Synthesis of two novel tricyclic rings: Triazolo[4,5-g]- quinolines and pyrido[2,3-g]quinoxalines derived from 6,7-diaminoquinolines

Article abstract of DOI:10.3987/COM-99-8766

A general simple route for the synthesis of triazolo[4,5-g]quinolines and pyrido[2,3-g]quinoxalines is described. The heterocycles obtained were fully characterised by their spectroscopical properties. A revision of the nitration of the 2,3-dichloroacetanilide is also discussed, since it afforded the request nitro derivative to build up the key intermediate 6,7- diaminoquinolines.

Full text of DOI:10.3987/COM-99-8766

HETEROCYCLES, Vol. 53, No. 2, 2000, pp. 423 - 432, Received, 28th September, 1999
SYNTHESIS OF TWO NOVEL TRICYCLIC RINGS: TRIAZOLO[4,5-g]-
QUINOLINES AND PYRIDO[2,3-g]QUINOXALINES DERIVED FROM
6,7-DIAMINOQUINOLINES
Paolo Sanna,*Antonio Carta, and Giuseppe Paglietti
Dipartimento Farmaco-Chimico-Tossicologico - University of Sassari
via Muroni, 23/a - 07100 Sassari, Italy
Abstract- A general simple route for the synthesis of triazolo[4,5-g]quinolines
and pyrido[2,3-g]quinoxalines is described. The heterocycles obtained were fully
characterised by their spectroscopical properties. A revision of the nitration of the
2,3-dichloroacetanilide is also discussed, since it afforded the request nitro
derivative to build up the key intermediate 6,7-diaminoquinolines.
Heterocyclic compounds continue to attract most of the researchers in both University and industry since
they dominate ought to the largest number of publications appearing in the literature. According to their
importance in various fields of applications,1 their interest from a medicinal chemistry point of view lies
upon the well known properties as antibiotic, neurotropic, cardiovascular and anticarcinogenic agents.
Thus, in line with our previous researches in this field, aimed to discover novel pharmacological agents in
the series of the triazolo[4,5-f]-2,3 and triazolo[4,5-h]quinolines4 we now planned to design new
fundamental heterocyclic nuclei belonging to the class of triazolo[4,5-g]quinolines (Ia,b) and pyrido[2,3-
g]quinoxalines (IIa,b) (see Scheme 1) to be further functionalized for a pharmacological evaluation. In
this context we also reprepared, using an alternative simpler route, the known imidazo[4,5-g]quinolines
1
(IIIa,b)5 which in this case were fully spectroscopically (IR, UV and H-NMR) characterised. Our
previous attempts of preparation of triazolo[4,5-g]quinolines starting from 5-aminobenzotriazoles by
condensation with activated acetylenic esters,6,7 suitable β-keto esters,8 β-diketones9 or via Skraup
synthesis10 led to angular triazolo[4,5-f]quinolines; in no way the desired [4,5-g] compounds could be
obtained. This fact prompted us to devise a new approach that is depicted in the Scheme 1. Thus, we have
found that the diamines (11a,b) underwent ring closure to Ia,b by diazotization with HNO2 and
cyclization of the corresponding diazonium salts at room temperature. Reaction of 11a,b with glyoxal
afforded the pyridoquinoxalines (IIa,b) via an expected nucleophilic addition-elimination mechanism

upon the 1,2-dicarbonyl compound under refluxing ethanol. Cyclization to imidazoquinolines (IIIa,b)
occurred with formic acid at 100 °C. In all cases the desired heterocycles were obtained in good yields.
H
N
8
9
1
7
6
2 N
3
5
4
N
N
R
Ia,b
HNO2
HC=O
C=O
N
NH2
NH2
9
1
10
5
8
7
2
H
3
6
4
N
N
N
R
R
11a,b
IIa,b
a, R = H
b, R = Cl
HCOOH
H
N
2
3
8
9
1
7
6
5
4
N
N
R
IIIa,b
Scheme 1
The necessary diamine (11a) is claimed to be formed by hydrogenation of the corresponding parent nitro
derivative by Lebenstedt and Schunack5 who did not isolate and characterize it. Our approach, outlined in
Scheme 2, is only partially similar to that used by the cited authors and allowed us to clear the course of
the nitration of the starting 2,3-dichloroacetanilide (1) according to the indications of the literature.11
Preparation of the key intermediate (6) has been the starting point of the experimental work of this paper.
Holleman11 claimed to have obtained by nitration of 1 the sole mononitro compound (5) that upon
hydrolysis was coincident with compound (2) previously described by Beilstein and Kurbatov,12 thus
concluding that despite the expectations the ortho orientation of the acetylamino group was prevailing.
This reaction instead proved to be more complicated since from the reaction mixture we were able to
isolate, after column chromatography, the requested compound (6) in the highest yield (44%) followed by
the known compounds: (2) (15%),11,12 (3) (traces),13 (4) (3.5%)14 and (5) (10%).11,15 The presence of the
deacetyl compounds (2), (3) and (4) clearly indicates that when the mixture is poured onto ice a partial
hydrolysis was occurring, due to exothermal reaction. On the whole the derivatives of para substitution of

aniline represent nearly 50% of the nitration products whereas a 25% is represented by the ortho
nitroaniline derivatives and only traces of the dinitro derivative (3) were detected. Our results confirm
what is generally accepted that both acetylamino and chlorine groups in benzene ring are ortho-para
directing by themselves just producing mixture of isomers, the para effect of acetylamino group
appearing twice predominant. Consequently in our opinion the Holleman's11 results are misleading and
must be corrected.
CH3CO
N
H
Cl
Cl
1
KNO3/H2SO4
O2N
H2N
O2N
H2N
O2N
NO2
Cl
NO2
NO2
+
+
+
+
CH3CO
Cl
N
H
Cl
Cl
H2N
Cl
CH3CO
N
H
Cl
6
Cl
Cl
Cl
Cl
(44%)
2
(15%)
3
5
(10%)
(traces)
4
(3.5%)
OH-/H+
(87%)
Skraup
NH3
H
N
NH2
NO2
Cl
NO2
NH2
H2N NH2
+
N
N
Cl
N
N
N
H2N
8
9
Cl
Ib Cl
Cl
Cl
7
NH3
Skraup
NO2
NH2
N
10
Cl
H2 / Pd-C
25 °C
H2 / Pd-C
60 °C
NH2
NH2
NH2
N
NH2
N
11a
11b
Cl
Scheme 2

For our purpose we then submitted the intermediate (4), also obtained by alkaline hydrolysis of 6, to
Skraup reaction to give the 7,8-dichloro-6-nitroquinoline (8) in 53% yield, from which, by nucleophilic
substitution with ammonia, the desired intermediate (10) (98%) was isolated. Alternatively, compound
(10) was also prepared starting from 6 via 7 after Skraup reaction. However, this conversion appeared to
be very disfavored since only a small amount (8%) of 10 was obtained. The latter underwent both
hydrogenolysis and reduction to the diamine (11a) operating with hydrogen and Palladised charcoal at 60
°C under moderate pressure (3 atm) while the hydrogenation carried out at 25 °C yielded the diamine
(11b). However, this step is a critical point because the variation of the temperature between 30-50 °C
influences the formation ratio of the compounds (11a) and (11b). As the temperature increases formation
of 11a dominates. This is an improvement in comparison with the results reported by Lebenstedt and
Schunack5 thus offering a possibility to obtain the two diamines by the same intermediate. The
availability of the intermediate (8) allowed us to extend the investigation of the reaction with hydrazine
hydrate that we had previously used on similar compounds in the aim to obtain triazolo[4,5-f]quinolines.10
From this reaction we could observe that hydrazine hydrate mainly reduced the nitro group to amine (9)
(50%) while the expected nucleophilic displacement of the chlorine in C-7 to give the triazolo[4,5-
g]quinoline (Ib) occurred in lower yield (22%) possibly via triazolo N-oxide not isolable under these
reducing conditions. The result obtained by this route was comparable in terms of overall yield (21%)
with that previously described but more immediate avoiding the multisteps leading to the diamine (11b).
The structures of all compounds described are supported by their analytical and spectroscopical data (IR,
1
UV and H-NMR). In particular the UV spectra of compounds (I, II and III) are the most characteristic
showing two regions of absorptions respectively in the range 220-260 nm (more intense) and 310-380
nm. In addition the triazolo[4,5-g]quinolines (Ia,b) exhibited a fine structure, very similar to those of the
previously reported angular triazolo[4,5-f]-2,3 and [4,5-h] analogues,4 and not present in the other triciclic
compounds (II) and (III). An hypsochromic shift of about 15-20 nm (230 nm compared 245-250 nm of
the angular derivatives) was also observed for the intense maxima of Ia,b in the region 220-260 nm,
associated with a batochromic shift of about 50-60 nm for absorptions in the region 310-380 nm.
EXPERIMENTAL
Melting points were determined in open capillaries in a Digital Electrothermal IA9100 melting point
apparatus and are uncorrected. In brackets are reported the recrystallization solvents. IR spectra were
recorded as nujol mulls with a Perkin-Elmer 781 spectrophotometer. UV spectra are qualitative and were
1
recorded in nm for solutions in ethanol with a Perkin-Elmer Lambda 5 spectrophotometer. H-NMR
spectra were measured at 200 MHz using a Varian XL-200 spectrometer, using TMS as internal standard.

The chemical shift values are reported in ppm (δ) and coupling constants (J) in Hertz (Hz). Signal
multiplicities are represented by s (singlet), d (doublet), dd (double doublet), t (triplet), m (multiplet), and
br s (broad singlet). MS spectra were performed on a combined HP 5790-HP 5970 GC/MS apparatus.
Silica gel 60 (Merck 70-230 and 230-400 mesh silica gel) was used for column chromatography. The
progress of the reactions and the purity of the final compounds were monitored by TLC using Merck F-
254 commercial plates. Light petroleum refers to the fraction with bp 40-60 °C. Elemental analyses were
performed at the Laboratorio di Microanalisi, Dipartimento di Scienze Farmaceutiche, University of
Padua.
Preparation of 2,3-dichloro-4-nitroacetanilide (6). To a solution of 10 g (49.0 mmol) of compound (1)
prepared as described12 in concentrated sulfuric acid (50 mL), cooled with an external ice bath, an
aqueous solution of potassium nitrate (9.9 g, 98.0 mmol) in concentrated sulfuric acid (15 mL) was
slowly added under mechanical stirring so that the inner temperature was always below 10 °C. After the
addition was complete, the reaction mixture was stirred below 10 °C for an additional 4 h and then poured
into crushed ice (300 g). The resulting precipitate was filtered off, thoroughly washed with water and
dried affording 10.8 g of crude reaction product, TLC of which showed to deal with a complex mixture.
Separation of the components was accomplished by chromatography on silica gel, eluting at first with a
7:3 mixture of ether-light petroleum, then with ether and eventually with a 8:2 mixture of ether-acetone,
to yield in sequence: 2,3-dichloro-6-nitroaniline (2) (1.56 g, 15%), mp 165-167 °C (lit.,11,12 164 °C);
2,3-dichloro-4,6-dinitroaniline (3) (0.07 g, 0.6%), mp 196-198 °C (lit.,13 197-198 °C); 2,3-dichloro-4-
nitroaniline (4) (0.35 g, 3.5%), mp 189-191 °C (lit.,14 180-181 °C); 2,3-dichloro-6-nitroacetanilide (5):
(1.23 g, 10%), mp 218-219 °C (acetone) (lit.,11 218 °C, lit.,15 222 °C); 2,3-dichloro-4-nitroacetanilide
(6) (5.36 g, 44%), mp 149-151 °C (acetone); IR: 3250, 1680, 1620, 1570 cm-1; UV: λmax 286, 236 sh, 218
nm; 1H-NMR (CDCl3+DMSO-d6): δ 8.99 (s, 1H, NH), 8.37 (d, 1H, J = 8.8 Hz, H-5), 7.84 (d, 1H, J = 8.8
Hz, H-6), 2.30 (s, 3H, CH3); MS: m/z 248 (M+). Anal. Calcd for C8H6N2O3Cl2: C, 38.58; H, 2.43; N,
11.25; Cl, 28.47. Found: C, 38.24; H, 2.30; N, 11.06; Cl, 28.29.
2,3-Dichloro-4-nitroaniline (4). The title compound was obtained starting from 6 (3.0 g, 12 mmol) in
87% yield (2.17 g) by hydrolysis with concentrated sulfuric acid (20 mL) at 100 °C for 2 h.
7,8-Dichloro-6-nitroquinoline (8). To a mixture of 4 (3.0 g, 14.5 mmol), freshly prepared dry glycerol
(5.3 g, 57.7 mmol), and arsenic pentoxide (9.2 g, 40.0 mmol) cooled at 0 °C with an ice bath, 4 mL of
concentrated sulfuric acid were added within 30 min under mechanical stirring. After complete addition,
the temperature was slowly arised to 150 °C and stirring continued for an additional 2 h. The mixture was

then allowed to cool to rt, poured into crushed ice (100 g) and the stirring continued for further 30 min.
The resulting precipitate was collected by filtration and purified by chromatography over silica gel, using
a 6:4 mixture of ether-light petroleum as eluent, to yield 8 (1.86 g, 53%) as yellowish crystals with mp
156-157 °C (acetone); IR: 1600, 1540, 1520 cm-1; UV: λmax 257, 223 nm; 1H-NMR (CDCl3+DMSO-d6): δ
9.21 (d, 1H, J = 4.2 Hz, H-2), 8.84 (s, 1H, H-5), 8.66 (d, 1H, J = 8.4 Hz, H-4), 7.81 (dd, 1H, J = 8.4 and
4.2 Hz, H-3); MS: m/z 242 (M+). Anal. Calcd for C9H4N2O2Cl2: C, 44.47; H, 1.66; N, 11.53; Cl, 29.17.
Found: C, 44.74; H, 1.74; N, 11.32; Cl, 28.89.
7-Amino-8-chloro-6-nitroquinoline (10).
Method A: from 8 using ethanolic ammonia solution.
A solution of 8 (1.65 g, 6.8 mmol) in ethanol (100 mL) saturated with dry gaseous ammonia was heated
in a sealed steel vessel at 160 °C under stirring for 22 h. Then the reaction mixture was cooled to rt, the
solvent was removed in vacuo and the solid residue thoroughly triturated with ether to give 10 (1.49 g,
98%); mp 222 °C (ethanol); IR: 3500, 3350, 1630, 1610, 1580 cm-1; UV: λmax 296, 264, 244 sh, 234, 201
nm; 1H-NMR (CDCl3): δ 8.96 (dd, 1H, J = 4.2 and 1.6 Hz, H-2), 8.64 (s, 1H, H-5), 8.08 (dd, 1H, J = 8.2
and 1.6 Hz, H-4), 7.23 (dd, 1H, J = 8.2 and 4.2 Hz, H-3), 6.43 (br s, 2H, NH2); MS: m/z 223 (M+). Anal.
Calcd for C9H6N3Cl: C, 48.34; H, 2.70; N, 18.79; Cl, 15.86. Found: C, 48.09; H, 2.40; N, 18.52; Cl,
15.67.
Method B: from 7 via Skraup synthesis.
To a mixture of 7 (0.5 g, 2.7 mmol), freshly prepared dry glycerol (1.0 g, 11.0 mmol), and arsenic
pentoxide (0.8 g, 3.5 mmol) cooled at 0 °C with an ice bath, 2.5 mL of concentrated sulfuric acid were
added dropwise over 30 min under mechanical stirring. After the addition was complete, the temperature
was slowly arised to 150 °C and the stirring continued for an additional 2 h. The reaction mixture was
then allowed to cool to rt, poured into crushed ice (30 g) and the stirring continued for an additional 30
min. The resulting precipitate was filtered off, the filtrate was made alkaline (pH ≅ 12) with concentrated
ammonia aqueous solution and extracted with chloroform (5 x 30 mL). The combined extracts, dried on
anhydrous sodium sulfate, were evaporated in vacuo to yield 10 (0.05; 8%) identical to a specimen
obtained under method A.
2-Chloro-4-nitro-1,3-benzenediammine (7). A solution of 6 (1.0 g, 4.0 mmol) in ethanol (100 mL)
saturated with dry gaseous ammonia was heated in a sealed steel vessel at 160 °C under stirring for 22 h.
After this time the reaction mixture was cooled to rt and the solvent was removed under reduced pressure.
The solid residue triturated with ether gave 7 (0.73 g, 97%); mp 164-166 °C (acetone); IR: 3480, 3350,

1640, 1620, 1580 cm-1; UV: λmax 383, 260, 217 nm; 1H-NMR (CDCl3+DMSO-d6): δ 7.89 (d, 1H, J = 9.4
Hz, H-5), 6.93 (br s, 2H, NH2), 6.24 (d, 1H, J = 9.4 Hz, H-6), 5.83 (s, 2H, NH2); MS: m/z 187 (M+). Anal.
Calcd for C6H6N3O2Cl: C, 38.41; H, 3.22; N, 22.40; Cl, 18.90. Found: C, 38.13; H, 3.43; N, 22.12; Cl,
18.73.
6,7-Diaminoquinoline (11a). A suspension of 10 (1.0 g, 4.5 mmol) and of 10% palladized charcoal (0.25
g) in ethanol (200 mL) was hydrogenated in Parr at 3 atm and 60 °C for 3.5 h. After filtration of the
catalyst, the solvent was removed in vacuo. The solid residue was dissolved with water and the resulting
solution, made alkaline (pH ≅ 10-11) using a sodium hydroxyde aqueous solution (2 M), was extracted
with chloroform (5 x 60 mL). The combined extracts, dried over anhydrous sodium sulfate, evaporated to
dryness gave 11a (0.42 g, 50%), mp 174-175 °C (acetone); IR: 3400, 3200, 1670, 1640, 1630, 1570 cm-1;
UV: λmax 342, 235, 204 nm; 1H-NMR (CDCl3+DMSO-d6): δ 8.45 (d, 1H, J = 4.0 Hz, H-2), 7.75 (d, 1H, J
= 8.2 Hz, H-4), 7.16 (s, 1H, H-8), 7.02 (dd, 1H, J = 8.2 and 4.0 Hz, H-3), 6.87 (s, 1H, H-5), 4.77 (br s,
2H, NH2), 4.58 (br s, 2H, NH2); MS: m/z 159 (M+). Anal. Calcd for C9H9N3: C, 67.90; H, 5.70; N, 26.40.
Found: C, 68.17; H, 5.60; N, 26.58.
6,7-Diamino-8-chloroquinoline (11b). A suspension of 10 (1.0 g, 4.5 mmol) and of 10% palladized
charcoal (0.20 g) in ethanol (200 mL) was hydrogenated in Parr at 20-25 °C and 3 atm for 3.5 h. After
filtration of the catalyst, the solvent was evaporated in vacuo and the solid residue was flash
chromatographed on silica gel with ether as eluent to afford 11b (0.77 g, 90%); mp 162-163 °C (ether);
1
IR: 3500, 3300, 1720, 1710, 1690, 1670, 1640 cm-1; UV: λmax 356, 250, 222 nm; H-NMR (CDCl3): δ
8.76 (dd, 1H, J = 4.2 and 1.6 Hz, H-2), 7.87 (dd, 1H, J = 8.2 and 1.6 Hz, H-4), 7.20 (dd, 1H, J = 8.2 and
4.2 Hz, H-3), 6.94 (s, 1H, H-5), 4.43 (br s, 2H, NH2), 3.78 (br s, 2H, NH2); MS: m/z 193 (M+). Anal.
Calcd for C9H8N3Cl: C, 55.82; H, 4.16; N, 21.70; Cl, 18.31. Found: C, 56.03; H, 4.19; N, 21.48; Cl,
18.09.
1H-1,2,3-Triazolo[4,5-g]quinoline (Ia). A solution of sodium nitrite (0.25 g, 3.5 mmol) in water (2 mL)
was added dropwise to an ice-cooled stirred solution of 11a (0.5 g, 3.14 mmol) in 2 M hydrochloric acid
solution (10 mL). Then the mixture was allowed to warm at rt and the stirring continued for an additional
7 h. A solid was formed and collected by filtration to give Ia (0.22 g, 42%); mp 209-211 °C (acetone);
1
IR: 3450, 1640, 1630, 1610, 1560 cm-1; UV: λmax 360 sh, 350, 332 sh, 320, 312 infl, 230 nm; H-NMR
(DMSO-d6): δ 9.42 (d, 1H, J = 4.4 Hz, H-6), 9.31 (d, 1H, J = 8.0 Hz, H-8), 9.12 (s, 1H, H-4), 8.77 (s, 1H,
H-9), 7.99 (dd, 1H, J = 8.0 and 4.4 Hz, H-7); MS: m/z 170 (M+). Anal. Calcd for C9H6N4: C, 63.52; H,
3.55; N, 32.93. Found: C, 63.34; H, 3.91; N, 33.12.

4-Chloro-1H-1,2,3-triazolo[4,5-g]quinoline (Ib).
Method A: from 11b using sodium nitrite.
A solution of sodium nitrite (0.25 g, 3.5 mmol) in water (2 mL) was added dropwise to an ice-cooled
stirred solution of 11b (0.5 g, 2.6 mmol) in 2 M hydrochloric acid aqueous solution (15 mL). After the
addition was complete, the mixture was allowed to warm at rt and the stirring continued for additional 7
h, when the pH of the aqueous phase was adjusted to 5 with concentrated ammonia aqueous solution. The
resulting precipitate was filtered off obtaining Ib (0.23 g, 43%); mp 283-284 °C (acetone); IR: 3450,
1670, 1610 cm-1; UV: λmax 378, 361, 346, 324, 316 sh, 231 nm; 1H-NMR (CDCl3+DMSO-d6): δ 9.07 (d,
1H, J = 3.6 Hz, H-6), 8.54 (m, 2H, H-8+H-9), 7.54 (dd, 1H, J = 8.4 and 3.6 Hz, H-7); MS: m/z 204 (M+).
Anal. Calcd for C9H5N4Cl: C, 52.82; H, 2.46; N, 27.38; Cl, 17.33. Found: C, 52.57; H, 2.59; N, 27.18; Cl,
17.11.
Method B: from 7,8-dichloro-6-nitroquinoline (8) using hydrazine hydrate.
A mixture of 8 (0.8 g, 3.3 mmol) and hydrazine hydrate (99%, 3.0 g, 60 mmol) in ethanol (70 mL) was
heated in a sealed steel vessel at 160 °C under stirring for 10 h. The reaction mixture was then cooled to rt
and the solvent was removed in vacuo. The solid residue obtained was chromatographed on silica gel
column, eluting with a 8:2 mixture of ether-light petroleum, to give: 6-amino-7,8-dichloroquinoline (9)
(0.35 g, 50%); mp 198-200 °C (ether); IR: 3440, 1640, 1610, 1580, 1550 cm-1; UV: λmax 364, 294 sh, 284
1
sh, 253, 221 nm; H-NMR (CDCl3): δ 8.79 (dd, 1H, J = 4.2 and 1.6 Hz, H-2), 7.92 (dd, 1H, J = 8.4 and
1.6 Hz, H-4), 7.35 (dd, 1H, J = 8.4 and 4.2 Hz, H-3), 6.98 (s, 1H, H-5), 4.46 (br s, 2H, NH2); MS: m/z 212
(M+). Anal. Calcd for C9H6N2Cl2: C, 50.73; H, 2.84; N, 13.15; Cl, 33.28. Found: C, 50.78; H, 3.07; N,
12.94; Cl, 33.09; further elution of the column with ether yielded 4-chloro-1H-1,2,3-triazolo[4,5-
g]quinoline (Ib) (0.15 g, 22%), identical with an authentic specimen as above described.
Pyrido[2,3-g]quinoxaline (IIa). Glyoxal (8.9 g, 61.3 mmol, 40% in water) was slowly dropwise added,
under stirring, to a refluxing solution of 11a (0.6 g, 3.8 mmol) in ethanol (15 mL) and the stirring
continued for an additional 2 h. After cooling the resulting solution was evaporated to dryness in vacuo to
give a solid residue. Purification of this was accomplished by flash chromatography on silica gel using as
eluent mixtures of ether-acetone with increasing percentages of acetone, to give IIa (0.61 g, 90%) as solid
very unstable to air, which decomposes at 140-150 °C; IR: 1670, 1610, 1590 cm-1; UV: λmax 358, 248,
206 nm; 1H-NMR (acetone-d6): δ 9.14 (dd, 1H, J = 4.0 and 1.4 Hz, H-7), 9.04 (s, 2H, H-2+H-3), 8.85 (s,
1H, H-5), 8.82 (s, 1H, H-10), 8.69 (d, 1H, J = 8.4 Hz, H-9), 7.66 (dd, 1H, J = 8.4 and 4.0 Hz, H-8); MS:
m/z 181 (M+). Anal. Calcd for C11H7N3: C, 72.91; H, 3.89; N, 23.19. Found: C, 73.12; H, 4.21; N, 22.98.

5-Chloropyrido[2,3-g]quinoxaline (IIb). To a refluxing solution of 11b (0.5 g, 2.6 mmol) in ethanol (10
mL), glyoxal (2.4 g, 41.6 mmol, 40% in water) was added dropwise and the reflux continued for an
additional 2 h. After removal of the ethanol, the residue was taken up with water (10 mL), made alkaline
(pH ≅ 12) with a sodium hydroxide aqueous solution (2 M) and in continuous extracted with chloroform.
The organic phase was then dried over anhydrous sodium sulfate and evaporated under reduced pressure
to give IIb (0.48 g, 86%); mp 175-177 °C (ethanol); IR: 1630, 1620, 1600, 1580 cm-1; UV: λmax 405 sh,
380 sh, 360, 254, 206 nm; 1H-NMR (CDCl3): δ 9.26 (d, 1H, J = 4.0 Hz, H-7), 9.09 (s, 1H, H-3), 9.02 (s,
1H, H-2), 8.68 (s, 1H, H-10), 8.50 (d, 1H, J = 8.4 Hz, H-9), 7.61 (dd, 1H, J = 8.4 and 4.0 Hz, H-8); MS:
m/z 215 (M+). Anal. Calcd for C11H6N3Cl: C, 61.27; H, 2.80; N, 19.49; Cl, 16.44. Found: C, 61.06; H,
3.05; N, 19.27; Cl, 16.31.
1H-Imidazo[4,5-g]quinoline (IIIa). A mixture of 11a (0.6 g, 3.8 mmol) and formic acid (4.9 g, 106
mmol) was stirred at 100 °C for 2 h. After cooling to rt, the solution was made alkaline (pH ≅ 12) with a
50% of sodium hydroxide aqueous solution and allowed to stand at rt for 48 h affording slowly IIIa (0.24
g, 37.5%) as solid with mp 219-221 °C (dimethyl sulfoxide) (lit.,5 222 °C); IR: 3420, 1640, 1600 cm-1;
UV: λmax 320 infl, 309, 221, 206 sh nm; 1H-NMR (CDCl3): δ 8.90 (dd, 1H, J = 4.2 and 1.4 Hz, H-6), 8.40
(s, 1H, H-4), 8.36 (s, 1H, H-9), 8.33 (d, 1H, J = 8.4 Hz, H-8), 8.17 (s, 1H, H-2), 7.36 (dd, 1H, J = 8.4 and
4.2 Hz, H-7), 4.58 (br s, 1H, NH).
4-Chloro-1H-imidazo[4,5-g]quinoline (IIIb). In an identical manner reported for preparation of IIIa,
starting from 11b (0.6 g, 3.1 mmol) and formic acid (4.9 g, 106 mmol), IIIb (0.57 g, 90%) was obtained;
mp 300-302 °C (dimethyl sufoxide) (lit.,5 304 °C); IR: 3410, 1640, 1600, 1590, 1570 cm-1; UV: λmax 350
sh, 325, 240, 216 nm; 1H-NMR (DMSO-d6): δ 8.96 (dd, 1H, J = 4.0 and 1.4 Hz, H-6), 8.67 (s, 1H, H-9),
8.57 (dd, 1H, J = 8.4 and 1.4 Hz, H-8), 8.20 (s, 1H, H-2), 7.52 (dd, 1H, J = 8.4 and 4.0 Hz, H-7).
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