, 3H), 3.0 (br s, 1H), 4.15±4.32 (m, 2H), 4.60±4.75 (br s, 1H), 5.0 (br s, 1H), 8.7 (br s,
H).
1
1