Unexpected formation of 1-vinyl-2-[2′-(6′-methylpyridyl)]pyrrole from dimethylglyoxime and acetylene in the Trofimov reaction

Article abstract of DOI:10.1070/MC2001v011n02ABEH001405

Dimethylglyoxime reacts with acetylene under pressure in the KOH-DMSO system to give 1-vinyl-2-[2′-(6′-methylpyridyl)]pyrrole along with the expected products of the Trofimov reaction (O-vinyloxime, pyrrole and dipyrrole).

Full text of DOI:10.1070/MC2001v011n02ABEH001405

,
2001, 11(2), 74–75
Unexpected formation of 1-vinyl-2-[2'-(6'-methylpyridyl)]pyrrole from
dimethylglyoxime and acetylene in the Trofimov reaction
Alexander M. Vasil’tsov, Alexey B. Zaitsev, Elena Yu. Schmidt,* Al’bina I. Mikhaleva and Andrey V. Afonin
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk,
Russian Federation. Fax: +7 3952 39 6046; e-mail: lschmidt@irioch.irk.ru
1
0.1070/MC2001v011n02ABEH001405
Dimethylglyoxime reacts with acetylene under pressure in the KOH–DMSO system to give 1-vinyl-2-[2'-(6'-methylpyridyl)]-
pyrrole along with the expected products of the Trofimov reaction (O-vinyloxime, pyrrole and dipyrrole).
Ketoximes react with acetylene in the KOH–DMSO system to
shifts of all relevant protons are consistent with those of 1-vinyl-
2-(2'-pyridyl)pyrrole.
1
–5
12
afford 1-H- and 1-vinylpyrroles (Trofimov reaction ), in some
6
–8
9–11
cases, intermediate O-vinylketoximes
and 3H-pyrroles
†
1H (250.1 MHz) and 13C NMR (62.9 MHz) spectra were measured in
being isolated. However, the dioximes of α-diketones have
never been studied in this reaction, although this might open a
new straightforward entry to the dipyrrole chemistry.
Here, we briefly report on the Trofimov reaction extended to
dimethylglyoxime 1, the simplest α-diketoxime.
CDCl , HMDS was used as a standard compound. The assignments of
3
1
13
15
H and C NMR spectra were performed by COSY, NOESY, HMQC
and HMBC experiments.
1
6
General procedure. A mixture of 4.0 g (34.5 mmol) of dimethyl-
glyoxime 1 and 1.9 g (27.4 mmol) of KOH·0.5H O in 100 ml of DMSO
2
In the reaction mixture obtained under normal conditions
was saturated with acetylene (14 atm), heated at 110 °C for 1 h and
cooled to room temperature. The mixture was diluted with 100 ml of
water and extracted with diethyl ether (4×30 ml). The extract was
washed with water (4×5 ml) and dried over K CO . After the removal
(
1
KOH–DMSO, 100–140 °C, acetylene pressure), unexpected
-vinyl-2-[2'-(6'-methylpyridyl)]pyrrole 2 was identified among
the anticipated products such as O-vinyldimethylglyoxime 3,
-acetyl-1-vinylpyrrole 4 and 1,1'-divinyl-2,2'-dipyrrole 5
2
3
2
(
of the extractant, a product mixture (1.6 g) was obtained. According to
Scheme 1).†
the 1H NMR spectrum, the mixture contains 36% of 1-vinyl-2-[2'-(6'-
methylpyridyl)]pyrrole 2, 18% of 2-acetyl-1-vinylpyrrole 4 and 15% of
1
,1'-divinyl-2,2'-dipyrrole 5. The products were isolated by column
4
'
3'
3
4
chromatography (Al O , light petroleum, bp 30–70 °C).
2
3
2
'
2
1-Vinyl-2-[2'-(6'-methylpyridyl)]pyrrole 2: nD 1.6084. 1H NMR, d:
20
5
'
5
Me
Me
NOH
N
7.84 (dd, 1H, H ), 7.55 (t, 1H, H-4'), 7.30 (d, 1H, H-3', 3J
.8 Hz), 7.19 (dd, 1H, H-5), 6.98 (d, 1H, H-5', J
(dd, 1H, H-3, JH-3–H-5 1.5 Hz), 6.26 (t, 1H, H-4, JH-3–H-4 = JH-4–H-5 =
3.0 Hz), 5.15 (dd, 1H, H , J
6
'
N
X
H-3'–H-4'
7.8 Hz), 6.55
3
HC CH
3
7
Me
H-4'–H-5'
3
C
HB
α
4
HON
HX
C
β
3
2
=
15.5 Hz), 4.71 (dd, 1H, H , J
1
B
HB–HX
A
HA–HB
3
13
0
.9 Hz, J
8.8 Hz), 2.58 (s, 3H, Me). C NMR, d: 157.59 (C-6'),
HA–HX
HA
2
151.30 (C-2'), 136.78 (C-4'), 133.54 (C ), 132.37 (C-2), 120.40 (C-5'),
α
1
19.99 (C-5), 119.65 (C-3'), 112.15 (C-3), 110.00 (C-4), 98.61 (C ),
β
–
1
a–c
c
a
a
Me 1 Me
Me
24.59 (Me). IR (neat, n/cm ): 3107–2822 , 1639 , 1588 , 1576 ,
2
b
b
b
c
b
c
a
1
543 , 1476 , 1459 , 1420 , 1389 , 1374 , 1326 (C–N), 1287 , 1261,
N
N
N
1243, 1229a, 1159a, 1091b, 1071b, 1036b, 995a, 968c, 865c, 806a, 786a,
HON
NO
O
b
b
c
1,15
7
20 , 653 , 593 (a – pyridine, b – pyrrole and c – vinyl moieties).
+
+
3
4
5
MS, m/z (%): 183 (16%, [M – H] ), 182 (100%, [M – 2H] ), 168 (38%,
+
+
[
M – H – Me] ), 157 (14%, [M – H – HCºCH] ), 130 (27%, [M – H –
Scheme 1
+
+
–
H C=CH–CºN] ), 91 (13%, [2-methylpyridine – 2H] ).
2
O-Vinyl dimethylglyoxime 3. [KOH–DMSO, 100 °C, 5 min, neutrali-
The pyridylpyrrole 2 content of the product mixture depends
zation of the reaction mixture with CO before the extraction, 10% yield
2
1
on the reaction conditions, reaching 36% in best cases ( H NMR
data). Compound 2 can be easily isolated by column chromato-
graphy (Al O ).
(10% conversion of dioxime 1)], white needle-shaped crystals (from
hexane), mp 63 °C. 1H NMR, d: 7.71 (s, 1H, OH), 6.95 (dd, 1H, H ),
X
3
4.66 (dd, 1H, H , J
B
2
14.3 Hz), 4.18 (dd, 1H, H , J
1.8 Hz,
2
3
HB–HX
A
HA–HB
3
13
The position of the methyl group in 2 follows from the sig-
nal shape of pyridine ring protons (two doublets and a triplet)
corresponding to the only possible structural unit X–CH=CH–
CH=Y having no protons at X and Y atoms. The chemical
JHA-HX 6.7 Hz), 2.04 (s, 6H, 1-Me, 2-Me). C NMR, d: 155.82 (C-2),
1
(
1
1
(
55.15 (C-1), 152.55 (C ), 88.96 (C ), 10.58 (2-Me), 9.45 (1-Me). IR
α β
–
1
KBr, n/cm ): 3600–3200 (OH), 3078, 2959, 2936, 2874, 1720, 1701,
685, 1642, 1601, 1561, 1540, 1508, 1459, 1367, 1341, 1282, 1182,
129, 1073, 993, 942, 892, 842, 795, 748, 687, 570. MS, m/z (%): 142
+
1%, M ), 58 (100%), 41 (46%).
Me
1
[1,3 H]
[3,3]
2-Acetyl-1-vinylpyrrole 4: H NMR, d: 7.99 (dd, 1H, H ), 7.27 (dd,
X
4
3
1
=
H, H-5), 7.01 (dd, 1H, H-3, J
1.0 Hz), 6.24 (t, 1H, H-4, J
=
N
N
N
H-3–H-5
H-3-H-4
ON
O
NH
3
3
J
3.3 Hz), 5.19 (dd, 1H, H , J
H , JHA–HB 1.2 Hz, JHA–HX 8.8 Hz), 2.48 (s, 3H, Me). C NMR, d:
15.8 Hz), 4.86 (dd, 1H,
H-4–H-5
2
B
HB–HX
3
13
A
6
7
1
1
1
1
88.92 (C=O), 133.71 (C ), 130.30 (C-2), 125.12 (C-5), 121.25 (C-3),
α
–
1
a–c
09.97 (C-4), 101.76 (C ), 27.53 (Me). IR (neat, n/cm ): 3114–2875
655 , 1637 , 1591 , 1576 , 1550 , 1529, 1474 , 1458 , 1426 , 1368 ,
328 (C-N), 1284 , 1244, 1203, 1161 , 1083 , 1036 , 966 , 941, 878 ,
787 , 742 , 631 , 594 (a – acetyl, b – pyrrole and c – vinyl moieties).
,1'-Divinyl-2,2'-dipyrrole 5: H NMR, d: 7.19 (dd, 1H, H-5), 6.68
(dd, 1H, H ), 6.29 (t, 1H, H-4, J
,
β
a
c
a
a
b
b
b
c
c
HC CH
O
HO
a
a
b
b
c
c
N
a
b
b
c
1
H NH
NH
1
1
3
3
8
9
= J
= 3.0 Hz), 6.22 (dd,
15.8 Hz), 4.59 (dd,
X
H-3–H-4
H-4–H-5
4
3
1
1
1
H, H-3, J
1.5 Hz), 5.04 (dd, 1H, H , J
H-3–H-5 B HB–HX
2
3
13
H, HA, JHA–HB 1.2 Hz, JHA-HX 9.1 Hz). C NMR, d: 131.27 (Cα),
[
1,3 H]
23.70 (C-2), 117.72 (C-5), 113.29 (C-3), 110.03 (C-4), 97.86 (C ). IR
HO
2
β
–
H O
2
–1
a,b
b
b
a
a
b
N
(neat, n/cm ): 3109–2852 , 1643 , 1598, 1551 , 1482 , 1459 , 1428 ,
377 , 1351, 1310, 1261, 1236, 1155, 1084 , 1067 , 1036 , 964 , 861 ,
98, 717 , 659 , 591 (a – pyrrole and b – vinyl moieties). MS, m/z (%):
83 (100%, [M – H] ), 157 (8%, [M – H – HCºCH] ), 130 (8%, [M –
N
b
a
a
a
b
b
1
7
1
–
b
a
b
1
10
+
+
Scheme 2
+
H – H C=CH–CºN] ).
2
–
74 –

,
2001, 11(2), 74–75
The formation of 2 may be rationalised as follows (Scheme 2):
O-vinylketoxime 6, a normal product of the Trofimov reaction
with 1, undergoes the [1,3] prototropic shift under the action
of the superbase KOH–DMSO to form vinylhydroxylamine 7,
further rearranging in a [3,3] sigmatropic manner to give imino-
aldehyde 8. The latter is intercepted by acetylene to form acety-
lenic alcohol 9 (Favorsky reaction), which undergoes cycli-
zation to hydroxymethylenetetrahydropyridine 10 and final
aromatization to 2.
On the other hand, this new extension of the Trofimov reac-
tion, in spite of the modest (unoptimised) yield of pyridyl-
pyrrole 2, may have a preparative value (particularly, when
optimized and supported with a modern isolation technique), as
a direct one-pot synthesis of alkaloids related to nicotine from
readily available starting materials (dimethylglyoxime and acety-
lene). Few known syntheses of pyridylpyrrole1
2–14
are multi-
step reactions involving the attachment of a second heterocycle.
Obviously, acetylenic alcohol 9 can be closed to form the
pyridine moiety in a number of ways including preliminary
prototropic rearrangements to aminovinyl 11 or allenyl 12
derivatives, and not only after but also before the formation of
the 1-vinylpyrrole counterpart (Scheme 3).
References
1
2
3
B. A. Trofimov and A. I. Mikhaleva, N-Vinilpirroly (N-Vinylpyrroles),
Nauka, Novosibirsk, 1984 (in Russian).
B. A. Trofimov, in Adv. Heterocycl. Chem., ed. A. R. Katritzky,
Academic Press, San Diego, 1990, vol. 51, p. 177.
B. A. Trofimov, in The Chemistry of Heterocyclic Compounds,
Pyrroles, ed. R. A. Jones, Wiley, New York, 1992, vol. 48, part 2,
p. 131.
9
HO
10
2
N
4
5
6
R. J. Tedeschi, in Encyclopedia of Physical Science and Technology,
Academic Press, New York, 1992, vol. 1, p. 27.
NH2
G. P. Bean, in The Chemistry of Heterocyclic Compounds, Pyrroles,
ed. R. A. Jones, Wiley, New York, 1990, vol. 48, part 1, p. 153.
B. A. Trofimov, A. I. Mikhaleva, A. N. Vasil’ev and M. V. Sigalov, Izv.
Akad. Nauk SSSR, Ser. Khim., 1979, 695 (Bull. Acad. Sci. USSR, Div.
Chem. Sci., 1979, 28, 651).
11
9
HO
10
2
N
NH
7
8
9
O. A. Tarasova, S. E. Korostova, A. I. Mikhaleva, L. N. Sobenina, R. N.
Nesterenko, S. G. Shevchenko and B. A. Trofimov, Zh. Org. Khim.,
1994, 30, 810 (Russ. J. Org. Chem., 1994, 30, 863).
B. A. Trofimov, A. I. Mikhaleva, A. M. Vasil’tsov, E. Yu. Schmidt, O. A.
Tarasova, L. V. Morozova, L. N. Sobenina, T. Preiss and J. Henkelmann,
Synthesis, 2000, 1125.
B. A. Trofimov, S. G. Shevchenko, S. E. Korostova, A. I. Mikhaleva
and V. V. Shcherbakov, Khim. Geterotsikl. Soedin., 1985, 1573 [Chem.
Heterocycl. Compd. (Engl. Transl.), 1985, 21, 1299].
12
Scheme 3
The transformation of alcohols 9 or 11 to pyridylpyrrole 2
can also occur via preliminary dehydration to vinylacetylenic
derivatives 13, 14 (Scheme 4).
1
1
0 T. N. Borisova, A. B. Varlamov, N. D. Sergeeva, A. T. Soldatenkov, O. V.
Zvolinsky, A. A. Astakhov and N. S. Prostakov, Khim. Geterotsikl.
Soedin., 1987, 937 [Chem. Heterocycl. Compd. (Engl. Transl.), 1987,
23, 799].
1 S. E. Korostova, S. G. Shevchenko and M. V. Sigalov, Khim. Geterotsikl.
Soedin., 1991, 1371 [Chem. Heterocycl. Compd. (Engl. Transl.), 1991,
9
(11)
–
H O
2
N
NH
13
27, 1101].
1
1
1
2 O. V. Petrova, A. I. Mikhaleva, L. N. Sobenina, E. Yu. Schmidt and
E. I. Kositsyna, Mendeleev Commun., 1997, 162.
3 R. M. Acheson, M. J. Ferris, S. R. Critcheley and D. J. Wartin, J. Chem.
Soc., Perkin Trans. 2, 1980, 326.
4 L. Brandsma, S. F. Vasilevsky and H. D. Verkruijsse, Application of
Transition Metal Catalysts in Organic Synthesis, Springer, Berlin,
2
N
NH2
14
1
997, p. 264.
Scheme 4
1
1
1
5 A. Bax and S. Subramanian, J. Magn. Reson., 1986, 67, 1986.
6 A. Bax and M. F. Summers, J. Am. Chem. Soc., 1986, 108, 2093.
7 A. R. Katritzky and A. P. Embler, in Physical Methods in Heterocyclic
Chemistry, ed. A. R. Katritzky, Academic Press, New York, 1963.
The isolation of 1-vinyl-2-[2'-(6'-methylpyridyl)]pyrrole 2
from the reaction mixture of 1 with acetylene is important for a
better understanding of the mechanism of the Trofimov pyrrole
synthesis. Although iminoaldehydes like 8 were long ago1
suggested to be formed in the reaction, they, together with
vinylhydroxylamines 7, remain the only two intermediates in
the multi-step pyrrole ring-closing scheme, which were not
isolated. The pyridine-ring closure now observed during the
pyrrole synthesis implies the trapping of the iminoaldehyde with
acetylene and hence can be considered as an additional experi-
–3
1
–3
1
–3
mental support to the proposed mechanism of the Trofimov
reaction.
Received: 5th December 2000; Com. 00/1731
–
75 –