Solvent-free alkylation of N-heteroaromatic compounds by RCOOH-Pb(OAc) 4 system

Article abstract of DOI:10.1007/s11172-005-0347-8

The solvent-free decarboxylation of carboxylic acids by Pb(OAc)₄ affords alkyl radicals, which alkylate 4-methylpyridine, quinoline, and 4-methylquinoline protonated with 2-chlorobenzoic acid. Mechanical activation is required for pyrazine alky

Full text of DOI:10.1007/s11172-005-0347-8

Russian Chemical Bulletin, International Edition, Vol. 54, No. 4, pp. 997—1002, April, 2005
997
Solventꢀfree alkylation of Nꢀheteroaromatic compounds
by RCOOH—Pb(OAc)4 system*
G. I. Nikishin,a L. L. Sokova,a V. M. Makhaev,b and N. I. Kapustinaaꢀ
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation. 47.
Fax: +7 (095) 135 5328. Еꢀmail: Nika@ioc.ac.ru
bInstitute of New Chemical Problems, Russian Academy of Sciences,
142432 Chernogolovka, Moscow Region, Russian Federation
The solventꢀfree decarboxylation of carboxylic acids by Pb(OAc)4 affords alkyl radiꢀ
cals, which alkylate 4ꢀmethylpyridine, quinoline, and 4ꢀmethylquinoline protonated with
2ꢀchlorobenzoic acid. Mechanical activation is required for pyrazine alkylation.
Key words: carboxylic acids, Nꢀheteroaromatic compounds, lead tetraacetate, oxidative
decarboxylation, alkylation, mechanical activation, solventꢀfree reaction.
Lead tetraacetate, being one of the reagents that are
most widely used in organic chemistry, long ago and firmly
has become a used efficient oxidant of functionalized orꢀ
ganic compounds. Among the variety of reactions involvꢀ
ing Pb(OAc)4, oxidative decarboxylation of carboxylic
acids plays an important role. Many carboxylic acids were
transformed into unsaturated hydrocarbons and haloꢀ and
acetoxyalkanes by Pb(OAc)4 and Pb(OAc)4 in combinaꢀ
tion with LiCl, Cu(OAc)2, and I2.1 The reactions were
carried out in the liquid phase in inert solvents.
changes and, as a sequence, different products are formed.
Alkanꢀ1ꢀoles in a benzene solution convert to 4ꢀchloroꢀ
alkanols, while esters are formed in the solid phase4
(Scheme 1).
Scheme 1
We began to use Pb(OAc)4 in solventꢀfree chemical
processes in the solid phase with and without mechanical
activation. Under these conditions, the selectivity and
yield of target products can be higher than in soluꢀ
tion. For example, naphthalene halogenation by the
Pb(OAc)4—LiCl(Br) system affords 1ꢀhalonaphthalene as
the main product along with 1,4ꢀdihalonaphthalene.
1ꢀHalonaphthalene is formed in the solid phase with a
higher selectivity than in the liquid phase.2 A similar efꢀ
fect was observed for the oxoalkylation of pyridines with
oxoalkyl radicals generated from 1ꢀalkylcycloalkanols unꢀ
der the action of Pb(OAc)4. In the solid phase, the radiꢀ
cals substitute hydrogen in the pyridine ring and are conꢀ
sumed in side reactions only by 5—20%; the fraction of
side reactions increases to 35—45% in an AcOH solution.3
Basically important results were obtained for the
oxidation of alkanꢀ1ꢀols and alkanedioic acids by a
Pb(OAc)4—metal chloride system: on going from the liqꢀ
uid to solid phase, the mechanism of these reactions
i. Solid phase. ii. Liquid phase.
Adipic acid in an acetic acid solution undergoes ring
closure to form δꢀvalerolactone, while in the solid phase
it is transformed into 1,4ꢀdichlorobutane (Scheme 2).5
Scheme 2
i. Solid phase. ii. Liquid phase.
* Dedicated to Corresponding Member of the Russian Acadꢀ
emy of Sciences E. P. Serebryakov on the occasion of his
70th birthday.
In this work, we continue our study of the solventꢀfree
reactions of Pb(OAc)4 with alcohols and carboxylic acids
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 973—978, April, 2005.
1066ꢀ5285/05/5404ꢀ0997 © 2005 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 54, No. 4, April, 2005
Nikishin et al.
with and without mechanical activation. The task was to
use carboxylic acids as alkylating agents for Nꢀheteroꢀ
aromatic compounds. To solve this problem, we chose
acids with different structures: hexanoic (1а), octaꢀ
noic (1b), 2ꢀmethylpropanoic (1с), 2ꢀethylhexanoic (1d),
3ꢀmethoxycarbonylpropanoic (1е), 3ꢀphenylpropaꢀ
noic (1f), and phenylacetic (1g). In addition, a series of
Nꢀheterocyclic compounds was studied: 4ꢀmethylpyriꢀ
dine (2), quinoline (3), 4ꢀmethylquinoline (4), and
pyrazine (5). The heterocycles were alkylated with
Cꢀradicals generated from acids 1а—f under the action of
Pb(OAc)4 (Scheme 3).
heteroaromatic compound 2—4), a viscous but still agile
mixture was formed and slowly solidified. The boundary
of phase changing in time was estimated visually. We
understand that this estimate only approximately characꢀ
terizes the phase state of the reaction mixture. Nevertheꢀ
less, these two steps are real, reflected in specific features
of the reactions of Nꢀheteroaromatic compounds with
acids, and expressed in particular figures. For instance,
the following characteristics were obtained for the reacꢀ
tions of 4ꢀmethylpyridine 2 with acids 1b and 1d: the time
of transition of the liquid phase into solid is ~26 and ~6 h,
respectively; the conversion of Pb(OAc)4 within this time
is 60 and 58%; and the yields of products 6b and 6d are 28
and 36%, respectively. Comparing these results with the
final yields of products 6b and 6d (63 and 71%, see Table 1,
entries 4 and 10) for the 100% conversion of the oxidant,
we can conclude that in the final step Pb(OAc)4 is more
purposefully consumed for alkylation and, to a less exꢀ
tent, for side reactions than in the initial step. This fact is
explained, most likely, by the transition of the reacting
system from the liquid to solid phase. As a whole, the
solventꢀfree alkylation of heterocycles 2—4 is characterꢀ
ized by the higher conversion of acids 1, yield of prodꢀ
ucts, and selectivity of the reactions than that in solution
using benzene as solvent and CF3COOH as a protonating
agent (see Table 1). These parameters are sharply worsꢀ
ened when trifluorobenzoic acid is replaced by CBA in a
benzene solution (entry 6). The replacement of CBA by
CF3COOH in the solventꢀfree reaction results in a fast
decomposition of Pb(OAc)4, which is not accompanied
by decarboxylation of acids 1 and generation of Cꢀradiꢀ
cals (entry 3). One of the reasons for the low conversion
(~35—55%) of acids 1 by alkylation in solution (benꢀ
zene + trifluoroacetic acid) is that Pb(OAc)4 is actively
reduced in the parallel reaction with Nꢀbases 2—4 involvꢀ
ing no acids 1. Indeed, in an experiment similar to entry 4
(see Table 1) but without acid 1b, the conversion of
Pb(OAc)4 was ~80%. This reaction is also solventꢀfree
but makes a lower contribution to the overall conversion
process PbIV acetate → PbII acetate.
Scheme 3
R = nꢀC5H11 (a), nꢀC7H15 (b), Pri (c), BunCH(Et) (d),
MeO2CCH2CH2 (e), PhCH2CH2 (f), PhCH2 (g)
The necessary condition for this process to occur is
the involvement of protonated Nꢀheterocycles 2—5. Proꢀ
tonation provides easy addition of nucleophilic Cꢀcenꢀ
tered radicals to an electrophilic heterocycle bearing a
positive charge.6 2ꢀChlorobenzoic acid (CBA), which was
earlier used successfully for the oxoalkylation of Nꢀhetꢀ
erocyclic compounds by 1ꢀalkylcycloalkanols, served as a
protonating agent.3 Benzoic acid can play the same role.
However, alkylation involving this acid proceeds less effiꢀ
ciently than that with CBA. The use of acetic and
trifluoroacetic acids for protonation of heterocycles 2—5
afforded no alkylation products.
The results of the solventꢀfree reactions of acids 1a—f
and bases 2—5 are presented in Tables 1 and 2. For comꢀ
parative estimation, experiments carried out under "usual"
conditions (in a benzene solution at 80 °C) are also inꢀ
cluded in the tables. The data indicate that alkylation
without mechanical activation primarily occurs in the liqꢀ
uid phase and is completed in the solid phase. In fact,
after mixing the reagents (Pb(OAc)4, RCOOH, CBA, and
According to the data in Table 1 (entries 4, 10, 20,
and 22), the reactivity of 4ꢀmethylquinoline 4 in the reacꢀ
tion with acids 1b and 1d is almost the same as that of
4ꢀmethylpyridine 2; alkylation occurs to position 2 of the
quinoxaline system to form 2ꢀheptylꢀ4ꢀmethylquinoline
(7b) and 2ꢀ(heptꢀ3ꢀyl)ꢀ4ꢀmethylquinoline (7d), respecꢀ
tively. Heptꢀ3ꢀyl radicals formed by alkylation with acid
1d attack, to an equal extent, both reaction centers of
quinoline to give two isomeric products with the alkyl
substituent in positions 2 and 4 (8d and 9d). Oxoalkyl
radicals generated from 1ꢀmethylcycloalkanols by
Pb(OAc)4 behave similarly in the solidꢀphase reaction.3
The results of oxidative decarboxylation of phenylaceꢀ
tic acid (1g) in the presence of CBAꢀprotonated base 2
are unexpected. Unlike Cꢀradicals generated from acids

Alkylation of Nꢀheteroaromatic compounds
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 4, April, 2005
999
Table 1. Solventꢀfree alkylation of Nꢀheteroaromatic compounds (4ꢀmethylpyridine (2), quinoline (3), and 4ꢀmethylꢀ
quinoline (4)) protonated with carboxylic acids 1 under the action of Pb(OAc)4 without mechanical activationа
Entry
Reagents
Protonating acid
τ/h
Conversionb 1 (%)
Product
Yieldc (%)
58 (89)
1
2
3
4
5d
6d,e
7
8
9
10
11d
12
13d
14
15d
16
17 f
18 g
1a +2
1b + 2
1b + 2
1b + 2
1b + 2
1b + 2
1с + 2
1с + 2
1с + 2
1d + 2
1d + 2
1e + 2
1e + 2
1f + 2
1f + 2
1g + 2
1g + 2
1d + 3
2ꢀClC6H4CООH
АсОH
CF3COOH
2ꢀClC6H4CООH
CF3COOH
2ꢀClC6H4COOH
АсОH
C6H5CООH
2ꢀClC6H4CООH
2ꢀClC6H4CООH
CF3COOH
2ꢀClC6H4CООH
CF3COOH
48
48
0.25
48
0.75
1.5
72
72
24
24
0.75
48
0.75
48
0.75
48
4
24
65
—
—
69
38
—
—
55
87
75
46
54
32
94
65
72
49
80
6a
—
—
6b
6b
6b
—
6c
6c
6d
6d
6e
6e
6f
63 (91)
36 (94)
16
51 (95)
77 (88)
71 (95)
45 (98)
53 (98)
30 (93)
91 (97)
64 (98)
64
2ꢀClC6H4CООH
CF3COOH
2ꢀClC6H4CООH
2ꢀClC6H4CООH
2ꢀClC6H4CООH
6f
10
10
8d
9d
8d
9d
7b
7b
7d
7d
44
35 (2)
41 (4)
23 (2)
29 (4)
65 (95)
40 (93)
72 (94)
44 (98)
19 d,h
1d + 3
CF3COOH
0.5
55
20
1b + 4
1b + 4
1d + 4
1d + 4
2ꢀClC6H4CООH
CF3COOH
2ꢀClC6H4CООH
CF3COOH
48
0.75
24
68
43
77
48
21d
22
23d
0.75
а Molar ratio 1 : 2—4 : Pb(OAc)4 : protonating acid = 1 : 4 : 1.1 : 4; 20 °C; 1, 5 mmoles.
b The conversion of Pb(OAc)4 is ~100%.
с The yield is presented with respect to the starting (in parentheses, with respect to converted) acid 1.
d Reaction in a benzene solution (10 mL) at 80 °C.
e The conversion of 1b was not determined.
f The reaction was carried out with mechanical activation.
g The overall yield of two isomers is 76 (95).
h The overall yield of two isomers is 52 (95).
а
Table 2. Alkylation of pyrazine 5 with carboxylic acids 1 under the action of Pb(OAc)4
Entry
Acid 1
Protonating acid
τ/h
Conversionb 1 (%)
Product
Yieldс (%)
1d
2d
3e
4e
5e
6 f
7
1b
1b
1b
1b
1b
1b
1d
1d
1e
1e
AcOH
72
48
4
4
4
0.75
4
0.75
4
—
—
—
—
82
41
89
50
64
39
—
—
—
2ꢀClC6H4COOH
2ꢀClC6H4COOH
AcOH
2ꢀClC6H4COOH
CF3COOH
2ꢀClC6H4COOH
CF3COOH
2ꢀClC6H4COOH
CF3COOH
—
11b
11b
11d
11d
11e
11e
80 (98)
40 (98)
88 (99)
48 (96)
60 (94)
36 (92)
8 f
9
10 f
0.75
а Molar ratio pyrazine : 1 : Pb(OAc)4 : protonating acid = 4 : 1 : 1.1 : 4; 1, 1 mmole.
b The conversion of Pb(OAc)4 is ~100%.
c The yield is presented with respect to the starting (in parentheses, with respect to converted) acid 1.
d Solventꢀfree reaction without mechanical activation.
e Under mechanical activation conditions.
f Reaction in a benzene solution (10 mL) at 80 °C.

1000
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 4, April, 2005
Nikishin et al.
2 m×3 mm with 5% FFAP and 5% SEꢀ30 on Chromaton
NꢀAWꢀHDMS (0.16—0.20 mm). 1H and 13C NMR spectra were
recorded on a Bruker ACꢀ200 spectrometer in CDCl3. GCꢀMS
spectra were obtained on a Finnigan MAT ITDꢀ700 spectromꢀ
eter (EI, 70 eV, temperature of the ion source—ion trap system
220 °C) and a Carlo Erba 4200 chromatograph equipped with an
Ultraꢀ1 column (Hewlett—Packard, 25 m×0.2 mm, layer thickꢀ
ness of the stationary phase (polymethylsiloxane) 0.33 µm, heꢀ
lium as carrier gas). Preparative GLC was used to isolate reacꢀ
tion products (copper column 2 m×10 mm with 5% SEꢀ30 on
Chromaton NꢀAWꢀHDMS, 0.25—0.36 mm). Starting hexanoic,
octanoic, methylpropanoic, 2ꢀethylhexanoic, 3ꢀphenylproꢀ
panoic, phenylpropanoic, phenylacetic, 3ꢀmethoxycarbonylꢀ
propanoic, acetic, 2ꢀchlorobenzoic, benzoic, and trifluoroacetic
acids (Acros); 4ꢀmethylpyridine, quinoline, 4ꢀmethylquinoline,
and pyrazine (Lancaster); and benzene (reagent grade) were
used as received. Lead tetraacetate (pure) was washed with glaꢀ
cial AcOH and dried in vacuo over alkali.
Solventꢀfree alkylation of Nꢀheteroaromatic compounds 2—5
by the acid 1—Pb(OAc)4 system without mechanical activation
(general procedure). A mixture of heterocycle 2—5, acid 1,
Pb(OAc)4, and CBA (PhCOOH or AcOH) (the ratio of reagents
are given in Tables 1 and 2) were thoroughly triturated in air for
5—10 min and left in a tightly closed weighing bottle at ~20 °C
until Pb(OAc)4 converted completely. The reaction mixture
gradually became viscous and heterogeneous and then solidiꢀ
fied. The duration of transition from one aggregate state to anꢀ
other (6—26 h) depends on the acid structure. After the end of
the reaction (Pb(OAc)4 conversion was monitored iodometriꢀ
cally7), solvents (CHCl3 and ether) were successively added,
and the yield of reaction products 6—11 and conversion of the
starting acid 1 were determined by GLC using internal standard.
To isolate reaction products, the organic layer was treated with a
3% aqueous solution of HCl, washed with a saturated solution
of Na2CO3, and dried with Na2SO4. The solvent was distilled
off. The products were isolated from the residue by preparative
GLC. The structure of the products was confirmed by 1H and
13C NMR spectroscopy, GCꢀMS spectrometry, and elemental
analysis.
1a—f, benzyl radicals formed from acid 1g do not add to
heterocycle 2. In the reaction zone they are oxidized by
PbIII and PbIV acetates and transformed into benzyl
2ꢀchlorobenzoate (10). We assumed that benzyl acetate is
primarily formed and then produces ester 10 due to ester
interchange. This assumption was based on the known1
ability of Pb(OAc)4 to acetoxylate Cꢀradicals. However,
as found in model experiments, no ester interchange ocꢀ
curs under the reaction conditions and, therefore, ester
10 is the primary oxidation product of benzyl radicals.
Unlike heterocycles 2—4, pyrazine 5 does not react
with a Pb(OAc)4—RCOOH—CBA system under the same
solventꢀfree conditions (see Table 2). In the liquid phase
in a benzene solution containing protonating trifluoroꢀ
acetic acid, alkane acids 1b,d,e alkylate 5 but their conꢀ
version at the molar ratio acid 1 : Pb(OAc)4 = 1 : 1.1 does
not exceed 50%. To perform this process as solventꢀfree,
we used mechanical activation that makes it possible, in
many cases, to intensify solidꢀphase reactions. It is found
that pyrazine is actively activated by the mechanical treatꢀ
ment of a mixture of reactants in a vibratory mill. In this
case, the conversion of acids 1b,d,e and the yield of prodꢀ
ucts 11b,d,e increase 1.5—2ꢀfold compared to the liquidꢀ
phase variant of the reaction (see Table 2). Such a proꢀ
nounced effect of mechanical activation indicates that
alkylation in a vibratory mill occurs predominantly in the
solid phase. We failed to perform the alkylation of pyrazine
5 by acid 1b under the mechanical activation conditions
without a protonating acid. The application of acetic acid
for pyrazine 5 protonation was unsuccessful, and only the
use of CBA gave target products 11b,d,e (Scheme 4).
Scheme 4
Solventꢀfree alkylation of pyrazine 5 by the acid 1—Pb(OAc)4
system using mechanical activation (general procedure). Mechaniꢀ
cal activation of a mixture of pyrazine 5, acid 1, Pb(OAc)4, and
CBA or AcOH with an overall weight of 1—2 g (the ratio of
reagents is indicated in Table 2) was carried out at ~20 °C on a
vibratory mill with a vibration frequency of 12 Hz and an ampliꢀ
tude of 11 mm in a sealed steel ~80ꢀcm3 reactor. Steel balls with
a diameter of 12.3 mm and an overall weight of ~150 g were used
as activating packing. The duration of mechanical action was 4 h,
and then the mixture was treated according to the aboveꢀpreꢀ
sented procedure.
Alkylation of Nꢀheteroaromatic compounds 2—5 with the
acid 1—Pb(OAc)4 system in a benzene—CF3COOH solution (genꢀ
eral procedure). A mixture of heterocycle 2—5, acid 1, and
Pb(OAc)4 in benzene containing CF3COOH (the ratios of reꢀ
agents are given in Tables 1 and 2) was heated (80 °C) with
vigorous stirring until PbIV converted completely. The solvent
was distilled off, and the mixture was treated according to the
aboveꢀpresented procedure.
R = nꢀC7H15 (b), BunCH(Et) (d), MeO2CCH2CH2 (e)
i. Solid phase.
Thus, in all aboveꢀconsidered solventꢀfree reactions
of carboxylic acids 1a—f with heteroaromatic compounds
2—5 in the presence of Pb(OAc)4, ~95—96% radicals
formed add to the protonated Nꢀring, which provides a
high selectivity of the reaction and a high yield of alkylaꢀ
tion products 6—9 and 11 with respect to the reacted acid.
Experimental
4ꢀMethylꢀ2ꢀpentylpyridine (6а). Found (%): C, 80.92;
H, 10.52; N, 8.56. C11H17N. Calculated (%): C, 80.98; H, 10.43;
N, 8.59. 1H NMR, δ: 0.88 (t, 3 H, Me, J = 3.2 Hz); 1.30—1.37
GLC analysis was carried out on an LKhMꢀ80 chromatoꢀ
graph using a flameꢀionization detector and analytical columns

Alkylation of Nꢀheteroaromatic compounds
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 4, April, 2005
1001
(m, 4 H, CH2); 1.63—1.75 (m, 2 H, CH2); 2.32 (s, 3 H, 4ꢀMe);
2.74 (t, 2 H, CH2, J = 3.9 Hz); 6.92 (d, 1 H, CH(5), J = 2.5 Hz);
6.97 (s, 1 H, CH(3)); 8.37 (d, 1 H, CH(6), J = 2.5 Hz).
13C NMR, δ: 13.96 (Me); 20.90 (4ꢀMe); 22.48, 29.59, 31.61,
38.22 (CH2); 121.76, 123.48 (C(3), C(5)); 147.10 (C(4)); 148.84
(C(6)); 162.23 (C(2)). Mass spectrum, m/z: 164 [M + H]+.
2ꢀHeptylꢀ4ꢀmethylpyridine (6b). Found (%): C, 81.30;
H, 10.91; N, 7.28. C13H21N. Calculated (%): C, 81.68; H, 10.99;
N, 7.33. 1H NMR, δ: 0.86 (t, 3 H, Me, J = 3.2 Hz); 1.26—1.32
(m, 8 H, CH2); 1.62—1.75 (m, 2 H, CH2); 2.35 (s, 3 H, 4ꢀMe);
2.72 (t, 2 H, CH2, J = 3.9 Hz); 6.89 (d, 1 H, CH(5), J = 2.5 Hz);
6.95 (s, 1 H, CH(3)); 8.35 (d, 1 H, CH(6), J = 2.5 Hz).
13C NMR, δ: 13.99 (Me); 20.88 (4ꢀMe); 22.56, 29.10,
29.34, 29.90, 31.70, 38.23 (CH2); 121.77, 123.46 (C(3), C(5));
147.09 (C(4)); 148.23 (C(6)); 162.18 (C(2)). Mass spectrum,
m/z: 192 [M + H]+.
2ꢀ(Heptꢀ3ꢀyl)ꢀ4ꢀmethylquinoline (7d). Found (%): C, 84.79;
H, 9.85; N, 6.01. C17H23N. Calculated (%): C, 84.65; H, 9.54;
N, 5.81. 1H NMR, δ: 0.83 (t, 6 H, Me, J = 3.6 Hz); 1.20—1.34,
1.70—1.83 (both m, 4 H each, CH2); 2.69 (s, 3 H, 4ꢀMe);
2.78—2.85 (m, 1 H, CH); 7.11 (s, 1 H, CH); 7.54 (t, 1 H, CH,
J = 3.7 Hz); 7.67 (t, 1 H, CH, J = 3.6 Hz); 7.96, 8.06 (both d,
1 H each, CH, J = 4.1 Hz). 13C NMR, δ: 12.20 and 13.95 (Me);
18.82 (4ꢀMe); 22.81, 28.55, 29.86, 35.10 (CH2); 50.46 (CH);
120.63, 123.50, 125.26, 126.98, 128.74, 129.50, 143.89, 147.55,
165.79 (C(2), C(3), C(4), C(5), C(6), C(7), C(8), C(9), C(10)).
Mass spectrum, m/z: 242 [M + H]+.
2ꢀ(Heptꢀ3ꢀyl)quinoline (8d). Found (%): C, 84.34; H, 8.99;
N, 6.21. C16H21N. Calculated (%): C, 84.58; H, 9.25; N, 6.17.
1H NMR, δ: 0.83 (t, 6 H, Me, J = 3.7 Hz); 1.10—1.24, 1.65—1.79
(both m, 4 H each, CH2); 2.79—2.91 (m, 1 H, CH); 7.31
(d, 1 H, CH, J = 4.0 Hz); 7.47, 7.68 (both t, 1 H each, CH,
J = 3.9 Hz); 7.78 (d, 1 H, CH, J = 4.0 Hz); 8.05—8.09 (dd,
2 H, CH). 13C NMR, δ: 12.12 and 13.91 (Me); 22.78, 28.56,
29.79, 35.06 (CH2); 50.48 (CH); 120.02, 125.47, 126.25, 127.36,
128.94, 129.02, 135.98, 147.73, 166.09 (C(2), C(3), C(4),
C(5), C(6), C(7), C(8), C(9), C(10)). Mass spectrum, m/z:
228 [M + H]+.
4ꢀ(Heptꢀ3ꢀyl)quinoline (9d). Found (%): C, 84.28; H, 9.03;
N, 6.31. C16H21N. Calculated (%): C, 84.58; H, 9.25; N, 6.17.
1H NMR, δ: 0.76—0.84 (m, 6 H, Me); 1.09—1.25, 1.63—1.80
(both m, 4 H each, CH2); 3.38—3.49 (m, 1 H, CH); 7.26 (d,
1 H, CH, J = 2.3 Hz); 7.55, 7.71 (both t, 1 H each, CH, J =
3.8 Hz); 8.14 (d, 2 H, CH, J = 4.3 Hz); 8.87 (d, 1 H, CH, J =
2.2 Hz). 13C NMR, δ: 11.87 and 13.88 (Me); 22.78, 28.88,
29.56, 35.30 (CH2); 40.51 (CH); 118.18, 123.15, 126.05, 128.27,
128.78, 130.26, 148.39, 150.05, 152.54 (C(2), C(3), C(4),
C(5), C(6), C(7), C(8), C(9), C(10)). Mass spectrum, m/z:
228 [M + H]+.
Benzyl 2ꢀchlorobenzoate (10). Found (%): C, 68.17;
H, 4.55; Cl, 14.30. C14H11ClO2. Calculated (%): C, 68.29;
H, 4.47; Cl, 14.23. Mass spectrum, m/z: 246 and 248 [M]+.
The 1H NMR spectrum coincides with that described preꢀ
viously.9
2ꢀHeptylpyrazine (11b). Found (%): C, 74.34; H, 10.04;
N, 15.56. C11H18N2. Calculated (%): C, 74.16; H, 10.11;
N, 15.73. 1H NMR, δ: 0.85 (t, 3 H, Me, J = 3.2 Hz); 1.25—1.33
(m, 8 H, CH2); 1.71—1.76 (m, 2 H, CH2); 2.77 (t, 2 H, CH2,
J = 3.8 Hz); 8.40 (d, 1 H, CH, J = 1.2 Hz); 8.45 (s, 1 H, CH(3));
8.47 (d, 1 H, CH, J = 1.2 Hz). 13C NMR, δ: 13.99 (Me); 22.38,
28.99, 29.18, 29.38, 31.65, 35.47 (CH2); 141.95, 143.97, 144.49
and 158.01 (C(2), C(3), C(5), C(6)). Mass spectrum, m/z:
179 [M + H]+.
2ꢀ(Heptꢀ3ꢀyl)pyrazine (11d). Found (%): C, 74.26; H, 10.45;
N, 15.91. C11H18N2. Calculated (%): C, 74.16; H, 10.11;
N, 15.73. 1H NMR, δ: 0.74—0.86 (m, 6 H, Me); 1.07—1.27,
1.66—1.817 (both m, 4 H each, CH2); 2.53—2.73 (m,
1 H, CH); 8.38 (d, 1 H, CH, J = 1.2 Hz); 8.44 (s, 1 H,
CH(3)); 8.47 (d, 1 H, CH, J = 1.2 Hz). Mass spectrum, m/z:
179 [M + H]+.
2ꢀIsopropylꢀ4ꢀmethylpyridine (6c).8 Found (%): C, 79.57;
H, 9.61; N, 10.91. C9H13N. Calculated (%): C, 80.00; H, 9.63;
1
N, 10.37. H NMR, δ: 1.24—1.29 (m, 6 H, Me); 2.29 (s, 3 H,
4ꢀMe); 2.93—3.07 (m, 1 H, CH); 6.89 (d, 1 H, CH(5), J =
2.5 Hz); 6.96 (s, 1 H, CH(3)); 8.36 (d, 1 H, CH(6), J = 2.5 Hz).
13C NMR, δ: 20.93, 22.45, 22.59 (Me); 36.04 (CH); 121.36,
121.90 (C(3), C(5)); 147.21 (C(4)); 148.63 (C(6)); 166.93 (C(2)).
Mass spectrum, m/z: 136 [M + H]+.
2ꢀ(Heptꢀ3ꢀyl)ꢀ4ꢀmethylpyridine (6d). Found (%): C, 81.41;
H, 11.18; N, 7.43. C13H21N. Calculated (%): C, 81.68; H, 10.99;
N, 7.33. 1H NMR, δ: 0.74—0.87 (m, 6 H, Me); 1.08—1.29,
1.62—1.77 (both m, 4 H each, CH2); 2.34 (s, 3 H, 4ꢀMe);
2.56—2.63 (m, 1 H, CH); 6.93 (d, 1 H, CH(5), J = 2.5 Hz); 6.95
(s, 1 H, CH(3)); 8.41 (d, 1 H, CH(6), J = 2.5 Hz). 13C NMR, δ:
12.23 and 14.10 (Me); 21.21 (4ꢀMe); 22.89, 28.63, 29.94,
35.21 (CH2); 49.40 (CH); 122.19, 123.69 (C(3), C(5)); 147.47
(C(4)); 148.60 (C(6)); 165.04 (C(2)). Mass spectrum, m/z:
192 [M + H]+.
2ꢀ(2ꢀEthylmethoxycarbonyl)ꢀ4ꢀmethylpyridine
(6e).
Found (%): C, 66.88; H, 7.37; N, 7.98. C10H13NO2. Calcuꢀ
lated (%): C, 67.04; H, 7.26; N, 7.82. 1H NMR, δ: 2.33 (s, 3 H,
4ꢀMe); 2.81, 3.08 (both t, 2 H each, CH2, J = 3.7 Hz); 3.67 (s,
3 H, Me); 6.96 (d, 1 H, CH(5), J = 2.5 Hz); 7.03 (s, 1 H,
CH(3)); 8.37 (d, 1 H, CH(6), J = 2.5 Hz). 13C NMR, δ: 21.01
(4ꢀMe); 32.51 and 33.15 (CH2); 51.60 (MeCOO); 122.50, 124.05
(C(3), C(5)); 147.94 (C(4)); 148.55 (C(6)); 159.50 (C(2));
173.49 (C=O).
2ꢀ(2ꢀEthylphenyl)ꢀ4ꢀmethylpyridine (6f). Found (%):
C, 85.31; H, 7.58; N, 7.38. C14H15N. Calculated (%): C, 85.28;
1
H, 7.61; N, 7.11. H NMR, δ: 2.31 (s, 3 H, 4ꢀMe); 3.03—3.08
(m, 4 H, CH2); 6.95 (d, 1 H, CH, J = 2.3 Hz); 7.17—7.33
(m, 6 H, CH); 8.44 (s, 1 H, CH). Mass spectrum, m/z:
198 [M + H]+.
2ꢀHeptylꢀ4ꢀmethylquinoline (7b). Found (%): C, 84.44;
H, 9.35; N, 5.78. C17H23N. Calculated (%): C, 84.65; H, 9.54;
1
N, 5.81. H NMR, δ: 0.84 (t, 3 H, Me, J = 3.2 Hz); 1.22—1.29
(m, 8 H, CH2); 1.64—1.74 (m, 2 H, CH2); 2.59 (s, 3 H, 4ꢀMe);
2.68 (t, 2 H, CH2, J = 3.9 Hz); 7.14 (s, 1 H, CH); 7.48, 7.66
(both t, 1 H each, CH, J = 3.6 Hz); 7.98, 8.10 (both d, 1 H each,
CH, J = 4.1 Hz). 13C NMR, δ: 13.95 (Me); 18.99 (4ꢀMe);
22.59, 29.09, 29.40, 29.98, 31.88, 38.27 (CH2); 120.88, 123.59,
125.33, 126.85, 128.78, 129.67, 143.88, 147.45, 165.80 (C(2),
C(3), C(4), C(5), C(6), C(7), C(8), C(9), C(10)). Mass specꢀ
trum, m/z: 242 [M + H]+.
2ꢀ(Ethylꢀ2ꢀmethoxycarbonyl)pyrazine (11е). Found (%):
C, 57.88; H, 6.38; N, 16.87. C8H10N2O2. Calculated (%):
C, 57.83; H, 6.02; N, 16.87. 1H NMR, δ: 2.82, 3.09 (both t,
2 H each, CH2, J = 3.7 Hz); 3.66 (s, 3 H, MeCOO); 8.41 (d,
1 H, CH, J = 1.2 Hz); 8.44 (s, 1 H, CH(3)); 8.46 (d, 1 H, CH,
J = 1.2 Hz). Mass spectrum, m/z: 167 [M + H]+.

1002
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 4, April, 2005
Nikishin et al.
3. G. I. Nikishin, L. L. Sokova, and N. I. Kapustina, Izv. Akad.
Nauk, Ser. Khim., 2002, 1666 [Russ. Chem. Bull., Int. Ed.,
2002, 51, 1812].
4. N. I. Kapustina, L. L. Sokova, V. D. Makhaev, A. P. Borisov,
and G. I. Nikishin, Izv. Akad. Nauk, Ser. Khim., 2000, 1870
[Russ. Chem. Bull., Int. Ed., 2000, 49, 1842].
5. G. I. Nikishin, L. L. Sokova, V. D. Makhaev, and N. I.
Kapustina, Mendeleev Commun., 2003, 264.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 02ꢀ03ꢀ
32810a) and the Foundation of the President of the Rusꢀ
sian Federation (Program for State Support of Leading
Scientific Schools, Grant 2121.2003.3).
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Transl.)].
Received December 21, 2004;
in revised form March 11, 2005