Features of reactions of quaternary salts derived from (4Z)-5-(bromomethyl) -2,2,6,6-tetra-methylhept-4-en-3-one. Synthesis of azolo[a]azepine and indolizine derivatives

Article abstract of DOI:10.1007/s10593-012-0994-2

The alkylation of 1-alkyl-2-methyl-1H-imidazoles, 1,2-dimethyl-1H- benzimidazole, and 2-R-pyridines by (4Z)-5-(bromomethyl)-2,2,6,6- tetramethylhept-4-en-3-one gives 1-alkyl-3-[(2Z)-2-tert-butyl-5,5-di-methyl-4- oxohex-2-en-1-yl]-2-methyl-1H-imidazol-3-ium, -1H-benzimidazol-3-ium, and 2-R-pyridinium bromides. Heating solutions of these diazolium salts in ethanol with potassium carbonate leads to 1,5-dihydroimidazo[1,2-a]azepinium and 5,10-dihydroazepino[1,2-a]benzimidazolium derivatives, while heating the pyridinium salts with triethylamine leads to indolizine derivatives. Heating solutions of quaternary salts derived from 1,2-dimethyl-1H-imidazole and 2-methylpyridine in acetic anhydride gives allylic rearrangement products, namely, 3-[(2Z)-2-tert-butyl-5,5-dimethyl-4-oxohex-1-en-1-yl]-1,2-dimethyl-1H- imidazol-3-ium and -2-methylpyridinium bromides, which under the action of base (MeONa for the diazolium salt and Et₃N for the pyridinium salt) are converted into 1,5-dihydroimidazo[1,2-a]azepinium and indolizine derivatives, respectively.

Full text of DOI:10.1007/s10593-012-0994-2

Chemistry of Heterocyclic Compounds, Vol. 48, No. 2, May, 2012 (Russian Original Vol. 48, No. 2, February, 2012)
FEATURES OF REACTIONS OF QUATERNARY SALTS
DERIVED FROM (4Z)-5-(BROMOMETHYL)-2,2,6,6-TETRA-
METHYLHEPT-4-EN-3-ONE. SYNTHESIS OF
AZOLO[a]AZEPINE AND INDOLIZINE DERIVATIVES
L. M. Potikha1*, A. R. Turelik1, and V. A. Kovtunenko1
The alkylation of 1-alkyl-2-methyl-1H-imidazoles, 1,2-dimethyl-1H-benzimidazole, and 2-R-pyridines
by (4Z)-5-(bromomethyl)-2,2,6,6-tetramethylhept-4-en-3-one gives 1-alkyl-3-[(2Z)-2-tert-butyl-5,5-di-
methyl-4-oxohex-2-en-1-yl]-2-methyl-1H-imidazol-3-ium, -1H-benzimidazol-3-ium, and 2-R-pyridinium
bromides. Heating solutions of these diazolium salts in ethanol with potassium carbonate leads to
1,5-dihydroimidazo[1,2-a]azepinium and 5,10-dihydroazepino[1,2-a]benzimidazolium derivatives,
while heating the pyridinium salts with triethylamine leads to indolizine derivatives. Heating solutions
of quaternary salts derived from 1,2-dimethyl-1H-imidazole and 2-methylpyridine in acetic anhydride
gives allylic rearrangement products, namely, 3-[(2Z)-2-tert-butyl-5,5-dimethyl-4-oxohex-1-en-1-yl]-
1,2-dimethyl-1H-imidazol-3-ium and -2-methylpyridinium bromides, which under the action of base
(MeONa for the diazolium salt and Et3N for the pyridinium salt) are converted into 1,5-dihydroimid-
azo[1,2-a]azepinium and indolizine derivatives, respectively.
Keywords: azepino[1,2-a][1,3]benzimidazole, hept-4-en-3-one, imidazo[1,2-a]azepine, allylic rearrange-
ment, cyclization.
In a continuation of our study of the heterocyclization of -substituted ,-unsaturated ketones, in this
work, we present the results of an investigation of the features of reactions of quaternary salts derived from
(4Z)-5-(bromomethyl)-2,2,6,6-tetramethylhept-4-en-3-one (1).
Earlier [1], we have discovered a convenient method for the synthesis of imidazo[1,2-a]azepine derivatives
involving base-induced cyclization of 1-R-3-[(Z)-2,4-diaryl-4-oxo-2-butenyl]-2-methyl-1H-imidazol-3-ium salts.
We have established that 5-(bromomethyl)heptenone 1, similar to -bromodipnones, gives 1-alkyl-3-[(2Z)-
2-tert-butyl-5,5-dimethyl-4-oxohex-2-en-1-yl]-2-methyl-1H-imidazol-3-ium bromides (2a,b) in high yield upon
maintaining a mixture of bromo ketone 1 with 1-alkyl-2-methyl-1H-imidazoles in benzene at room temperature
for several days.
Under the same conditions, in contrast to the reactions of -bromodipnones, the reaction of bromo
ketone 1 with 1,2-dimethyl-1H-benzimidazole gives a quaternary benzimidazolium salt, namely, 3-[(2Z)-2-tert-
butyl-5,5-dimethyl-4-oxohex-2-en-1-yl]-1,2-dimethyl-1H-benzimidazol-3-ium bromide (2c) as indicated by
_______
*To whom correspondence should be addressed, e-mail: potikha_l@mail.ru.
1Taras Shevchenko Kyiv National University, 64 Volodymyrska St., 01033 Kyiv, Ukraine.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 355-363, February, 2012. Original
article submitted October 30, 2010. Revision submitted December 17, 2012.
334
0009-3122/12/4802-0334©2012 Springer Science+Business Media, Inc.

1H NMR spectroscopy. Bromide 2c could not be isolated as a pure compound because the sample prepared had
an impurity of starting 1,2-dimethyl-1H-benzimidazole, which, in an attempt to isolate the bromide 2c by
recrystallization, initiated subsequent transformations of this salt. The structures of salts 2a-c were established
1
using the H NMR and IR spectral data (Table 1), which are in accord with the previous results for 3-[(2Z)-
2-tert-butyl-5,5-dimethyl-4-oxohex-2-en-1-yl]-1-methyl-1H-imidazol-3-ium bromides [2].
Bu-
t
Bu-t
N
_
N
N
_
O
O
Me
Br
Br
Me
N
R
Bu-
t-Bu
t
+
N
+
N
Me
Bu-t
Bu-
t
O
Br
Me
Me
N
N
1
R
Me
2a,b
2c
K2CO3
Ac2O
O
K2CO3
Bu
t-
_
Bu-
t
Br
Bu- t
Bu-
+
N
t
+
_
N
MeONa
+
N
Br
Bu-
Me
_
Br
N
N
N
Bu-
t
t
R
Me
3a,b
5a
4
Me
Ar
O
_
_
Br
+
Br
Ar
+
N
O
N
B:
Ar
Me
Ar
Me
5b–d
N
N
R
R
2d–f
2, 3 a R = Me, b R = Bn; 2d, 5b R = Me, Ar = 4-BrC6H4; 2e, 5c R= Bn, Ar = 4-ClC6H4;
2f, 5d R = 4-BrC6H4CH2, Ar = 4-ClC6H4
Heating salts 2a-c in ethanol at reflux in the presence of potassium carbonate leads to the formation of
1-alkyl-6,8-di-tert-butyl-1,5-dihydroimidazo[1,2-a]azepin-4-ium bromides (3a,b) and 7,9-di-tert-butyl-5-methyl-
5,10-dihydroazepino[1,2-a]benzimidazol-11-ium bromide (4), respectively. The structures of these products
were established using the spectral data presented in Table 1. NOESY, HMQC, and HMBC data obtained for
salt 3b were used to establish the structures of compounds 3a,b and 4 as derivatives of the fused
diazolo[a]azepine system (Fig. 1). Salts 3b and 4 were obtained in both high yield and high purity, while the
1
sample of salt 3a contained up to 30% of an acyclic product. The H NMR spectrum of this mixture showed
signals of two methyl groups and one methylene group in the aliphatic region with shifts not in accord with
starting salt 2a along with the readily identified signals of imidazo[1,2-a]azepinium salt 3a. The IR spectrum of
the mixture showed a strong band at 1701 cm-1 in the region characteristic for unconjugated ketones. These
results indicate the formation of the product of the allylic rearrangement of salt 2a, namely, 3-(2-tert-butyl-
5,5-dimethyl-4-oxohex-1-en-1-yl)-1,2-dimethyl-1H-imidazol-3-ium bromide (5a).
A similar phenomenon of formation of an isomeric salt of type 5 was observed in our previous work [1]
in a study of the properties of 1-R-3-[(Z)-2,4-diaryl-4-oxo-2-butenyl]-2-methyl-1H-imidazol-3-ium bromides
2d-f. Comparison of the spectral data for bromides 5a and 5b isolated in pure state [1] supported our
conclusion concerning the structure of product 5a.
335

NOE
NOE
4.65
1.15
Bu-t
H
H
7.91
H
45.8
NOE
NOE
151.0
120.6
N
+
124.6
122.0
6.20
7.97
H
H
142.3
162.4
N
107.0
Bu-t
1.17
H
6.85
Ph
H
H
5.55
NOE
NOE
Fig. 1. Structurally significant HMBC (→) and NOESY correlations (↔) for salt 3b.
The conversion of diarylsubstituted imidazolium salts 2d-f into isomeric salts 5b-d by the action of base
results from the effect of the electron-withdrawing substituents (halogen atoms) on the benzene rings and at the
N-1 atom in the imidazole ring (when R = CH2Ar), while no formation of salts of type 5 occurs when R = Me and
Ar = Ph [1]. Such substituents facilitate deprotonation at C-1' by initiating formation of product 5 through the
scheme 2→6→7→5. The existence of species with structure 7 was supported by the results of the reactions of
1-R-3-[(2Z)-2,4-diaryl-4-oxobut-2-en-1-yl]-1H-benzimidazol-3-ium bromides, which may convert to {1-[2-
(alkylamino)phenyl]-4-phenyl-1H-pyrrol-3-yl}(phenyl)methanones by the action of base [3]. Different behavior
is noted for di-tert-butyl derivatives 2a-c: a stronger electron-donor substituent is found at C-1' in bromide 2a
(the N-methylimidazole residue), while the formation of products of type 5 could not be detected when more
electron-withdrawing substituents are present (the N-benzimidazole residue in salt 2b or the N-methyl-
benzimidazole residue in salt 2c). Hence, we may conclude that the mechanism for the formation of bromide 5a
is different. It is known that ,-unsaturated ketones may enolize in different ways, for example,
photochemically or by the action of base and acid catalysts [4, 5]. Apparently dienol 8 is formed when the
reaction is carried out in ethanol in the case of salt 2a, which has electron-donor substituents in the enone
fragment (t-Bu groups), which enhance the basicity of the carbonyl group oxygen atom. Then, the action of
_
Br
+
N
R
R
R
+
+
Y
Y
N
R
R
O
O
R1
R
OH
B:
O
7
10
6
BH+
R
R
R
BH+
B:
O
R
+
Y
2
+
Y
BH+;
Ac2O
R
R
5
B:
+
Y
+
Y

R
R
BH+
O
XO
9
8
+
+
=
N
Y
; X = H, Ac
336

base induces formation of enolate 9, whose -protonation leads to structure 5. The extension of the conjugated
bond system in the structure of salt 5a in comparison with compound 2a likely is an additional factor favoring
the formation of this product. Hence, acid catalysts may facilitate the conversion of compound 2a to 5a. Indeed,
imidazolium bromide 5a is obtained as a pure compound in 79% yield upon heating salt 2a in acetic anhydride.
The structure of salt 5a was supported by the NOE experiment data, which also permitted us to determine
E-configuration for this product: saturation of the 3'-CH2 methylene group gave increased intensity of the
signals of both tert-butyl groups and the signal of H-4, while saturation at the frequency of the signal for 1'-CH
gave increased intensity of the for the 2'-t-Bu group and H-4 ( < 4%) signals.
TABLE 1. Spectral Characteristics of Compounds 2-11
1Н NMR spectra (DMSO-d6), , ppm (J, Hz)
Com-
IR spectra, , сm–1
Protons at С-sp2
Protons at С-sp3
pound
1
2
3
4
2a
2b
7.62 (1Н, br. s, Н-5);
7.19 (1Н, br. s, Н-4);
6.89 (1Н, s, 3'-CH)
4.88 (2Н, s, 1'-CН2);
3.81 (3Н, s, 1-СН3);
2.72 (3Н, s, 2-СН3);
1.14 (9Н, s, 4'-С(СН3)3);
1.07 (9Н, s, 2'-С(СН3)3)
3098, 2963, 2868,
1678 (С=О), 1620,
1477, 1368, 1239,
1091, 786
7.74 (1Н, d, 3J = 2.0, Н-5);
7.43–7.39 (3Н, m, Н-3,4,5 Ph);
7.31 (2Н, d, 3J = 7.5, Н-2,6 Ph);
7.25 (1Н, d, 3J = 2.0, Н-4);
6.82 (1Н, s, 3'-CH)
5.48 (2Н, s, 1-СН2Ph);
4.94 (2Н, s, 1'-CН2);
2.76 (3Н, s, 2-СН3);
1.16 (9Н, s, 4'-С(СН3)3);
1.01 (9Н, s, 2'-С(СН3)3)
3126, 3070, 2969,
2868, 1678 (С=О),
1622, 1477, 1368,
1094, 730, 699
2c*
8.01 (1Н, d, 3J = 7.5, Н-4);
7.94 (1Н, d, 3J = 7.5, Н-7);
7.80 (2Н, m, Н-5,6);
5.42 (2Н, s, 1'-CН2);
4.04 (3Н, s, 1-СН3);
3.02 (3Н, s, 2-СН3);
1.27 (9Н, s, 4'-С(СН3)3);
0.65 (9Н, s, 2'-С(СН3)3)
–
6.66 (1Н, s, 3'-CH)
2i
8.96 (2Н, d, 3J = 8.0, Н-2,6);
8.63 (1Н, t, 3J = 8.0, Н-4);
8.16 (2Н, t, 3J = 8.0, Н-3,5);
7.04 (1Н, s, 3'-CH)
5.51 (2Н, s, 1'-CН2);
1.14 (9Н, s, 4'-С(СН3)3);
1.07 (9Н, s, 2'-С(СН3)3)
3036, 2958, 1673
(С=О), 1620, 1488,
1371, 1097, 864,
775, 683
2j
8.49 (2Н, m, Н-4,6);
5.25 (2Н, s, 1'-CН2);
2.97 (3Н, s, 2-СН3);
1.21 (9Н, s, 4'-С(СН3)3);
1.04 (9Н, s, 2'-С(СН3)3)
3036, 2975,2868,
1676 (С=О), 1628,
1603, 1496, 1477,
1099, 1012, 783
8.12 (1Н, d, 3J = 7.5, Н-3);
7.85 (1Н, t, 3J = 7.5, Н-5);
7.05 (1Н, s, 3'-CH)
3a
3b
7.92 (1Н, br. s, Н-2);
7.83 (1Н, br. s, Н-3);
6.85 (1Н, s, Н-9);
6.26 (1Н, s, Н-7)
7.97 (1Н, d, 3J = 1.5, Н-2);
7.91 (1Н, d, 3J = 1.5, Н-3);
7.42 (2Н, m, Н-3,5 Ph);
7.38 (1Н, m, Н-4 Ph);
7.33 (2Н, d, 3J = 8.0, Н-2,6 Ph);
6.85 (1Н, s, Н-9);
4.65 (2Н, s, 5-СН2);
3.86 (3Н, s, 1-СН3);
1.24 (9Н, s, 8-С(СН3)3);
1.16 (9Н, s, 6-С(СН3)3)
3008, 2964, 2868,
1636, 1594, 1469,
1368, 1250, 1242,
814, 797
5.56 (2Н, s, 1-СН2Ph);
4.65 (2Н, s, 5-СН2);
1.17 (9Н, s, 8-С(СН3)3);
1.15 (9Н, s, 6-С(СН3)3)
3092, 2969, 1636,
1594, 1474, 1457,
1368, 1178, 733, 710
6.20 (1Н, s, Н-7)
4
8.40 (1Н, m, Н-1); 8.00 (1Н, m, Н-4); 4.91 (2Н, s, 10-CН2);
2964, 1636, 1586,
1564, 1474, 1413,
772
7.67 (2Н, m, Н-2,3);
7.10 (1Н, s, Н-6);
6.42 (1Н, s, Н-8)
4.08 (3Н, s, 5-СН3);
1.32 (9Н, s, 7-С(СН3)3);
1.22 (9Н, s, 9-С(СН3)3)
5a
7.66 (1Н, d, 3J = 1.5, Н-5);
7.34 (1Н, d, 3J = 1.5, Н-4);
6.73 (1Н, s, 1'-CH)
3.77 (3Н, s, 1-СН3);
3.49 (2Н, s, 3'-CН2);
2.51 (3Н, s, 2-СН3);
1.11 (9Н, s, 2'-С(СН3)3);
0.99 (9Н, s, 4'-С(СН3)3)
3053, 2969, 2868,
1701 (С=О), 1533,
1477, 1415, 1368,
1259, 1063, 1013,
772, 655
5e*2
9.74 (1Н, s, Н-2);
4.90 (2Н, m, СН2СN);
3.55 (2Н, s, 3'-CН2);
3.31 (2Н, m, 1-СН2);
1.19 (9Н, s, 2'-С(СН3)3);
0.86 (9Н, s, 4'-С(СН3)3)
1703 (С=О), 1555,
1480, 1365, 1063
8.23 (2Н, m, Н-4,7);
4.76 (2Н, m, Н-5,6);
7.02 (1Н, s, 1'-CH)
337

TABLE 1 (continued)
1
2
3
4
5f
8.71 (1Н, d, 3J = 7.5, Н-6);
8.54 (1Н, t, 3J = 7.5, Н-4);
8.12 (1Н, d, 3J = 7.5, Н-3);
7.96 (1Н, t, 3J = 7.5, Н-5);
7.21 (1Н, s, 1'-CH)
3.54 (2Н, s, 3'-CН2);
2.78 (3Н, s, 2-СН3);
1.15 (9Н, s, 2'-С(СН3)3);
0.87 (9Н, s, 4'-С(СН3)3)
3013, 2972, 2873,
1708 (С=О), 1625,
1496, 1470, 1367,
1062, 799
11а
7.76 (1Н, d, 3J = 8.5, Н-8);
7.55 (1Н, s, Н-3);
2.67 (3Н, s, СН3)
7.47 (2Н, d, 3J = 8.0, Н-2',6');
7.28 (1Н, t, 3J = 8.0, Н-4');
7.19 (2Н, d, 3J = 8.0, Н-2'',6'');
7.16–7.06 (6Н, m,
Н-7,3',5',3'',4'',5'');
6.77 (1Н, d, 3J = 7.0, Н-6)
11b
8.22 (1Н, d, 3J = 6.0, Н-5);
7.46 (1Н, s, Н-3);
1.30 (9Н, s, СОС(СН3)3);
1.27 (9Н, s, 2-С(СН3)3)
2958, 1645 (С=О),
1505, 1399, 1357,
1306, 929, 744, 730,
680, 649
7.28 (1Н, d, 3J = 8.0, Н-8);
6.84 (1Н, t, 3J = 7.5, Н-7);
6.59 (1Н, t, 3J = 7.0, Н-6)
11c
7.22 (2Н, m, Н-3,8);
6.84 (1Н, m, Н-7);
6.53 (1Н, m, Н-6)
1.33 (9Н, s, СОС(СН3)3);
1.27 (9Н, s, 2-С(СН3)3);
1.09 (3Н, s, 5-СН3)
2958, 1653 (С=О),
1599, 1477, 1463,
1362, 1231, 929,
769, 738, 669
_______
*The signals for the major component, 2c (60%), are given.
*2The 1H NMR and IR signals are given after subtraction of the corresponding
spectra of compound 2g [6] from the spectra of the mixture of 2g+5e.
Salt 5a proved more stable upon heating with base than its isomer, salt 2a. However, the cyclization of
salt 5a could be achieved in the presence of MeONa to give imidazoazepine 3a as a pure compound.
Thus, these findings for the transformation of salt 2a into 5a support our previous proposals concerning
the scheme of cyclization of 3-[(2Z)-2,4-diaryl-4-oxobut-2-en-1-yl]-1-(2-cyanoethyl)-1H-imidazol-3-ium
bromide [6] and 3-[(2Z)-2-tert-butyl-5,5-dimethyl-4-oxohex-2-en-1-yl]-1-methyl-1H-imidazol-3-ium bromide
[2] upon heating their solutions in acetic anhydride. The reaction proceeds through the pathway 2→8→9.
-Protonation is achieved by means of an internal source, namely, H-2 proton in the imidazole fragment, which
induces cyclization to give imidazo[1,2-a]pyridinium derivatives 10. This scheme can be used to explain the
failure to effect cyclization of 1H-benzimidazol-3-ium and 1H-1,2,4-triazol-4-ium salts of type 2 derived from
-bromodipnone [6] using acetic anhydride as the solvent as a consequence of the electron-withdrawing effect
of the -substituent (Y+) in ketones of type 2, which lower the probability of their conversion to dienol 8.
However, when electron-donor substituents (R = t-Bu) are found in the enone fragment, the probability of
forming the dienol increases.
Thus, heating 3-[(2Z)-2-tert-butyl-5,5-dimethyl-4-oxohex-2-en-1-yl]-1-(2-cyanoethyl)-1H-benzimidazol-
3-ium bromide (2g) in acetic anhydride [6] gives 3-[(2Z)-2-tert-butyl-5,5-dimethyl-4-oxohex-1-en-1-yl]-1-(2-cyano-
ethyl)-1H-benzimidazol-3-ium bromide (5e). Conversion efficiency carrying out this reaction heated for 30 min
is about 50%. Further heating leads only to the accumulation of undetermined side products, which, in
particular, may indicate the formation of an equilibrium mixture of species of types 2 and 5 in acetic anhydride
solution. The composition of the mixture was determined from the spectral data. The presence of species of type
5 is indicated primarily by the presence in the IR spectrum of the C=O band at 1703 cm-1 characteristic for
unconjugated ketones. The 1H NMR spectrum of the mixture shows a double set of signals for the protons of the
isomeric structures with approximately equal intensity. Some of the key signals for compound 5e, namely, H-2,
1'-CH, and 3'-CH2, may be reliably assigned. Attempts to isolate compound 5e from the product mixture by
crystallization or chromatography were unsuccessful, presumably due to the greater reactivity of this
338

compound in comparison with its isomer 2g. This conclusion can be drawn from an analysis of the position of
the signal for H-2 proton in the isomeric structures. This signal is located at lower field in compound 5e than in
compound 2g [6].
Bu-
t
_
_
O
Br
Br
Bu-t
+
N
+
N
O
Ac2O
Bu- t
t
Bu-
N
N
(CH2)2CN
(CH2)2CN
5e
2g
Bu-
t
_
Br
_
O
Br
R
Bu-t
R
Me
+
N
+
N
O
N
Ac2O
Bu-
t
1
Bu-t
2i,j
5f
Et3N
Et3N
_
Ph
R
Br
O
Ac2O
N
R1
O
Me
+
N
Ph
R1
2h
11a–c
2 i R = H, j R = Me; 11 a R= Me, R1 = Ph, b R = H, R1 = t-Bu, c R = Me, R1 = t-Bu
An additional type of heterocyclization of -substituted quaternary salts derived from enones, in which
enolization is a key condition, involves transformation of 1-[(2Z)-4-oxo-2,4-diphenylbut-2-en-1-yl]pyridinium
salts by the action of bases to give indolizines [7, 8]. The data already obtained on the mechanism of reactions
proceeding upon heating quaternary azolium salts 2a-g in acetic anhydride suggest that similar effects would by
found also for pyridinium salts. Indeed, prolonged heating of 2-methyl-1-[(2Z)-4-oxo-2,4-diphenylbut-2-en-
1-yl]pyridinium bromide (2h) [7] at reflux in acetic anhydride (8 h) leads to cyclization and formation of
phenyl(5-methyl-2-phenylindolizin-1-yl)methanone (11a). However, the conversion of salt 2h to the cyclic product
1
11a under these conditions is very low (<15%). The formation of compound 11a was established by H NMR
spectroscopy and HPLC/MS. Under the same conditions, a dialkyl analog, namely, 1-(2-tert-butyl-5,5-di-
methyl-4-oxohex-2-en-1-yl)-2-methylpyridinium bromide (2j) gives 1-(2-tert-butyl-5,5-dimethyl-4-oxohex-1-en-
1
1-yl)-2-methylpyridinium bromide (5f) in 89% yield. The reaction time in this case was 30 min. The H NMR
and IR spectra of isomeric salts 2j and 5f show the same differences as for the pairs 2a,5a and 2g,5e examined
above. Thus, the behavior of the pyridinium salts confirms the regularities found: electron-withdrawing
substituents decrease the probability of formation of dienol 8, while electron-donor substituents facilitate the
formation of this product. Subsequent reketonization in these pyridinium salts may proceed through two
pathways: by addition to the electrophilic pyridine ring carbon atom, leading to formation of cyclic product 11
or through -protonation by means of an acid. The second pathway is evidently favored.
339

Upon the action of base (Et3N in acetone), di-tert-butyl-substituted pyridinium salts 2i,j, similar to their
diphenyl analogs of type 2h, readily form zwitter-ionic species of type 7 and cyclize to give 1-(2-tert-
butylindolizin-1-yl)-2,2-dimethylpropan-1-ones 11b,c in good yield. A similar result was obtained also in
reaction with isomeric salt 5f.
Summarizing the results presented in this paper we can conclude that quaternary diazolium and
pyridinium salts derived from (4Z)-5(bromomethyl)-2,2,6,6-tetramethylhept-4-en-3-one are readily converted to
allylic rearrangement products. Acid catalysis facilitates this reaction. The allylic rearrangement products,
namely, salts 5a,f, are more stable in the presence of base than the starting derivatives with enone structure
(salts 2a-c,i,j). Intramolecular cyclization by the action of bases in both cases leads to products with identical
structure. The imidazolium salts give 1-alkyl-6,8-di-tert-butyl-1,5-dihydroimidazo[1,2-a]azepin-4-ium bromides
3, while the pyridinium salts give 1-(2-tert-butylindolizin-1-yl)-2,2-dimethylpropan-1-ones 11.
EXPERIMENTAL
The IR spectra were recorded on a Perkin-Elmer Spectrum BX spectrometer using KBr pellets. The 1H
NMR spectra were recorded on a Bruker Avance DRX-500 spectrometer at 500 MHz. The two-dimensional
correlation spectroscopy experiments were carried out on a Varian Mercury 400 spectrometer at 400 MHz for
1H NMR spectra and 100 MHz for 13C NMR spectra with TMS as internal standard. The purity of the products
was monitored by HPLC/MS on an Agilent 1100 Series mass spectrometer with an Agilent LC/MSD SL
selective detector. The sample was introduced in a CF3CO2H matrix. Electron impact ionization was used.
1-Alkyl-3-[(2Z)-2-tert-butyl-5,5-dimethyl-4-oxohex-2-en-1-yl]-2-methyl-1H-imidazol-3-ium Bromides
2a,b (General Method). 1-Alkyl-2-methyl-1H-imidazole (3.32 mmol) was added to a solution of bromo ketone
1 (0.87 g, 3.32 mmol) in benzene (30 ml). The mixture was maintained for 24-48 h at room temperature. The
precipitate formed was filtered off, washed with acetone, and recrystallized from nitromethane.
3-[(2Z)-2-tert-Butyl-5,5-dimethyl-4-oxohex-2-en-1-yl]-1,2-dimethyl-1H-imidazol-3-ium Bromide (2a).
Yield 0.95 g (80%); mp 148-150°C (MeNO2). Found, %: C 57.01; H 8.20; Br 22.33; N 7.90. С17H29BrN2O.
Calculated, %: C 57.14; H 8.18; Br 22.36; N 7.84.
1-Benzyl-3-[(2Z)-2-tert-butyl-5,5-dimethyl-4-oxohex-2-en-1-yl]-2-methyl-1H-imidazol-3-ium Bromide
(2b). Yield 1.14 g (79%); mp 198–200°C (MeNO2). Found, %: C 63.65; H 7.70; Br 18.47; N 6.43. С23H33BrN2O.
Calculated, %: C 63.74; H 7.67; Br 18.44; N 6.46.
1-[(2Z)-2-tert-Butyl-5,5-dimethyl-4-oxohex-2-en-1-yl]pyridinium bromides 2i,j were obtained
according to the procedure for the preparation of bromides 2a,b using pyridine or 2-methylpyridine.
1-[(2Z)-2-tert-Butyl-5,5-dimethyl-4-oxohex-2-en-1-yl]pyridinium Bromide (2i). Yield 1.01 g (90%);
mp 186–188°C (MeNO2). Found, %: C 59.91; H 7.64; Br 23.50; N 4.18. С17H26BrNO. Calculated, %: C 60.00;
H 7.70; Br 23.48; N 4.12
1-[(2Z)-2-tert-Butyl-5,5-dimethyl-4-oxohex-2-en-1-yl]-2-methylpyridinium Bromide (2j). Yield
0.95 g (81%); mp 176-178°C (MeNO2). Found, %: C 60.96; H 8.02; Br 22.59; N 3.98. С18H28BrNO. Calculated,
%: C 61.02; H 7.97; Br 22.55; N 3.95.
6,8-Di-tert-butyl-1-methyl-1,5-dihydroimidazo[1,2-a]azepin-4-ium Bromide (3a). Sodium (0.25 g,
11 mmol) was dissolved in ethanol (25 ml), and salt 5a (0.71 g, 2.00 mmol) was added with stirring. The
mixture was heated at reflux for 1 h. The solvent was evaporated to 50% of original volume. The precipitate was
filtered off and washed with diethyl ether. Yield 0.54 g (80%); mp 252-254°C (2-PrOH). Found, %: C 60.03;
H 7.97; Br 23.56; N 8.30. С17H27BrN2. Calculated, %: C 60.16; H 8.02; Br 23.55; N 8.26.
1-Benzyl-6,8-di-tert-butyl-1,5-dihydroimidazo[1,2-a]azepin-4-ium Bromide (3b). A mixture of salt
2b (0.50 g, 1.15 mmol) and potassium carbonate (0.32 g, 2.3 mmol) in ethanol (15 ml) was heated at reflux for
1 h. After cooling, the precipitate was filtered off. The solvent was evaporated off the filtrate, and 2-propanol
340

(30 ml) was added to the residue. The precipitate formed was filtered off and washed with a small amount of
2-propanol. Yield 0.41 g (86%); mp 155-156°C (2-PrOH). 13С NMR spectrum (DMSO-d6), , ppm: 162.4 (C-8);
151.0 (C-6); 142.3 (C-9a); 135.4 (C-1 Ph); 129.7 (C-3,5 Ph); 129.3 (C-4 Ph); 128.7 (C-2,6 Ph); 124.7 (C-2);
122.0 (C-7); 120.6 (C-3); 107.0 (C-9); 51.5 (1-CH2); 45.8 (C-5); 38.1 (8-C(CH3)3); 37.6 (6-C(CH3)3); 29.8
(8-C(CH3)3); 28.3 (6-C(CH3)3). Found, %: C 66.42; H 7.56; Br 19.20; N 6.77. С23H31BrN2. Calculated, %:
C 66.50; H 7.52; Br 19.23; N 6.74.
7,9-Di-tert-butyl-5-methyl-5,10-dihydroazepino[1,2-a]benzimidazol-11-ium Bromide (4). 1,2-Di-
methyl-1H-benzimidazole (0.49 g, 3.32 mmol) was added to a solution of bromo ketone 1 (0.87 g, 3.32 mmol)
in benzene (30 ml). The mixture was maintained for 72 h at room temperature. The precipitate formed was
filtered off and washed with acetone to give a 3:2 mixture of 3-[(2Z)-2-tert-butyl-5,5-dimethyl-4-oxohex-2-en-
1-yl]-1,2-dimethyl-1H-benzimidazol-3-ium bromide (2c) and the starting benzimidazole. The mixture was
dissolved in ethanol (15 ml). Then, potassium carbonate (0.30 g) was added and the mixture was heated for 1 h.
After cooling, the precipitate was filtered off. The solvent was evaporated off the filtrate and 2-propanol (30 ml)
was added to the residue. The precipitate formed was filtered off and washed with a small amount of
2-propanol. Yield 0.58 g (45%); mp 182–184°C (2-PrOH). Found, %: C 64.66; H 7.55; Br 20.50; N 7.20.
С21H29BrN2. Calculated, %: C 64.78; H 7.51; Br 20.52; N 7.20.
3-(2-tert-Butyl-5,5-dimethyl-4-oxohex-1-en-1-yl)-1,2-dimethyl-1H-imidazol-3-ium Bromide (5a).
Salt 2a (1 g, 2.80 mmol) was dissolved in acetic anhydride (15 ml) and heated at reflux for 20 min. The solvent
was evaporated off in vacuum, and acetone (20 ml) was added to the residue. The precipitate formed was
filtered off and washed with acetone. Yield 0.79 g (79%); mp 232-234°C (2-PrOH). Found, %: C 56.95; H 8.20;
Br 22.40; N 7.81. С17H29BrN2O. Calculated, %: C 57.14; H 8.18; Br 22.36; N 7.84.
1-(2-tert-Butyl-5,5-dimethyl-4-oxohex-1-en-1-yl)-2-methylpyridiniium bromide (5f) was obtained
analogously to the preparation of bromide 5a, using bromide 2j. Yield 0.85 g (86%); mp 201-202°C (MeCN).
Found, %: C 60.93; H 8.00; Br 22.60; N 3.92. С18H28BrNO. Calculated, %: C 61.02; H 7.97; Br 22.55; N 3.95.
(5-Methyl-2-phenylindolizin-1-yl)(phenyl)methanone (11a). 2-Methyl-1-[(2Z)-4-oxo-2,4-diphenyl-
but- 2-en-1-yl]pyridinium bromide 2h [7] (1 g, 2.54 mmol) was dissolved in acetic anhydride (25 ml) and
heated at reflux for 8 h. The solvent was evaporated in vacuum, and diethyl ether (20 ml) was added to the
residue. The precipitate formed was filtered off, washed with ether, and recrystallized thrice from 2-propanol.
Yield 0.08 g (11%); mp 132-133°C (2-PrOH) (mp 135°C [7]).
1-(2-tert-Butylindolizin-1-yl)-2,2-dimethylpropan-1-ones 11b,c (General Method). Triethylamine
(1 ml) was added to a suspension of pyridinium salt 2i,j or 5f (2 mmol) in acetone (30 ml) and heated at reflux
for 2 h. After cooling, the precipitate formed was filtered off and washed with acetone.
1-(2-tert-Butylindolizin-1-yl)-2,2-dimethylpropan-1-one (11b). Yield 0.42 g (81%); mp 80-82°C
(2-PrOH). Found, %: C 79.15; H 9.20; N 5.45. С17H23NO. Calculated, %: C 79.33; H 9.01; N 5.44.
1-(2-tert-Butyl-5-methylindolizin-1-yl)-2,2-dimethylpropan-1-one (11c). The yield from salt 2j was
0.37 g (68%), while the yield from salt 5f was 0.38 g (70%); mp 75–77°C (2-PrOH). Found, %: C 79.53;
H 9.31; N 5.20. С18H25NO. Calculated, %: C 79.66; H 9.28; N 5.16.
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