Full text of DOI:10.1007/BF02659553

N- M E T H Y L- 5 - E T H Y N Y L I N D O L E A N D
ITS D E R I V A T I V E S
Io L. K o t l y a r e v s k i i and L. A . P a v l y u k h i n a ,
UDC 542.91:547.362:547.753
Acetylenic derivatives of indole are not described in the literature. Nevertheless, there is reason to
believe that they can exhibR physiological activity, especially the aminoacetylenic derivatives of indole, by
amlogy with the corresponding aromatic compounds [1]. The purpose of the preseut paper was to develop
methods for the sy-~hesis of ethynylindoles on the example of N-methyl-5-ethynylindole ([). Two methods for
the synthesis of ([) were proposed by us previously [2]. The f i r s t method was the direct conversion of N-
methyl-5-acetylimiole (]I) to (I) by successive treatme-~ with PCII and NaNHl. Ketone (II) was obtained by the
oxidation of N-met. hyl-5-acetylindoline (Ill) with chloranU or, as it proved, even better with MnO2, but all of
the attempts to convert it to (I) ended in failure. The seco~xi route was the oxidation of N-methyl-5-ethynylin-
doline (IV) by treatme,~ with MnO~ in benzene and it led to (I) in high yield, in which connection the reaction
time at elevated temperature is greatly shortened without lowering the yield of the product. For additional
confirmation of the structure, (I) was oxidized to the d i m e r (V).
The reaction of (I) with CHIO and secondary amines gave the aminoacetylenic derivatives of N-methylin-
dole (VI)-(VKI). N-Methyl-5-(3'-piperidino-l'-propynyl)i~dole (VII) was obtained by counter syr~hesis, by
the oxidation of N-methyl-5-(3'-piperidino-l'-propynyl)indoline (IX) [2] with MnO~, and proved to be identical
with the sample synthesized from (I). In c o ~ a s t to the indoline analogs, the hydrochlorides of bases (VI)-
(VH[) are easily obtained bythe passage of dry HCI i~o an ether solution of the bases, and are stable crystal-
line compounds.
The structure of all of the obtained compounds was proved by the analytical and spectral data. All of the
traneformations were carried out by the following scheme:
HsCOC
H~COC
( n z )
N
( n )
N
I
I
CH,
CH.
L PCl°
I
2. NOrH,
X
I
I
HC_=C
(iv)
HC_=C
__/,/(C=C~
C L ~
, . o o , _
i,i
(il
I
I
I
I
CH,
CH~
CH,
(V)
CHs
RCHr--C_~C
R--CHr-C~C
I
I
CHI
Gitll
0
N (VIII)
R--(/--~NN__/ (IX)
B--(CIF~)t.'N(VI); C N (VII);
Institute of Chemical Kinetics and Combustion, Siberian Branch of the Academy of Sciences of the USSR,
Novosibirsk.
Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2363-2364,
October, 1976. Origi--I article submitted March 10, 1976.
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E X P E R I M E N T A
L
The IR spectra of the compounds were taken on a U R - 2 0 instrument as CCI4 solutions, while the N M R
spectra were taken on a Bruker instrument (using TIV~ as the internal standard and CCI4 as the solvent).
N-Methyl-5-acetylindole
(II). A. A mixture of 0.5 g (2.86 mmoles) of (III) [2] and 0.45 g (1.83 mmoles)
of chloranil in 25 ml of xylene was heated for 7 h at 140°, after which it was treated with 20% N a O H solution,
filtered, and the xylene layer was separated and washed in succession with N a O H solution, water, 1 :I HCI
solution, and water. After distilling off the solvent the residue was purified by chronmtography on Al203 (II
activity).
The yield of (II) was 0.3 g (60-1%), m p 87-88°. Found:
C
76.18; H 6.48;
N
7.99%.
CiiNiINO.
Calculated:
C
76.13; H 6.52; N 8.09%. Infrared spectrum (CCI4, v, cm-l): 1677 (C=O).
B.
A mixture of 3.5 g (0.02 mole) of (III) and 8.5 g of M n O 2 in abs. benzene was stirred for 50-55 h at
20°C, after which it was filtered, evaporated, and passed in ether solution through a small layer of A12(3~
(II activity). Yield 2.9 g (64%).
N-Methyl-5-ethyn~ltndole
(I). A mixture of 0.55 g (0.0035 mole) of (IV) [2] and 1.5 g of MnO2 in abs.
benzene was stirred at ~20° for 48-50 h (for 3 h at 60°), after which it was filtered, evaporated, dissolved in
ether, and passed through AI20s (II activity). The yield of (I) was 0.52 g (97%), mp 40-40.5" (purified by
vacuum-sublimation).
Found: N 8.76%. CtIHgN. Calculated: N 9.03%. Infrared spectrum (CCI4, v, cm-i):
2112 (C-C), 3320 (-ffiCH). NMR spectrum (5, ppm CCI4): 3.52 (CH3N); 2.74 (HC=); 6.2-7.6 (aromatic pro-
tone).
D i m e r (V).
A mixture of 0.35 g (2.26 mmoles) of (I) and 0.05 g (0.5 mmole) of CuCl in 20 ml of pyridine
was shaken in an O2 atmosphere until absorption was complete, and then it was poured into water, and the ob-
tained product was washed in succession with water, dilute NH4OH solution (1:1), and ether. The yield of (V)
was 0.29g (83%), m p 234.5-235.5 ° (from a 1:1 acetone--alcohol mixture). Found: C 85.74; H 5.13; N 8.89%.
C22HIsN2. Calculated:
N-Methyl-5-(3'-plperidino-l'-propynyl)indole
and 0.5 g of M n O 2 in abe. benzene was stirred for 48-50 h, after which it was filtered and purified by chromato-
graphy o n A l 2 0s (II activity). The yield of (VII) was 0.22 g (82%). Found: 10.68%. CIzH20N2. Calculated:
11.10%. Infrared spectrum: 2214, 2236 (--C =- C--)~
B. A mixture of 0.4 g (2.56 mmoles) of (I), 0.08 g (2.8 m m o l e s ) of CH20, 0.24 g (2.84 moles) of piperi-
C
85.68;
H 5.23; N 9.09%.
(VII). A.
A mixture of 0.27 g (1.06 mmoles) of (IX) [2]
N
N
dine, and 0.01 g (0.0001 mole) of CuCl in dioxane was heated for 2 h, after which it was filtered, evaporated
to dryness, and passed as an ether solution through Al20s (II activity). The yield of (VII) was 0.64 g (89%).
Hydrochlorlde,
N-Methyl-5-(3'-dlethylamino-l'-propynyl)Indole
as (VID in 85% yield. Found: 11.62%. CleHz0Nz. Calculated: N 11.66%. N M R spectrum (5, ppm; CC14):
m p 201-202°. Found: Cl 12.08c~. CITHI0N2.HCI. Calculated: Cl 12.28%.
(VI). The compound was obtained in the same m a n n e r
N
3.65 (CHIN); 3.52 (NCH2C---); 2.54 (CH2N); 1.04 (CH3); 6.22-7.5 (aromatic protons).
157-158% Found: C112.93%. CIeH~0N2..HCI. Calculated: C112.81%.
Hydrochloride, m p
N-Methyl-5-(3'-morpholino-l'-propynyl)Indole
9@~yleld. Found: Nll.06%. CIsHIsN20. Calculated: N11.29%. Infrared spectrum (#, cm-i): 1120 (COC),
2332 (C e C). Hydrochloride, m p 177-178% Found: CI 12.34%. CI6HIsN20-HCI. Calculated: Cl 12.19%.
(VIH). Obtained in the same m a n n e r as (VI) and (VII) in
C
O N C L U S I O N S
A method was developed for the synthesis of N-msthyl-5-ethynylindole, and a number of its derivatives
was obtained by the Mannich reaction.
L I T E R A T U R E C I T E D
I. L. Kotlyarevskii, Paper Delivered at Fourth All-Union Conference on Acetylene Chemistry [in Rus-
s fan], Vol. 1, InSt. I~tm. Nauk AN KazSSR, Alma-Ata (1972), p. 3.
1.
I. L. Kotlyarevskfi and L. A. Pavlyukhina, Izv. Akad. Nauk SSSR, Ser. Khim., 1169 (1976).
A. P. Terent'ev, M. N. Preobrazhenskaya, andG. M. Sorokim, Zh. Obshch. Khim., 29, 2875 (1959).
E. Pratt and T. McGovern, J. Org. Chem., 29, 1540 (1964).
2.
3.
4.
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