Isocyanide-based three-component synthesis of highly substituted 1,6-dihydro-6,6-dimethylpyrazine-2,3-dicarbonitrile, 3,4-dihydrobenzo[g] quinoxalin-2-amine, and 3,4-dihydro-3,3-dimethyl-quinoxalin-2-amine derivatives

Article abstract of DOI:10.1002/hlca.201100270

A novel and efficient isocyanide-based multicomponent reaction between alkyl or aryl isocyanides 1, 2,3-diaminomaleonitrile (2), naphthalene-2,3- diamines (6) or benzene-1,2-diamine (9), and 3-oxopentanedioic acid (3) or Meldrum's acid (4) or ketones 7 wa

Full text of DOI:10.1002/hlca.201100270

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Isocyanide-Based Three-Component Synthesis of Highly Substituted 1,6-
Dihydro-6,6-dimethylpyrazine-2,3-dicarbonitrile, 3,4-
Dihydrobenzo[g]quinoxalin-2-amine, and 3,4-Dihydro-3,3-dimethyl-
quinoxalin-2-amine Derivatives
by Ahmad Shaabani*, Fatemeh Hajishaabanha, Hamid Mofakham, Mojtaba Mahyari, and Bagher Lali
Department of Chemistry, Shahid Beheshti University, P.O. Box 19396-4716, Tehran, Iran
(e-mail: a-shaabani@cc.sbu.ac.ir)
A novel and efficient isocyanide-based multicomponent reaction between alkyl or aryl isocyanides 1,
2,3-diaminomaleonitrile (2), naphthalene-2,3-diamines (6) or benzene-1,2-diamine (9), and 3-oxopen-
tanedioic acid (3) or Meldrumꢀs acid (4) or ketones 7 was developed for the ecologic synthesis, at room
temperature under mild conditions, of 1,6-dihydropyrazine-2,3-dicarbonitriles 5a – 5f in H2O without
using any catalyst, and of 3,4-dihydrobenzo[g]quinoxalin-2-amine and 3,4-dihydro-3,3-dimethyl-
quinoxalin-2-amine derivatives 8a – 8g and 10a – 10e, respectively, in the presence of a catalytic amount
of p-toluenesulfonic acid (TsOH) in EtOH, in good to excellent yields (Scheme 1).
Introduction. – Quinoxalines and their derivatives are an important class of
benzoheterocycles [1 – 3] displaying a broad spectrum of biological activities [4 – 7],
including antidiabetic [8] and antiviral effects, in particular against retroviruses such as
HIV [9]. They also are inhibitors of aldose reductase [10][11], partial agonists of the g-
aminobutyric acid (GABA)/benzodiazepine receptor complex [12], and antagonists of
the AMPA and angiotensin II receptors [13]. They have found applications as dyes
[14 – 16] and also as building blocks in the synthesis of organic semiconductors [17][18].
They also serve as useful rigid subunits in macrocyclic receptors for molecular
recognition [19][20] and chemically controllable switches [21][22].
Multicomponent reactions (MCRs), especially isocyanide-based MCRs (IMCRs),
are used extensively in medicinal chemistry as fast and selective methods for the
synthesis of large libraries of organic molecules by simply varying each component
through a chain of consecutive elementary transformations [23 – 25]. The great
potential of isocyanides for the development of multicomponent reactions lies in their
functional-group tolerance, diversity of bond-forming processes, and high levels of
chemo-, regio-, and stereoselectivity [24][25].
Results and Discussion. – In view of our current studies on isocyanide-based
multicomponent reactions (IMCRs) and a full account of our previous works [26][27],
we disclose herein a novel ecologic IMCR for the synthesis of 1,6-dihydro-6,6-
dimethylpyrazine-2,3-dicarbonitriles 5a – 5f via a condensation reaction between an
isocyanide 1, 2,3-diaminomaleonitrile (¼(2E)-2,3-diaminobut-2-enedinitrile; 2), and 3-
oxopentanedioic acid (3) or Meldrumꢀs acid (¼2,2-dimethyl-1,3-dioxane-4,6-dione; 4)
in H2O at room temperature without using a catalyst, and of 3,4-dihydrobenzo[g]qui-
ꢁ 2012 Verlag Helvetica Chimica Acta AG, Zꢂrich

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noxalin-2-amines 8a – 8g and 3,4-dihydro-3,3-dimethyl-quinoxalin-2-amines and 10a –
10e via a condensation reaction between diamines 6 or 9, ketones 7 or 3-
oxopentanedioic acid (3), and an isocyanide 1 in the presence of a catalytic amount
of p-toluenesulfonic acid (TsOH · H2O) in EtOH at room temperature in good to
excellent yields (Scheme 1).
Scheme 1. Synthesis of 1,6-Dihydro-6,6-dimethylpyrazine-2,3-dicarbonitriles 5a – 5f, 3,4-Dihydroben-
zo[g]quinoxalin-2-amines 8a – 8g, and 3,4-Dihydro-3,3-dimethylquinoxalin-2-amines 10a – 10e
In an exploratory experiment, 2, 3, and cyclohexyl isocyanide were stirred in H2O at
room temperature. After completion of the reaction (1 h), workup afforded 5-
(cyclohexylamino)-1,6-dihydro-6,6-dimethylpyrazine-2,3-dicarbonitrile (5a; Fig. 1) in
90% yield (Table). To investigate the scope and limitations of this reaction, we replaced
3 by Meldrumꢀs acid (4) and conducted the reaction under the same conditions but for
24 h, when the transformation was complete: 5a was obtained in 70% yield (Table).
Then, a variety of aliphatic, alicyclic, and aromatic isocyanides were treated under
similar conditions with 3 or 4, yielding the dicarbonitriles 5b – 5f (Fig. 1). The results
are listed in the Table, showing clearly the scope of these reactions. The reactions
proceeded very cleanly under mild conditions at room temperature, and no undesirable
side reactions were observed. The transformations not only were faster with 3 relative
to 4, but also the yields were higher with 3. It should be mentioned that the formation of
the intermediate imine derivative 12 from 3 is faster than from 4 (see below; Scheme 4).
Next, we extended the reaction to naphthalene-2,3-diamine (6) instead of 2. In pilot
experiments, 6, ketones 7, and isocyanides 1 in EtOH were stirred at room temperature
in the presence of a catalytic amount of p-toluenesulfonic acid hydrate (TsOH · H2O)
to yield, after aqueous workup, 3,4-dihydrobenzo[g]quinoxalin-2-amine derivatives
8a – 8g in 60 – 70% yield (Scheme 2 and Fig. 2). These reactions proceeded very cleanly

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Helvetica Chimica Acta – Vol. 95 (2012)
Table. Synthesis of 1,6-Dihydro-6,6-dimethylpyrazine-2,3-dicarbonitriles 5a – 5f (Fig. 1) by Using 3-
Oxopentanedioic Acid (3) or Meldrumꢀs Acid (4)
R
Product With 3
With 4
M.p. [8]
time [h] yield [%]a) time [h] yield [%]a) found
reported [27]
Cyclohexyl
tert-Butyl
1,1,3,3-Tetramethylbutyl 5c
5a
5b
1
1
2
2
2
2
90
85
80
78
80
75
24
24
24
24
24
24
70
65
60
60
65
60
252 – 255 255 – 258
220 – 223 225 – 228
149 – 151 150 – 151
190 – 192 189 – 191
151 – 153 152 – 154
EtOC(¼O)CH2
5d
5e
5f
Benzyl
2,6-Dimethylphenyl
260 – 262
–
a) Yield of isolated product.
Fig. 1. Synthesized 1,6-dihydro-6,6-dimethylpyrazine-2,3-dicarbonitriles 5a – 5f
Scheme 2. Synthesis of 3,4-Dihydrobenzo[g]quinoxalin-2-amines 8a – 8g
under mild reaction conditions, and no undesirable side reactions were observed. It is
important to note that the reaction did not occur in H2O in the absence or presence of
catalyst.
To further investigate this IMCR, we extended it to 3-oxopentanedioic acid (3)
instead of ketones 7. Thus, naphthalene-2,3-diamine (6) or benzene-1,2-diamine (9), 3,
and an isocyanide 1 in EtOH were stirred at room temperature in the presence of a
catalytic amount of TsOH · H2O to give, after aqueous workup, 3,4-dihydro-3,3-
dimethylbenzo[g]quinoxalin-2-amines 8a – 8c or 3,4-dihydro-3,3-dimethylquinoxaline-

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Fig. 2. Synthesized 3,4-dihydrobenzo[g]quinoxalin-2-amines 8a – 8g. Yields in parentheses.
2-amines, 10a – 10e respectively, in 62 – 65% yield (Scheme 3 and Fig. 3). Again the
reaction did not work in H2O in the absence of or in the presence of catalyst.
Scheme 3. Synthesis of 3,4-Dihydro-3,3-dimethylbenzo[g]quinoxalin-2-amines 8a – 8c and 3,4-Dihydro-
3,3-dimethylquinoxalin-2-amines 10a – 10e
A possible mechanism for the formation of products 5a – 5f is shown in Scheme 4. It
is conceivable that the initial event is the formation of imine derivative 11 by a
condensation of 2 and 3 [28 – 33]. In the case of Meldrumꢀs acid (4), the reaction may
be rationalized by initial formation of malonic acid (15) and acetone (16) by the well-
known hydrolysis of 4 in H2O [34]. In the next step, imine derivative 12 is obtained by
decarboxylation of 11 [35] or by condensation of 2 and 16. On the basis of the well-
established chemistry of the reaction of isocyanides with imines [24][25][36][37],
intermediate 13 is produced by a nucleophilic attack of isocyanide 1 on 12, followed by
an intramolecular nucleophilic attack by the NH2 group at the activated nitrile moiety
to give intermediate 14. Finally, imine-enamine tautomerization of intermediate 14
produces the 1,6-dihydropyrazine-2,3-dicarbonitrile derivatives 5a – 5f.
To clarify the proposed mechanism for the reaction with Meldrumꢀs acid (4),
dinitride 2, acetone (16), and cyclohexyl isocyanide in the presence of malonic acid (15)

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Fig. 3. Synthesized 3,4-dihydro-3,3-dimethylbenzo[g]quinoxalin-2-amines 8a – 8c and 3,4-dihydro-3,3-
dimethylquinoxalin-2-amines 10a – 10. Yields in parentheses.
Scheme 4. Possible Mechanism of Formation of Products 5a – 5f
were subjected to the IMCR under the usual conditions (in H2O for 1 h at r.t.), and
indeed, 5a was obtained in a yield of 90%.
To illustrate the role of malonic acid (15), the reaction of 2, acetone (16), and
cyclohexyl isocyanide was performed in the absence of 15: reaction occured, not even
after 24 h at room temperature, thus establishing that malonic acid acts as a catalyst in
this reaction. Moreover, GC analysis of the reaction mixture of 4, 2, and cyclohexyl

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isocyanide revealed the formation of malonic acid (15) as a by-product, which supports
the proposed mechanism.
Compounds 5a – 5f, 8a – 8g, and 10a – 10e were stable solids whose structures were
1
identified by their IR, H- and 13C-NMR, and MS data, and by elemental analysis.
Products 5a – 5e are known compounds, and their IR and NMR data and melting points
were compared with reported values [27].
Conclusion. – We developed an IMCR for the synthesis of pharmaceutically
relevant, highly substituted 1,6-dihydropyrazine-2,3-dicarbonitriles, 3,4-dihydroben-
zo[g]quinoxalin-2-amines, especially a spiro-type compound, i.e. 8e, and 3,4-dihydro-
3,3-dimethylquinoxalin-2-amines in good to excellent yields. The reactions were easy to
perform and allowed the introduction of at least three local sites of diversity in the final
products and access to a multitude of compounds. Workup procedures were simple and
free of chromatographic separations, and the obtained target materials were of high
purity.
We gratefully acknowledge financial support from the Research Council of the Shahid Beheshti
University.
Experimental Part
General. All chemicals were obtained from Fluka or Merck and were applied without further
purification. M.p.: Electrothermal-9100 apparatus. IR Spectra: Bomem-MB FT-IR spectrophotometer; in
KBr; ˜n in cmꢀ1. 1H- and 13C-NMR Spectra: Bruker-DRX-300-Avance spectrometer; in (D6)DMSO; d in
ppm rel. to Me4Si as internal standard, J in Hz. MS: Shimadzu-GCMS-QP-1100EX mass spectrometer; at
70 eV; in m/z. Elemental analyses: Elementaranalysensysteme GmbH VarioEL, CHNS mode.
5-Amino-6,6-dimethyl-1,6-dihydropyrazine-2,3-dicarbonitriles (5): Typical Procedure for 5a. A soln.
of 2,3-diaminomaleonitrile (2; 1.0 mmol), 3-oxopentanedioic acid (3; 1.1 mmol) or Meldrumꢀs acid (4;
2.0 mmol), and cyclohexyl isocyanide (1.0 mmol) in H2O (3 ml) was stirred for 1 h or 24 h, at r.t., resp.
After completion of the reaction, (TLC (AcOEt/hexane 3 :1) monitoring), the precipitate was filtered
off and then crystallized from acetone: 5a. Colorless crystals.
3,4-Dihydrobenzo[g]quinoxalin-2-amines 8a – 8g and 3,4-Dihydroquinoxalin-2-amines 10a – 10e:
General Procedure. To a soln. of diamine 6 or 9 (1 mmol), 3-oxopentanedioic acid (3; 1.1 mmol) or
ketone 7 (1.0 mmol), and isocyanide 1 (1.0 mmol) in EtOH (3 ml) was added TsOH · H2O (5 mol-%).
The resulting mixture was stirred for 4 h at r.t. After completion of the reaction (TLC (AcOEt/hexane
2 :1) monitoring), the product was precipitated by addition of H2O (10 ml). The residue was crystallized
from EtOH: pure 8a – 8g and 10a – 10e.
5-(Cyclohexylamino)-1,6-dihydro-6,6-dimethylpyrazine-2,3-dicarbonitrile (5a): Colorless crystals.
M.p. 252 – 2558. IR: 3342, 3080, 2933, 2850, 2217, 1578, 1538, 1456, 1391. 1H-NMR: 1.00 – 2.00 (m, 5
CH2 of chx, 2 Me); 3.68 (m, CH of chx); 6.87 (d, J ¼ 7.5, NH); 7.12 (s, NH). 13C-NMR: 24.3; 25.2; 25.7;
31.9; 49.6; 50.0; 110.2; 110.8; 114.9; 118.4; 155.8. MS: 257 (20, Mþ), 242 (25), 175 (25), 160 (100), 133
(22), 57 (45), 41 (75). Anal. calc. for C14H19N5: C 65.34, H 7.44, N 27.22; found: C 65.28, H 7.33, N 27.20.
5-[(1,1-Dimethylethyl)amino)-1,6-dihydro-6,6-dimethylpyrazine-2,3-dicarbonitrile (5b): Light yel-
low crystals. M.p. 220 – 2238. IR: 3412, 3323, 2976, 2929, 2861, 2212, 1564, 1540, 1497, 1461, 1367, 1309.
1H-NMR: 1.18 (s, 2 Me); 1.32 (s, 3 Me); 6.18 (s, NH); 7.15 (s, NH). 13C-NMR: 24.0; 28.5; 49.4; 52.5; 110.0;
110.2; 114.9; 118.4; 154.8. MS: 232 (20, [M þ 1]þ), 160 (100), 133 (26), 57 (50), 41 (75). Anal. calc. for
C12H17N5: C 62.31, H 7.41, N 30.28; found: C, 62.24, H 7.33, N 30.18.
1,6-Dihydro-6,6-dimethyl-5-[(1,1,3,3-tetramethylbutyl)amino]pyrazine-2,3-dicarbonitrile (5c): White
powder. M.p. 149 – 1518. IR: 3412, 3344, 2981, 2966, 2950, 2903, 2861, 2212, 1577, 1559, 1542, 1448, 1393,
1372. 1H-NMR: 0.93 (s, 3 Me); 1.17 (s, 2 Me); 1.36 (br. s, 2 Me); 1.82 (br. s, CH2); 6.04 (s, NH); 7.12 (s,

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Helvetica Chimica Acta – Vol. 95 (2012)
NH). 13C-NMR: 23.9; 29.3; 31.6; 31.8; 49.2; 49.8; 56.4; 109.8; 110.1; 114.9; 118.4; 154.0. MS: 287 (17, Mþ),
176 (48), 160 (100), 133 (15), 97 (17), 57 (60), 41 (63). Anal. calc. for C16H25N5: C 66.86, H 8.77, N 24.37;
found: C 66.75, H 8.71, N 24.27.
Ethyl 2-[(5,6-Dicyano-3,3-dimethyl-3,4-dihydropyrazin-2-yl)amino]acetate (5d): Colorless crystals.
M.p. 190 – 1928. IR: 3379, 3293, 3080, 3049, 2997, 2960, 2934, 2217, 1744, 1579, 1502, 1461, 1406, 1322.
1H-NMR: 1.17 (t, J ¼ 7.2, Me); 1.24 (s, 2 Me); 3.90 (d, J ¼ 5.4, CH2); 4.09 (q, J ¼ 6.9, CH2); 7.37 (s, NH);
7.77 (br. s, NH). 13C-NMR: 14.5; 24.4; 43.0; 50.0; 60.8; 106.5; 109.6; 111.7; 114.5; 118.2; 156.6; 169.8. MS:
262 (50, [M þ 1]þ), 246 (45), 172 (100), 133 (25), 42 (27). Anal. calc. for C12H15N5O2: C 55.16, H 5.79, N
26.80; found: C 55.11, H 5.72, N 26.70.
1,6-Dihydro-6,6-dimethyl-5-[(phenylmethyl)amino]pyrazine-2,3-dicarbonitrile (5e): Brown powder.
M.p. 151 – 1538. IR: 3431, 3185, 3044, 2966, 2918, 2210, 1574, 1554, 1513, 1455, 1419, 1317. 1H-NMR: 1.26
(s, 2 Me); 4.45 (d, J ¼ 5.3, CH2); 7.20 – 7.35 (m, 6 H, arom. H, NH); 7.88 (t, J ¼ 5.0, NH). 13C-NMR: 24.4;
44.3; 50.0; 110.4; 110.9; 114.8; 119.3; 127.2; 127.5; 128.8; 139.3 165.6. MS: 266 (3, [M þ 1]þ), 250 (4), 193
(6), 174 (9), 132 (22), 108 (45), 43 (100). Anal. calc. for C15H15N5: C 67.90, H 5.70, N 26.40; found: C,
67.80, H 5.66, N 26.32.
5-[(2,6-Dimethylphenyl)amino]-1,6-dihydro-6,6-dimethylpyrazine-2,3-dicarbonitrile (5f): Colorless
crystals. M.p. 260 – 2628. IR: 3346, 3387, 3341, 3190, 2981, 2918, 2850, 2211, 1597, 1576, 1549, 1524, 1457,
1
1393, 1367, 1312. H-NMR: 1.40 (2 Me); 2.10 (2 Me); 7.10 (3 arom. H); 7.45 (s, NH); 8.60 (s, NH).
13C-NMR: 18.2; 24.6; 50.3; 109.9; 111.7; 114.6; 118.2; 127.4; 128.3; 135.5; 136.0; 155.3. MS: 280 (10, [M þ
1]þ), 264 (20), 248 (4), 207 (2), 158 (6), 183 (100), 77 (15), 43 (10). Anal. calc. for C16H17N5: C 68.79, H
6.13, N 25.07; found: C 68.69, H 6.03, N 25.00.
N-Cyclohexyl-3,4-dihydro-3,3-dimethylbenzo[g]quinoxalin-2-amine (8a). Green powder. M.p. 252 –
2548. IR: 3287, 3047, 2931, 2857, 1655, 1599, 1534, 1504, 1454. 1H-NMR: 0.80 – 2.20 (m, 5 CH2, 2 Me); 4.02
(m, CHꢀN); 6.82 (s, NH); 7.00 – 7.80 (m, 6 arom. H); 9.00 (d, J ¼ 7.6, NH). 13C-NMR: 21.2; 24.8; 25.1;
25.5; 32.1; 52.1; 53.4; 109.1; 115.2; 123.7; 126.0; 127.7; 127.8; 128.6; 132.5; 134.2; 138.2; 161.8. MS: 308 (65,
[Mþ þ 1]), 210 (100), 183 (90), 140 (15), 107 (25), 91 (75), 65 (45), 41 (60). Anal. calc. for C20H25N3: C
78.14, H 8.20, N 13.67; found: C 78.10, H 8.10, N 13.57.
3,4-Dihydro-3,3-dimethyl-N-(phenylmethyl)-benzo[g]quinoxalin-2-amine (8b): Grass green pow-
der. M.p. 248 – 2508. IR: 3401, 2935, 2855, 1602, 1456. 1H-NMR: 1.54 (br. s, 2 Me); 4.86 (m, CH2ꢀN); 6.89
(s, NH); 7.00 – 7.80 (m, 11 arom. H); 9.98 (s, NH). 13C-NMR: 21.2; 45.7; 53.6; 109.2; 115.4; 123.6; 126.0;
126.3; 127.7; 127.8; 128.3; 128.6; 129.2; 132.5; 134.4; 135.7; 138.4; 163.3. MS: 316 (15, [M þ 1]þ), 300 (25),
209 (25), 183 (30), 140 (15), 107 (15), 91 (100), 65 (35), 39 (20). Anal. calc. for C20H25N3: C 78.14, H 8.20,
N 13.67; found: C 78.10, H 8.10, N 13.57.
N-(1,1-Dimethylethyl)-3,4-dihydro-3,3-dimethylbenzo[g]quinoxalin-2-amine (8c): Green powder.
1
M.p. 142 – 1448. IR: 3454, 3382, 2957, 2851, 1635, 1580, 1525, 1475. H-NMR: 1.28 (s, 2 Me); 1.45 (s, 3
Me); 6.01 (s, NH); 6.70 – 7.45 (m, 6 arom. H); 7.53 (s, NH). 13C-NMR: 26.6; 29.1; 50.8; 51.7; 106.1; 118.8;
121.6; 123.7; 125.1; 126.9; 128.9; 131.6; 136.6; 137.7; 161.6. MS: 282 (10, [M þ 1]þ), 224 (100), 195 (15), 57
(52), 41 (45). Anal. calc. for C22H29N3: C 76.83, H 8.24, N 14.93; found: C 76.78, H 8.15, N 14.90.
N-Cyclohexyl-3,3-diethyl-3,4-dihydrobenzo[g]quinoxalin-2-amine (8d). Grass green powder. M.p.
106 – 1088. IR: 3452, 3383, 2958, 2850, 1633, 1588, 1521, 1480. 1H-NMR: 0.80 – 2.20 (m, 5 CH2, 2 Me); 1.95
(m, 2 CH2); 5.36 (m, CHꢀN); 5.88 (s, NH); 6.60 – 7.50 (m, 6 arom. H); 7.47 (d, J ¼ 7.8, NH). 13C-NMR:
8.7; 29.6; 31.8; 31.9; 33.1; 52.0; 55.8; 58.5; 100.2; 103.0; 118.8; 120.8; 123.7; 124.5; 126.7; 128.2; 132.2;
135.5; 138.5; 151.9. MS: 336 (10, [M þ 1]þ), 224 (100), 197 (10), 57 (50), 41 (55). Anal. calc. for C22H29N3:
C 78.76, H 8.71, N 12.53; found: C 78.72, H 8.69, N 12.45.
N-Cyclohexylspiro[benzo[g]quinoxaline-(1H)2,1’-cyclohexan]-3-amine (8e): Green powder. M.p.
1
> 2608. IR: 3283, 2937, 2845, 1644, 1620, 1554, 1464, 1320. H-NMR: 0.80 – 2.25 (m, 10 CH2); 4.10 (m,
CHꢀN); 6.85 (s, NH); 7.00 – 7.75 (m, 6 arom. H); 8.50 (d, J ¼ 7.6, NH). 13C-NMR: 19.6; 21.2; 24.7; 24.8;
25.2; 31.2; 52.1; 55.1; 110.0; 115.2; 123.6; 123.7; 126.0; 127.7; 127.9; 132.3; 133.6; 138.3; 161.7. MS: 361 (6,
Mþ), 347 (80), 290 (30), 265 (75), 222 (50), 195 (90), 140 (35), 107 (60), 91 (100), 55 (90). Anal. calc. for
C23H29N3: C 79.50, H 8.41, N 12.09; found: C 79.41, H 8.35, N 12.00.
N-Cyclohexyl-3,4-dihydro-3-methyl-3-(4-nitrophenyl)benzo[g]quinoxalin-2-amine (8f): Green pow-
der. M.p. 181 – 1828. IR: 3287, 2931, 1655, 1454, 1183, 1121. 1H-NMR: 1.00 – 2.20 (m, 5 CH2, 1 Me); 4.00
(m, CHꢀN); 6.79 (s, NH); 7.00 – 7.70 (m, 10 arom. H); 8.92 (m, NH). 13C-NMR: 21.2; 24.8; 25.5; 31.1;

Helvetica Chimica Acta – Vol. 95 (2012)
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52.1; 53.4; 109.1; 115.2; 123.6; 126.0; 126.2; 127.9; 128.6; 132.5; 134.2; 138.3; 161.8. MS: 308 (25, [M –
106]þ), 292 (42), 210 (100), 183 (90), 140 (15), 107 (20), 91 (60), 65 (40), 41 (40). Anal. calc. for
C25H26N4O2: C 72.44, H 6.32, N 13.52; found: C 72.40, H 6.22, N 13.42.
3,4-Dihydro-3-methyl-3-(4-nitrophenyl)-N-(phenylmethyl)benzo[g]quinoxalin-2-amine (8g):Green
powder. M.p. 154 – 1568. IR: 3361, 1603, 1522, 1478, 1346, 1261. 1H-NMR: 1.93 (s, Me); 4.46 (s, CH2ꢀN);
6.80 (s, NH); 7.00 – 8.30 (m, 15 arom. H); 8.32 (m, NH). 13C-NMR: 30.2; 81.6; 99.7; 122.0; 123.9; 125.5;
126.8; 130.3; 141.2; 146.9; 154.8. MS: 422 (5, Mþ), 290 (65), 260 (25), 244 (65), 183 (75), 158 (40), 140
(35), 115 (100), 76 (40), 51 (35). Anal. calc. for C25H26N4O2: C 72.44, H 6.32, N 13.52; found: C 72.40, H
6.22, N 13.42.
N-Cyclohexyl-3,4-dihydro-3,3-dimethyl-6-nitroquinoxalin-2-amine (10a): Orange powder. M.p. >
1
2508. IR: 3263, 2934, 2851, 1651, 1604, 1530, 1458, 1339. H-NMR: 0.80 – 2.10 (m, 5 CH2, 2 Me); 3.99
(m, CHꢀN); 6.52 (s, NH); 7.30 – 7.80 (m, 3 arom. H); 9.16 (s, NH). 13C-NMR: 25.4; 25.8; 26.2; 32.3; 49.2;
50.4; 106.9; 114.6; 121.9; 136.5; 141.6; 142.8; 161.1. MS: 302 (30, Mþ), 287 (65), 205 (100), 178 (20), 159
(35), 132 (15), 107 (30), 91 (65), 65 (25), 41 (22). Anal. calc. for C16H22N4O2: C 63.55, H 7.33, N 18.53;
found: C 63.47, H 7.23, N 18.43.
3,4-Dihydro-3,3-dimethyl-6-nitro-N-(1,1,3,3-tetramethylbutyl)quinoxalin-2-amine (10b): Yellow crys-
tals. M.p. 190 – 1928. IR: 3234, 2971, 2850, 1645, 1602, 1532, 1498, 1429. 1H-NMR: 0.98 (s, 3 Me); 1.43 (s, 2
Me); 1.58 (s, 2 Me); 2.07 (s, CH2); 7.35 – 7.80 (m, 3 arom. H); 7.76 (s, NH); 8.39 (s, NH). 13C-NMR: 21.2;
24.7; 28.5; 31.5; 31.9; 50.3; 52.5; 53.2; 114.2; 125.9; 128.6; 135.0; 138.2; 145.9; 160.0. MS: 332 (4, Mþ), 261
(1), 205 (100), 159 (20), 91 (20), 57 (25), 41 (25). Anal. calc. for C18H28N4O2: C 65.03, H 8.49, N 16.85;
found: C 64.93, H 8.40, N 16.78.
3,4-Dihydro-3,3-dimethyl-6-nitro-N-(phenylmethyl)quinoxalin-2-amine (10c): Green powder. M.p.
1
198 – 2008. IR: 3230, 1644, 1601, 1542, 1497, 1435. H-NMR: 1.51 (s, 2 Me); 4.82 (m, CH2 – N); 6.87 (s,
NH); 7.00 – 7.80 (m, 8 arom. H); 8.15 (s, NH). 13C-NMR: 21.2; 46.2; 53.3; 109.2; 114.4; 122.0; 125.2; 127.8;
128.4; 129.1; 129.2; 135.2; 135.3; 145.3; 162.1. MS: 310 (5, Mþ), 295 (6), 249 (3), 221 (1), 204 (2), 172 (10),
107 (15), 91 (100), 65 (20), 39 (15). Anal. calc. for C17H18N4O2: C 65.79, H 5.85, N 18.05; found: C 65.70,
H 5.75, N 18.00.
N-(1,1-Dimethylethyl)-3,4-dihydro-3,3-dimethyl-6-nitroquinoxalin-2-amine (10d): Red powder. M.p.
215 – 2178. IR: 3230, 2957, 2851, 1642, 1601, 1542, 1496, 1434. 1H-NMR: 1.25 (s, 2 Me); 1.43 (s, 3 Me); 6.07
(s, NH); 6.33 (s, NH); 6.84 (ABq, J ¼ 8.3, 1 arom. H); 7.37 (s, 1 arom. H); 7.45 (ABq, J ¼ 8.1, 1 arom. H).
13C-NMR: 26.1; 29.0; 50.2; 52.4; 107.1; 114.5; 122.3; 136.4; 141.8; 142.2; 162.0. Anal. calc. for C14H20N4O2:
C 60.85, H 7.30, N 20.28; found: C 60.85, H 7.30, N 20.28.
[2-(Cyclohexylamino)-3,4-dihydro-3,3-dimethyl-quinoxalin-6-yl)](phenyl)methanone (10e): White
1
crystals. M.p. 181 – 1828. IR: 3274, 2929, 2845, 1650, 1607, 1508, 1461, 1320. H-NMR: 0.80 – 2.00 (m, 5
CH2, 2 Me); 3.96 (m, CHꢀN); 6.84 (s, NH); 7.00 – 7.80 (m, 8 arom. H); 9.04 (s, NH). 13C-NMR: 21.2; 24.7;
25.2; 32.0; 52.3; 53.1; 116.1; 117.8; 121.3; 128.9; 129.7; 132.8; 134.4; 134.6; 137.9; 145.9; 160.5; 195.3. MS:
361 (20, Mþ), 346 (75), 264 (80), 237 (30), 172 (20), 105 (100), 91 (60), 77 (100), 55 (50), 41 (55). Anal.
calc. for C23H27N3O: C 76.42, H 7.53, N 11.62; found: C 76.38, H 7.43, N 11.52.
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Received June 29, 2011