Synthesis of 2-aryl-5,5-dimethyl-5,6-dihydro-1,2,4-triazolo-[3,4-a] isoquinolinium tetrafluoroborates

Full text of DOI:10.1134/S1070428008070270

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 7, pp. 1091−1093. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © V.A. Glushkov, E.V. Vedernikova, M.S. Kotelev, E.V. Baigachev, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44,
No. 7, pp. 1100−1102.
SHORT
COMMUNICATIONS
Synthesis of 2-Aryl-5,5-dimethyl-5,6-dihydro-1,2,4-triazolo-
[3,4-a]isoquinolinium Tetrafluoroborates
V. A. Glushkova, E. V. Vedernikovab, M. S. Kotelevb, and E. V. Baigachevaa
aInstitute of Chemical Engineering, Ural Division, Russian Academy of Sciences, Perm, 614013 Russia
e-mail: glusha@nm.ru
bPerm State University, Perm, Russia
Received November 21, 2007
DOI: 10.1134/S1070428008070270
The developed method of preparation of the target
compound consisted in the cyclization of amidrazones
IIa–IIe, obtained via methylsulfanyl derivatives Ia and
Ib, carried out in excess ethyl orthoformate in the
presence of ammonium tetrafluoroborate.
Recently the chemistry of N-heterocyclic carbenes
made rapid progress, as seen from a large number of
freshly published reviews [1–4] and a monograph [5]. In
the modern organic synthesis the N-heterocyclic carbenes
are used either directly [1, 2] or in complexes with
transition and nontransition metals [3].
Amidrazones IIa–IIe were obtained by heating 1-
methylsulfanyl-3,4-dihydroisoquinolines Ia and Ib [12]
with arylhydrazines in an argon atmosphere at ~170–
180°C for 0.5–1 h. Compounds IIa and IIb have been
isolated as yellow oily substances darkening in air and
stable at room temperature for several days; amidrazone
IIe can be stored at room temperature for 6 months
without visible signs of decomposition . The attempts to
isolate intermediate amidrazones IIc and IId in pure state
failed due to their fast oxidation in air, therefore we
further used them direct after the synthesis in the
cyclization into the target compounds IIIc and IIId.
Amidrazones IIa–IIe may exist in two tautomer forms
but 1H NMR spectra detect the form shown in the scheme
as indicated by the downfield shift of the signal belonging
to proton HC8 [13].
N-heterocyclic carbenes known now and their deriv-
atives known now contain metal complexes based on salts
of 1,2,4-triazole substituted with chiral functional groups
[6] and of 1,2,4-triazole fused with pyrrolidine [7],
oxazole [8], oxazine [9], morpholine [10], indeno[2,1-b]-
morpholine [11], and also with indeno[1,2-b]pyrroline,
naphtho[1,2-b]pyrroline, and naphtho[2,1-b]morpholine [2].
Yet the heterocyclic system of triazolo[3,4-a]isoquinoline
was notused as a precursor of N-heterocyclic carbenes.
The target of the present study was the preparation of
2-aryl-5,5-dimethyl-5,6-dihydro-1,2,4-triazolo[3,4-a]iso-
quinolinium salts and their 8,9-dimethoxy analogs as
precursors N-heterocyclic carbenes. We chose for counter-
ion the tetrafluoroborate anion since unlike chlorides and
bromides 2-aryl-5,5-dimethyl-5,6-dihydro-1,2,4-triazolo-
[3,4-a]isoquinolinium tetrafluoroborates were nonhydro-
scopic, heat-resistant, and formed well-developed crystals.
Salts IIIa–IIIe are colorless or light-yellow (IIIb and
IIIe) crystalline substances soluble in DMF, DMSO,
R
R
Me
R
R
Me
Me
R
R
Me
Me
Me
NH
+N
N
BF4_
N
N
N
NHAr
IIa IIe
Ar
_
_
Ia, Ib
IIIa IIIe
I, R = H (a), OMe (b); II, III, Ar = Ph, R = H (a), OMe (b); Ar = 4-FC6H4, R = H (c), OMe (d); Ar = 4-NO2C6H4, R = H (e).
1091

GLUSHKOV et al.
1092
the reaction mixture was boiled for 20–30 min. To the
resulting mixture 12 mmol of ammonium tetrafluoro-
borate was added, 15–20 ml of acetonitrile was poured
(to dissolve the inorganic salt), the mixture was boiled
for 10 min more, and then acetonitrile was distilled off
in a vacuum on a water bath. The residue was diluted
with a little ethyl acetate, the precipitated crystals of salts
IIIa–IIIe were filtered off and recrystallized from
methanol.
sparingly soluble in ethanol, chloroform insoluble in
ethyl acatete, toluene, hexane, and water. Their structure
was confirmed by elemental analysis, IR and 1H NMR
spectra. 2-Aryl-5,5-dimethyl-8,9-di-R-5,6-dihydro-1,2,4-
triazolo[3,4-a]isoquinolinium tetrafluoroborates IIIa–
IIIe we plan to use further as precursors of N-heterocyclic
carbenes of new structural type. It is evident that the
gem-dimethyl fragment of the isoquinoline system in
these compounds operates as a spatially hindering
function indispensable for increasing the stability of the
N-heterocyclic carbenes.
5,5-dimethyl-2-phenyl-5,6-dihydro-1,2,4-triazolo-
[3,4-a]isoquinolinium tetrafluoroborate (IIIa). Yield
0.9 g (25%), mp 237–239°C. IR spectrum, ν, cm–1: 1668,
1612, 1596 (C=C), 1572, 1536, 1492 (C=C), 1340, 1288,
1252, 1228, 1196, 1180, 1160, 1048, 1104, 1070, 1026,
3,3-Dimethyl-1-phenylhydrazono-1,2,3,4-tetra-
hydroisoquinoline (IIa) was obtained by heating
10 mmol of methylsulfanylisoquinoline Ia with 10 mmol
of phenylhydrazine in an argon atmosphere at ~170–
180°C for 30 min. Yield 2.09 g (82%), yellow oily
1
976, 924, 876, 846. H NMR spectrum (DMSO-d6), δ,
ppm: 1.68 s (6H, 2CH3), 3.34 s (2H, C6H2), 7.54–7.77 m
(6H, Harom), 8.04 d.d (2H, H6',2', 3J 8, 4J 1.2 Hz), 8.12 d.d
(1H, C10H, 3J 8, 4J 1.8 Hz), 10.97 C (1H, =CH). Found,
1
substance. H NMR spectrum (CDCl3), δ, ppm: 1.24 s
(6H, 2CH3), 2.81 s (2H, C4H2), 5.24 br.s (1H, N2H), 6.09
+
–
br.s (1H, ArNH), 6.82 m (1H, Harom), 7.03 d.d (2H, H6',2'
,
%: C 59.28; H 4.93; N 11.81. C18H18N3 ·BF4 .
Calculated, %: C 59.53; H 4.99; N 11.57.
3J 6.6, 4J 1.2 Hz), 7.09–7.41 m (5H, Harom), 8.19 m (1H,
H8).
5,5-dimethyl-8,9-dimethoxy-2-phenyl-5,6-
dihydro-1,2,4-triazolo[3,4-a]isoquinolinium
tetrafluoroborate (IIIb). Yield 0.8 g (19%), mp 269–
271°C, light-yellow crystals. IR spectrum, ν, cm–1: 1596
(C=C), 1538, 1494 (C=C), 1348, 1288, 1256 [νas(C–O–
3,3-Dimethyl-6,7-dimethoxy-1-phenylhydrazono-
1,2,3,4-tetrahydroisoquinoline (IIb) was similarly
obtained from methylsulfanylisoquinoline Ib and
phenylhydrazine. Yield 2.36 g (75%), yellow oily sub-
stance. 1H NMR spectrum (CDCl3), δ, ppm: 1.25 s (6H,
2CH3), 2.76 s (2H, C4H2), 3.88 s (6H, 2OCH3), 5.25 br.s
(1H, N2H), 5.86 br.s (1H, ArNH), 6.60 d (1H, Harom),
6.81 m (1H, H4'), 6.99 d (1H, Harom), 7.15 C (1H, H5),
7.21 m (2H, Harom), 7.72 C (1H, H8).
1
C)], 1224, 1196, 1168, 1084 [νs(C–O–C)], 868. H NMR
spectrum (DMSO-d6), δ, ppm: 1.69 s (6H, 2CH3), 3.26 s
2H, C6H2), 3.90 s (3H, OCH3), 3.91 s (3H, OCH3),
7.15 s (1H, C7H), 7.55 s (1H, C10H), 7.66 m (1H, H4'),
7.74 m (2H, H3',5'), 8.05 d.d (2H, H2',6', 3J 8, 4J 1.5 Hz),
10.88 s (1H, =CH). Found, %: C 56.67; H 5.20; N 9.85.
3,3-Dimethyl-1-(4-nitrophenylhydrazono)-1,2,3,4-
tetrahydroisoquinoline (IIe) was obtained by boiling
10 mmol of thioether Ia with 10 mmol of p-nitro-
phenylhydrazine in 60 ml of ethanol for 12 h. Yield
1.35 g (45%), dark-violet crystals, mp 186–187°C (from
ethanol). 1H NMR spectrum (DMSO-d6), δ, ppm: 1.30 s
(6H, 2CH3), 2.82 C (2H, C4H2), 6.23 br.s (1H, N2H),
7.05 d (2H, H6',2'), 7.15 d (1H, H5), 7.28 m (2H, H6,7),
8.00 d (1H, H3',5'), 8.00 d (1H, H6,7), 8.10 d (1H, H8),
9.46 br.s (1H, ArNH).
–
+
C20H22N3O2 ·BF4 . Calculated, %: C 56.76; H 5.24; N 9.93.
5,5-dimethyl-2-(4-fluorophenyl)-5,6-dihydro-
1,2,4-triazolo[3,4-a]-isoquinolinium tetrafluoroborate
(IIIc). Yield 1.4 g (32%), mp 270–272°C. IR spectrum,
ν, cm–1: 1596 (C=C), 1572, 1538, 1508 (C=C), 1344,
1302, 1252, 1194, 1164, 1064, 976, 844. 1H NMR spec-
trum (DMSO-d6), δ, ppm: 1.71 s (6H, 2CH3), 3.38 s (1H,
C6H2), 7.57–7.75 m (2Harom), 7.73 t (1Harom, J 7.8 Hz),
8.15 d (1H, H10, J 7.8 Hz), 8.35 d (2H, H2',6', 3J 9.3 Hz),
8.61 d (2H, H3',5', 3J 9.3 Hz), 11.18 s (1H, =CH). Found,
2-Aryl-5,5-dimethyl-8,9-di-R-5,6-dihydro-1,2,4-
triazolo[3,4-a]isoquinolinium tetrafluoroborates
IIIa–IIIe. General procedure. Into a flask filled with
argon equipped with a reflux condenser cooled by an air
flow was charged 10 mmol of thioether Ia or Ib and 10
mmol of an appropriate arylhydrazine, and the mixture
was heated to 170–180°C for 30–40 min, then it was
cooled, a triple excess of ethyl orthoformate was added
to the melt, and 1–2 drops of formic acid as catalyst, and
%: C 57.00; H 4.29; N 10.93. C18H17FN+ ·BF4–. Calculat-
3
ed, %: C 56.72; H 4.49; N 11.02.
5,5-dimethyl-8,9-dimethoxy-2-(4-fluorophenyl)-
5,6-dihydro-1,2,4-triazolo[3,4-a]-isoquinolinium
tetrafluoroborate (IIId). Yield 0.7 g (16%), mp 236–
238°C. IR spectrum, ν, cm–1: 1608 (C=C), 1576, 1540,
1502 (C=C), 1468, 1356, 1288, 1260 [νas(C–O–C)],
1228, 1192, 1166, 1068 [νs(C–O–C)], 984, 976, 916, 872,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 7 2008

SYNTHESIS OF 2-ARYL-5,5-DIMETHYL-5,6-DIHYDRO-1,2,4-TRIAZOLO[3,4-A]ISOQUINOLINIUM
1093
860, 848, 816. 1H NMR spectrum (DMSO-d6), δ, ppm:
1.71 s (6H, 2CH3), 3.41 s (1H, C6H2), 3.92 s (6H,
2OCH3), 7.19 s (1H, C7H), 7.57 s (1H, C10H), 7.65 d.d
(2H, H2',6', 3J 8.4, 4J 2.1 Hz), 8.15 m (2H, H3',5'), 10.93 s
(1H, =CH). Found, %: C 54.51; H 4.73; N 9.46.
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2
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3
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1
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 7 2008