Effect of alkali metal cations on the synthesis of 4,5,6,7-tetrahydroindole and its vinyl derivative from cyclohexanone oxime and acetylene in MOH-DMSO systems

Full text of DOI:10.1134/S0012500808110025

ISSN 0012-5008, Doklady Chemistry, 2008, Vol. 423, Part 1, pp. 273–275. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © A.I. Mikhaleva, E.Yu. Shmidt, N.I. Protsuk, N.V. Zorina, B.A. Trofimov, 2008, published in Doklady Akademii Nauk, 2008, Vol. 423, No. 1, pp. 66–68.
CHEMISTRY
Effect of Alkali Metal Cations on the Synthesis
of 4,5,6,7-Tetrahydroindole and Its Vinyl Derivative
from Cyclohexanone Oxime and Acetylene
in MOH–DMSO Systems
A. I. Mikhaleva, E. Yu. Shmidt, N. I. Protsuk, N. V. Zorina, and Academician B. A. Trofimov
Received April 29, 2008
DOI: 10.1134/S0012500808110025
In recent years, the synthesis of 4,5,6,7-tetrahy- example of pyrrole synthesis by the Trofimov reac-
droindole (THI) and N-vinyl-4,5,6,7-tetrahydroin- tion [1–4], has attracted the attention of synthetic
dole (VTHI) from cyclohexanone oxime (CHO) and chemists [5–8] and chemical engineers [9, 10] as a
acetylene in MOH–DMSO superbasic media (M is simple and efficient route to indole and its deriva-
Li, Na, K, Cs; DMSO is dimethyl sulfoxide), an tives (Scheme 1).
MOH– DMSO
+
HC≡CH
+
1
00–140°C
N
N
H
THI
NOH
CHO
M = Li, Na, K, Cs
VTHI
Scheme 1.
Until recently, THI was one of the hardest to obtain
The process involves two different reactions: the
[
11] derivatives of indole and pyrrole, but now it is heterocyclization of CHO with acetylene to form
becoming a real industrial intermediate for preparing THI (1) and the vinylation of the resultant THI with
not only synthetic indole [10] but also its various α- acetylene (2).
substituted derivatives, whose synthesis is generally
MOH– DMSO
CHO + HC≡CH
THI + H O,
(1)
(2)
still a difficult task. As distinct from indole, THI (which
is pyrrole in terms of chemical behavior) is readily
functionalized at the α position and produces the corre-
sponding α-substituted indole after catalytic dehydra-
tion [12].
2
MOH– DMSO
THI + HC≡CH
VTHI.
These reactions respond differently to variations in
reaction conditions, first of all, the nature and composi-
tion of the catalytic system. The heterocyclization of
ketoximes readily proceeds in the presence of LiOH or
NaOH [1, 2], whereas the vinylation of resulting pyr-
roles is markedly encumbered in the NaOH–DMSO
system and does not take place with LiOH [1, 2].
However, these features were established only at the
qualitative level and mainly for aromatic ketoximes
1, 2]. It is unclear whether they are valid for CHO.
The selectivity of formation of pyrroles and
N-vinylpyrroles from ketoximes and acetylene depends
substantially on the nature of the alkali metal cation in
the catalytic system [1–3]. It was noted [1] that the
activity of catalyst for a number of ketoximes increases
with metal atomic number; the KOH–DMSO system
showed the highest activity.
[
Moreover, control over the selectivity and efficiency of
THI and VTHI synthesis (Scheme 1) requires quantita-
tive data on the effect of alkali metal cations in MOH–
DMSO catalytic systems on the rates of reactions (1)
and (2). Therefore, we studied the kinetics of the reac-
Favorskii Institute of Chemistry, Siberian Branch,
Russian Academy of Sciences, ul. Favorskogo 1,
Irkutsk, 664033 Russia
2
73

2
74
MIKHALEVA et al.
ë, mol/L
(
a)
(c)
1
1
1
0
0
0
0
.4
.2
.0
.8
.6
.4
.2
0
CHO
CHO
THI
VTHI
THI
1
1
1
0
0
0
0
.4
.2
.0
.8
.6
.4
.2
(
b)
(d)
CHO
CHO
VTHI
VTHI
THI
THI
0
1
2
3
4
5
6
7
8
t, h
0
1
2
3
4
5
6
7
8
t, h
Fig. 1. Variations in CHO, THI, and VTHI concentrations in the course of the reaction of CHO with acetylene in MOH–DMSO
systems ([MOH] = 0.25 mol/L, [CHO] = 1.33 mol/L, 130°C, atmospheric pressure, acetylene flow rate is about 30 mL/min):
(a) M = Li, (b) M = Na, (c) M = K, (d) M = LiOH–CsF (1 : 1 molar ratio).
ë, mol/L
(‡)
(b)
1
1
1
0
0
0
0
.4
.2
.0
.8
.6
.4
.2
CHO
CHO
THI
THI
VTHI
VTHI
0
1
2 3
4
5
6
7
8
t, h
0
1
2 3
4
5
6
7
8
t, h
Fig. 2. Variations in CHO, THI, andVTHI concentrations in the course of the reaction of CHO with acetylene in MOH–CsF–DMSO
systems ([MOH] = 0.25 mol/L, [CsOH] = 0.25 mol/L, [CHO] = 1.33 mol/L, 130°C, atmospheric pressure, acetylene flow rate is
about 30 mL/min): (a) M = Na, (b) M = K.
tion of CHO with acetylene in DMSO in the presence tion increases, reaches a maximum, and begins to
of LiOH, NaOH, KOH, and LiOH–CsF (0.25 mol/L) at decrease; at the same time, the concentration of VTHI,
1
30°C.
the vinylation product of THI, slowly rises. It is seen
distinctly that the THI formation rate increases sharply
on passing from LiOH to NaOH and then to KOH and
the LiOH–CsF system. At the same time, no vinylation
Because of known difficulties in dehydrating
CsOH · ç O, we used an equimolar LiOH–CsF mix-
ture producing CsOH in situ:
2
(
2) occurs in the presence of LiOH, but the reaction is
LiOH + CsF = LiF + CsOH.
rather fast for NaOH, KOH, and CsOH.
Figure 1 shows typical concentration profiles for the
Figure 2 shows kinetic curves for the NaOH–CsF
initial oxime (CHO) and the reaction products (THI and and KOH–CsF systems obtained under the same condi-
VTHI) for all four systems. Their character corre- tions. The effect of the NaOH–CsF system on the over-
sponds to a process with two consecutive reactions: as all process proved to be unexpected. The selectivity of
the CHO concentration decreases, the THI concentra- THI formation rises and the vinylation reaction is sup-
DOKLADY CHEMISTRY Vol. 423 Part 1 2008

EFFECT OF ALKALI METAL CATIONS ON THE SYNTHESIS
275
pressed. In the KOH–CsF system, the overall reaction VTHI from CHO and acetylene in order of increasing
also proceeds slower than with KOH. A possible expla- metal atomic weight (Li < Na < K < Cs) are likely to
nation of this effect is that more ionized cesium oxi-
mate and indolate suppress (according to the mass
action law) the ionization of the corresponding sodium
result from the growth of their basicity and ability to
form complexes with acetylene in the same order.
(
potassium) derivatives, which results in a decrease in
The key stage of the synthesis (Scheme 1) is the
nucleophilic addition of ambident oximate anion 1 to
the total concentration of reactive nucleophiles.
The fundamental reasons for the accelerating effect acetylene to yield O-vinyloxime 2, which further
of alkali metal hydroxides on the synthesis of THI and undergoes rearrangement into THI (Scheme 2) [1, 2].
–
O
+
HC≡CH
O
N
N
N
H
THI
1
2
Scheme 2.
The reactivity (nucleophilicity) of the oximate anion
and, hence, the rate of its addition to acetylene
increases with the basicity of the medium (due to a
decrease in its solvation). In its turn, acetylene forms
complexes with alkali metal hydroxides, according to
experimental data [13] and ab initio quantum-chemical
calculations [13, 15]. In so doing, its reactivity toward
nucleophiles rises.
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ACKNOWLEDGMENTS
This work was supported by the Council for Grants
of the President of the Russian Federation for Support
of Leading Scientific Schools (grant no. NSh–
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DOKLADY CHEMISTRY Vol. 423 Part 1 2008