Synthesis of the first example of a tetrahydroindeno[2,1-c]azonine system by the reaction of 2,3-dihydro-1H-indeno[2,1-c]pyridyinium methylide with methyl acetylene dicarboxylate [3]

Full text of DOI:10.1007/s10593-007-0076-z

Chemistry of Heterocyclic Compounds, Vol. 43, No. 4, 2007
SYNTHESIS OF THE FIRST EXAMPLE OF A TETRAHYDROINDENO[2,1-c]AZONINE
SYSTEM BY THE REACTION OF 2,3-DIHYDRO-1H-INDENO[2,1-c]PYRIDYINIUM
METHYLIDE WITH METHYL ACETYLENE DICARBOXYLATE
A. T. Soldatenkov, S. V. Volkov, and S. A. Soldatova
Keywords: methyl acetylenedicarboxylate, 2,3-dihydro-1H-indeno[21-c]pyridinium methylide, N-ylide,
tetrahydroindeno[2,1-c]azonin
N-Ethoxycarbonylmethylides of 1,2,3,6-tetrahydropyridines undergo a variety of reactions, the direction
of which depends on the nature of the substituents on the heterocycle. Six-membered heterocycles may decyclize
into pentadienamines [1], recyclize with constriction of the ring to derivatives of pyrrolidine [2], or recyclization
with expansion of a seven-membered azacycle [3]. When the anhydrobase is generated in the presence of methyl
acetylenedicarboxylate (MADC) the latter readily reacts with the carbanion center to give addition products [4]
or products of cyclization of the indolizine type [5-7].
However when a solution of an equimolar mixture of MADC, 2-methoxycarbonylmethyl-2-methyl-
9-phenyl-2,3-dihydro-1H-indeno[2,1-c]pyridinium bromide (1) and triethylamine in methylene chloride was
kept at ~20°C for 3 h the indenoazonine 2 was unexpectedly formed and was isolated in 47% yield by column
chromatography.
COOMe
6
–
7
Br
8
Me
COOMe
COOMe
Et3N
7b
7a
+
N
3
O
O
O
O
12a
CH2COOMe
Me
N
2
11a
11
12
Ph
1
Me
Me
Ph
1
2
In its 1H NMR spectrum two three proton singlets (at 3.19 ppm, NMe and 3.30 ppm, 3-COOMe) and one
six proton singlet at 3.71 (two COOMe groups) were observed. At strong field (3.04-4.60 ppm), four double signals
were observed from protons of two CH2 groups with large geminal coupling constants (2J = 14.6-16.3 Hz). A broad
singlet was observed at 6.31 ppm, which can be assigned to the methyne proton H-3, under the descreening
influence of the nitrogen atom and the COOMe group. Finally in the same region (7.62 ppm) there is a slightly
broadened singlet signal which is evidently assignable to the proton H-7 of the vinyl group. These results in
combination with the presence in the mass spectrum of a molecular ion peak at [M]+ with m/z 473 confirm the
structure of the indenoazonine derivative 2.
__________________________________________________________________________________________
Peoples' Friendship University of Russia, Moscow 117198; e-mail: asoldatenkov@mail.ru. Translate
from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 613-615, April, 2007. Original article submitted
November 29, 2006.
508
0009-3122/07/4304-0508©2007 Springer Science+Business Media, Inc.

Evidently the tetrahydroindenoazonine 2 can be formed by electrophilic addition of MADC to the
intermediate N-ylid, which arises from the corresponding 1,4-zwitterion and recyclization of the latter with
expansion of the six-membered piperidiene unit into the nine-membered azacycle. Thus a new direction of
recyclization of an N-ylid system is observed on interaction of a quaternary tetrahydroindenopyridium salt with a
base in the presence of MADC. The 2-methyl-9-phenyl-2,3-dihydro-1H-indeno[2,1-c]pyridine was prepared by
method [8].
1H NMR spectra of CDCl3 solutions with TMS as internal standard were recorded on a Bruker WM-400
(400 MHz) machine. Mass spectra were recorded on a MAT-112 spectrometer with direct input of the sample
into the ion source with an ionizing current of 70 eV. IR spectra of KBr disks were recorded on an IR-75
spectrometer. Silufol UV-254 strips (developed with iodine vapor) were used for TLC. Column chromatography
was carried out on silica gel (Silicagel L 32/63).
2-Methoxycarbonylmethyl-2-methyl-9-phenyl-2,3-dihydro-1H-indeno[2,1-c]pyridinium Bromide
(1). Methyl bromoacetate (6.11 g, 0.04 mol) was added with stirring to a solution of 2-methyl-9-phenyl-
2,3-dihydro-1H-indeno[2,1-c] pyridine (10 g, 0.4 mol) in THF. The mixture was boiled for 1 h in an atmosphere
of argon. The precipitate of the quaternary salt was filtered off, washed with ether, and dried in air to give yellow
crystals of salt 1 (16 g, 97%); mp 178-180°C. Found, %: N 3.45. C22H22NO2Br. Calculated, %: N 3.40.
2-Methyl-3,4,5-trimethoxycarbonyl-1,2,3,6-tetrahydroindeno[2,1-c]azonine [2]. Triethylamine (0.7
ml, 0.5 g, 5.8 mmol) and methyl acetylenedicarboxylate (0.61 ml, 0.71 g, 5.8 mmol) were added dropwise to a
suspension of salt 1 (2.06 g, 5.8 mmol) in dichloromethane. The mixture was stirred at 20°C for 3h. the solvent
was evaporated and compound 3 (1.27 g, 47%); mp 89-90°C, was isolated from the residue as brownish red
crystals by chromatography. IR spectrum, ν, cm-1: 1731 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 3.04 (1H, d,
J = 14.5, H-1); 3.19 (3H, s, NCH3); 3.30 (3H, s, OCH3); 3.71 (6H, s, OCH3); 3.73 (1H, d, J =14.5, H-1); 3.88
(1H, d, J =16.2, H-6); 4.60 (1H, d, J =16.2, H-6); 6.31 (1H, s, H-3); 7.09 (1H, d, J = 6.9 (H-11); 7.23-7.51 (5H,
m, Harom); 7.58 (1H, d, J = 6.9, H-9); 7.62 (1H, s, H-7). Mass spectrum, m/z: 473 [M]+ (57), 442 (7), 414 (100),
357 (33), 294 (28), 281 (29), 239 (78), 216 (76), 202 (78), 77 (16), 59 (100). Found, %: C 70.81; H 5.73; N 2.88.
C28H27NO6. Calculated, %: C 70.95; H 5.70; N 2.95.
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