Metal- and solvent-free synthesis of N-sulfonylformamidines

Article abstract of DOI:10.1039/c3gc40797g

A solvent-free green synthesis of N-sulfonylformamidines is reported via the direct condensation of N,N-dimethylformamide dimethyl acetal (DMF-DMA) and sulfonamide derivatives at room temperature. The described method avoids the use of metal catalysts as

Full text of DOI:10.1039/c3gc40797g

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Metal- and solvent-free synthesis of
N-sulfonylformamidines†
Cite this: Green Chem., 2013, 15, 2294
Nisha Chandna,a,b Navneet Chandak,a Pawan Kumar,a Jitander K. Kapoorb and
Pawan K. Sharma*a
A solvent-free green synthesis of N-sulfonylformamidines is reported via the direct condensation of
N,N-dimethylformamide dimethyl acetal (DMF-DMA) and sulfonamide derivatives at room temperature.
The described method avoids the use of metal catalysts as well as hazardous solvents, which are not
permitted for pharmaceutical manufacture, for the reactions or isolation of products. Hence, the current
work presents a fast and efficient alternative to earlier reported methods. The mild nature of the
procedure is demonstrated by varied functional group tolerance.
Received 28th April 2013,
Accepted 12th June 2013
DOI: 10.1039/c3gc40797g
www.rsc.org/greenchem
anhydrous conditions.6,13 A more direct method has been
recently reported by Chen et al., which involves the direct con-
Introduction
N-Sulfonylamidines present a versatile class of compounds as densation of the sulfonamide group with DMF in the presence
they widely serve as useful synthetic intermediates for com- of NaI/TBHP.7 Although it is a convenient approach and free
pounds of immense biological importance.1–3 In addition, the from a transition-metal catalyst, this method requires an elev-
sulfonamide group itself is a unique pharmacophore and ated temperature, an oxidant, longer reaction times (of the
forms an integral part of various drugs or drug-like mole- order of several hours), and the use of column chromato-
cules.4,5 Within the field of antisense technology, we have graphy to isolate pure products. Thus, a fast, efficient, and
shown that the efficient stacking of sulfonamide substituted greener procedure which avoids the use of column chromato-
phenyltriazoles attached to the 5-position of the 2′-deoxyuri- graphy, is desirable. This motivated us to develop a solvent-
dine leads to the formation of a very stable DNA : RNA hybrid free green and spontaneous synthesis of N-sulfonylamidines.
duplexes.6 However, the sulfonamide group often requires pro- In continuation of our interest in sulfonamide derivatives of
tection during the synthesis of drugs/drug-ike molecules, and potential pharmacological interests,6,13b,14 we now wish to
N-sulfonylformamidines present a valuable choice for chemists report a green and general method for the synthesis of N-sulfo-
due to the ease of their removal under mild conditions.6,7
nylformamidines by the direct condensation of sulfonamide
A variety of methods are known for the synthesis of N-sulfo- derivatives and N,N-dimethylformamide dimethyl acetal
nylamidines. However, they suffer with one or more major (DMF-DMA). The use of DMF-DMA for the formation of N-sul-
drawbacks in terms of generality or reaction conditions. For fonylamidines has received very little attention even though it
instance, metal catalyzed reactions are often used to synthesize was initially introduced by Vandenheuvel and Gruber over 37
N-sulfonylamidine derivatives involving the use of transition years ago at the submicrogram level for analytical purposes.15
metal catalysts.8 In this field, Cu-catalyzed reactions9–11 have Our newly developed procedure does not involve any transition
received a lot of attention due to the tolerance of various func- metal catalyst/oxidants or potentially explosive materials, and
tionalities. Another approach to synthesize this class of com- can be carried out at room temperature under solvent-free
pounds requires the use of sulfonyl azide, which is known to conditions. Moreover, the aqueous work-up of the reaction
be explosive in nature.12 POCl3 and DMF are used for the mixture and isolation of products without column chromato-
preparation of amidines but suffer from the serious limitations graphy make our procedure highly practical.
of using harsh and corrosive reagent POCl3 and requiring
Results and discussion
aDepartment of Chemistry, Kurukshetra University, Kurukshetra-136 119, India.
E-mail: pksharma@kuk.ac.in; Fax: +91 1744 238277; Tel: +91 94164 57355
Initially we treated benzenesulfonamide (S1) with 2 equivalents
bDepartment of Chemistry, National Institute of Technology, Kurukshetra-136119,
of DMF-DMA in DMF at 90 °C to obtain N-[(dimethylamino)-
India
methylidene]benzenesulfonamide (P1) (Scheme 1), albeit in
†Electronic supplementary information (ESI)
available. See DOI:
10.1039/c3gc40797g
moderate yield (70%). Next, we took up the challenge to avoid
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without the use of column chromatography. The purity of the
1
product was determined by the H NMR spectrum as well as
by comparing the melting point and mixed melting point with
an authentic sample purified by column chromatography.
Next, we investigated the generality and scope of this reac-
tion, by reacting a range of benzenesulfonamide derivatives
under the optimized conditions and it is interesting to
note that the instantaneous completion of the reaction was
Scheme 1 Synthesis of N-[(dimethylamino)methylidene]benzenesulfonamide (P1) observed in most of the cases (Table 1). Moreover, the work-up
from benzenesulfonamide (S1).
simply amounted to adding water after the reaction reached
completion and filtering the pure product, which was free
from any associated impurities. In few cases (P11, P12, P17 and
the use of a solvent and treated S1 with neat DMF-DMA. A clean P18), the product had to be extracted with ethyl acetate due to
and instantaneous reaction was observed at elevated tempera- the partial solubility of the product in water. To our satisfac-
tures. It was intriguing to run the reaction at room temperature tion, the reaction was found to be independent of the substitu-
with 1 equivalent of DMF-DMA in order to see the effect of ents on the phenyl group and an instant reaction was observed
temperature as well as quantifying the optimum equivalents of in the case of electron-donating as well as electron-withdraw-
the reagent required for this reaction. To our surprise, the reac- ing groups (entries 1–4, Table 1). Other functional groups such
tion was found to be complete in no time with 1 equivalent of as azides, esters, as well as heterocyclic moieties were found
DMF-DMA and afforded the desired product in 98% yield to be well tolerated under the developed conditions (entries
Table 1 Examples studied for N-sulfonylformamidine protection by DMF-DMA
Molar ratio of DMF-DMA
required
%
yield
a
Entry Substrate (S1–25
)
Product (P1–25
)
1
1
98
97
98
98
97
98
97
2
3
4
5
6
7
8
1
1.1
1
1
1
1
1
98
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Table 1 (Contd.)
Molar ratio of DMF-DMA
required
%
yield
a
Entry Substrate (S1–25
)
Product (P1–25
)
9
1
1
4
4
97
98
10
11
12
13
95
95
96
1
1
14
15
16
92
98
1
1
98
94
17
18
1.1
1
1
96
98
19
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Table 1 (Contd.)
Molar ratio of DMF-DMA
required
%
yield
a
Entry Substrate (S1–25
)
Product (P1–25
)
20
98
1
21
22
98
1
1
99
98
23
24
1.2
1.2
98
25
1
2
50
98
a Reactions were usually instantaneously complete, but in no case did the reaction take more than 15 minutes to reach completion.
5–7, 11–13, Table 1). However, 4 equivalents of DMF-DMA in an excellent yield of 92%, indicating the generality of the
were required for substrates S11 and S12 bearing pyrazolyl moi- procedure.
eties (entries 11 and 12, Table 1) for N-sulfonylformamidine
The selectivity of the developed protocol for sulfonamide
protection and we are at a loss to explain this exceptional be- groups over aromatic amino groups was also investigated.
haviour. No acceleration or retardation of the rate of reaction Interestingly, the reaction was found to be chemoselective for
was observed upon changing the position of the substituent the sulfonamide group, as a single product was observed for
on the phenyl ring, and an instantaneous reaction was 4-aminobenzenesulfonamide (entry 15, Table 1). This might be
observed in all cases (entries 8–10, Table 1). Hereafter, we due to the higher acidity of the sulfonamide group compared
investigated if the developed protocol could be applied to ali- to the amino group. A similar observation was reported in the
phatic derivatives of sulfonamide by subjecting methanesulfo- case of 3-aminobenzenesulfonamide, where only the sulfona-
namide to similar conditions (entry 14, Table 1). An efficient mide moiety was protected (entry 16, Table 1). Next, we
and clean reaction was observed to afford the desired product attempted to see if an amino group attached to the aromatic
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heterocyclic ring, such as pyrazole, can also be differentiated electrical melting point apparatus (Navyug Udyog, Ambala
from the sulfonamide moiety attached to the phenyl ring. It Cantt., India) and are uncorrected. The infrared (IR) spectra
was found that the reaction proceeds chemoselectively at the were recorded on a ABB MB 3000 DTGS FT-IR Spectropho-
sulfonamide group (entries 17 and 18, Table 1), leaving the tometer. 1H NMR and 13C NMR spectra were recorded either in
pyrazolylamino group unchanged. The hydrazones bearing a pure DMSO-d6 or in CDCl3–DMSO-d6 mixtures on a Bruker
sulfonamide group (entries 19–24, Table 1) were the next to be NMR spectrometer at 300 MHz and 75.5 MHz respectively
treated with DMF-DMA under the developed conditions and using tetramethylsilane (TMS) as internal standard. Mass
the corresponding N-sulfonylformamidines were obtained in spectra (DART-MS) were recorded on a AB Sciex 3200 Q Trap
excellent yields while the NH from the hydrazones remained LC MS/MS Mass spectrometer having a DART (Direct Analysis
intact. However, the amino group of 2-amino-1,3-benzothia- in Real Time) source in +Q1 mode. Chemical shifts are
zole-6-sulfonamide was found to react under the described expressed in δ, ppm. The purity of the compounds was
1
conditions to afford the fully protected product (entry 25, checked by H NMR and thin layer chromatography (TLC) on
Table 1).16 Considering the substitution at position-2 of ben- silica gel plates using a mixture of petroleum ether (60–80 °C)
zothiazole, it is well known that the nature of benzothiazole as and ethyl acetate as eluent. Iodine or a UV lamp was used as a
a whole is electron-withdrawing, keeping the lone-pair of elec- visualizing agent. Abbreviations ‘s’ for singlet, ‘d’ for doublet,
trons on the amino nitrogen busy within the ring, and thus ‘m’ for multiplet, ‘ex’ for exchangeable proton are used for
making the amino functionality less basic.17 It has recently NMR assignments and ‘vs’ for very strong, ‘s’ for strong, ‘m’
been reported by us that an amino group not involved in any for medium, ‘w’ for weak for IR assignments. ‘Mp’ stands for
type of cyclization/aromatization through lone-pair of electrons melting point. DMF-DMA was procured from Spectrochem
is basic enough to become easily acylated by simply refluxing Private Limited, Mumbai, India.
in acetic acid.14g On the other hand if the lone-pair of electrons
on the amino group is being withdrawn, making it less basic,
General procedure for the synthesis of
N-sulfonylformamidines
then it has to be refluxed/treated with acetic anhydride for acy-
lation.17 The newly developed DMF-DMA treatment protocol To neat DMF-DMA (6 mmol) was added benzenesulfonamide
could be a better practical test for knowing the nature of an (6 mmol, S1–25) in a vial. The reaction mixture was magnetically
amino group in terms of relative basicity. This observation stirred and the progress monitored through TLC (after taking a
also allowed us to conclude that as the basicity of amino group sample from stirred mixture and dissolving it in methanol for
(whether attached to aromatic or aliphatic moiety) decreases, easy spotting on TLC plate). After completion of the reaction
the selectivity of DMF-DMA to distinguish between the amino (less than 15 min in all cases), water was added to the reaction
and sulfonamido group vanishes and both get protected simul- mixture where a precipitate of the product P1–25 was formed
taneously when treated with DMF-DMA. Remarkably, the and then collected by filtration, followed by washing with
reaction could be readily scaled up to the multigram scale and diethyl ether and drying.
the desired N-sulfonylformamidines could be obtained in
good yield, thus rendering this methodology highly practical.
Note: Products P11, P12, P17 and P18 were extracted from
water by ethyl acetate due to their partial solubility in water.
N-[(Dimethylamino)methylidene]benzenesulfonamide P1. Mp
130–132 °C (lit.,8a 128–130 °C); νmax/cm−1 1620 vs (CN), 1335 s
and 1149 s (SO2); δH (300 MHz; DMSO-d6; Me4Si) 2.90 (3H, s,
NCH3), 3.14 (3H, s, NCH3), 7.49–7.60 (3H, m, Ar), 7.75–7.78
(2H, m, Ar), 8.21 (1H, s, CHvN); δC (75.5 MHz; DMSO-d6;
Me4Si) 35.5 (NCH3), 41.3 (NCH3), 126.3, 129.4, 132.1, 143.5,
160.2; DART MS m/z 213.19 (M + H)+, C9H12N2O2SH+ calcd
213.06.
N-[(Dimethylamino)methylidene]-4-methylbenzenesulfona-
mide P2. Mp 137–139 °C (lit.,13a 133–134 °C); νmax/cm−1 1620
vs (CN), 1342 s and 1134 s (SO2); δH (300 MHz; DMSO-d6; Me4Si)
2.35 (3H, s, CH3), 2.89 (3H, s, NCH3), 3.13 (3H, s, NCH3), 7.32
(2H, d, J = 8.4 Hz, Ar), 7.64 (2H, d, J = 8.4 Hz, Ar), 8.19 (1H, s,
CHvN); δC (75.5 MHz; DMSO-d6; Me4Si) 21.1 (CH3), 35.4
(NCH3), 41.4 (NCH3), 126.2, 129.9, 139.7, 143.1, 159.7; DART
MS m/z 227.21 (M + H)+, C10H14N2O2SH+ calcd 227.07.
Conclusions
We have developed a metal and solvent free green and efficient
protocol for the synthesis of N-sulfonylformamidines using
neat N,N-dimethylformamide dimethylacetal (DMF-DMA).
Reactions were performed at room temperature and were
found to be independent of an attached electron-withdrawing
or electron-donating group. In addition, N-sulfonylformami-
dine formation was accomplished chemoselectively in the
presence of an amine group. Besides being solvent-free, the
aqueous work-up further makes this synthesis greener, featur-
ing high atom economy, easily available starting materials, a
lack of microwave/conventional heating, operational simplicity,
good tolerance to diverse functional groups and easy isolation.
4-Chloro-N-[(dimethylamino)methylidene]benzenesulfona-
mide P3. Mp 128–130 °C (lit.,7 not given); νmax/cm−1 1620 vs
(CN), 1342 s and 1142 s (SO2); δH (300 MHz; DMSO-d6; Me4Si)
2.91 (3H, s, NCH3), 3.15 (3H, s, NCH3), 7.60 (2H, d, J = 8.4 Hz,
Experimental section
General information
All reactions were carried out under atmospheric pressure. Ar), 7.78 (2H, d, J = 8.4 Hz, Ar), 8.22 (1H, s, CHvN); δC
Melting points were determined in open glass capillaries in (75.5 MHz; DMSO-d6; Me4Si) 35.5 (NCH3), 41.5 (NCH3), 128.1,
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129.5, 137.6, 141.3, 159.9; DART MS m/z 247.19 (M + H)+,
N-[(Dimethylamino)methylidene]-2-iodo-1,3-benzothiazole-
6-sulfonamide P13. Mp 188–190 °C; νmax/cm−1 1636 vs (CN),
C9H11ClN2O2SH+ calcd 247.02.
N-[(Dimethylamino)methylidene]-4-iodobenzenesulfon- 1535 s (CN), 1342 s and 1149 s (SO2); δH (300 MHz; DMSO-d6;
amide P4. Mp 173–174 °C (lit.,6b 172–174 °C).
Me4Si) 2.92 (3H, s, NCH3), 3.15 (3H, s, NCH3), 7.88 (1H, d, J =
N-[(Dimethylamino)methylidene]-4-azidobenzenesulfon- 8.7 Hz, Ar), 8.03 (1H, d, J = 8.7 Hz, Ar), 8.23 (1H, s, CHvN),
amide P5. Mp 154–156 °C (lit.,6a 155–156 °C).
8.58 (s, 1H, Ar); δC (75.5 MHz; DMSO-d6; Me4Si) 35.6 (NCH3),
Methyl 4-({[N-(dimethylamino)methylidene]amino}sulfonyl)- 41.4 (NCH3), 121.5, 123.2, 125.1, 136.4, 140.8, 152.5, 157.1,
benzoate P6. Mp 163–165 °C (lit.,7 not given); νmax/cm−1 1728 160.2; DART MS m/z 395.98 (M + H)+, C10H10IN3O2S2H+ calcd
s (CO), 1628 vs (CN), 1335 s and 1149 s (SO2); δH (300 MHz; 395.92.
DMSO-d6; Me4Si) 2.92 (3H, s, NCH3), 3.16 (3H, s, NCH3), 3.88
N-[(Dimethylamino)methylidene]methanesulfonamide
(3H, s, OCH3), 7.91 (2H, d, J = 7.8 Hz, Ar), 8.08 (2H, d, J = P14. Mp 81–82 °C (lit.,8a 80–81 °C).
7.8 Hz, Ar), 8.24 (1H, s, CHvN); δC (75.5 MHz; DMSO-d6; Me4Si)
4-Amino-N-[(dimethylamino)methylidene]benzenesulfonamide
35.6 (NCH3), 41.4 (NCH3), 52.9 (OCH3), 126.7, 130.2, 132.7, P15. Mp 167–169 °C (lit.,18 168.5–170 °C); δH (300 MHz;
147.5, 160.4, 165.7; DART MS m/z 271.17 (M
+
H)+, DMSO-d6; Me4Si) 2.86 (3H, s, NCH3), 3.09 (3H, s, NCH3),
C11H14N2O4SH+ calcd 271.06.
5.80 (2H, s, ex, NH2), 6.56 (2H, d, J = 8.4 Hz, Ar), 7.38 (2H, d,
N-[4-({[(Dimethylamino)methylidene]amino}sulfonyl)phenyl]- J = 8.4 Hz, Ar), 8.09 (1H, s, CHvN); δC (75.5 MHz; DMSO-d6;
acetamide P7. Mp 196–198 °C (lit.,7 not given); νmax/cm−1 Me4Si) 35.3 (NCH3), 41.1 (NCH3), 113.0, 128.1, 129.1, 152.3,
3340 m (NH), 1697 s (CO), 1620 vs (CN), 1319 s and 1134 s 159.4.
(SO2); δH (300 MHz; DMSO-d6; Me4Si) 2.07 (3H, s, NHCOCH3),
3-Amino-N-[(dimethylamino)methylidene]benzenesulfonamide
2.89 (3H, s, NCH3), 3.12 (3H, s, NCH3), 7.69 (4H, s, Ar), 8.17 P16. Mp 158–160 °C; νmax/cm−1 3464 w and 3364 w (NH), 1620
(1H, s, CHvN), 10.25 (s, NHCO); δC (75.5 MHz; DMSO-d6; vs (CN), 1335 s and 1134 s (SO2); δH (300 MHz; DMSO-d6;
Me4Si) 24.4 (NHCOCH3), 35.4 (NCH3), 41.3 (NCH3), 119.1, Me4Si) 2.89 (3H, s, NCH3), 3.13 (3H, s, NCH3), 5.48 (2H, s, ex,
127.4, 128.1, 137.4, 142.5, 159.9, 169.5 (NHCOCH3).
N-[(Dimethylamino)methylidene]-3-iodobenzenesulfonamide (1H, s, Ar), 7.12 (1H, t, J = 7.8 Hz, Ar), 8.12 (1H, s, CHvN); δC
P8. Mp 141–142 °C (lit.,6b 140–143 °C).
(75.5 MHz; DMSO-d6; Me4Si) 35.4 (NCH3), 41.4 (NCH3), 111.2,
NH2), 6.68 (1H, d, J = 7.8 Hz, Ar), 6.83 (2H, J = 7.8 Hz, Ar), 6.95
N-[(Dimethylamino)methylidene]-3-azidobenzenesulfonamide 113.9, 118.0, 130.1, 143.2, 148.9, 159.7; DART MS m/z 228.24
P9. Mp 135–137 °C (lit.,6b 136–138 °C).
(M + H)+, C9H13N3O2SH+ calcd 228.07.
N-[(Dimethylamino)methylidene]-3-nitrobenzenesulfonamide
4-[5-Amino-3-(4-methylphenyl)-1H-pyrazol-1-yl]-N-[(dimethyl-
P10. Mp 140–142 °C; νmax/cm−1 1628 vs (CN), 1350 s and 1157 amino)methylidene]benzenesulfonamide P17. Mp 160–162 °C;
s (SO2); δH (300 MHz; DMSO-d6; Me4Si) 2.93 (3H, s, NCH3), νmax/cm−1 3364 w (NH), 1620 vs (CN), 1335 s and 1149 s (SO2);
3.17 (3H, s, NCH3), 7.84 (1H, t, J = 7.8 Hz, Ar), 8.21 (1H, d, J = δH (300 MHz; DMSO-d6; Me4Si) 2.32 (3H, s, CH3), 2.92 (3H, s,
7.8 Hz, Ar), 8.29 (1H, s, Ar), 8.41 (1H, d, J = 7.8 Hz, Ar), 8.47 NCH3), 3.16 (3H, s, NCH3), 5.61 (2H, s, ex, NH2), 5.91 (1H, s,
(1H, s, CHvN); δC (75.5 MHz; DMSO-d6; Me4Si) 35.6 (NCH3), pyrazole C4-H), 7.21 (2H, d, J = 7.8 Hz, Ar), 7.65 (2H, d, J = 6.9 Hz,
41.6 (NCH3), 120.8, 126.9, 131.5, 132.5, 144.6, 148.0, 160.3; Ar), 7.86 (4H, s, Ar), 8.25 (1H, s, CHvN); δC (75.5 MHz;
DART MS m/z 258.21 (M + H)+, C9H11N3O4SH+ calcd 258.04.
DMSO-d6; Me4Si) 21.3 (CH3), 35.5 (NCH3), 41.3 (NCH3), 88.3,
N-[(Dimethylamino)methylidene]-4-(3,5-dimethyl-1H-pyrazol- 122.6, 125.5, 127.5, 129.5, 130.9, 137.5, 140.3, 142.3, 149.2,
1-yl)benzenesulfonamide P11. Mp 136–137 °C; νmax/cm−1 1628 151. 4, 160.2; DART MS m/z 384.39 (M + H)+, C19H21N5O2SH+
vs (CN), 1342 s and 1149 s (SO2); δH (300 MHz; DMSO-d6; calcd 384.14.
Me4Si) 2.18 (3H, s, CH3), 2.35 (3H, s, CH3), 2.93 (3H, s, NCH3),
4-[5-Amino-3-(4-chlorophenyl)-1H-pyrazol-1-yl]-N-[(dimethyl-
3.16 (3H, s, NCH3), 6.12 (1H, s, pyrazole C4-H), 7.67 (2H, d, J = amino)methylidene]benzenesulfonamide P18. Mp 178–180 °C;
8.4 Hz, Ar), 7.85 (2H, d, J = 8.4 Hz, Ar), 8.24 (1H, s, CHvN); δC νmax/cm−1 1628 vs (CN), 1335 s and 1149 s (SO2); δH (300 MHz;
(75.5 MHz; DMSO-d6; Me4Si) 12.8 (CH3), 13.6 (CH3), 35.5 DMSO-d6; Me4Si) 2.92 (3H, s, NCH3), 3.15 (3H, s, NCH3), 5.68
(NCH3), 41.4 (NCH3), 108.7, 124.0, 127.5, 140.2, 141.2, 142.4, (2H, s, ex, NH2), 5.97 (1H, s, pyrazole C4-H), 7.45 (2H, d, J =
149.4, 160.2; DART MS m/z 307.33 (M + H)+, C14H18N4O2SH+ 8.1 Hz, Ar), 7.78 (2H, d, J = 8.1 Hz, Ar), 7.83–7.90 (4H, m, Ar), 8.24
calcd 307.11.
(1H, s, CHvN); δC (75.5 MHz; DMSO-d6; Me4Si) 35.5 (NCH3),
N-[(Dimethylamino)methylidene]-2-(3,5-dimethyl-1H-pyrazol- 41.4 (NCH3), 88.5, 122.7, 127.1, 127.5, 128.7, 132.3, 132.9,
1-yl)-1,3-benzothiazole-6-sulfonamide P12. Mp 254–256 °C; 140.4, 142.1, 149.0, 150.4, 159.9; DART MS m/z 404.29
νmax/cm−1 1636 vs (CN), 1535 s (CN), 1342 s and 1149 s (SO2); (M + H)+, C18H18ClN5O2SH+ calcd 404.08.
δH (300 MHz; DMSO-d6; Me4Si) 2.24 (3H, s, CH3), 2.72 (3H, s,
N-[(Dimethylamino)methylidene]-4-[2-(phenylethylidene)-
CH3), 2.92 (3H, s, NCH3), 3.15 (3H, s, NCH3), 6.30 (1H, s, pyra- hydrazino]benzenesulfonamide P19. Mp 251–252 °C; νmax
/
zole C4-H), 7.83 (1H, d, J = 8.7 Hz, Ar), 7.95 (1H, d, J = 8.7 Hz, cm−1 3302 w (NH), 1628 vs (CN), 1589 s (CN), 1342 s and 1135 s
Ar), 8.24 (1H, s, Ar), 8.53 (1H, s, CHvN); δC (75.5 MHz; DMSO- (SO2); δH (300 MHz; DMSO-d6; Me4Si) 2.28 (3H, s, CH3), 2.89
d6; Me4Si) 13.6 (CH3), 13.9 (CH3), 35.5 (NCH3), 41.5 (NCH3), (3H, s, NCH3), 3.12 (3H, s, NCH3), 7.28–7.42 (5H, m, Ar), 7.60
111.6, 121.1, 122.5, 124.8, 132.9, 139.4, 142.9, 153.1, 153.5, (2H, d, J = 8.7 Hz, Ar), 7.80 (2H, d, J = 6.9 Hz, Ar), 8.15 (1H, s,
160.1, 164.3; DART MS m/z 364.21 (M + H)+, C15H17N5O2S2H+ CHvN), 9.72 (1H, br s, ex, NH); δC (75.5 MHz; DMSO-d6;
calcd 364.08.
Me4Si) 13.5 (CH3), 35.3 (NCH3), 41.2 (NCH3), 112.5, 125.9,
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127.9, 128.5, 128.7, 132.7, 139.2, 143.7, 149.0, 159.6; DART MS
N-[(Dimethylamino)methylidene]-2{[dimethylamino)methy-
lidene]amino}-1,3-benzothiazole-6-sulfonamide P25. Mp 212–
m/z 345.26 (M + H)+, C17H20N4O2SH+ calcd 345.13.
N-[(Dimethylamino)methylidene]-4-{2-[1-(4-methylphenyl)- 214 °C; νmax/cm−1 1620 vs (CN), 1342 s and 1149 s (SO2); δH
ethylidene]hydrazino}benzenesulfonamide P20. Mp 180–182 °C; (300 MHz; DMSO-d6; Me4Si) 2.90 (3H, s, NCH3), 3.05 (3H, s,
νmax/cm−1 3340 w (NH), 1620 vs (CN), 1589 s (CN), 1342 s NCH3), 3.14 (3H, s, NCH3), 3.20 (3H, s, NCH3), 7.62 (1H, d, J =
and 1126 s (SO2); δH (300 MHz; DMSO-d6; Me4Si) 2.25 (3H, s, 8.7 Hz, Ar), 7.68 (1H, d, J = 8.7 Hz, Ar), 8.20–8.22 (2H, m,
CH3), 2.31 (3H, s, CH3), 2.88 (3H, s, NCH3), 3.11 (3H, s, NCH3), CHvN, Ar), 8.54 (1H, s, CHvN); δC (75.5 MHz; DMSO-d6;
7.20 (2H, d, J = 8.1 Hz, Ar), 7.27 (2H, d, J = 8.4 Hz, Ar), Me4Si) 17.1 (CH3), 114.8, 119.7, 128.1, 129.0, 129.1, 129.5,
7.58 (2H, d, J = 8.4 Hz, Ar), 7.69 (2H, d, J = 8.1 Hz, Ar), 8.13 130.2, 131.2, 131.6, 139.1, 147.8, 150.5, 153.5, 166.6, 171.2;
(1H, s, CHvN), 9.64 (1H, br s, ex, NH); δC (75.5 MHz; DMSO- DART MS m/z 340.17 (M + H)+, C13H17N5O2S2H+ calcd 340.08.
d6; Me4Si) 13.5 (CH3), 21.1 (CH3), 35.3 (NCH3), 41.2 (NCH3),
112.5, 125.8, 127.9, 129.3, 132.5, 136.5, 137.9, 144.0, 149.1,
159.6; DART MS m/z 359.23 (M + H)+, C18H22N4O2SH+ calcd
359.14.
Acknowledgements
4-{2-[1-(4-Chlorophenyl)ethylidene]hydrazino}-N-[(dimethyl- Nisha Chandna and Navneet Chandak are grateful to the
amino)methylidene]-benzenesulfonamide P21. Mp 170–172 °C; Council of Scientific and Industrial Research (CSIR), New
νmax/cm−1 3333 w (NH), 1620 vs (CN), 1589 s (CN), 1342 s and Delhi for the award of senior research fellowship.
1134 s (SO2); δH (300 MHz; DMSO-d6; Me4Si) 2.27 (3H, s, CH3),
2.89 (3H, s, NCH3), 3.12 (3H, s, NCH3), 7.30 (2H, d, J = 8.7 Hz,
Ar), 7.45 (2H, d, J = 8.7 Hz, Ar), 7.60 (2H, d, J = 8.7 Hz, Ar), 7.82
(2H, d, J = 8.7 Hz, Ar), 8.16 (1H, s, CHvN), 9.79 (1H, br s, ex,
Notes and references
NH); δC (75.5 MHz; DMSO-d6; Me4Si) 13.4 (CH3), 35.3 (NCH3),
41.2 (NCH3), 112.6, 127.6, 128.0, 128.7, 133.02, 133.07,
138.1, 142.5, 148.8, 159.6; DART MS m/z 379.16 (M + H)+,
C17H19ClN4O2SH+ calcd 379.09.
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N-[(Dimethylamino)methylidene]-2-{2-[1-(4-methylphenyl)-
ethylidene]hydrazino}-1,3-benzothiazole-6-sulfonamide
P23. Mp 216–218 °C; νmax/cm−1 1628 vs (CN), 1543 s (CN),
1342 s and 1142 s (SO2); δH (300 MHz; DMSO-d6; Me4Si) 2.35
(3H, s, CH3), 2.50 (3H, s, CH3), 2.90 (3H, s, NCH3), 3.14 (3H, s,
NCH3), 7.25 (2H, d, J = 7.8 Hz, Ar), 7.43 (1H, br m, Ar), 7.66
(1H, d, J = 8.7 Hz, Ar), 7.72 (2H, d, J = 7.8 Hz, Ar), 8.17–8.20
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(NCH3), 120.5, 124.7, 126.3, 129.4, 135.4, 136.2, 139.2, 160.0;
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2-{2-[1-(4-Chlorophenyl)ethylidene]hydrazino}-N-[(dimethyl-
amino)methylidene]-1,3-benzothiazole-6-sulfonamide P24. Mp
230–232 °C; νmax/cm−1 3240 w (NH), 1628 vs (CN), 1551 s (CN),
1342 s and 1142 s (SO2); δH (300 MHz; DMSO-d6; Me4Si) 2.36
(3H, s, CH3), 2.90 (3H, s, NCH3), 3.14 (3H, s, NCH3), 7.43 (1H,
br m, Ar), 7.51 (2H, d, J = 8.1 Hz, Ar), 7.66 (1H, d, J = 8.4 Hz,
Ar), 7.83 (2H, d, J = 8.1 Hz, Ar), 8.16–8.20 (2H, m, CHvN, Ar);
δC (75.5 MHz; DMSO-d6; Me4Si) 14.7 (CH3), 35.4, 41.3, 120.6,
124.8, 128.1, 128.9, 134.3, 136.3, 137.0, 160.0; DART MS m/z
436.16 (M + H)+, C18H18ClN5O2S2H+ calcd 436.05.
2300 | Green Chem., 2013, 15, 2294–2301
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