Novel method for the preparation of 2h-1,2,4-benzothiadiazin-3(4h)-one 1,1-dioxides via a curtius rearrangement

Full text of DOI:10.1007/s10593-012-1108-x

Chemistry of Heterocyclic Compounds, Vol. 48, No. 7, October, 2012 (Russian Original Vol. 48, No. 7, July, 2012)
NOVEL METHOD FOR THE PREPARATION OF
2H-1,2,4-BENZOTHIADIAZIN-3(4H)-ONE 1,1-DIOXIDES
VIA A CURTIUS REARRANGEMENT
E. M. Ivanova1, D. A. Borovika1, I. V. Vozny1,
P. Trapencieris1, and R. Žalubovskis1*
Keywords: acylazide, 2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide, hydrazide, saccharin, Curtius
rearrangement, intramolecular cyclization.
1,2,4-Benzothiadiazines are known for their antiviral activity [1, 2], hence work on their synthesis has
been carried out for quite some time. Hence in the study [3] it was shown that a series of 1,2,4-benzo-
thiadiazinones could be prepared by the reaction of anilines with chlorosulfonyl isocyanate and cyclization of
the N-chlorosulfonyl ureas. More recently the palladium-catalyzed cyclocarbonylation of o-aminobenzenesulfon-
amides has been reported [4]. We have developed a novel method for the preparation of the 2H-1,2,4-benzo-
thiadiazin-3(4H)-one 1,1-dioxides 5a,b from saccharin derivatives, the key stage of which is a Curtius
rearrangement followed by an intramolecular cyclization.
O
O
O
O
O
S
R
O
S
R
R
NH2
S
NH2
H2NNH2
Dioxane
NaNO2
NH
O
O
HNO3, H2O
0°C
HN
O
N3
1a,b
NH2
3a,b
2a,b
O
O
O
O
S
R
S
R
NH2
Toluene
NH

N
N
H
O
C
O
5a,b
4a,b
a R = H, b R = SO2NH2
This method is distinguished by its originality, simplicity in use, and the availability of starting materials
and reagents at a low cost. The major part of the synthetic process is carried out in a one-pot manner without the
isolation and purification of the intermediate products, and this undoubtedly adds value to the method.
_______
*To whom correspondence should be addressed, e-mail: raivis@osi.lv.
1Latvian Institute of Organic Synthesis, 21 Aizkraukles St., Riga LV-1006, Latvia.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1194-1196, July, 2012, Original
article submitted March 23, 2012.
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0009-3122/12/4807-1114©2012 Springer Science+Business Media New York

Reaction of the saccharins 1a,b with hydrazine gives the hydrazides 2a,b. The nitrosation of the latter leads to
the acylazides 3a,b which undergo a thermal Curtius rearrangement when refluxed in toluene, to give the
isocyanates 4a,b. Under the reaction conditions they undergo an intramolecular cyclization involving the
nitrogen atom of the sulfonamide group and yield the target compounds 5a,b.
1
The structure of the compounds 5a,b obtained was confirmed from H NMR and 13C NMR
spectroscopic data and also by elemental analysis.
1H and 13C NMR spectra were recorded on a Varian 400 spectrometer (400 and 100 MHz, respectively)
using DMSO-d6 with the residual solvent signals for reference (2.50 ppm for the 1H nuclei and 39.5 ppm for 13C
nuclei). Elemental analysis was carried out on an EA 1108 Elemental Analyzer and melting points for the
crystalline materials were determined on an SRS OptiMelt apparatus.
2-(Hydrazinocarbonyl)benzenesulfonamide (2a). Saccharin (1a) (5.49 g, 30 mmol) was dissolved in
dioxane (80 ml), and hydrazine monohydrate (1.45 ml, 30 mmol) was added. The product was refluxed for 5 h,
cooled to room temperature, and evaporated under reduced pressure to give an oil, which crystallized from ethanol.
Yield 3.12 g (48%); mp > 179ºC (decomp.) (mp 180ºC (decomp., EtOH) [5], 179-181ºC [6]). 1H NMR spectrum, ,
ppm (J, Hz): 4.72 (2H, br. s, NHNH2); 7.19 (2H, br. s, SO2NH2); 7.49-7.53 (1H, m, H Ar); 7.63-7.71 (2H, m, H Ar);
7.91-7.95 (1H, m, H Ar); 9.93 (1H, br. s, NHNH2). 13C NMR spectrum, , ppm: 117.0; 122.0; 122.6; 123.5; 134.0;
135.1 (C Ar); 150.6 (CO). Found, %: C 38.95; H 4.23; N 19.47. C7H9N3O3S. Calculated, %: C 39.06; H 4.21;
N 19.52.
4-(Hydrazinocarbonyl)benzene-1,3-disulfonamide (2b) was prepared similarly to compound 2a from
6-sulfamoylsaccharin (1b) [7] (5.00 g, 19 mmol) and hydrazine monohydrate (1.77 ml, 57 mmol) in dioxane (80
ml). The reaction mixture was refluxed for 8 h. Yield 5.50 g (98%); mp 220-222ºC (EtOH). 1H NMR spectrum,
, ppm (J, Hz): 4.65 (2H, br. s, NHNH2); 7.52 (4H, br. s, 2SO2NH2); 7.71 (1H, d, J = 8.0, H-5); 8.07 (1H, dd,
J = 1.8, J = 8.0, H-6); 8.34 (1H, d, J = 1.8, H-2); 10.04 (1H, br. s, NHNH2). 13C NMR spectrum, , ppm: 124.4;
129.1; 130.5; 136.2; 141.9; 145.4 (C Ar); 166.3 (CO). Found, %: C 28.63; H 3.42; N 18.93. C7H10N4O5S2.
Calculated, %: C 28.57; H 3.42; N 19.04.
2H-1,2,4-Benzothiadiazin-3(4H)-one 1,1-Dioxide (5a). Compound 2a (2.50 g, 11.6 mmol) was
dissolved in 2 M HNO3 (60 ml), and a solution of NaNO2 (0.96 g, 13.9 mmol) in water (12 ml) was added at
0ºC. The reaction mixture was stirred at 0ºC for 2 h. The precipitate formed was filtered off and dried under
reduced pressure, then without further purification suspended in toluene (50 ml). The mixture was refluxed for 5
h, cooled, the precipitate filtered off, and recrystallized from EtOH. Yield 0.91 g (40%); mp 296-298ºC (mp
1
299-300ºC (DMF) [8]). H NMR spectrum, , ppm (J, Hz): 7.22-7.31 (2H, m, H Ar); 7.61-7.67 (1H, m, H Ar);
7.75-7.80 (1H, m, H Ar); 11.22 (1H, s, СОNH); 12.67 (1H, br. s, SO2NH). 13C NMR spectrum, , ppm: 117.0;
122.0; 122.6; 123.5; 134.0; 135.1 (C Ar); 150.6 (CO). Found, %: C 42.55; H 2.85; N 13.98. C7H6N2O3S.
Calculated, %: C 42.42; H 3.05; N 14.13.
3-Oxo-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide (5b) was prepared
similarly to compound 5a from compound 2b (3.40 g, 11.6 mmol), NaNO2 (0.96 g, 13.9 mmol), and 2 M HNO3
(80 ml). The product was recrystallized from a mixture of water and MeCN. Yield 0.48 g (15%); mp > 304ºC
1
(decomp.). H NMR spectrum, , ppm (J, Hz): 7.39 (1H, d, J = 8.6, H-5); 7.52 (2H, br. s, SO2NH2); 8.02 (1H,
dd, J = 2.0, J = 8.6, H-6); 8.17 (1H, d, J = 2.0, H-8); 11.66 (1H, s, NH). 13C NMR spectrum, , ppm: 117.8;
120.5; 122.1; 130.9; 137.7; 138.9 (C Ar); 151.2 (CO). Found, %: C 30.34; H 2.70; N 15.01. C7H7N3O5S2.
Calculated, %: C 30.32; H 2.54; N 15.15.
This work was carried out with the financial support of the European Social Fund (project No.
2009/0203/1DP/1.1.1.2.0/09/APIA/VIAA/023).
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