2-Halobenzenesulfonyl chlorides in the synthesis of pyrido[2,1-c][1,2,4]benzothiadiazine 5,5-dioxide derivatives

Article abstract of DOI:10.1007/s11172-016-1518-5

A number of new functional derivatives of pyrido[2,1-c][1,2,4]benzothiadiazine 5,5-dioxide was obtained based on the reactions of 2-halobenzenesulfonyl chlorides with 2-aminopyridine derivatives. A quantitative criterion for the evaluation of a possibility for the reaction to proceed under noncatalytic conditions depending on the type of halogen and substituents in the starting compounds was suggested.

Full text of DOI:10.1007/s11172-016-1518-5

Russian Chemical Bulletin, International Edition, Vol. 65, No. 7, pp. 1839—1845, July, 2016
1839
2ꢀHalobenzenesulfonyl chlorides in the synthesis
of pyrido[2,1ꢀc][1,2,4]benzothiadiazine 5,5ꢀdioxide derivatives*
R. M. Shlenev,a S. I. Filimonov,a A. V. Tarasov,a A. S. Danilova,a P. A. Agat´ev,a and S. A. Ivanovskiib
aYaroslavl State Technical University,
88 Moskovskii prosp., 150023 Yaroslavl, Russian Federation.
Eꢀmail: schlenev.roman@yandex.ru
bK. D. Ushinsky Yaroslavl State Pedagogical University
108 ul. Respublikanskaya, 150000 Yaroslavl, Russian Federation.
Fax: +7 (485) 273 1529. Eꢀmail: s.ivanovskiy@yspu.org
A number of new functional derivatives of pyrido[2,1ꢀc][1,2,4]benzothiadiazine 5,5ꢀdiꢀ
oxide was obtained based on the reactions of 2ꢀhalobenzenesulfonyl chlorides with 2ꢀaminoꢀ
pyridine derivatives. A quantitative criterion for the evaluation of a possibility for the reaction
to proceed under noncatalytic conditions depending on the type of halogen and substituents in
the starting compounds was suggested.
Key words: 2ꢀhalobenzenesulfonyl chlorides, 2ꢀaminopyridine, sulfoacylation, cycloꢀ
condensation, pyrido[2,1ꢀc][1,2,4]benzothiadiazine 5,5ꢀdioxide derivatives.
Scheme 1
In the last several years, the interest to the synthesis of
fused compounds derived from quinoline and 4(3H)ꢀ
quinazoline annulated with different 5ꢀ and 6ꢀmembered
heterocyclic fragments1—3 and possessing various practiꢀ
cally useful properties noticeably increased. Particular atꢀ
tention was paid to high tuberculostatic activity of some
pyrido[1,2ꢀa]quinazolineꢀ6ꢀone derivatives.4
Pyrido[1,2ꢀa]quinazolinꢀ6ꢀone derivatives
Pyrido[2,1ꢀc][1,2,4]benzothiadiazine 5,5ꢀdioxides are
close structural analogs of these compounds. Like aboveꢀ
mentioned quinazolines, they can be synthesized from the
corresponding benzenesulfonyl chlorides 1 containing acꢀ
tivated halogen at position 2 and 2ꢀaminopyridine derivaꢀ
tives 2 (Scheme 1). Earlier,5 this method was used to synꢀ
thesize a small series of pyrido[2,1ꢀc][1,2,4]benzothiadiꢀ
azine 5,5ꢀdioxides (4).
Reaction conditions: i. without catalyst; ii. potassium or copper
salts as catalysts.
lysts), or in two steps, using potassium or copper salts in
the cyclocondensation step of the intermediate sulfonaꢀ
mides 3 (see Scheme 1, ii). It was also shown5 that the key
factors influencing a possibility of the formation and the
yields of cyclic compounds in the reactions under considꢀ
eration are the type of the halogen; electron effects of
substituents which activate the halogen; steric hindrance
of the intramolecular nucleophilic attack in compounds 3.
The purpose of the present work is the experimental
determination of this method scope in the synthesis of
derivatives 4 under noncatalytic conditions.
Depending on the structure of the starting compounds,
the reactions can proceed either in one step (without cataꢀ
* Based on the materials of the International Congress on the
Heterocyclic Chemistry "KOSTꢀ2015" (October 18—23, 2015,
Moscow, Russia).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1839—1845, July, 2016.
1066ꢀ5285/16/6507ꢀ1839 © 2016 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 65, No. 7, July, 2016
Shlenev et al.
Results and Discussion
The analysis of the relationship between the structure
of the starting compounds and a possibility of cyclic comꢀ
pounds 4 formation in several model syntheses (Table 1)
allowed us to reveal a quantitative criterion, which was
sufficient for the formulation of requirements to the type
of substituent R1 in compounds 1 depending on the type of
halogen. The influence of steric factors in the chosen set
of reagents was minimized. In the case of sulfonyl chlorꢀ
ides 1 (or sulfonamides 3) containing one type of halogen,
which is activated due to different substituents at paraꢀ
and metaꢀpositions, the possibility of cyclocondensation
to proceed is mainly determined by their electron effects,
with the σp or σm values from the Hammett equation indiꢀ
rectly serving as the measure of quantitative account for
them.6—8
Sulfonyl chlorides 1 (see Table 1) containing electronꢀ
withdrawing groups and having the σp values in the range
from 0.78 to 0.23 were used for model reactions.8 The
sulfoacylation step of aminopyridines 2 (see Scheme 1, i)
was carried out in refluxing pyridine over 3 h. In the case
when cyclic compound 4 was not isolated in the first step,
the intermediate compounds were additionally refluxed in
DMF for 3 h (see Scheme 1, ii).
Compound 1
a
R1
NO2
R2
H
Hal
Cl
b
H
Cl
c
d
e
f
g
h
i
N≡C
ClO2S
ClO2S
MeOC(O)
MeOC(O)
NH2C(O)
NH2C(O)
NH2C(O)
Cl
H
H
H
H
Cl
H
H
H
Cl
Cl
Br
Cl
Cl
Cl
Br
Cl
F
k
l
Cl
Compound
I
I
III
IV
R1
NO2
NO2
MeOC(O)
MeOC(O)
R2
H
H
H
H
Hal
Br
F
Br
F
Compound 2
R1
H
H
R2
H
Cl
H
R3
H
H
a
b
c
The results showed that the target pyrido[2,1ꢀc]ꢀ
[1,2,4]benzothiadiazine 5,5ꢀdioxides 4 were not obtained
Me
H
Table 1. Model reactions of benzenesulfonyl chlorides with 2ꢀaminopyridine derivatives
a
Entry
Sulfonyl
chlorides
Aminoꢀ
pyridines
σ /σ
Cyclic productb
II
Yield
(%)
p
m
I
1
2
3
4
5
6
7
8
Ic
2c
2a
2b
2c
2d
2c
2c
2b
2c
2c
2c
2c
2c
2c
2c
2b
2c
2c
0.78/—
0.78/—
0.78/—
0.78/—
0.78/—
0.78/—
0.68/—
0.66/—
0.65e/—
0.65e/—
0.45/—
0.45/—
0.45/0.37
0.45/0.37
0.36/—
0.36/—
0.36/—
0.23/0.37
4
—
—
—
—
— (3a)
—
—
65
81
75
66
94
34
12
48
53
—
41
19
91
52
46
63
60
1a
1a
1a
1a
IIc
1b
1c
1dd
1e
IIIc
1f
1g
IVc
1h
1i
1k
1l
4a
4b
4c
—
4
—
—
—
—
3
—
—
4
—
—
—
—
4d
4e
9
— (3b)
— (3c)
—
— (3d)
4f
10
11
12
13
14
15
16
17
18
—
— (3e)
— (3f)
4g
— (3g)
a The ratio for substituent in sulfonamide 3.
b Cyclic product was isolated selectively in the step: I in the reaction i (Py, Δ, 3 h); II in the reaction ii (DMF, Δ, 3 h).
c According to the data in the work.5
d A twoꢀfold molar excess of 2 was used.
e The value for the SO2NHPh group was used.8

2ꢀHalobenzenesulfonyl chlorides
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 7, July, 2016
1841
in all the cases. The presence in the molecule of the startꢀ
ing sulfonyl chloride 1 of the most strong accepting subꢀ
stituent, the nitro group (σp = 0.78), allowed us to selecꢀ
tively obtain cyclic compounds 4a—c in one step in the
reactions 1–4 and 6 (see Table 1) independent of the type
of halogen. An exception was only sulfonamide 3a, in
which, probably, the steric hindrance created by the meꢀ
thyl group of the pyridine fragment blocked proceeding
the cyclocondensation even upon prolonged reflux in DMF
(in the case of reaction 5).
rides 1d and 1e with derivatives 2 (reactions 9 and 10) led
to the selective formation of disulfonamides 3b and 3c,
which upon further prolonged heating in DMF did not
form cyclic compounds. Thus, this value of σp is on the
borderline, after which the activity of chlorine and broꢀ
mine atoms is already insufficient for the intramolecular
nucleophilic substitution reactions to proceed.
As it was expected, the reactions 11 and 12 involving
sulfonyl chlorides 1 bearing an ester group (σp = 0.45) led
to the selective formation of the corresponding sulfonꢀ
amides. However, the presence of an additional activating
substituent at metaꢀposition to chlorine (σm = 0.37) in
compound 1g allowed us to obtain (reaction 13) benzoꢀ
thiadiazine 4f in two steps. Replacement of chlorine with
fluorine in the starting sulfonyl chloride considerably faꢀ
cilitated proceeding of the cyclocondensation reaction, as
it was shown in the case of entry 14.
The steric structure of formed compounds, in addition
to the information obtained earlier,5 was for the first time
1
1
confirmed by H—1H and H—13C correlation NMR
spectroscopy on a model compound 4a (Fig. 1). The key
signals confirming its angular structure are the crossꢀpeaks
between the protons H(1) and H(10) in the 2D NOESY
spectrum and between the proton H(10) and the carbon
nucleus C(11a) in the 2D HMBC spectrum.
A decrease in the σp value of substituent to 0.36 in
compounds 1h—k containing a carboxamide group led to
the fact that the formation of benzothiadiazine 4g (reacꢀ
tion 17) takes place only in the case of sulfonyl chloride 1k
and only in two steps. In other cases, the corresponding
sulfonamides 3e and 3f were isolated (reactions 15 and 16).
The fluorine atom undergoes intramolecular nucleoꢀ
philic substitution the most readily in the reactions of this
type. Among electronꢀwithdrawing substituents, which are of
interest for subsequent functionalization or which possess
pharmacophoric activity, the σp values in most cases are
within the range 0.78—0.36. Thus, 2ꢀfluorineꢀcontaining
derivatives 1 are the most promising starting objects for
the preparation of the target pyrido[2,1ꢀc][1,2,4]benzothiaꢀ
diazine 5,5ꢀdioxides 4 under noncatalytic conditions.
In particular, successful synthesis of compound 4g
opens wide possibilities for the preparation of its analogs
containing both the aliphatic and aromatic component in
the composition of the carboxamide fragment. The synꢀ
thesis of the starting sulfonyl chlorides in this case is posꢀ
sible by two methods (Scheme 2).
A decrease in the σp value to 0.68 for the substituent in
compound 1b led to the fact that its reaction with derivaꢀ
tive 2 (see Table 1, entry 7) in pyridine resulted in the
formation of a mixture predominantly containing the corꢀ
responding sulfonamide with insignificant amount of the
target cyclic compound 4d. However, further heating of
this mixture in DMF allowed us to selectively obtain the
target benzothiadiazine 4d.
Similar results were obtained in the reaction 8 with
involvement of sulfonyl chloride 1c containing a carboꢀ
nitrile group (σp = 0.66), however, the yield of compound 4f
was considerably lower as compared to that of 4d.
A further decrease in the reactivity of halogen was obꢀ
served when the substituent σp value decreased to 0.65.
The results showed that the reactions of disulfonyl chloꢀ
a
The first of them (see Scheme 2, i) is based on the
reaction of intramolecular transamidation9 of sulfonaꢀ
mides 5 in chlorosulfonic acid. In this case, sulfonyl chloꢀ
rides 1k,m were obtained in 30 and 44% yields, respectꢀ
ively. Another method (see Scheme 2, ii) is based on usage
of a significantly higher reactivity of COCl group (in
100—900 times) compared to SO2Cl group in the reactions
of 3ꢀsulfobenzoyl dichlorides 6 with aromatic amines.10
This specific feature allows one to remain intact the free
chlorosulfonyl group in compounds 1n—p.
b
Based on sulfonyl chlorides 1k,n—p in all the cases we
have obtained the corresponding benzothiadiazines 4g—k.
1
The H NMR spectra showed the presence of the signals
for the protons corresponding to the carboxamide fragꢀ
ments and the absence of the signals for the protons of the
sulfonamide groups, which also agreed with the IR specꢀ
troscopy and mass spectrometry data.
Fig. 1. (a) The 1H—1Hꢀcorrelation scheme in the NOESY specꢀ
1
trum of compound 4a. (b) Remote H—13Cꢀinteractions in the
2D HMBC spectrum of compound 4a.

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Russ.Chem.Bull., Int.Ed., Vol. 65, No. 7, July, 2016
Shlenev et al.
Scheme 2
1: NR´R´´ = NH2 (k), NHMe (m), NHPh (n), NH(4ꢀCN)Ph (o), NH(2ꢀCF3)Ph (p)
4: NR´R´´ = NH2 (g), NHMe (h), NHPh (i), NH(4ꢀCN)Ph (j), NH(2ꢀCF3)Ph (k)
Reagents and conditions: i. NHR´R´´, MeCN; ii. SOCl2, DMF, Δ; iii. HSO3Cl, 1—1.5 h, 90—100 °C; iv. NHR´R´´, Py, MeCN, 1 h,
20 °C; v. 1) Py, Δ, 3 h; 2) DMF, Δ, 3 h.
crystals, m.p. 85—86.5 °C. IR, ν/cm–1: 3105 (Carom—H); 1576
(Carom—Carom); 1383, 1368, 1182, 1168 (SO2); 1286; 1256; 1116;
Experimental
1038; 821; 699; 682; 644; 634; 604.
1
H and 13C NMR spectra were recorded on Bruker DRX400
Methyl 4ꢀchloroꢀ3ꢀchlorosulfonylbenzoate (1f). Methanol
and Bruker DRX500 spectrometers (solvent DMSOꢀd6, an inꢀ
ternal standard TMS). IR spectra were recorded on a RXꢀ1 Perkin
Elmer Fourierꢀtransform spectrometer with the wavelength of
700—4000 cm–1. The analyzed sample was placed in the instruꢀ
ment as a suspension in Nujol between KBr plates. Mass spectra
for compounds 4a—c were recorded on a Finnigan MAT Incos
50 spectrometer with the ionization potential of electrons 70 eV
and the ionization chamber temperature 100—220 °C. For other
compounds mass spectra were recorded on a Shimadzu Promiꢀ
nence LCMSꢀ2020 HPLC/MS spectrometer equipped with
a chromatography column (40 °C, eluent acetonitrile) and a mass
spectrometer (LCMSꢀ2020, the m/z range of 0—2000, ESI/ACPI
ionization modes).
5ꢀ(4ꢀChlorobenzeneꢀ1ꢀsulfonyl)ꢀ2ꢀchlorobenzeneꢀ1ꢀsulfonyl
chloride (1b) was synthesized according to the known procedure.11
The yield was 0.971 g (55%), white crystals, m.p. 173—176 °C.
IR, ν/cm–1: 3088 (Carom—H); 1572 (Carom–Carom); 1381, 1334,
1186, 1164 (SO2); 1283; 1111; 1089; 1034; 1012; 839; 814; 758;
706; 680; 641.
(0.148 mL, 3.656 mmol) was added to a solution of 3ꢀchlorosulꢀ
fonylꢀ4ꢀchlorobenzoyl chloride (1 g, 3.656 mmol) in acetoniꢀ
trile (10 mL), followed by a gradual addition of triethylamine to
the mixture to pH 7—8. The reaction product was isolated by the
addition of some cold water with subsequent recrystallization of
formed precipitate from toluene. The yield was 0.879 g (89%),
white crystals, m.p. 153—157 °C.
Methyl 2,4ꢀdichloroꢀ5ꢀchlorosulfonylbenzoate (1g) was obꢀ
tained similarly to compound 1f. The yield was 0.927 g (94%),
white crystals, m.p. 109—112 °C. IR, ν/cm–1: 3094 (Carom—H);
1720 (C=O); 1583, 1458, 1434 (Carom—Carom); 1381, 1351, 1184
(SO2); 1267 (C—O); 1141; 1073; 965; 920; 887; 802; 780; 680; 623.
2ꢀBromoꢀ5ꢀcarbamoylbenzeneꢀ1ꢀsulfonyl chloride (1h). Chloroꢀ
sulfonic acid (2.2 mL, 0.032 mol) was added to 3ꢀsulfamoylꢀ4ꢀ
bromobenzoic acid (3 g, 0.011 mol). After thorough stirring, the
reaction mixture was heated for 2.5 h at 90 °C. The reaction
product was isolated by pouring on ice (10 g) with subsequent
recrystallization of formed precipitate from toluene. The yield
was 2.172 g (68%), white crystals, m.p. 176—178 °C. IR, ν/cm–1
:
2ꢀChloroꢀ5ꢀcyanobenzeneꢀ1ꢀsulfonyl chloride (1c). Commerꢀ
cially available agent (Atomax Chemicals Co. Ltd., CAS 942199ꢀ
56ꢀ6). M.p. 102—106 °C.
3466, 3361, 3300, 1617 (NH2); 1685 (C=O); 1588 (Carom—Carom);
1378, 1351, 1184, 1165 (SO2); 1284; 1249; 1104; 1025; 927; 847;
799; 688; 655.
4ꢀBromobenzeneꢀ1,3ꢀdisulfonyl dichloride (1d). Chlorosulꢀ
fonic acid (7.5 mL, 0,114 mol) was added to bromobenzene (3 g,
0.019 mol). The reaction mixture was heated for 3 h at 140 °C.
The reaction product was isolated pouring on ice (100 g) with
subsequent recrystallization of the precipitate from toluene. The
yield was 4.45 g (66%), white crystals, m.p. 98—102 °C. IR,
ν/cm–1: 3093 (Carom—H); 1569 (Carom—Carom); 1377, 1181, 1168
(SO2); 1282; 1256; 1101; 1094; 1023; 810; 722; 694; 678; 624.
4ꢀChlorobenzeneꢀ1,3ꢀdisulfonyl dichloride (1e) was obtained
similarly to compound 1d. The yield was 2.90 g (35%), white
Compounds 1i—m were obtained similarly to compound 1h.
5ꢀCarbamoylꢀ2ꢀchlorobenzeneꢀ1ꢀsulfonyl chloride (1i). The
reaction time was 2 h, the temperature 90 °C. The yield was
1.833 g (57%), white crystals, m.p. 145—148 °C. IR, ν/cm–1
:
3464, 3361, 3300, 1618 (NH2); 3094 (Carom—H); 1684 (C=O),
1592 (Carom—Carom); 1379, 1353, 1180, 1167 (SO2); 1287; 1250;
1114; 1104; 1038; 928; 853; 799; 693; 675.
5ꢀCarbamoylꢀ2ꢀfluorobenzeneꢀ1ꢀsulfonyl chloride (1k). The
reaction time was 2 h, the temperature 90 °C. The yield was
0.979 g (30%), white crystals, m.p. 134—135.5 °C. IR, ν/cm–1
:

2ꢀHalobenzenesulfonyl chlorides
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 7, July, 2016
1843
3471, 3360, 3147 (NH2); 3077 (Carom—H); 1686 (C=O); 1600,
1495 (Carom—Carom); 1387, 1370, 1188 (SO2); 1303; 1280; 1232;
1061; 936; 879; 851; 795; 704; 692.
2,4,5ꢀTrichlorobenzeneꢀ1ꢀsulfonyl chloride (1l). The reaction
time was 3 h, the temperature 145 °C. The yield was 2.00 g (43%),
white crystals, m.p. 65—67 °C. IR, ν/cm–1: 3097 (Carom—H);
1565, 1534 (Carom—Carom); 1379, 1179, 1156 (SO2); 1320; 1118;
1066; 909; 880; 688; 657; 623.
H(10), 3J = 6.7 Hz, 4J = 2.1 Hz). 13C NMR (125 MHz),
δ: 113.71 (C(9)), 119.05 (C(4)), 122.88 (C(1)), 123.79 (C(7)),
127.11 (C(4a)), 127.33 (C(2)), 133.15 (C(10)), 139.43 (C(11a)),
141.35 (C(8)), 146.95 (C(3)), 152.59 (C(6a)). MS (EI, 70 eV),
m/z (Irel (%)): 277 [M]+ (14), 213 (59), 168 (8), 167 (91), 166
(17), 155 (23), 140 (35), 113 (8), 78 (23), 75 (21), 74 (9), 63 (32),
62 (14), 52 (11), 51 (27), 50 (16), 46 (34), 44 (19), 39 (10),
30 (100), 29 (7), 28 (14).
5ꢀ(NꢀMethyl)carbamoylꢀ2ꢀfluorobenzeneꢀ1ꢀsulfonyl chloride
(1m). The reaction time was 1.5 h, the temperature 100 °C. The yield
was 1.418 g (44%), needleꢀlike white crystals, m.p. 124—126 °C.
IR, ν/cm–1: 3303, 3107 (CON—H); 3086, 3043 (Carom—H);
1639 (C=O); 1604, 1492 (Carom—Carom); 1558 (N—H); 1397,
1377, 1187 (SO2); 1326; 1275; 1242; 1156; 1066; 906; 891; 868;
811; 768; 726; 714; 626.
9ꢀChloroꢀ3ꢀnitroꢀ5Hꢀpyrido[2,1ꢀc][1,2,4]benzothiadiazine
5,5ꢀdioxide (4b). Dark yellow plate crystals, m.p. 290—292 °C.
Found (%): C, 42.48; H, 1.93; N, 13.53. C11H6ClN3O4S. Calcuꢀ
lated (%): C, 42.39; H, 1.94; N, 13.48. M 311.70. IR, ν/cm–1
:
1643 (C=N, C=C); 1605, 1590, 1501 (Carom—Carom); 1523, 1356
(NO2); 1306, 1176, 1150, 1129 (SO2); 1220; 1065; 958; 929; 894;
839; 818; 752; 726; 697; 597. 1H NMR (500 MHz), δ: 7.23 (d, 1 H,
H(7), 3J = 9.7 Hz); 7.98 (dd, 1 H, H(8), 3J = 9.7 Hz, 4J = 2.2 Hz);
8.56 (d, 1 H, H(1), 3J = 9.5 Hz); 8.60 (d, 1 H, H(4), 4J = 2.6 Hz);
5ꢀ(NꢀPhenyl)carbamoylꢀ2ꢀfluorobenzeneꢀ1ꢀsulfonyl chloride
(1n). A mixture of aniline (0.35 mL, 3.890 mmol), pyridine
(0.31 mL, 3.890 mmol), and acetonitrile (10 mL) was added to
a solution of compound 6 (1 g, 3.890 mmol) in acetonitrile
(10 mL) at 20 °C with vigorous stirring over 15 min. Then, the
mixture was allowed to stand for 1 h under the same conditions.
The reaction product was isolated by pouring in water (100 mL)
with subsequent recrystallization of formed precipitate from toluene.
The yield was 1.118 g (92%), white crystals, m.p. 191—193 °C.
IR, ν/cm–1: 3292, 3195, 3140 (CON—H); 3080 (Carom—H);
1655 (C=O); 1600, 1490 (Carom—Carom); 1556, 1544 (N—H);
1381, 1186 (SO2); 1331; 1262; 921; 842; 763; 711; 695.
Compounds 1o and 1p were obtained similarly to compound 1n.
5ꢀ[(Nꢀ4ꢀCyanophenyl)carbamoyl]ꢀ2ꢀfluorobenzeneꢀ1ꢀsulfonꢀ
yl chloride (1o). The yield was 1.247 g (95%), light beige crystals,
m.p. 190—193 °C. IR, ν/cm–1: 3358 (N—H); 3066 (Carom—H);
2230 (C≡N); 1690 (C=O); 1602, 1507, 1492 (Carom—Carom);
1528 (N—H); 1380, 1323, 1181 (SO2); 1279; 1260; 1244; 1099;
1066; 918; 847; 754; 719; 650; 627.
5ꢀ([Nꢀ(2ꢀTrifluoromethyl)phenyl]carbamoyl)ꢀ2ꢀfluorobenzꢀ
eneꢀ1ꢀsulfonyl chloride (1p). The yield was 1.221 g (82%), white
crystals, m.p. 130—133 °C. IR, ν/cm–1: 3203 (N—H); 3044
(Carom—H); 1669, 1651 (C=O); 1603, 1591, 1496, 1483
(Carom—Carom); 1541 (N—H); 1379, 1318, 1188 (SO2); 1265;
1125; 1058; 1036; 929; 882; 844; 823; 766; 760; 740; 710; 652;
634; 608; 564.
Oneꢀstep synthesis of pyrido[2,1ꢀc][1,2,4]benzothiadiazine
5,5ꢀdioxide derivatives (4a—c) (general procedure). An equimolar
amount of the corresponding 2ꢀaminopyridine derivative 2 and
pyridine (3 mL) were added to the starting sulfonyl chloride 1
(0.5 g). The reaction mixture was refluxed for 3 h. On compleꢀ
tion, the pyridine was evaporated at normal pressure and water
(40 mL) was added. A precipitate of compound 4 was collected
by filtration and purified by recrystallization from a mixture of
DMF—acetonitrile—water (3 : 1 : 1, v/v).
3
4
8.65 (dd, 1 H, H(2), J = 9.5 Hz, J = 2.6 Hz); 9.13 (d, 1 H,
H(10), J = 2.2 Hz). MS (EI, 70 eV), m/z (Irel (%)): 313 [M]+
4
(10), 311 [M]+ (27), 249 (22), 248 (9), 247 (71), 203 (30),
202 (14), 201 (100), 191 (7), 189 (26), 176 (6), 174 (22), 167 (10),
166 (72), 165 (19), 139 (11), 138 (6), 114 (8), 112 (18), 88 (11),
77 (7), 76 (42), 75 (27), 74 (23), 73 (10), 64 (14), 63 (31), 62 (17),
51 (6), 50 (8), 46 (11), 44 (8), 30 (27).
8ꢀMethylꢀ3ꢀnitroꢀ5Hꢀpyrido[2,1ꢀc][1,2,4]benzothiadiazine
5,5ꢀdioxide (4c). Brown needleꢀlike crystals, m.p. 312—315 °C.
Found (%): C, 49.33; H, 3.12; N, 14.36. C12H9N3O4S. Calcuꢀ
lated (%): C, 49.48; H, 3.11; N, 14.43. M 291.28. IR, ν/cm–1
:
1659 (C=N, C=C); 1609, 1595, 1507 (Carom—Carom); 1538, 1354
(NO2); 1302, 1175, 1154, 1131 (SO2); 1226; 1070; 976; 938; 893;
883; 870; 831; 793; 748; 700; 658. 1H NMR (500 MHz), δ: 2.43
3
(d, 3 H, Me, J = 1.5 Hz); 7.01 (dd, 1 H, H(9), J = 7.3 Hz,
4
4J = 2.1 Hz); 7.04 (d, 1 H, H(7), J = 2.1 Hz); 8.41 (d, 1 H,
H(1), 3J = 9.5 Hz); 8.57 (d, 1 H, H(4), 4J = 2.6 Hz); 8.65 (dd, 1 H,
H(2), 3J = 9.5 Hz, 4J = 2.6 Hz); 8.84 (d, 1 H, H(10), 3J = 7.3 Hz).
MS (EI, 70 eV), m/z (Irel (%)): 291 [M]+ (13), 228 (9), 227 (73),
182 (15), 181 (100), 180 (9), 179 (12), 169 (22), 166 (19), 154 (10),
153 (7), 127 (13), 78 (6), 77 (9), 76 (11), 75 (17), 74 (12), 65 (20),
64 (10), 63 (22), 62 (8), 52 (10), 51 (9), 50 (8), 46 (24), 44 (6),
39 (22), 38 (6), 30 (65), 28 (11), 27 (6).
Twoꢀstep synthesis of pyrido[2,1ꢀc][1,2,4]benzothiadiazine
5,5ꢀdioxide derivatives (4d—g) (general procedure). The first step
was similar to that given above for compounds 4a—c. Dimethylꢀ
formamide (3 mL) was added to the intermediate sulfonamide 3
(or a mixture of 3 and 4) (0.5 g). The reaction mixture was
refluxed for 3 h. The reaction product was isolated by the addiꢀ
tion of acetonitrile (1 mL) and water (1 mL).
3ꢀ(4ꢀChlorobenzeneꢀ1ꢀsulfonyl)ꢀ8ꢀmethylꢀ5Hꢀpyrido[2,1ꢀc]ꢀ
[1,2,4]benzothiadiazine 5,5ꢀdioxide (4d). Light yellow crystals,
m.p. 292—294 °C. Found (%): C, 51.24; H, 3.13; N, 6.63.
C18H13ClN2O4S2. Calculated (%): C, 51.37; H, 3.11; N, 6.66.
M 420.89. IR, ν/cm–1: 3060 (Carom—H); 1656 (C=N); 1585,
1522 (Carom—Carom); 1335, 1320, 1178, 1155 (SO2); 1292; 1225;
1123; 1092; 1080; 1040; 1015; 978; 861; 830; 821; 774; 758; 728;
707; 700; 649; 614; 590; 562; 548. 1H NMR (400 MHz), δ: 2.37
3ꢀNitroꢀ5Hꢀpyrido[2,1ꢀc][1,2,4]benzothiadiazine 5,5ꢀdiꢀ
oxide (4a). Yellow crystals, m.p. 333—335 °C. Found (%): C, 47.54;
H, 2.53; N, 15.22. C11H7N3O4S. Calculated (%): C, 47.65; H, 2.54;
N, 15.16. M 277.26. IR, ν/cm–1: 1648 (C=N, C=C); 1609, 1596,
1508 (Carom—Carom); 1536, 1353 (NO2); 1328, 1299, 1176, 1155,
1127 (SO2); 1224; 1072; 1002; 960; 930; 894; 858; 834; 797; 766;
3
4
(s, 3 H, CH3); 6.97 (dd, 1 H, H(9), J = 7.3 Hz, J = 1.8 Hz);
1
750; 656; 565. H NMR (500 MHz), δ: 7.11 (m, 1 H, H(9),
7.00 (d, 1 H, H(7), 4J = 1.8 Hz); 7.74 (d, 2 H, H(3)Ph, H(5)Ph
,
4
3
3J = 6.7 Hz, J = 2.1 Hz); 7.19 (dd, 1 H, H(7), J = 6.7 Hz,
3J = 8.6 Hz); 8.14 (d, 2 H, H(2)Ph, H(6)Ph, 3J = 8.6 Hz); 8.34—8.39
(m, 2 H, H(1), H(4)); 8.44 (dd, 1 H, H(2), 3J = 9.1 Hz, 4J = 2.2 Hz);
8.76 (d, 1 H, H(10), 3J = 7.3 Hz). MS (ESI), m/z (Irel (%)): 421
[M]+ (42), 420 [M]+ (25), 419 [M]+ (100), 275 (3), 173 (6).
4J = 2.1 Hz); 7.92 (m, 1 H, H(8), 3J = 6.7 Hz, 4J = 2.1 Hz); 8.44
(d, 1 H, H(1), J = 9.5 Hz); 8.58 (d, 1 H, H(4), J = 3.3 Hz);
8.66 (dd, 1 H, H(2), J = 9.5 Hz, J = 3.3 Hz); 8.92 (dd, 1 H,
3
4
3
4

1844
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 7, July, 2016
Shlenev et al.
3
4
9ꢀChloroꢀ5Hꢀpyrido[2,1ꢀc][1,2,4]benzothiadiazineꢀ3ꢀcarbꢀ
onitrile 5,5ꢀdioxide (4e). Light brown crystals, m.p. 242—244 °C.
Found (%): C, 49.57; H, 2.07; N, 14.36. C12H6ClN3O2S. Calcuꢀ
(dd, 1 H, H(9), J = 7.3 Hz, J = 1.9 Hz); 7.00 (d, 1 H, H(7),
4J = 1.9 Hz); 7.14 (t, 1 H, H(4)Ph, J = 7.7 Hz); 7.39 (t, 2 H,
3
3
H(3)Ph, H(5)Ph, J = 7.7 Hz); 7.81 (d, 2 H, H(2)Ph, H(6)Ph
,
3
lated (%): C, 49.41; H, 2.07; N, 14.40. M 291.71. IR, ν/cm–1
:
3J = 7.7 Hz); 8.30 (d, 1 H, H(1), J = 9.0 Hz); 8.42 (dd, 1 H,
H(2), 3J = 9.0 Hz, 4J = 2.1 Hz); 8.60 (d, 1 H, H(4), 4J = 2.1 Hz);
8.82 (d, 1 H, H(10), 3J = 7.3 Hz); 10.65 (br.s, 1 H, CONH). MS
(ESI), m/z (Irel (%)): 365 [M]+ (24), 364 [M]+ (100), 285 (3), 275
(4), 239 (5), 222 (3), 173 (15), 113 (4), 59 (4).
2238 (C≡N); 1641 (C=N, C=C); 1606, 1513 (Carom—Carom);
1304, 1154, 1136 (SO2); 1262; 1102; 953; 834; 821; 806; 740;
707; 658. 1H NMR (500 MHz), δ: 7.23 (d, 1 H, H(7), 3J = 9.6 Hz);
3
4
7.94 (dd, 1 H, H(8), J = 9.6 Hz, J = 2.1 Hz); 8.37 (dd, 1 H,
H(2), 3J = 9.0 Hz, 4J = 1.8 Hz); 8.48 (d, 1 H, H(1), 3J = 9.0 Hz);
8.55 (d, 1 H, H(4), 4J = 1.8 Hz); 9.07 (d, 1 H, H(10), 4J = 2.1 Hz).
Methyl 2ꢀChloroꢀ8ꢀmethylꢀ5Hꢀpyrido[2,1ꢀc][1,2,4]benzoꢀ
thiadiazineꢀ3ꢀcarboxylate 5,5ꢀdioxide (4f). Light yellow crystals,
m.p. 281—283 °C. Found (%): C, 49.46; H, 3.29; N, 8.24.
C14H11ClN2O4S. Calculated (%): C, 49.64; H, 3.27; N, 8.27.
M 338.77. IR, ν/cm–1: 3076 (Carom—H); 1741 (C=O); 1659 (C=N);
1601, 1574, 1499 (Carom—Carom); 1351, 1163, 1134 (SO2); 1294
(C—O); 1186; 1102; 1034; 973; 891; 867; 849; 805; 775; 758;
722; 712; 665. 1H NMR (400 MHz), δ: 2.38 (s, 3 H, Me); 3.86—3.94
(m, 3 H, CO2Me); 6.94 (dd, 1 H, H(9), 3J = 7.3 Hz, 4J = 2.0 Hz);
6.98 (d, 1 H, H(7), 4J = 2.0 Hz); 8.33 (s, 1 H, H(1)); 8.47 (s, 1 H,
H(4)); 8.81 (d, 1 H, H(10), 3J = 7.3 Hz). MS (ESI), m/z (Irel (%)):
339 [M]+ (39), 338 [M]+ (18), 337 [M]+ (100), 173 (4).
8ꢀMethylꢀ5Hꢀpyrido[2,1ꢀc][1,2,4]benzothiadiazineꢀ3ꢀ(Nꢀ
4ꢀcyanophenyl)carboxamide 5,5ꢀdioxide (4j). The yield was 0.123 g,
beige crystals, m.p. >350 °C. Found (%): C, 61.34; H, 3.60;
N, 14.38. C20H14N4O3S. Calculated (%): C, 61.53; H, 3.61;
N, 14.35. M 390.42. IR, ν/cm–1: 3377 (N—H); 3072 (Carom—H);
2225 (C≡N); 1670 (C=N); 1653 (C=O); 1598, 1512 (Carom—Carom);
1538 (N—H); 1352, 1336, 1183, 1152 (SO2); 1312; 1287; 1272;
1252; 1228; 1120; 1109; 1075; 1038; 868; 851; 784; 755; 713;
1
659; 625; 595; 566; 554. H NMR (400 MHz), δ: 2.39 (s, 3 H,
CH3); 6.98 (dd, 1 H, H(9), 3J = 7.3 Hz, 4J = 1.8 Hz); 7.00 (d, 1 H,
H(7), 4J = 1.8 Hz); 7.85 (d, 2 H, H(3)Ph, H(5)Ph, 3J = 8.8 Hz);
8.02 (d, 2 H, H(2)Ph, H(6)Ph, 3J = 8.8 Hz); 8.32 (d, 1 H, H(1),
3J = 9.1 Hz); 8.42 (dd, 1 H, H(2), 3J = 9.1 Hz, 4J = 2.0 Hz); 8.60
4
3
(d, 1 H, H(4), J = 2.0 Hz); 8.82 (d, 1 H, H(10), J = 7.3 Hz);
10.99 (s, 1 H, CONH). MS (ESI), m/z (Irel (%)): 390 [M]+ (24),
389 [M]+ (100), 235 (3), 191 (3), 174 (3), 173 (24).
8ꢀMethylꢀ5Hꢀpyrido[2,1ꢀc][1,2,4]benzothiadiazineꢀ3ꢀcarbꢀ
oxamide 5,5ꢀdioxide (4g). Beige crystals, m.p. 329—331 °C.
Found (%): C, 53.83; H, 3.85; N, 14.48. C13H11N3O3S. Calcuꢀ
8ꢀMethylꢀ5Hꢀpyrido[2,1ꢀc][1,2,4]benzothiadiazineꢀ3ꢀ[Nꢀ
(2ꢀtrifluoromethyl)phenyl]carboxamide 5,5ꢀdioxide (4k). The
yield was 0.163 g, dark beige crystals, m.p. 228—230 °C. Found (%):
C, 55.59; H, 3.27; N, 9.66. C20H14F3N3O3S. Calculated (%):
C, 55.43; H, 3.26; N, 9.70. M 433.40. IR, ν/cm–1: 3412 (N—H);
3068 (Carom—H); 1686 (C=N); 1656 (C=O); 1609, 1585, 1507
(Carom—Carom); 1348, 1323, 1159, 1127 (SO2); 1294; 1247; 1228;
1104; 1076; 1054; 1033; 896; 868; 813; 774; 762; 660; 652; 566.
1H NMR (400 MHz), δ: 2.40 (s, 3 H, Me); 6.98 (dd, 1 H, H(9),
lated (%): C, 53.97; H, 3.83; N, 14.52. M 289.31. IR, ν/cm–1
:
3386, 3305 (NH2); 1678 (C=N); 1658 (C=O); 1625 (NH2); 1612,
1580, 1514, 1486 (Carom—Carom); 1536 (N–H); 1356, 1181, 1150
(SO2); 1284; 1225; 1123; 1079; 1039; 994; 977; 910; 870; 843;
1
793; 755; 718; 708; 690; 658; 601; 565. H NMR (400 MHz),
δ: 2.38 (s, 3 H, Me); 6.95 (dd, 1 H, H(9), 3J = 7.3 Hz, 4J = 1.9 Hz);
6.98 (d, 1 H, H(7), 4J = 1.9 Hz); 7.71 (s, 1 H, CONH2); 8.24 (d, 1 H,
H(1), 3J = 9.2 Hz); 8.32 (dd, 1 H, H(2), 3J = 9.2 Hz, 4J = 2.0 Hz);
8.41 (s, 1 H, CONH2); 8.46 (d, 1 H, H(4), 4J = 2.0 Hz); 8.80 (d,
3J = 7.3 Hz, J = 1.8 Hz); 7.01 (d, 1 H, H(7), J = 1.8 Hz);
7.54—7.62 (m, 2 H, H(3)Ph, H(4)Ph); 7.77 (t, 1 H, H(5)Ph
3J = 7.7 Hz); 7.83 (d, 1 H, H(6)Ph, J = 7.7 Hz); 8.32 (d, 1 H,
H(1), 3J = 9.1 Hz); 8.38 (dd, 1 H, H(2), 3J = 9.1 Hz, 4J = 1.8 Hz);
8.57 (d, 1 H, H(4), 4J = 1.8 Hz); 8.83 (d, 1 H, H(10), 3J = 7.3 Hz);
10.65 (s, 1 H, CONH). MS (ESI), m/z (Irel (%)): 433 [M]+ (25),
432 [M]+ (100).
Nꢀ(6ꢀMethylpyridinꢀ2ꢀyl)ꢀ2ꢀchlorobenzeneꢀ1ꢀsulfonamide
(3a). Yellow crystals, m.p. 192—194 °C. Found (%): C, 43.83;
H, 3.07; N, 12.78. C12H10ClN3O4S. Calculated (%): C, 43.98;
H, 3.08; N, 12.82. M 327.74. IR, ν/cm–1: 3238 (N—H); 1616
(C=N); 1603 (Carom—Carom); 1528, 1355 (NO2); 1355, 1147,
1124 (SO2); 1283; 1246; 1064; 1037; 892; 858; 841; 807; 738;
4
4
3
1 H, H(10), J = 7.3 Hz). MS (ESI), m/z (Irel (%)): 288 [M]+
,
3
(100), 275 (8), 250 (5), 191 (10), 173 (26), 113 (9), 77 (6), 59 (14).
8ꢀMethylꢀ5Hꢀpyrido[2,1ꢀc][1,2,4]benzothiadiazineꢀ3ꢀ(Nꢀ
methyl)carboxamide 5,5ꢀdioxide (4h). The yield was 0.274 g,
brown plate crystals, m.p. 333—335 °C. Found (%): C, 55.62;
H, 4.30; N, 13.92. C14H13N3O3S. Calculated (%): C, 55.43; H,
4.32; N, 13.85. M 303.34. IR, ν/cm–1: 3353 (N–H); 1655 (C=O,
C=N); 1612, 1581, 1510 (Carom—Carom); 1540 (N—H); 1355,
1303, 1179, 1150 (SO2); 1304; 1273; 1226; 1120; 1079; 1041;
994; 980; 904; 866; 843; 792; 763; 713; 706; 659; 602; 564.
1H NMR (400 MHz), δ: 2.37 (s, 3 H, Me); 2.83 (d, 3 H, NHCH3,
3J = 4.4 Hz); 6.94 (dd, 1 H, H(9), 3J = 7.3 Hz, 4J = 1.8 Hz); 6.98
4
3
1
(d, 1 H, H(7), J = 1.8 Hz); 8.24 (d, 1 H, H(1), J = 9.0 Hz);
706; 676; 632; 588. H NMR (400 MHz), δ: 2.35 (s, 3 H, Me);
3
4
8.29 (dd, 1 H, H(2), J = 9.0 Hz, J = 1.8 Hz); 8.42 (d, 1 H,
H(4), 4J = 1.8 Hz); 8.79 (d, 1 H, H(10), 3J = 7.3 Hz); 8.90 (d, 1 H,
CONH, 3J = 4.4 Hz). MS (ESI), m/z (Irel (%)): 303 [M]+ (20),
302 [M]+ (100), 275 (7), 225 (5), 191 (4), 173 (25), 113 (5),
77 (3), 59 (9).
6.70 (d, 1 H, H(5)Py,3J = 7.6 Hz); 7.11 (d, 1 H, H(3)Py,3J = 7.6 Hz);
7.73 (t, 1 H, H(4)Py, 3J = 7.6 Hz); 7.86 (d, 1 H, H(3), 3J = 8.8 Hz);
4
8.33 (dd, 1 H, H(4), 3J = 8.8 Hz, J = 2.1 Hz); 8.76 (d, 1 H,
4
H(6), J = 2.1 Hz); 13.54 (s, 1 H, SO2NH). MS (ESI), m/z
(Irel (%)): 328 [M]+ (39), 327 [M]+ (16), 326 [M]+ (100), 321 (16).
4ꢀBromoꢀN1,N3ꢀbis(4ꢀmethylpyridinꢀ2ꢀyl)benzeneꢀ1,3ꢀdiꢀ
sulfonamide (3b). Brown crystals, m.p. 264—266 °C. Found (%):
C, 43.31; H, 3.47; N, 11.31. C18H17BrN4O4S2. Calculated (%):
C, 43.47; H, 3.45; N, 11.26. M 497.39. IR, ν/cm–1: 3227 (N—H);
1633 (C=N); 1612, 1514 (Carom—Carom); 1341, 1304, 1158, 1143
(SO2); 1275; 1244; 1185; 1093; 1044; 1024; 995; 976; 943; 893;
834; 804; 739; 712; 676; 648; 618; 598, 582; 567. 1H NMR
(400 MHz), δ: 2.19 (s, 3 H, Me); 2.26 (s, 3 H, CH3); 6.64—6.72
(m, 2 H, H(5)Py); 6.97 (d, 1 H, H(3)Py, 4J = 1.7 Hz); 7.05 (d, 1 H,
8ꢀMethylꢀ5Hꢀpyrido[2,1ꢀc][1,2,4]benzothiadiazineꢀ3ꢀ(Nꢀ
phenyl)carboxamide 5,5ꢀdioxide (4i). The yield was 0.195 g, beige
crystals, m.p. >350 °C. Found (%): C, 62.62; H, 4.12; N, 11.45.
C19H15N3O3S. Calculated (%): C, 62.45; H, 4.14; N, 11.50.
M 365.41. IR, ν/cm–1: 3300 (N—H), 3078 (Carom—H); 1669
(C=N); 1655 (C=O); 1598, 1500 (Carom—Carom); 1534 (N—H);
1326, 1178, 1156 (SO2); 1286; 1273; 1254; 1224; 1119; 1079;
1034; 984; 956; 926; 905; 880; 870; 824; 776; 748; 714; 698; 956;
1
616; 592; 564. H NMR (400 MHz), δ: 2.39 (s, 3 H, Me); 6.97

2ꢀHalobenzenesulfonyl chlorides
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 7, July, 2016
1845
4
3
H(3)Py, J = 1.7 Hz); 7.74 (d, 1 H, H(6)Py, J = 6.2 Hz); 7.79
(d, 1 H, H(6)Py, 3J = 6.2 Hz); 7.83—7.91 (m, 2 H, H(3), H(4)); 8.49
(d, 1 H, H(6), 4J = 1.7 Hz); 12.5—13.5 (br.s, 2 H, SO2NH). MS
(ESI), m/z (Irel (%)): 498 [M]+ (21), 497 [M]+ (100), 495 [M]+
(89), 415 (6), 190 (5), 113 (3).
756; 712; 699; 679; 628; 587. 1H NMR (400 MHz), δ: 7.05 (d, 1 H,
H(3)Py, 3J = 8.8 Hz); 7.66 (s, 1 H, CONH2); 7.72 (d, 1 H, H(3),
3
4
3J = 8.3 Hz); 7.81 (dd, 1 H, H(4)Py, J = 8.8 Hz, J = 2.6 Hz);
3
4
8.08 (dd, 1 H, H(4), J = 8.3 Hz, J = 2.1 Hz); 8.11 (d, 1 H,
H(6)Py, 4J = 2.6 Hz); 8.30 (s, 1 H, CONH2); 8.60 (d, 1 H, H(6),
4J = 2.1 Hz); 11.89 (br.s, 1 H, SO2NH). MS (ESI), m/z (Irel (%)):
346 [M]+ (16), 347 [M]+ (71), 345 [M]+ (100), 235 (10), 218 (5),
113 (5).
4ꢀChloroꢀN1,N3ꢀbis(4ꢀmethylpyridinꢀ2ꢀyl)benzeneꢀ1,3ꢀdisulfꢀ
onamide (3c). Light brown crystals, m.p. 276—278 °C. Found (%):
C, 47.60; H, 3.77; N, 12.42. C18H17ClN4O4S2. Calculated (%):
C, 47.73; H, 3.78; N, 12.37. M 452.93. IR, ν/cm–1: 3229 (N—H);
1631 (C=N); 1612, 1517 (Carom—Carom); 1340, 1306, 1159, 1144
(SO2); 1275; 1244; 1184; 1097; 1038; 996; 977; 945; 896; 836;
803; 740; 718; 680; 649; 626; 598, 583; 568. 1H NMR (400 MHz),
δ: 2.19 (s, 3 H, Me); 2.26 (s, 3 H, CH3); 6.64—6.72 (m, 2 H,
Nꢀ(4ꢀMethylpyridinꢀ2ꢀyl)ꢀ2,4,5ꢀtrichlorobenzeneꢀ1ꢀsulfonꢀ
amide (3g). White crystals, m.p. 287—290 °C. Found (%): C, 40.90;
H, 2.59; N, 7.99. C12H9Cl3N2O2S. Calculated (%): C, 40.99;
H, 2.58; N, 7.97. M 351.64. IR, ν/cm–1: 3238 (N—H); 1634 (C=N);
1614, 1515 (Carom—Carom); 1326, 1150 (SO2); 1274; 1253; 1183;
1110; 1067; 1046; 1002; 978; 946; 896; 867; 822; 798; 744; 732;
695; 686; 649; 614; 588; 561. 1H NMR (400 MHz), δ: 6.72 (d, 1 H,
H(5)Py); 6.99 (d, 1 H, H(3)Py, 4J = 1.7 Hz); 7.05 (d, 1 H, H(3)Py
,
4J = 1.7 Hz); 7.69 (d, 1 H, H(3), J = 8.2 Hz); 7.74 (d, 1 H,
3
3
3
H(6)Py, J = 6.2 Hz); 7.79 (d, 1 H, H(6)Py, J = 6.2 Hz); 7.96
H(5)Py, 3J = 5.9 Hz); 7.09 (s, 1 H, H(3)Py); 7.79 (d, 1 H, H(6)Py
,
3J = 5.9 Hz); 7.97 (s, 1 H, H(4)); 8.21 (s, 1 H, H(6)). MS (ESI),
m/z (Irel (%)): 351 [M]+ (99), 349 [M]+ (100).
3
3
(dd, 1 H, H(4), J = 6.2 Hz, J = 1.7 Hz); 8.48 (d, 1 H, H(6),
4J = 1.7 Hz); 12.8—13.4 (br.s, 2 H, SO2NH). MS (ESI), m/z
(Irel (%)): 454 [M]+ (9), 453 [M]+ (43), 451 [M]+ (100), 416 (4),
190 (5), 113 (3).
Methyl 4ꢀchloroꢀ3ꢀ[(4ꢀmethylpyridinꢀ2ꢀyl)sulfamoyl]benzoꢀ
ate (3d). Light beige crystals, m.p. 236—238 °C. Found (%):
C, 49.52; H, 3.83; N, 8.18. C14H13ClN2O4S. Calculated (%):
C, 49.34; H, 3.85; N, 8.22. M 340.78. IR, ν/cm–1: 3065 (Carom—H);
1732 (C=O); 1609, 1592, 1516 (Carom—Carom); 1303, 1152 (SO2);
1241 (C–O); 1037; 894; 803; 757; 738; 708; 678; 650; 601.
1H NMR (400 MHz), δ: 2.26 (s, 1 H, Me); 3.90 (s, 3 H, CO2CH3);
6.68 (dd, 1 H, H(5)Py, J = 6.2 Hz, J = 1.8 Hz); 7.06 (d, 1 H,
H(3)Py, 4J = 1.8 Hz); 7.72 (d, 1 H, H(1), 3J = 8.3 Hz); 7.77 (d, 1 H,
H(6)Py, 3J = 6.2 Hz); 8.05 (dd, 1 H, H(4), 3J = 8.3 Hz, 4J = 2.1 Hz);
8.60 (d, 1 H, H(4), 4J = 2.1 Hz); 12.8—13.3 (br.s, 1 H, SO2NH).
MS (ESI), m/z (Irel (%)): 341 [M]+ (39), 340 [M]+ (19), 339
[M]+ (100), 173 (5).
4ꢀBromoꢀ3ꢀ[(4ꢀmethylpyridinꢀ2ꢀyl)sulfamoyl]benzamide (3e).
Light beige crystals, m.p. 297—299 °C. Found (%): C, 42.33;
H, 3.28; N, 11.39. C13H12BrN3O3S. Calculated (%): C, 42.17;
H, 3.27; N, 11.35. M 370.22. IR, ν/cm–1: 3402, 3313, 3244
(CONH2, SO2NH), 3086 (Carom—H); 1690 (C=O); 1625, 1553
(NH2); 1585, 1516 (Carom—Carom); 1379, 1158, 1143, 1122
(SO2); 1346; 1292; 1253; 1186; 1095; 1002; 978; 946; 894; 827;
742; 708; 700; 653; 594; 576. 1H NMR (400 MHz), δ: 2.25 (s, 3 H,
CH3); 6.66 (dd, 1 H, H(5)Py, 3J = 6.2 Hz, 4J = 0.5 Hz); 7.05 (d,
1 H, H(3)Py, 4J = 0.5 Hz); 7.56 (s, 1 H, CONH2); 7.75 (d, 1 H,
H(6)Py, 3J = 6.2 Hz); 7.83 (d, 1 H, H(3), 3J = 8.1 Hz); 7.87 (dd,
1 H, H(4), 3J = 8.1 Hz, 4J = 1.7 Hz); 8.25 (s, 1 H, CONH2); 8.59
(d, 1 H, H(6), 4J = 1.7 Hz); 12.95 (br.s, 1 H, SO2NH). MS (ESI),
m/z (Irel (%)): 371 [M]+ (14), 370 [M]+ (100), 369 [M]+ (13).
4ꢀChloroꢀ3ꢀ[(5ꢀchloropyridinꢀ2ꢀyl)sulfamoyl]benzamide (3f).
Light beige crystals, m.p. 242—244 °C. Found (%): C, 41.75;
H, 2.63; N, 12.08. C12H9Cl2N3O4S. Calculated (%): C, 41.63;
H, 2.62; N, 12.14. M 346.19. IR, ν/cm–1: 3470, 3374,
3199 (CONH2, SO2NH); 1678 (C=O); 1630 (NH2); 1599
(Carom—Carom); 1527 (N—H); 1377, 1152, 1141 (SO2); 1294;
1278; 1248; 1237; 1124; 1105; 1039; 979; 930; 904; 847; 795;
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Received January 21, 2016;
in revised form March 28, 2016