On the tautomerism of cinnolin-4-ol, cinnoline-4-thiol, and cinnolin-4-amine

Article abstract of DOI:10.3987/COM-07-11177

Detailed NMR spectroscopic investigations (¹H, ¹³C, ¹⁵N) with cinnolin-4-ol (1) reveal this compound to exist exclusively in the cinnolin-4(1H)-one form in deuteriodimethyl sulfoxide solution. This finding is confirmed by comparison of the NMR spectroscopic data of 1 with those of the corresponding 'fixed' O-methyl and N-methyl derivatives, i.e. 4-methoxycinnoline (3) and 1-methylcinnolin-4(1H)-one (5). Similarly, cinnoline-4-thiol (4) is present in the thione form in deuteriodimethyl sulfoxide, whereas cinnolin-4-amine (7) exists in the amino form. In addition, in-depth analyses of the NMR spectra of some simple 4-substituted cinnolines are provided.

Full text of DOI:10.3987/COM-07-11177

HETEROCYCLES, Vol. 75, No. 1, 2008
77
HETEROCYCLES, Vol. 75, No. 1, 2008, pp. 77 - 86. © The Japan Institute of Heterocyclic Chemistry
Received, 20th July, 2007, Accepted, 14th September, 2007, Published online, 20th September, 2007. COM-07-11177
ON THE TAUTOMERISM OF CINNOLIN-4-OL, CINNOLINE-4-THIOL,
AND CINNOLIN-4-AMINE
Wolfgang Holzer,* Gernot A. Eller, and Simeon Schönberger
Department of Drug and Natural Product Synthesis, Faculty of Life Sciences,
University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria
E-mail: wolfgang.holzer@univie.ac.at
Abstract – Detailed NMR spectroscopic investigations (1H, 13C, 15N) with
cinnolin-4-ol (1) reveal this compound to exist exclusively in the
cinnolin-4(1H)-one form in deuteriodimethyl sulfoxide solution. This finding is
confirmed by comparison of the NMR spectroscopic data of 1 with those of the
corresponding
‘fixed’
O-methyl
and
N-methyl
derivatives,
i.e.
4-methoxycinnoline (3) and 1-methylcinnolin-4(1H)-one (5). Similarly,
cinnoline-4-thiol (4) is present in the thione form in deuteriodimethyl sulfoxide,
whereas cinnolin-4-amine (7) exists in the amino form. In addition, in-depth
analyses of the NMR spectra of some simple 4-substituted cinnolines are
provided.
INTRODUCTION
Prototropic tautomerism of heteroaromatic compounds has been extensively studied for a long period and
is the subject of several excellent reviews.1–3 This phenomenon is not only of academic interest but of the
highest biological importance as, for instance, the tautomeric form of the nucleic acid bases is crucial for
base pairing in the DNA molecule.4 In particular, prototropic ring chain tautomerism of six-membered
heteroaromatic systems such as that in hydroxypyridines or aminopyridines has been investigated by a
large variety of experimental and theoretical methods.5 Also the corresponding benzo-annulated systems
show such a behavior.5 In this respect, hydroxy- or aminocinnolines represent rarely assayed moieties to
which relatively little attention has been focused. Thus, from early reports – mainly based on UV, pKa,
and IR investigations – it was concluded that cinnolin-4-ol (1) and cinnoline-4-thiol (4) predominantly
exist as oxo or thioxo tautomers (1b) and (4b), respectively, whereas for cinnolin-4-amine (7) the amino
form (7a) is preferred (Figure 1).5–10 Also the role of zwitterionic forms of type (c) (Figure 1) has been

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HETEROCYCLES, Vol. 75, No. 1, 2008
discussed.5,8–11 In this study we report on continuative investigations with cinnolin-4-ol (1),
cinnoline-4-thiol (4), cinnolin-4-amine (7), and related compounds employing modern NMR
spectroscopic methods including also 13C-NMR and 15N-NMR spectroscopy. Since comparatively little is
13
15
known concerning the C- and N-NMR spectra of simple 4-substituted cinnolines6,12 we here present
detailed data in this respect. Moreover, some improvements in the syntheses of the investigated
compounds are specified, amongst these also one for the preparation of cinnolin-4-ol (1), which
represents the central synthon in the construction of 4-substituted cinnolines due to its simple availability
from 2-aminoacetophenone via Borsche synthesis.13
XH
N
X
X
N
N+
N
N
N
H
H
1: X = O
4: X = S
7: X = NH
b
a
c
Figure 1
RESULTS AND DISCUSSION
Syntheses
The syntheses of the investigated compounds were largely carried out according to known procedures
(Scheme 1). However, in some cases specific modifications emerged to be advantageous compared to the
original procedures. Details in this respect are given in the Experimental part. Compound (8), which
hitherto had not been described in the literature, was obtained by treatment of 2 with isopropylamine.
NMR Spectroscopic Investigations
Detailed NMR spectroscopic analyses for all prepared compounds are reported. Full and unambiguous
assignment for all proton, carbon, and nitrogen resonances was achieved by combined application of
1
standard NMR spectral techniques,14 such as NOE-difference experiments, fully H-coupled 13C-NMR
spectra, APT, HMQC, and HMBC spectra as well as experiments with selective excitation such as
selective long-range INEPT experiments in a 1D15 and a 2D version.16 The 15N-NMR spectra were mainly
recorded using the gradient selected, sensitivity enhanced HMBC sequence.17 The obtained data show a
high degree of consistency and are summarized in Table 1 (1H-NMR chemical shifts), Table 2 (1H,1H
coupling constants), Table 3 (13C-NMR chemical shifts and selected 13C,1H spin coupling constants), and
Table 4 (15N-NMR chemical shifts). Coupling constants are given in absolute values (signs not
determined).

HETEROCYCLES, Vol. 75, No. 1, 2008
79
O
O
O
O
N
NaNO2 / HCl
K2CO3 / MeI
CH3
+
N+
N
N
acetone
'Borsche-synthesis'
N
H
N
NH2
Me
Me
6
5
1b
POCl3
PhCl
picoline
Cl
OMe
S
thiourea
MeOH
NaOMe
N
N
N
MeOH
N
N
N
H
4b
3
2
.
NH2NH2 H2O
NHNH2
i-PrNH2
Me
N
25% NH3
water
150°
NH2
HN
N
Me
N
N
N
N
9
7a
8
Scheme 1
Due to the very limited solubility of cinnolin-4-ol (1) in non-polar solvents such as CDCl3 the recording
13
15
15
of C-NMR or N-NMR spectra was only possible from DMSO-d6 solution. Especially the N-NMR
spectral data – but also the 13C-NMR spectra – unequivocally indicate compound 1 to exist as NH-isomer
1b [i.e. as cinnolin-4(1H)-one]. This assignment is mainly based on the following observations (Figure
2):
13
•
•
In the C-NMR spectrum of 1 the C-4 signal appears at δ 170.3 ppm. This shift is typical for a
carbonyl-C atom and not for a =C−OH moiety. In the latter the carbon atom is expected to have a
somewhat smaller chemical shift.
Comparison of the H-, 13C- and 15N-NMR data of 1 with those of the corresponding ‚fixed’
1
tautomeric
forms,
i.e.
4-methoxycinnoline
(3)
(as
fixed
OH-form)
and
1-methylcinnolin-4(1H)-one (5) (as fixed NH-form) shows a high degree of consistence with the
data of 5 (Figure 2).
•
The 15N-NMR spectrum of 1 exhibits two essentially different types of N-atoms (δ −42.2 ppm and
15
−206.8 ppm), whereas the ‘aromatic’ 4-methoxycinnoline (3) expectedly shows two related N
resonances with larger chemical shifts (δ 41.3 ppm for N-2 and δ 15.7 ppm for N-1).

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HETEROCYCLES, Vol. 75, No. 1, 2008
On the basis of similar criteria it can be deduced that 4 is present as cinnoline-4(1H)-thione (4b) in
DMSO-d6 solution (N-1: δ −191.2 ppm, N-2: δ −62.4 ppm, Figure 2). In contrast, 7 exists in the amino
form (7a), what can be derived not only by the 15N chemical shifts of the cinnoline N-atoms (N-1: δ −20.1
ppm, N-2: δ 26.4 ppm), but also from that of the exocyclic nitrogen atom (δ −312.7 ppm, triplet
1
1
multiplicity in a DEPT experiment without H-decoupling, J = 89.7 Hz) (Figure 2). Similarly, the
presence of 8 as secondary amine follows from the 15N-NMR data (N-1: δ −17.2 ppm, N-2: δ 29.9 ppm,
i-PrNH: δ −288.9 ppm; in DMSO-d6 solution). The 1H- and 13C-NMR spectra of 4-hydrazinocinnoline (9)
are characterized by pronounced line broadening indicating a dynamic behavior. This phenomenon
15
(chemical exchange in the range of the NMR timescale) also can explain the fact that N-NMR signals
1
could not be found for 9 in HSQC, HMBC, INEPT, or DEPT experiments. Comparison of the H- and
13C-NMR chemical shifts of the investigated compounds (in DMSO-d6) shows that isomers of type (b)
exhibit smaller chemical shifts for H-3 (7.69–8.47 ppm) and C-8a (136.5–140.9 ppm) compared to
‘aromatic’ cinnolines of type (a), which have 8.64–9.50 ppm for H-3 and 148.2–150.3 ppm for C-8a.
Considering these data, the chemical shifts of H-3 (δ 7.71 ppm) and C-8a (δ 138.2 ppm) in 9 suggest a
substantial proportion of forms similar to (b) in the overall tautomeric composition.
NOE
169.8 ppm
7.69 ppm
170.3 ppm
7.74 ppm
152.3 ppm
H
O
H
OMe
O
N
H
9.18 ppm
H
H
H
H
H
H
H
H
H
N
N
N
N
–42.4 ppm
N
H
–31.7 ppm
41.3 ppm
H NOE
H
H NOE Me
–214.4 ppm
–206.8 ppm
15.7 ppm
5 (DMSO-d6)
–312.7 ppm
3 (DMSO-d6)
1 (DMSO-d6)
NOE
186.7 ppm
8.47 ppm
142.3 ppm
8.64 ppm
H
S
N
H
H2N
H
H
H
H
H
N
N
–62.4 ppm
H
N
26.4 ppm
–20.1 ppm
H
NOE H
H
–191.2 ppm
4 (DMSO-d6)
7 (DMSO-d6)
Figure 2. Selected 1H-, 13C- and 15N-NMR Chemical Shifts of Compounds (1), (3–5), and (7).
In conclusion, our multinuclear NMR-spectroscopic studies confirm the previous findings that title
compounds (1) and (4) are present as cinnolin-4(1H)-one and -4(1H)-thione, respectively, in DMSO-d6
solution, whereas 7 is present in the amino form. (7a). Moreover, we have demonstrated the outstanding
utility of 15N-NMR spectroscopy in the investigation of cinnolines capable of prototropic tautomerism.

HETEROCYCLES, Vol. 75, No. 1, 2008
81
Table 1. 1H-NMR Chemical Shifts (δ, ppm) of Compounds (1−10)
Comp.
Solvent
H-3
H-5
H-6
H-7
H-8
Other H
1
DMSO-d6
7.74
8.02
7.42
7.79
7.58
13.52 (NH)
2
3
4
5
6
CDCl3
9.32
9.50
8.16
8.08
7.84
7.98
7.90
8.01
8.53
8.47
−
−
DMSO-d6
CDCl3
8.91
9.18
8.07
8.08
7.61
7.76
7.74
7.88
8.37
8.34
4.07 (OMe)
4.14 (OMe)
DMSO-d6
CDCl3
8.51
8.47
8.58
8.36
7.46
7.53
7.75
7.84
7.39
7.66
10.39 (NH)
14.41 (NH)
DMSO-d6
CDCl3
7.74
7.69
8.26
8.07
7.38
7.47
7.71
7.84
7.39
7.71
4.05 (NMe)
4.05 (NMe)
DMSO-d6
CDCl3
7.88
8.21
8.33
8.08
7.53
7.51
7.72
7.75
7.81
7.78
4.32 (NMe)
4.30 (NMe)
DMSO-d6
7
8
DMSO-d6
8.64
8.20
7.56
7.71
8.05
7.27 (NH2)
CDCl3
8.66
8.66
7.89
8.34
7.57
7.59
7.73
7.73
8.31
8.07
5.39 (NH), 4.02 (CH), 1.42 (Me)
7.12 (NH), 4.02 (CH), 1.27 (Me)
DMSO-d6
9
DMSO-d6
7.71
7.69
7.01
7.27
7.00
5–11 (NH, NH2)a
a Very broad signal.
Table 2. 1H,1H Spin Coupling Constants (Hz) of Compounds (1−10)
Comp.
Solvent
3J(5,6)
4J(5,7)
5J(5,8)
3J(6,7)
4J(6,8)
3J(7,8)
1
DMSO-d6
8.2
1.5
0.6
7.0
1.1
8.5
2
3
4
5
6
CDCl3
8.4
8.2
1.5
1.5
0.7
0.7
6.9
6.9
1.3
1.4
8.4
8.4
DMSO-d6
CDCl3
8.4
8.3
1.5
1.4
0.8
0.6
6.9
6.8
1.3
1.2
8.5
8.5
DMSO-d6
CDCl3
8.4
8.4
1.4
1.4
0.6
7.0
6.9
1.1
1.2
8.5
DMSO-d6
0.6
a
8.5
a
CDCl3
8.0
8.1
1.6
1.6
7.0
7.0
1.0
0.9
DMSO-d6
0.6
8.7
CDCl3
8.2
8.1
1.5
1.4
0.7
0.8
6.8
6.5
1.3
1.8
8.5
8.6
DMSO-d6
7
8
DMSO-d6
8.5
8.5
1.3
1.1
0.6
0.6
6.8
6.8
1.2
1.1
8.6
8.5
b
CDCl3
c
DMSO-d6
8.4
1.3
1.0
6.8
1.3
8.5
a
a
a
a
a
a
9
DMSO-d6
a Not unambiguously determined. b 3J(CH3,CH) = 6.3 Hz. c 3J(CH3,CH) = 6.3 Hz, 3J(CH,NH) = 7.9 Hz.

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HETEROCYCLES, Vol. 75, No. 1, 2008
Table 3. 13C-NMR Shifts (δ, ppm) and Selected 13C,1H Coupling Constants (Hz, in Italics) of Compounds (1–10)
Co
mp.
Solv.
C-3
1J
C-4
C-4a
C-5
C-6
C-7
C-8
C-8a
Other C
J of Other C
2J(3), 3J(5), 4J(8)
3J(3), 3J(6), 3J(8)
3J(5), 3J(7)
1
b
a
140.2
184.1
144.3
170.3
5.2, 3.5, 1.7
134.7
122.8
3.7, 8.1, 4.9
124.7
123.8
122.9
124.9
132.1
133.8
131.4
116.4
130.0
140.9
7.3, 9.7
150.9
−
2
−
189.0
144.1
128.7
181.4
129.6
183.6
150.9
149.7
2.0, 5.6, 2.0
133.9
4.6, 8.8, 5.1
123.7
118.4
4.6, 8.8, 5.2
117.6
6.2, 8.5
150.3
150.3
6.0, 9.3
149.7
6.0, 9.2
135.8
bb
a
122.5
120.6
133.0
129.6
132.2
130.5
129.3
128.6
−
3
152.8c
56.1 (OMe)
146.1 (1J)
56.7 (OMe)
146.9 (1J)
−
2.9, 4.0, 1.6
b
152.3c
120.4
130.0
130.9
128.2
2.9, 3.8, 1.6
190.7
4.5, 8.7, 5.1
133.4
4
5
a
b
128.1
126.6
127.1
127.4
134.9
134.8
116.0
117.9
186.7
132.6
136.5
−
189.5
139.9
185.5
139.0
184.9
132.2
6.8, 4.4, 1.0
171.0
4.3, 8.5, 5.0
124.3
7.2, 9.9
141.0
6.7, −
140.7d
7.6, 9.6
149.4
a
b
a
b
b
125.6
124.4
123.7
122.8
121.9
124.8
125.1
128.2
127.3
127.2
133.8
134.0
132.7
132.5
130.4
114.8
116.4
126.3
125.9
128.0
43.5 (NMe)
140.7 (1J)
169.8
4.9, 3.6, 1.7
171.1
123.8
3.6, 7.9, 5.0
126.3
−, 8.5, −
125.3
3.2, 8.2, 4.0
114.9
4.3, 8.7, 5.1
115.5
43.6
141.2 (1J)
6
52.0 (NMe)
143.2 (1J), 3.1 (3J)
51.4 (NMe)
143.6 (1J), 3.4 (3J)
−
183.7, 3.2 (3J)
133.2
169.9
2.0, 3.5, −
142.3
5.1, 3.8, 1.4
139.5
139.3
5.4, 3.6, 1.7
133.1
148.8
6.6, 7.9
148.8
6.1, 8.9
148.0
148.2
6.2, 8.9
138.2
186.3, 3.1 (3J)
132.3
7
8
179.4
a
b
128.6
119.1
121.5
128.2
127.2
130.2
129.9
128.8
128.2
44.4 (CH), 22.5 (Me)
43.3 (CH), 21.9 (Me)
128.4e
180.0
115.3
4.7, 8.8, 5.3
119.2
9
b
128.7
121.1
123.3
129.1
114.7
−
a a = CDCl3, b = DMSO-d6. b Decomposes rapidly in DMSO-d6 solution. c 3J(C4,OMe) = 4.0 Hz. d 3J(C8a,Me) = 2.1 Hz. e 2J(C3,NH) = 6.2 Hz.

HETEROCYCLES, Vol. 75, No. 1, 2008
83
Table 4. 15N-NMR Chemical Shifts (δ, ppm) of Compounds (1−10)
Compd.
Solvent
N-1
N-2
–42.4a
Compd.
Solvent
CDCl3
N-1
N-2
1
DMSO-d6
−206.8
6
−88.8
−91.8
−137.4
−132.0
DMSO-d6
2
3
CDCl3
34.3
34.7
7 b
8
DMSO-d6
−20.1c
26.4d
e
CDCl3
12.5
15.7
35.7
41.3
CDCl3
−29.1
−17.2
g
20.0
29.9
g
f
DMSO-d6
DMSO-d6
4
5
DMSO-d6
−191.2
−62.4
9
DMSO-d6
CDCl3
−217.3
−214.4
−33.8
−31.7
DMSO-d6
a 2J(N2,H3) = 14.0 Hz. b δ(NH2) = −312.7 ppm, 1J = 89.7 Hz. c 3J(N1,H3) = 4.6 Hz.
d 2J(N2,H3) = 11.6 Hz. e δ(NH) = −290.6 ppm. f δ(NH) = −288.9 ppm. g Not found.
EXPERIMENTAL
Melting points were determined on a Reichert–Kofler hot-stage microscope and are uncorrected. Mass
spectra were obtained on a Shimadzu QP 1000 instrument (EI, 70 eV) and on a Finnigan MAT 8230
instrument (EI, 70 eV, HRMS). IR spectra were recorded on a Perkin-Elmer FTIR 1605
1
spectrophotometer or on a Perkin-Elmer FTIR spectrum 1000 spectrometer. H- and 13C-NMR spectra
were recorded on a Varian UnityPlus 300 spectrometer at 28 °C (299.95 MHz for 1H, 75.43 MHz for 13C)
or on a Bruker Avance 500 spectrometer at 293 K (500.13 MHz for 1H, 125.77 MHz for 13C). The centre
of the solvent signal was used as an internal standard which was related to TMS with δ = 7.26 ppm (1H in
CDCl3), δ = 2.49 ppm (1H in DMSO-d6), δ = 77.0 ppm (13C in CDCl3), and δ = 39.5 ppm (13C in
DMSO-d6). 15N-NMR spectra were obtained on a Bruker Avance 500 instrument with a ‘directly’
detecting broadband observe probe at 300K and were referenced against external nitromethane (coaxial
capillary). The digital resolutions were as following: 0.25 Hz/point for the 1H-NMR spectra, 0.5 Hz/point
for the 1H-broadband decoupled and 0.4 Hz/point for the 1H-coupled 13C-NMR spectra, 1 Hz/point for the
15
15
1D N-NMR spectra (refocused INEPT) and ≤ 59 Hz/point for the N,1H-HMBC spectra. Preparative
layer chromatography was carried out on Merck PLC plates, silica gel 60F254, 20×20 cm, layer thickness
2 mm. 2-Aminoacetophenone is commercially available (Aldrich). Yields of products were not optimized.
Cinnolin-4(1H)-one (1)
According to lit.,18 to a solution of 2-aminoacetophenone (5.40 g, 40 mmol) in glacial acetic acid (4 mL)
were added 6.8 mL of concd HCl and 15 mL of water and the resulting mixture was cooled to 0 °C. Then
an ice-cold solution of NaNO2 (3.04 g, 44 mmol) in 10 mL of water was added dropwise keeping the

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HETEROCYCLES, Vol. 75, No. 1, 2008
temperature between 0 °C and 5 °C. After the addition was complete, the suspension was stirred at
0–5 °C for 1 h, then 0.2 g of urea were added and stirring was continued for another h at this temperature.
Then a solution of sodium acetate (41.0 g, 500 mmol), in 100 mL of water, and 50 mL of CH2Cl2 were
added and the mixture was stirred for 15 h to gradually reach rt. The red-brown precipitate was filtered
off with suction, washed with water and CH2Cl2, and dried in a desiccator to yield 4.43 g (76%) of a
1
red-brown solid, mp 234–236 °C (lit.,19 mp: 236 °C), which was pure according to H-NMR spectral
analysis. MS (m/z, %): 146 (M+, 100), 119 (45), 92 (49).
4-Chlorocinnoline (2)20
A mixture of 1 (3.00 g, 20.6 mmol), POCl3 (4.68 g, 30.5 mmol), 2-methylpyridine (606 mg, 6.5 mmol),
and chlorobenzene (75 mL) was refluxed for 1 h. After cooling to rt, the mixture was poured onto
ice/water and immediately made slightly alkaline with a saturated Na2CO3 solution (ca. 10 mL). Then the
mixture was extracted with CH2Cl2 (3 × 25 mL), the combined organic phases were washed with water,
dried (Na2SO4), and evaporated under reduced pressure. The dark, solid residue was treated with boiling
light petroleum (50 mL) for 10 minutes and the hot supernatant yellow liquid was rapidly filtered through
glass wool. After storing in the refrigerator for some hours the precipitated crystals were filtered off and
dried to afford 2.24 g (66%) of fine yellowish needles, mp: 74–76 °C (lit.,19 mp: 76–77 °C). MS (m/z, %):
166 (M+, 19), 164 (M+, 55), 136 (20), 101 (100), 75 (35).
4-Methoxycinnoline (3)
Compound (3) was prepared in 85% yield from 2 and methanolic NaOMe similarly as described in lit.22
MS (m/z, %): 160 (M+, 60), 102 (54), 89 (100), 75 (14), 63 (39).
Cinnoline-4(1H)-thione (4)
Compound (4) was prepared in 78% yield from 2 and thiourea according to lit.23 MS (m/z, %): 162 (M+,
100), 135 (44), 118 (16), 108 (36), 91 (25), 81 (29), 69 (34), 68 (20).
1-Methylcinnolin-4(1H)-one (5) and 2-Methylcinnolin-2-ium-4-olate (6)
On the basis of lit.,24 a mixture of 1 (438 mg, 3 mmol), K2CO3 (9.18 g, 66.4 mmol), and MeI (6.98 g, 49.2
mmol) in acetone (180 mL) was stirred at rt for 10 h. Then the solvent was removed under reduced
pressure and the residue was subjected to preparative layer chromatography (eluent: CH2Cl2, extraction of
the adsorbed materials by repeated treatment with hot EtOAc/MeOH 4:1). From the faster eluted
component (5) (Rf ~ 0.5) 107 mg (22%) of beige crystals were obtained, mp 110–115 °C (lit.,24 mp:
113–115 °C), MS (m/z, %): 160 (M+, 100), 132 (44), 105 (41), 104 (79), 78 (37), 77 (31), 64 (17), 63 (24).

HETEROCYCLES, Vol. 75, No. 1, 2008
85
The slower eluted compound (6) (Rf ~ 0.2) afforded 58 mg (12%) of a light brown solid, mp 163–167 °C
(lit.,25 mp: 162–164 °C). MS (m/z, %): 160 (M+, 100), 132 (62), 131 (41), 104 (18), 63 (18).
Cinnolin-4-amine (7)
In a pressure vessel, a mixture of 2 (823 mg, 5 mmol) and 25% NH3 in water (30 mL) was heated at
150 °C for 12 h.26 Immediately after reaching ~ 50 °C the reaction mixture was quickly filtered and the
filtrate was kept in a refrigerator overnight. The separated crystals were filtered off, washed with water
and dried to afford 375 mg (52%) of 7 as orange-yellow needles, mp 210 °C (lit.,21 mp 211 °C). MS
(m/z, %): 145 (M+, 100), 90 (58), 89 (61), 72 (34), 58 (34).
N-Isopropylcinnolin-4-amine (8)
A mixture of 4-chlorocinnoline (2) (164 mg, 1 mmol) and isopropylamine (660 mg, 11.2 mmol) was
stirred at rt for 24 h. Then excess isopropylamine was removed under reduced pressure and the red-brown
residue was subjected to preparative layer chromatography (eluent: EtOAc/NH3 100:1, Rf ~ 0.2,
extraction of the adsorbed materials by repeated treatment with hot EtOAc/MeOH 4:1) to afford 108 mg
(58%) of a light brown solid (pure 8 according to NMR spectral analysis). Subsequent recrystallization
from toluene gave 60 mg (32%) of colourless crystals, mp 189−190 °C. IR (KBr): ν (cm-1) 3209 (NH),
1564, 1521, 1291, 1130; MS (m/z, %): 187 (M+, 83), 172 (100), 145 (10), 117 (20), 116 (24), 101 (23), 90
(24), 89 (20), 75 (12), 63 (14). Anal. Calcd for C11H13N3: C, 70.56; H, 7.00; N, 22.44. Found: C, 70.45; H,
6.92; N, 22.18. HRMS Calcd for C11H13N3: 187.1109. Found: 187.1112 ± 0.0009.
4-Hydrazinocinnoline (9)
Compound (9) was prepared in 82% yield from 2 and hydrazine hydrate according to ref.27 MS (m/z, %):
160 (M+, 100), 159 (16).130 (19), 102 (18), 90 (14), 77 (15), 76 (15).
ACKNOWLEDGEMENTS
We are grateful to Dr. L. Jirovetz for recording the MS spectra.
REFERENCES AND NOTES
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be more convenient than that via column chromatography.21
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