Synthesis of 2,3-disubstituted pyrazines and quinoxalines by Heck cross-coupling reactions of 2,3-dichloropyrazine and 2,3-dichloroquinoxaline. Influence of the temperature on the product distribution

Article abstract of DOI:10.1016/j.tet.2010.01.021

Heck cross-coupling reactions of 2,3-dichloropyrazine provide a convenient approach to 2,3-dialkenyl-, 2-alkenyl-3-alkyl-, and 2,3-dialkylpyrazines depending on the reaction conditions.

Full text of DOI:10.1016/j.tet.2010.01.021

Tetrahedron 66 (2010) 1637–1642
Contents lists available at ScienceDirect
Tetrahedron
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Synthesis of 2,3-disubstituted pyrazines and quinoxalines by Heck cross-coupling
reactions of 2,3-dichloropyrazine and 2,3-dichloroquinoxaline. Influence of the
temperature on the product distribution
a
a
a
a
b
´
Imran Malik , Munawar Hussain , Asad Ali , Serge-Mitherand Tengho Toguem , Fatima Z. Basha ,
Christine Fischer c, Peter Langer a
,c,
*
a
¨
Institut fu¨r Chemie, Universitat Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b International Center for Chemical and Biological Sciences, University of Karachi, Pakistan
c Leibniz-Institut fu¨r Katalyse e. V. an der Universita¨t Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Heck cross-coupling reactions of 2,3-dichloropyrazine provide a convenient approach to 2,3-dialkenyl-,
2-alkenyl-3-alkyl-, and 2,3-dialkylpyrazines depending on the reaction conditions.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 27 October 2009
Received in revised form 4 January 2010
Accepted 5 January 2010
Available online 11 January 2010
Keywords:
Catalysis
Cross-coupling reactions
Pyrazine
Palladium
1. Introduction
thione,13 3-amino-6-methoxy-1H-pyridine-2-thione,14 2-amino-
benzeneselenol,15 and pyrid-2-yl-acetonitrile.16 Open-chained
Pyrazines and quinoxalines are of considerable pharmacological
relevance and are present in various natural products. Examples
include various simple alkyl-substituted pyrazine derivatives,1
botryllazines A and B,2 or 2,5-bis(3-indolylmethyl)pyrazine.3 The
quinoxaline echinoserine shows antibiotic activity.4 Antimicrobial
activity has been reported also for naturally occurring phenazines.5
Biopterin6 and pteridine7 represent nucleobase-type natural
products, which are also pharmacologically active (e.g., inhibition
of tRNA-guanine transglycosylase). Other properties of pyrazines
include anticoagulant activity8 and promotion of the melamine
synthesis.9 The cephalostatins and ritterazines are prominent pyr-
azine natural products, which exhibit a strong cytotoxic and can-
cerostatic activity.10
pyrazines have been prepared by reaction of 2,3-dichloropyrazine
with 1 equiv of different enolates,17 2 equiv of thiols,18 and DMAP.19
Transition metal-catalyzed reactions of 2,3-dichloropyrazine have
only scarcely been reported. 2,3-Diarylpyrazines and 2,3-
di(alkynyl)pyrazines have been recently prepared by Suzuki20 and
Sonogashira reactions, respectively.21 Herein, we report what are,
to the best of our knowledge, the first Heck reactions of 2,3-
23
dichloropyrazine and -quinoxaline.22,
These reactions provide,
depending on the reaction conditions, a convenient approach to
2,3-dialkenyl-, 2-alkenyl-3-alkyl-, and 2,3-dialkylpyrazines and
their quinoxaline derivatives.
2. Results and discussion
2,3-Dichloropyrazine and 2,3-dichloroquinoxaline represent
useful building blocks for the synthesis of substituted and annu-
lated pyrazines and quinoxalines. Condensed heterocycles have
been prepared by cyclization of 2,3-dichloropyrazine with 2-ami-
nobenzenethiol,11 2-aminophenol,12 3-hydroxy-1H-pyridine-2-
The reaction of 2,3-dichloropyrazine (1a) with ethyl acrylate
(2a), in the presence of Pd(OAc)2 (5 mol %) and Xphos24 (10 mol %),
afforded the 2,3-dialkenylpyrazine 3a in 83% yield (Scheme 1, Table
1). The employment of Pd(PPh3)4 was less successful in terms of
yield. The best yields were obtained when 5 mol % of the catalyst,
10 mol % of the ligand, and a slight excess of the alkene (2.5 equiv)
were employed and when the reaction mixture was stirred at 90 ꢀC
for 48 h. Partial hydrogenation was observed when the reaction
* Corresponding author. Fax: þ49 381 4986412.
E-mail address: peter.langer@uni-rostock.de (P. Langer).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.01.021

1638
I. Malik et al. / Tetrahedron 66 (2010) 1637–1642
Table 2
Synthesis of 4a–h
was carried out at higher temperature (vide infra). On the other
hand, the yields also decreased when the temperature was de-
creased, due to lower conversion of the starting material.
1
2
4
R1
R2
R3
% (4)a
T [ꢀC]
a
a
a
a
a
a
a
b
g
a
i
j
k
l
a
b
c
d
e
f
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CO2Me
CO2Et
78
71
74
75
83
79
69
75
110
110
110
110
110
110
110
130
R3
R1
R2
N
N
Cl
Cl
R1
R2
N
N
R3
R3
CO2nBu
CO2iBu
CO2tBu
CO2nHex
CO2Rb
2a-i
i
3a-l
1a,b
m
k
g
h
Scheme 1. Synthesis of 2,3-di(alkenyl)pyrazines and quinoxalines 3a–l. Conditions: I,
2a–I (2.5 equiv), Pd(OAc)2 (5 mol %), Xphos (for 3a,b,e–l) or SPhos (for 3c,d) (10 mol %,
structures, see Scheme 2), NEt3, DMF, 90 ꢀC.
–(CH]CH)2–
CO2tBu
a
Yield of isolated products.
R¼CH2CH(Et)(CH2)3CH3.
b
The Pd(OAc)2-catalyzed reaction of 1a with 2.5 equiv of acry-
lates 2i–k,m, carried out at 140 ꢀC, afforded the 2,3-dialkylpyr-
azines 5a–c in good yield (Scheme 4, Table 3). The formation of
products 5a–c can be explained by complete reduction, due to the
high temperatures. The reaction of 1b with 2m and 2k, carried out
at 150 ꢀC, afforded the 2,3-dialkylquinoxalines 5d and 5e, re-
spectively. The formation of products 5a–e can be again explained
by protodemetalation or reduction.
PCy2
iPr
PCy2
OMe
iPr
MeO
Cy = Cyclohexyl
iPr
SPhos
XPhos
R3
2i-k,m
Scheme 2. Biaryl monophosphine ligands developed by Buchwald and co-workers
(Ref. 24).
R1
R2
N
N
Cl
Cl
R1
R2
N
N
R3
R3
i
5a-e
1
Table 1
Synthesis of 3a–l
Scheme 4. Synthesis of 2,3-dialkylpyrazines and -quinoxalines 5a–e. Conditions: I:
2i–k,m (2.5 equiv), Pd(OAc)2 (5 mol %), Xphos (10 mol %), NEt3, DMF, 140 ꢀC, 48 h
(for 5a–c), 24 h (for 5d, e).
1
2
3
R1
R2
R3
% (3)a
T [ꢀC]
a
a
a
a
a
a
b
b
b
b
b
b
a
b
c
d
e
f
g
h
b
f
a
b
c
d
e
f
g
h
i
H
H
H
H
H
H
H
H
H
H
H
H
CO2Et
Ph
83
82
78b
82b
66
64
78
67
72
67
83
69
90
90
90
90
90
Table 3
Synthesis of 5a–e
4-(MeO)C6H4
4-MeC6H4
4-ClC6H4
4-(tBuO)C6H4
CO2Me
1
2
5
R1
R2
R3
% (5)a
T [ꢀC]
90
a
a
a
b
b
i
j
k
m
k
a
b
c
d
e
H
H
H
H
H
H
CO2nBu
CO2iBu
CO2tBu
CO2Rb
69
76
70
69
77
140
140
140
150
150
–(CH]CH)2–
–(CH]CH)2–
–(CH]CH)2–
–(CH]CH)2–
–(CH]CH)2–
–(CH]CH)2–
120
120
120
120
120
120
cHex
Ph
j
k
l
4-(tBuO)C6H4
4-(MeO)C6H4
4-tBuC6H4
–(CH]CH)2–
–(CH]CH)2–
CO2tBu
c
i
a
Yield of isolated products.
R¼CH2CH(Et)(CH2)3CH3.
b
a
Yield of isolated products.
Sphos instead of Xphos was used.
b
The Pd(OAc)2-catalyzed reaction of 1b with 1.25 rather than
2.5 equiv of 2h, carried out at 120 ꢀC, afforded the 2-alkenylqui-
noxaline 6 in 70% yield (Scheme 5). The formation of product 6 can
be explained by partial reduction of the in situ formed 2-bromo-3-
alkenylquinoxaline.
The Pd(OAc)2-catalyzed reaction of 1a with styrenes 2b–f, in the
presence of Xphos or SPhos24, gave the 2,3-dialkenylpyrazines 3b–f
in 64–83% yields. The reaction of 2,3-dichloroquinoxaline (1b) with
2b,c,f,–I afforded the 2,3-dialkenylquinoxalines 3g–l in 67–83%
yields. The synthesis of the quinoxaline derivatives had to be car-
ried out at 120 instead of 90 ꢀC to obtain good yields.
cHex
2h
N
N
Cl
Cl
N
The Pd(OAc)2-catalyzed reaction of 2,3-dichloropyrazine (1a)
with acrylates 2a,g,i–m (2.5 equiv), carried out at 110 rather than
90 ꢀC, afforded the 2-alkenyl-2-alkylpyrazines 4a–g in 69–83%
yield (Scheme 3, Table 2). The formation of products 4a–g can be
explained by partial reduction of the in situ formed 2,3-
dialkenylpyrazines. The reaction of 2,3-dichloroquinoxaline (1b)
with tert-butyl acrylate (2k), carried out at 130, gave 2-alkenyl-2-
alkylquinoxaline 4h. The formation of products 4a–h might be
explained by protodemetalation or reduction.25
i
N
cHex
1b
6 (70%)
Scheme 5. Conditions: I, Pd (OAc)2 (5 mol %), Xphos (10 mol %), 2 h (1.25 equiv) NEt3,
DMF, 120 ꢀC, 48 h.
In conclusion, we have reported the synthesis of 2,3-dialkenyl-,
2-alkenyl-3-alkyl-, and 2,3-dialkylpyrazines and their quinoxaline
derivatives based on Heck cross-coupling reactions of 2,3-dichloro-
pyrazine and -quinoxaline. An increase of the reaction temperature
results in partial or complete hydrogenation of the double bond.
R3
2a,g,i-m
R1
R2
N
Cl
Cl
R1
R2
N
N
R3
R3
3. Experimental section
3.1. General comments
N
i
4a-h
1a,b
Scheme 3. Synthesis of 2-alkenyl-3-alkylpyrazines and -quinoxalines 4a–h. Condi-
tions: I,: 2a,g,i–m (2.5 equiv), Pd(OAc)2 (5 mol %), Xphos (10 mol %), NEt3, DMF, 110 ꢀC,
48 h (for 4a–g), 24 h (for 4h).
All solvents were dried by standard methods and all reactions
were carried out under an inert atmosphere. For 1H and 13C NMR

I. Malik et al. / Tetrahedron 66 (2010) 1637–1642
1639
spectra the deuterated solvents indicated were used. Mass spec-
trometric data (MS) were obtained by electron ionization (EI,
70 eV), chemical ionization (CI, isobutane) or electrospray ioniza-
tion (ESI). For preparative scale chromatography silica gel 60
(0.063–0.200 mm, 70–230 mesh) was used.
7.34 (d, 2H, J¼15.4), 7.44 (d, 4H, J¼8.0 Hz, ArH), 7.72 (d, 2H,
J¼15.7 Hz), 8.30 (br s, 2H, ArH). 13C NMR (75.5 MHz, CDCl3):
¼21.4
d
(CH3), 121.0, 127.3, 129.5 (CH), 133.8 (C), 136.4 (CH), 139.0 (C), 142.2
(CH), 147.9 (C). IR (KBr): v¼3046, 3023, 2920, 2860 (w), 1710, 1444,
1414 (m), 1391, 1360 (w), 1220, 1180, 1153 (m), 971 (s), 905, 866, 845
(w), 803 (s), 750, 656, 596 (w) cmꢂ1. GC–MS (EI, 70 eV): m/z
(%)¼311 ([Mꢂ1]þ, 100), 297 (8), 281 (2), 221 (24), 195 (7), 141 (13).
HRMS (EI, 70 eV): calcd for C22H19N2 [Mꢂ1]þ: 311.15428; found:
311.15432.
3.2. General procedure for the twofold Heck
cross-coupling reactions
In a pressure tube (glass bomb) a suspension of Pd(OAc)2
(12 mg, 0.05 mmol, 2.5 mol % per Cl) and dicyclohexyl (20,40,60-
triisopropylbiphenyl-2-yl)phosphine (Xphos) (47 mg, 0.10 mmol)
in DMF (5 mL) was purged with Ar and stirred at 20 ꢀC to get
a yellowish or brownish transparent solution. To the stirred solu-
tion were added 2,3-dichloropyrazine (1a) (149 mg, 1.0 mmol),
NEt3 (1.1 mL, 8.0 mmol), and the acrylate or styrene (1.25 equiv per
Br). The reaction mixture was stirred at the indicated temperature
for 48 h. The solution was cooled to 20 ꢀC, poured into H2O, and
CH2Cl2 (25 mL each), and the organic and the aqueous layer were
separated. The latter was extracted with CH2Cl2 (3ꢁ25 mL). The
combined organic layers were washed with H2O (3ꢁ20 mL), dried
(Na2SO4), and concentrated in vacuo. The residue was purified by
chromatography (flash silica gel, heptanes/EtOAc).
3.2.5. 2,3-Bis(4-chlorostyryl)pyrazine (3e). Compound 3e was pre-
pared from 1a (149 mg, 1.0 mmol), following the general procedure,
as a light yellowish highly viscous oil (232 mg, 66%). Reaction
temperature: 90 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.27–7.38 (m,
6H), 7.45–7.56 (m, 4H), 7.69–7.79 (m, 2H), 8.35 (br s, 2H, ArH). 13C
NMR (62.9 MHz, CDCl3):
d
¼122.7, 128.5, 129.0 (CH), 134.9, 134.6 (C),
135.3, 142.6 (CH), 147.4 (C). IR (KBr): v¼3026 (w), 2927 (s), 2854
(m), 1706 (s), 1603 (w), 1490, 1090 (s), 1013, 966, 827 (m), 765, 700
(w) cmꢂ1. GC–MS (EI, 70 eV): m/z (%)¼351 ([Mꢂ1]þ, 100), 317 (10),
280 (02), 241 (48), 227 (07). HRMS (EI, 70 eV): calcd for C20H13N2Cl2
[Mꢂ1]þ: 351.04503; found: 351.04518.
3.2.6. 2,3-Bis(4-tert-butoxystyryl)pyrazine (3f). Compound 3f was
prepared from 1a (149 mg, 1.0 mmol) as a brownish solid (274 mg,
64%), mp¼125–127 ꢀC. Reaction temperature: 90 ꢀC. 1H NMR
3.2.1. (2E,20E)-Diethyl 3,30-(pyrazine-2,3-diyl)diacrylate (3a). Com-
pound 3a was prepared from 1a (149 mg, 1.0 mmol) as a light
brown highly viscous oil (229 mg, 83%). Reaction temperature:
(300 MHz, CDCl3):
d
¼1.30 (s,18H, 6CH3), 6.94 (d, 4H, J¼8.2 Hz, ArH),
7.30 (d, 2H, J¼15.9 Hz), 7.45 (d, 4H, J¼8.6 Hz, ArH), 7.71 (d, 2H,
90 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.28 (t, 6H, J¼7.2 Hz, 2CH3),
J¼15.5 Hz), 8.30 (br s, 2H, ArH). 13C NMR (62.9 MHz, CDCl3):
¼28.9
d
4.23 (q, 4H, J¼7.1, 14.2 Hz, 2CH2O), 7.05 (d, 2H, J¼15.2 Hz, 2CH), 7.94
(CH3), 79.02 (C), 120.6, 124.0, 128.1 (CH), 131.6 (C), 135.9, 142.1 (CH),
147.8, 156.4 (C). IR (KBr): v¼3029 (w), 2972 (m), 2928 (w), 1600 (m),
1503 (s), 1445, 1388, 1363 (m), 1234,1154 (s), 1089 (w), 975 (m), 892
(s), 848 (m), 713 (w) cmꢂ1. GC–MS (EI, 70 eV): m/z (%)¼428 ([M]þ,
9), 372 (4), 316 (100), 285 (3), 223 (30), 210 (15). HRMS (EI, 70 eV):
calcd for C28H32N2O2 [M]þ: 428.24583; found: 428.24676.
(d, 2H, J¼15.2 Hz, 2CH), 8.48 (s, 2H, ArH). 13C NMR (62.9 MHz,
CDCl3):
d
¼14.2 (CH3), 60.9 (CH2O), 126.8, 136.3, 145.0 (CH), 146.3
(C), 166.0 (CO). IR (KBr): v¼2978 (m), 2934 (w), 1715 (s), 1638 (w),
1400 (m), 1294 (s), 1266 (m), 1177 (s), 1033, 974 (m), 911, 797 (w)
cmꢂ1. GC–MS (EI, 70 eV): m/z (%)¼276 ([M]þ, 11), 231 (42), 186 (5),
175 (44), 157 (34), 131 (73). HRMS (EI, 70 eV): calcd for C14H16N2O4
[M]þ: 276.11046; found: 276.11092.
3.2.7. Dimethyl 3,30-(quinoxaline-2,3-diyl)diacrylate (3g). Compound
3g was prepared from 1b (199 mg, 1.0 mmol) as a light yellow solid
(232 mg, 78%), mp¼134–136 ꢀC. Reaction temperature: 120 ꢀC. 1H
3.2.2. 2,3-Distyrylpyrazine (3b). Compound 3b was prepared from
1a (149 mg, 1.0 mmol) as a light yellow solid (233 mg, 82%),
mp¼105–107 ꢀC. Reaction temperature: 90 ꢀC. 1H NMR (300 MHz,
NMR (300 MHz, CDCl3):
d
¼3.90 (s, 6H, 2CH3O), 7.30 (d, 2H,
J¼15.2 Hz), 7.80–7.83 (m, 2H, ArH), 8.08–8.11 (m, 2H, ArH), 8.20 (d,
CDCl3):
d
¼7.28–7.35 (m, 6H, ArH), 7.41 (d, 2H, J¼15.6), 7.54–7.57 (m,
2H, J¼15.2 Hz). 13C NMR (62.9 MHz, CDCl3):
¼52.0 (CH3O), 127.1,
d
4H, ArH), 7.76 (d, 2H, J¼15.6 Hz), 8.34 (br s, 2H, ArH). 13C NMR
129.5, 131.2, 137.2 (CH), 142.4, 146.4 (C), 166.4 (CO). IR (KBr):
v¼3303, 2956, 2920 (w), 1710 (s), 1638 (w), 1433, 1308 (m), 1269,
1170 (s), 1027, 969 (m), 757 (s), 717 (m), 611, 543 (w) cmꢂ1. GC–MS
(EI, 70 eV): m/z (%)¼298 ([M]þ, 8), 283 (3), 267 (26), 239 (100), 223
(8), 207 (25),195 (38). HRMS (EI, 70 eV): calcd for C16H14N2O4 [M]þ:
298.0951; found: 298.0954.
(75.5 MHz, CDCl3):
d¼121.9,127.4,128.8,128.9 (CH),136.5 (C),136.6,
142.5 (CH), 147.8 (C). IR (KBr): v¼3369, 3024 (w), 1626 (m), 1599,
1575 (w), 1493, 1447, 1392, 1154, 1072, 962 (m), 744 (s), 687 (s)
cmꢂ1. GC–MS (EI, 70 eV): m/z (%)¼283 ([Mꢂ1]þ, 100), 268 (2), 226
(2), 207 (24),141 (18). HRMS (EI, 70 eV): calcd for C20H15N2 [Mꢂ1]þ:
283.12298; found: 283.12297.
3.2.8. 2,3-Bis(E-2-cyclohexylvinyl)quinoxaline (3h). Compound 3h
was prepared from 1b (199 mg, 1.0 mmol) as a light yellow highly
viscous oil (222 mg, 64%). Reaction temperature: 120 ꢀC. 1H NMR
3.2.3. 2,3-Bis(4-methoxystyryl)pyrazine (3c). Compound 3c was
prepared from 1a (149 mg, 1.0 mmol) as a light brown highly vis-
cous oil (268 mg, 78%). Reaction temperature: 90 ꢀC. 1H NMR
(300 MHz, CDCl3):
2H, J¼15.4 Hz), 6.96 (dd, 2H, J¼6.7, 15.4 Hz), 7.52–7.55 (m, 2H),
7.87–7.91 (m, 2H). 13C NMR (62.9 MHz, CDCl3):
d¼1.62–1.86 (m, 20H), 2.16–2.28 (m, 2H), 6.77 (d,
(300 MHz, CDCl3):
d
¼3.85 (s, 6H, 2 ꢀCH3), 6.95 (d, 4H, J¼8.6 Hz,
ArH), 7.36 (d, 2H, J¼15.6 Hz), 7.59 (d, 4H, J¼8.6 Hz, ArH), 7.80 (d, 2H,
d
¼25.9, 26.1, 32.5
J¼15.6 Hz), 8.38 (br s, 2H, ArH). 13C NMR (62.9 MHz, CDCl3):
d
¼55.3
(CH2), 41.5,122.7,128.7,128.8 (CH),141.3 (C),146.7 (CH),149.4 (C). IR
(KBr): v¼3065 (w), 2922 (s), 2850, 1700, 1447 (m), 1259, 1091, 1019
(s), 798 (m), 758 (s), 698, 589 (w) cmꢂ1. GC–MS (EI, 70 eV): m/z
(%)¼346 ([M]þ, 35), 303 (6), 263 (100), 251 (7), 169 (20). HRMS (EI,
70 eV): calcd for C24H30N2 [M]þ: 346.24035; found: 346.23992.
(CH3), 114.2, 119.8, 128.8 (CH), 129.4 (C), 135.8, 141.9 (CH), 147.9 I,
160.2 (C). IR (KBr): v¼3400, 3033 (w), 2954,1708 (m),1601,1508 (s),
1440 (m), 1399 (w), 1301 (m), 1243, 1028 (s), 970 (m), 823 (s), 708
(w) cmꢂ1. GC–MS (EI, 70 eV): m/z (%)¼344 ([M]þ,100), 329 (12), 313
(4), 299 (4), 237 (30), 172 (05). HRMS (EI, 70 eV): calcd for
C22H20N2O2 [M]þ: 344.15193; found: 344.15154.
3.2.9. 2,3-Distyrylquinoxaline (3i). Compound 3i was prepared
from 1b (199 mg, 1.0 mmol) as a yellow solid (240 mg, 72%),
mp¼143–145 ꢀC. Reaction temperature: 120 ꢀC. 1H NMR (300 MHz,
3.2.4. 2,3-Bis(4-methylstyryl)pyrazine (3d). Compound 3d was
prepared from 1a (149 mg, 1.0 mmol) as a yellow solid (256 mg,
82%), mp¼111–113 ꢀC. Reaction temperature: 90 ꢀC. 1H NMR
CDCl3):
d
¼7.24–7.37 (m, 6H), 7.55 (d, 2H, J¼15.5 Hz), 7.58–7.61 (m,
6H), 7.91 (d, 2H, J¼15.5 Hz), 7.94–7.98 (m, 2H). 13C NMR (62.9 MHz,
(300 MHz, CDCl3):
d¼2.30 (s, 6H, 2CH3), 7.12 (d, 4H, J¼8.1 Hz, ArH),
CDCl3):
d
¼122.6, 127.6, 128.8, 128.9, 129.0, 129.5 (CH), 136.5 (C),

1640
I. Malik et al. / Tetrahedron 66 (2010) 1637–1642
137.9 (CH), 141.6, 149.0 (C). IR (KBr): v¼3060, 3029, 2930, 2853 (w),
1706 (m), 1682, 1491 (w), 1320, 1106 (m), 981 (w), 763, 697 (s), 601
(w) cmꢂ1. GC–MS (EI, 70 eV): m/z (%)¼334 ([M]þ, 93), 333 (100),
257 (62), 243 (19), 204 (32), 167 (17). HRMS (EI, 70 eV): calcd for
C24H18N2 [M]þ: 334.14645; found: 334.14539.
J¼7.1, 14.3 Hz, CH2O), 7.01 (d, 1H, J¼15.4 Hz, CH), 7.86 (d, 1H,
J¼15.4 Hz), 8.34–8.37 (m, 2H, ArH). 13C NMR (62.9 MHz, CDCl3):
d
¼14.1, 14.2 (CH3), 28.4, 31.6 (CH2), 60.5, 60.8 (CH2O), 125.6, 137.4,
142.2, 144.1 (CH), 146.4, 154.0 (C), 166.3, 172.5 (CO). IR (KBr):
v¼2981 (m), 2934 (w), 1712 (s), 1640, 1446 (w), 1404, 1368 (m),
1290 (s), 1174 (s), 1099 (m), 1031 (s), 974, 857 (m), 710 (w) cmꢂ1
.
3.2.10. 2,3-Bis(4-tert-butoxystyryl)quinoxaline (3j). Compound 3j
was prepared from 1b (199 mg, 1.0 mmol) as a yellow highly vis-
cous oil (319 mg, 67%). Reaction temperature: 120 ꢀC. 1H NMR
GC–MS (EI, 70 eV): m/z (%)¼278 ([M]þ, 3), 249 (4), 233 (46), 205
(100), 159 (54), 131 (60). HRMS (EI, 70 eV): calcd for C14H18N2O4
[M]þ: 278.12611; found: 278.126717.
(300 MHz, CDCl3):
7.43 (d, 2H, J¼15.5 Hz), 7.49–7.54 (m, 6H), 7.84 (d, 2H, J¼15.6 Hz),
7.86–7.91 (m, 2H). 13C NMR (62.9 MHz, CDCl3):
(C), 121.3, 124.0, 128.3, 128.8, 129.2 (CH), 131.5 (C), 137.7 (CH), 141.5,
149.2, 156.6 (C). IR (KBr): v¼3031 (w), 2922 (s), 2851 (m), 1677 (w),
1601 (m), 1504 (s), 1459,1364,1237 (m),1156 (s), 1014, 972 (w), 893,
759 (m), 607, 537 (w) cmꢂ1. GC–MS (EI, 70 eV): m/z (%)¼478 ([M]þ,
3), 422 (4), 366 (61), 273 (22), 260 (12), 212 (05). HRMS (EI, 70 eV):
calcd for C32H34N2O2 [M]þ: 478.26148; found: 478.26059.
d
¼1.27 (s,18H, 6CH3), 6.92 (d, 4H, J¼8.5 Hz, ArH),
3.2.15. (E)-Butyl 3-(3-(3-butoxy-3-oxopropyl)pyrazin-2-yl)acrylate
(4c). Compound 4c was prepared from 1a (149 mg, 1.0 mmol) as
a light yellow highly viscous oil (247 mg, 74%). Reaction tempera-
d
¼28.9 (CH3), 79.1
ture: 110 ꢀC. 1H NMR (300 MHz, CDCl3):
d¼0.84 (t, 3H, J¼7.3 Hz,
CH3), 0.89 (t, 3H, J¼7.4 Hz, CH3), 1.23–1.40 (m, 4H, 2CH2), 1.48–1.65
(m, 4H, 2CH2), 2.79 (t, 2H, J¼7.2 Hz, CH2), 3.22 (t, 2H, J¼7.0 Hz, CH2),
4.00 (t, 2H, J¼6.8 Hz, CH2O), 4.16 (t, 2H, J¼6.8 Hz, CH2O), 7.02 (d, 1H,
J¼15.3 Hz, CH), 7.9 (d, 1H, J¼15.2 Hz, CH), 8.35–8.37 (m, 2H, ArH).
13C NMR (75.5 MHz, CDCl3):
d
¼13.7 (CH3), 19.0, 19.1, 28.4, 30.6, 30.7,
3.2.11. 2,3-Bis(4-methoxystyryl)quinoxaline (3k). Compound 3k
was prepared from 1b (199 mg, 1.0 mmol) as a yellow highly vis-
cous oil (327 mg, 83%). Reaction temperature: 120 ꢀC. 1H NMR
31.6 (CH2), 64.5, 64.7 (CH2O), 125.7, 137.4, 142.2, 144.1 (CH), 146.5,
154.0 (C),166.4,172.7 (CO). IR (KBr): v¼2958 (m), 2933 (w),1720 (s),
1455, 1405 (m), 1263 (w), 1170 (s), 1063, 1021, 975 (m), 857, 754 (w)
cmꢂ1. GC–MS (EI, 70 eV): m/z (%)¼334 ([M]þ, 5), 277 (03), 261 (31),
233 (100),177 (16),159 (47). HRMS (EI, 70 eV): calcd for C18H26N2O4
[M]þ: 334.18871; found: 334.18877.
(300 MHz, CDCl3):
d
¼3.76 (s, 6H, 2 ꢀCH3), 6.85 (d, 4H, J¼8.8 Hz,
ArH), 7.42 (d, 2H, J¼15.5 Hz), 7.52–7.57 (m, 6H, ArH), 7.85 (d, 2H,
J¼15.6 Hz), 7.90–7.94 (m, 2H, ArH). 13C NMR (62.9 MHz, CDCl3):
d
¼55.35 (OCH3), 114.2, 120.4, 128.7, 129.0, 129.1 (CH), 129.3 (C),
137.3 (CH), 141.5, 149.3 (C), 160.4 (CO). IR (KBr): v¼3004, 2963, 2838
(w), 1598 (s), 1541(w), 1508 (s), 1460, 1420 (m), 1299 (w), 1247, 1172
(s), 1109 (m), 1022, 969, 829, 760 (s), 610 (m), 535 (w) cmꢂ1. GC–MS
(EI, 70 eV): m/z (%)¼394 ([M]þ, 61), 379 (15), 335 (4), 288 (11), 275
(41), 227 (13), 191 (8). HRMS (EI, 70 eV): calcd for C26H22N2O2 [M]þ:
394.16758; found: 394.16667.
3.2.16. (E)-Isobutyl 3-(3-(3-isobutoxy-3-oxopropyl)pyrazin-2-yl)-
acrylate (4d). Compound 4d was prepared from 1a (149 mg,
1.0 mmol) as a brown highly viscous oil (251 mg, 75%). Reaction
temperature: 110 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼0.81 (d, 6H,
J¼6.7 Hz, 2CH3), 0.91 (d, 6H, J¼6.9 Hz, 2CH3), 1.76–1.99 (m, 2H, CH),
2.80 (t, 2H, J¼7.1 Hz, CH2), 3.2 (t, 2H, J¼7.1 Hz, CH2), 3.78 (d, 2H,,
J¼6.7 Hz, CH2O), 3.94 (d, 2H, J¼6.4 Hz, CH2O), 7.0 (d, 1H, J¼15.3 Hz,
CH), 7.9 (d, 1H, J¼15.3 Hz, CH), 8.35–8.37 (m, 2H, ArH). 13C NMR
3.2.12. 2,3-Bis(4-tert-butylstyryl)quinoxaline (3l). Compound 3l
was prepared from 1b (199 mg, 1.0 mmol) as a highly viscous
brownish oil (321 mg, 72%). Reaction temperature: 120 ꢀC. 1H NMR
(75.5 MHz, CDCl3):
d
¼19.0 (CH3), 27.6, 27.7 (CH), 28.4, 31.5 (CH2),
70.7, 70.9 (CH2O), 125.7, 137.4, 142.2, 144.2 (CH), 146.5, 153.9 (C),
166.4, 172.6 (CO). IR (KBr): v¼2960 (m), 2874 (w), 1716 (s), 1640 (w),
1469, 1405 (m), 1166 (s), 1008 (m), 854, 710 (w) cmꢂ1. GC–MS (EI,
70 eV): m/z (%)¼334 ([M]þ, 7), 277 (4), 261 (51), 233 (100), 205 (12),
177 (44). HRMS (EI, 70 eV): calcd for C18H26N2O4 [M]þ: 334.18871;
found: 334.18918.
(300 MHz, CDCl3):
(d, 4H, J¼8.5 Hz, ArH), 7.59–7.70 (m, 4H), 7.78 (d, 2H, J¼16.3 Hz),
7.96–8.01 (m, 4H). 13C NMR (75.5 MHz, CDCl3):
d¼1.28 (s, 18H, 6CH3), 7.28 (d, 2H, J¼16.3 Hz), 7.37
d¼31.3 (CH3), 33.7
(C), 125.9, 127.3, 129.1, 130.3 (CH), 135.3 (C), 136.3 (CH), 143.4 (C),
144.4 (CH), 149.8, 151.6 (C). IR (KBr): v¼3059 (w), 2922 (s), 2852,
1632 (m), 1512 (w), 1457, 1362, 1267, 1202 (m), 1106 (s), 971, 820 (m),
759 (s), 610, 562 (w) cmꢂ1. GC–MS (EI, 70 eV): m/z (%)¼446 ([M]þ,
13), 433 (8), 391 (12), 301 (40), 285 (7), 245 (8). HRMS (EI, 70 eV):
calcd for C32H34N2 [M]þ: 446.28869; found: 446.28780.
3.2.17. (E)-tert-Butyl
3-(3-(3-tert-butoxy-3-oxopropyl)pyrazin-2-
yl)acrylate (4e). Compound 4e was prepared from 1a (149 mg,
1.0 mmol) as a light yellow highly viscous oil (277 mg, 83%). Re-
action temperature: 110 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.34 (s,
3.2.13. (E)-Methyl 3-(3-(3-methoxy-3-oxopropyl)pyrazin-2-yl)acry-
late (4a). Compound 4a was prepared from 1a (149 mg, 1.0 mmol)
as a brown highly viscous oil (195 mg, 78%). Reaction temperature:
9H, 3CH3), 1.46 (s, 9H, 3CH3), 2.68 (t, 2H, J¼7.2 Hz, CH2), 3.16 (t, 2H,
J¼7.2 Hz, CH2), 6.93 (d, 1H, J¼15.2 Hz, CH), 7.76 (d, 1H, J¼15.3 Hz,
CH), 8.33–8.35 (m, 2H, ArH). 13C NMR (62.9 MHz, CDCl3):
d¼28.0
110 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼2.80 (t, 2H, J¼7.2 Hz, CH2),
(CH3), 28.6, 32.8, (CH2), 80.2, 80.9 (C), 127.6, 136.5, 142.1, 143.9 (CH),
146.6, 154.1 (C), 165.6, 171.7 (CO). IR (KBr): v¼2976 (m), 2931 (w),
1708 (s), 1638, 1455 (w), 1366, 1295 (m), 1144 (s), 975, 847 (m), 758,
711 (w) cmꢂ1. GC–MS (EI, 70 eV): m/z (%)¼334 ([M]þ, 1), 261 (31),
222 (23), 205 (64), 177 (100), 159 (22). HRMS (EI, 70 eV): calcd for
C18H26N2O4 [M]þ: 334.18871; found: 334.18930.
3.23 (t, 2H, J¼7.1 Hz, CH2), 3.61 (s, 3H, OCH3), 3.76 (s, 3H, OCH3),
7.02 (d, 1H, J¼15.2 Hz, CH), 7.87 (d,1H, J¼15.3 Hz, CH), 8.35–8.38 (m,
2H, ArH). 13C NMR (62.9 MHz, CDCl3):
d
¼28.4, 31.3 (CH2), 51.7, 51.9
(OCH3), 125.2, 137.6, 142.3, 144.2 (CH), 146.4, 153.8 (C), 166.8, 173.0
(CO). IR (KBr): v¼2953 (m), 2932 (w), 1713 (s), 1530 (w), 1436, 1361,
1294, 1171 (m), 1103, 1032, 977, 858, 711 (w) cmꢂ1. GC–MS (EI,
70 eV): m/z (%)¼250 ([M]þ, 2), 235 (2), 219 (32), 191 (100), 159 (44),
131 (63). HRMS (EI, 70 eV): calcd for C12H14N2O4 [M]þ: 250.09481;
found: 250.09556.
3.2.18. (E)-Hexyl 3-(3-(3-(hexyloxy)-3-oxopropyl)pyrazin-2-yl)acry-
late (4f). Compound 4f was prepared from 1a (149 mg, 1.0 mmol)
as a light yellow highly viscous oil (308 mg, 79%). Reaction tem-
perature: 110 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼0.78–0.85 (m, 6H,
3.2.14. (E)-Ethyl 3-(3-(3-ethoxy-3-oxopropyl)pyrazin-2-yl)acrylate
(4b). Compound 4b was prepared from 1a (149 mg, 1.0 mmol) as
a light yellow highly viscous oil (196 mg, 71%). Reaction tempera-
2CH3), 1.20–1.27 (m, 12H, 6CH2), 1.47–1.65 (m, 4H, 2CH2), 2.79 (t,
2H, J¼7.4 Hz, CH2), 3.22 (t, 2H, J¼7.0 Hz, CH2), 3.99 (t, 2H, J¼6.7 Hz,
CH2O), 4.15 (t, 2H, J¼6.7 Hz, CH2O), 7.02 (d, 1H, J¼15.3 Hz), 7.86 (d,
1H, J¼15.3 Hz), 8.35–8.37 (m, 2H, ArH). 13C NMR (62.9 MHz, CDCl3):
ture: 110 ꢀC. 1H NMR (300 MHz, CDCl3):
CH3), 1.26 (t, 3H, J¼7.2 Hz, CH3), 2.78 (t, 2H, J¼7.2 Hz, CH2), 3.22 (t,
2H, J¼7.1 Hz, CH2), 4.05 (q, 2H, J¼7.1, 14.3 Hz, CH2O), 4.21 (q, 2H,
d
¼1.15 (t, 3H, J¼7.2 Hz,
d
¼14.0 (CH3), 22.4, 22.5, 25.5, 25.6, 28.4, 28.5, 28.6, 31.3, 31.4, 31.6
(CH2), 64.7, 65.0 (CH2O), 125.7, 137.3, 142.2, 144.1, (CH), 146.5, 154.0

I. Malik et al. / Tetrahedron 66 (2010) 1637–1642
1641
(C), 166.4, 172.6 (CO). IR (KBr): v¼2928 (m), 2857 (w), 1716 (s), 1530
(w), 1404 (m), 1358 (w), 1289 (m), 1168 (s), 976 (m), 854, 725 (w)
cmꢂ1. GC–MS (EI, 70 eV): m/z (%)¼390 ([M]þ, 17), 289 (22), 261
(100), 205 (9), 177 (18), 159 (35). HRMS (EI, 70 eV): calcd for
C22H34N2O4 [M]þ: 390.25131; found: 390.25141.
highly viscous oil (235 mg, 70%). Reaction temperature: 140 ꢀC. 1H
NMR (300 MHz, CDCl3):
d
¼1.35 (s, 18H, 6CH3), 2.68 (t, 4H, J¼7.1 Hz,
2CH2), 3.04 (t, 4H, J¼7.1 Hz, 2CH2), 8.21 (s, 2H, ArH). 13C NMR
(75.5 MHz, CDCl3):
d¼28.2 (CH3), 28.6, 32.5 (CH2), 80.3 (C), 141.1
(CH), 153.7 (CH), 172.3 (C). IR (KBr): v¼2976 (m), 2931 (w), 1723 (s),
1456, 1392 (w), 1366 (m), 1248 (w), 1146 (s), 978 (w), 846 (m), 755
(w) cmꢂ1. GC–MS (EI, 70 eV): m/z (%)¼336 ([M]þ, 2), 280 (27), 263
(60), 224 (98), 207 (92), 188 (29), 180 (100), 161 (30). HRMS (EI,
70 eV): calcd for C18H28N2O4 [M]þ: 336.20436; found: 336.20490.
3.2.19. (E)-2-Ethylhexyl
3-(3-(3-(2-ethylhexyloxy)-3-oxopropyl)
pyrazin-2-yl)acrylate (4g). Compound 4g was prepared from 1a
(149 mg, 1.0 mmol) as a light yellow highly viscous oil (306 mg,
69%). Reaction temperature: 110 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼0.86–0.93 (m, 12H, 4CH3), 1.24–1.35 (m, 16H), 1.50–1.68 (m, 2H),
3.2.24. Bis(2-ethylhexyl) 3,30-(quinoxaline-2,3-diyl) dipropanoate
(5d). Compound 5d was prepared from 1b (199 mg, 1.0 mmol) as
a light brown highly viscous oil (344 mg, 69%). Reaction tempera-
2.87 (t, 2H, J¼7.1 Hz), 3.30 (t, 2H, J¼7.1 Hz), 3.99 (d, 2H, J¼7.7 Hz),
4.15 (d, 2H, J¼7.1 Hz), 7.10 (d, 1H, J¼15.2 Hz), 7.94 (d, 1H, J¼15.7 Hz),
8.42–8.44 (m, 2H, ArH). 13C NMR (62.9 MHz, CDCl3):
d¼10.9, 13.9
ture: 150 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼0.77–0.80 (m, 12H),
(CH3), 22.9, 22.9, 23.6, 23.8, 28.3, 28.8, 28.9, 30.3, 30.4, 31.5 (CH2),
38.6, 38.8 (CH), 66.9, 67.2 (CH2O), 125.7, 137.3, 142.2, 144.1 (CH),
146.5, 153.9, 166.5 (C), 172.7 (CO). IR (KBr): v¼2957 (m), 2872 (w),
1.16–1.22 (m, 16H), 1.42–1.52 (m, 2H), 2.95 (t, 4H, J¼7.1 Hz), 3.26 (t,
4H, J¼6.9 Hz), 3.93 (d, 4H, J¼5.8 Hz, 2CH2O), 7.54–7.58 (m, 2H, ArH),
7.86–7.89 (m, 2H, ArH). 13C NMR (75.5 MHz, CDCl3):
d¼10.9, 14.0
1717 (s), 1461, 1404, 1264 (m), 1168 (s), 975 (m), 771, 710 (w) cmꢂ1
.
(CH3), 22.9, 23.7, 28.9, 29.1, 30.4, 30.9 (CH2), 38.7 (CH), 66.9 (CH2O),
128.5, 128.7 (CH), 140.7, 153.8 (C), 173.3 (CO). IR (KBr): v¼3063 (w),
2958, 2928 (s), 2860 (m), 1731 (s), 1654 (m), 1545 (s), 1458, 1418,
1378 (m), 1169 (s), 1079 (w), 758 (s), 608 (m), 541 (w) cmꢂ1. GC–MS
(EI, 70 eV): m/z (%)¼498 ([M]þ, 52), 469 (30), 441 (69), 385 (56), 356
(100), 313 (18), 226 (40), 184 (33). HRMS (EI, 70 eV): calcd for
C30H46N2O4 [M]þ: 498.27568; found: 498.27498.
GC–MS (EI, 70 eV): m/z (%)¼446 ([M]þ, 59), 417 (8), 389 (5), 335
(45), 317 (73), 289 (100). HRMS (EI, 70 eV): calcd for C26H42N2O4
[M]þ: 446.31391; found: 446.314336.
3.2.20. (E)-tert-Butyl 3-(3-(3-tert-butoxy-3-oxopropyl) quinoxalin-
2-yl) acrylate (4h). Compound 4h was prepared from 1b (199 mg,
1.0 mmol) as a light brown viscous oil (288 mg, 75%). Reaction
temperature: 130 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.36 (s, 9H,
3.2.25. tert-Butyl 3,30-(quinoxaline-2,3-diyl)dipropanoate (5e). Com-
pound 5e was prepared from 1b (199 mg,1.0 mmol) as a light yellow
highly viscous oil (297 mg, 77%). Reaction temperature: 150 ꢀC. 1H
3CH3), 1.49 (s, 9H, 3CH3), 2.82 (t, 2H, J¼7.1 Hz, CH2), 3.35 (t, 2H,
J¼7.1 Hz, CH2), 7.10 (d, 1H, J¼15.4 Hz), 7.61–7.65 (m, 2H), 7.89–7.98
(m, 3H). 13C NMR (62.9 MHz, CDCl3):
d¼27.5, 28.1 (CH3), 29.6, 32.3
NMR (300 MHz, CDCl3):
2CH2), 3.21 (t, 4H, J¼7.0 Hz, 2CH2), 7.54–7.57 (m, 2H), 7.86–7.89
(m, 2H). 13C NMR (62.9 MHz, CDCl3):
d¼1.36 (s, 18H, 6CH3), 2.83 (t, 4H, J¼7.2 Hz,
(CH2), 80.4, 81.1 (C), 128.6, 128.7, 129.4, 129.5, 130.2, 136.7 (CH),
141.1, 142.0, 147.2, 154.0 (C), 165.5, 172.0 (CO). IR (KBr): v¼3062 (w),
2976, 2931 (m), 1710 (s), 1482, 1456 (w), 1366, 1247 (m), 1147 (s),
975 (w), 845 (m), 760 (s), 611 (w) cmꢂ1. GC–MS (EI, 70 eV): m/z
(%)¼384 ([M]þ, 1), 328 (9), 311 (25), 272 (15), 255 (25), 227 (100),
209 (13), 181 (32). HRMS (EI, 70 eV): calcd for C22H28N2O4 [M]þ:
384.20436; found: 384.20525.
d¼28.1 (CH3), 29.3, 32.0 (CH2),
80.2 (C), 128.5, 128.6 (CH), 140.6, 154.1 (C), 172.4 (CO). IR (KBr):
v¼2977, 2930 (w), 1722 (s), 1488 (w), 1365, 1314, 1256 (m), 1143 (s),
953 (w), 846 (m), 760 (s), 662, 609 (w) cmꢂ1. GC–MS (EI, 70 eV): m/z
(%)¼386 ([M]þ, 16), 330 (34), 313 (37), 274 (84), 257 (74), 230 (100),
211 (31), 183 (36). HRMS (EI, 70 eV): calcd for C22H30N2O4 [M]þ:
386.22001; found: 386.22006.
3.2.21. Dibutyl 3,30-(pyrazine-2,3-diyl)dipropanoate (5a). Compound
5a was prepared from 1a (149 mg, 1.0 mmol) as a light yellow
highly viscous oil (232 mg, 69%). Reaction temperature: 140 ꢀC. 1H
3.2.26. (E)-2-(2-Cyclohexylvinyl)quinoxaline (6). Compound 6 was
prepared starting with 1b (199 mg, 1.0 mmol) as a light yellow solid
NMR (300 MHz, CDCl3):
d
¼0.83 (t, 6H, J¼7.4 Hz, 2CH3), 1.23–1.31
(167 mg, 70%). 1H NMR (300 MHz, CDCl3):
d
¼1.46–1.85 (m, 10H),
(m, 4H, 2CH2), 1.49–1.54 (m, 4H, 2CH2), 2.79 (t, 4H, J¼7.2 Hz, 2CH2),
3.09 (t, 4H, J¼7.1 Hz, 2CH2), 4.00 (t, 4H, J¼6.7 Hz, 2CH2O), 8.21 (s,
2.18–2.27 (m, 1H), 6.61 (d, 1H, J¼15.91 Hz), 6.91 (dd, 1H, J¼6.8,
16.1 Hz, CH), 7.57–7.68 (m, 2H), 7.94–7.99 (m, 2H), 8.86 (s, 1H). 13C
2H, ArH). 13C NMR (62.9 MHz, CDCl3):
d¼13.6 (CH3), 19.0, 28.4, 30.6,
NMR (75.5 MHz, CDCl3):
d
¼25.9, 26.0, 32.3 (CH2), 41.4, 125.3, 128.9,
31.2 (CH2), 64.3(CH2O), 141.1(CH), 153.5 (C), 173.0 (CO). IR (KBr):
v¼2958 (m), 2873 (w), 1729 (s), 1536, 1456 (w), 1412 (m), 1165 (s),
1109 (m), 1020, 944, 849, 738 (w) cmꢂ1. GC–MS (EI, 70 eV): m/z
(%)¼336 ([M]þ, 66), 2263 (65), 235 (100), 207 (6), 188 (12), 161 (71).
HRMS (EI, 70 eV): calcd for C18H28N2O4 [M]þ: 336.20436; found:
336.20440.
129.0, 130.2 (CH), 141.3 (C), 143.9, 146.1 (CH), 151.1, 158.1 (C). IR
(KBr): v¼3060 (w), 2923 (s), 2850, 1708 (m), 1590, 1544 (w), 1447,
1361, 1247 (m), 1109 (s), 974 (w), 759 (s), 565, 537 (m) cmꢂ1. GC–MS
(EI, 70 eV): m/z (%)¼238 ([M]þ, 100), 223 (17), 209 (19), 195 (24),
195 (24), 181 (34), 169 (16). HRMS (EI, 70 eV): calcd for C16H18N2
[M]þ: 238.14700; found: 238.14701.
3.2.22. Isobutyl 3,30-(pyrazine-2,3-diyl)dipropanoate (5b). Compound
5b was prepared from 1a (149 mg,1.0 mmol) as a light brown highly
viscous oil (255 mg, 76%). Reaction temperature: 140 ꢀC. 1H NMR
Acknowledgements
Financial support by the Goverment of Pakistan (Higher Edu-
cation Commission (HEC) scholarships for I.M. and M.H.), by the
DAAD (scholarships for S.-M.T.T. and A.A.) and by the Fr.-Irmgard-
Harms-Stiftung (scholarship for A.A.) is gratefully acknowledged.
(300 MHz, CDCl3):
d
¼0.82 (d, 12H, J¼6.9 Hz, 4CH3), 1.77–1.88(m, 2H,
2CH), 2.81 (t, 4H, J¼7.3 Hz, 2CH2), 3.10 (t, 4H, J¼6.9 Hz, 2CH2), 3.79 (d,
4H, J¼6.9 Hz, 2CH2O), 8.20 (s, 2H, Ar-H). 13C NMR (62.9 MHz, CDCl3):
d
¼18.9 (CH3), 27.6(CH), 28.4, 31.1 (CH2), 70.6 (CH2O),141.2 (CH),153.4
(C), 173.0 (CO). IR (KBr): v¼2959 (m), 2874 (w), 1729 (s), 1535 (w),
1469, 1411, 1379 (m), 1160 (s), 1109, 992 (m), 851, 796 (w) cmꢂ1. GC–
MS (EI, 70 eV): m/z (%)¼336 ([M]þ, 49), 279 (23), 261 (52), 233 (100),
219 (15), 177 (51), 159 (46). HRMS (EI, 70 eV): calcd for C18H28N2O4
[M]þ: 336.20436; found: 336.20453.
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