Sulfamic acid: an efficient, cost-effective and recyclable catalyst for thesynthesis of triazole[1,2-a]indazole-trione derivatives{

Mazaahir Kidwai{* and Ritika Chauhan

Received 25th February 2012, Accepted 19th June 2012

DOI: 10.1039/c2ra20662e

Sulfamic acid (SA) is successfully utilized as a green, cost-effective

and reusable catalyst for the synthesis of triazole[1,2-a]indazole-

trione derivatives involving the one-pot, three-component con-

densation of urazole, aldehydes and cyclic b-diketones in high

yields in water as a sole solvent. The salient features of this new

methodology are cheaper process, easy availability of the catalyst,

mild conditions, versatility, and the catalyst could be recycled

easily without affecting the catalytic activity.

Introduction

Developing a simple, eco-friendly approach for the synthesis of

compound libraries of medicinal scaffolds is a lucrative area of

research in both academic and pharmaceutical R & D.1 MCR

protocols in water will be one of the most suitable strategies which

will meet the requirements of green chemistry as well as for

developing libraries of compounds of pharmaceutical importance.2

With the emphasis on the adoption of cleaner green chemistry

processes and concerns over the environmental impact of using

volatile organic solvents (VOCs), the potential of water or non-

classical solvents has become highly relevant.3 In addition to its

abundance and for economical and safety reasons, water has

naturally become a substitute and an environmentally benign solvent

in organic synthesis.4 Moreover, since the pioneering studies by

Breslow5,6 on Diels–Alder reactions, there has been an increasing

recognition that organic reactions could proceed well in aqueous

media offering key advantages over organic solvents, such as rate

enhancement and insolubility of the final products, which facilitates

their isolation. The hydrophobic effect of water generates internal

pressure and promotes the association of reactants in the solvent

cavity during the activation process and accelerates the reaction. Any

factor which increases the hydrophobic effect will increase the

reaction rate.7 The use of the aqueous medium as solvent also

reduces the harmful effects of organic solvents on the environment.

This becomes further sophisticated if these reactions can be

performed using inexpensive reagents.

The development of mild, low-cost and high-performance acid

catalysts has attracted much interest for green chemistry.8 In this

regard, sulfamic acid has emerged as a promising substitute for

conventional Bronsted- and Lewis acid catalysts. It is water soluble,

relatively stable, non-volatile, non-hygroscopic, and non-corrosive

and is a commercially available cheap chemical. This catalyst could

be easily recycled and reused due to its very high miscibility in water.

It has displayed an excellent activity over a vast array of acid-

catalyzed organic transformations as witnessed by numerous reports

published in the past.9 Nitrogen-containing heterocyclic molecules

are of importance as they are part of many natural products, fine

chemicals and biologically active pharmaceuticals that are vital for

enhancing the quality of life.10 Among them, heterocycles containing

a urazole [1,2,4-triazolidine-3,5-diones] moiety and its derivatives are

of interest as they exhibit a wide range of biological and clinical

applications.11 Urazole derivatives also possess anticonvulsant12 or

fungicidal activity13 as well as catalytic activity in radical polymer-

ization.14 Literature reveals a number of methods for the synthesis of

heterocycles containing urazole moiety.15,16 Despite the available

methodologies, there still exists a demand for devising a more

efficient and environmentally benign procedure which allows the

ready synthesis of urazole polycyclic systems.

In continuation of our studies aimed at devising new and greener

approaches for synthesis of nitrogen containing heterocyclic

compounds,17 we herein report a simple, convenient and eco-friendly

protocol for the preparation of triazolo[1,2-a]indazolones by one-pot,

three-component condensation of urazole, aldehydes and cyclic

b-diketones using sulfamic acid (SA) as a reusable catalyst in water

as a sole solvent (Scheme 2).

Results and discussion

Our initial efforts were focused on the search for a catalyst for the

condensation reaction between urazole, aldehydes and cyclic

b-diketones. For this purpose, representative reactions involving

urazole 1 (1 mmol), benzaldehyde 2a (1.2 mmol) and cyclohexane-

1,3-dione 3a (1 mmol) were carried out in the presence of a variety of

Bronsted- and Lewis acid-catalysts at different levels of loading in

water as a solvent at 50 uC (Scheme 1). After systematic screening,

sulfamic acid was found to be the best possible catalyst for this multi-

component reaction. Though the various catalysts progressed the

Green Chemistry Research Laboratory, Department of Chemistry,University of Delhi, Delhi 110007, India.E-mail: kidwai.chemistry@gmail.com; Fax: +91 1127666235;Tel: +91 1127666235{ Electronic supplementary information (ESI) available. See DOI:10.1039/c2ra20662e{ Presently working as Vice-chancellor (President), Jiwaji University,Gwalior (M. P.), India.

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reaction to a good extent, from the view point of performance, price,

toxicity and ease of handling, SA was found to be the best potential

candidate for carrying out this reaction. The results summarized in

Table 1 clearly indicate the essentiality as well as the high catalytic

activity of sulfamic acid to yield the desired product 4a in good yields

(82%) within a shorter reaction time (70 min). However, the

uncatalyzed reaction did not yield any product, even after 15 h

(Table 1, entry 1).

With the best catalyst in hand, we then studied the influence of

different amounts of catalyst (Table 2) and temperature on the

reaction time and yield (Fig. 1) for the model reaction. The best

catalytic activity of sulfamic acid was optimized to be at 20 mol% at

50 uC and any excess of the catalyst, beyond this proportion did not

have any significant effect on the conversion and yield of product.

Further prolongation of the reaction time and increasing the

temperature seemed ineffective for improvement of the product

yield. Thus, using the model reaction (Scheme 1) when carried out in

the presence of 20 mol% of SA in water at 50 uC, the corresponding

product 4a was obtained after 40 min in 92% yield (Table 2, Entry 6).

The present method is better in terms of yield as well as mildness of

the reaction conditions as compared to the methods reported earlier

by Bazgir et al. and Hamidian et al.16 These methods are inferior in

terms of lower yield (90%) and harshness of reaction conditions

employed.

The efficacy of our protocol was well evaluated using a wide range

of aldehydes (Scheme 2). As indicated in Table 3, it seemed that there

was no remarkable electronic effect from the substituents on

aldehyde moiety, since the aryl aldehydes with both electron-

donating and electron-withdrawing groups could be applied as

efficient candidates for the synthesis of corresponding triazolo[1,2-

a]indazolone derivatives in good yields. However, the aliphatic

aldehydes reacted slowly as compared to the aryl aldehydes and gave

low yields of the products (Table 3, entries 18–21). The present

reaction was further investigated using ketones like acetophenone,

cyclohexanone etc. as the carbonyl source in place of aldehyde but

they were ineffective and the reaction did not proceed under the

optimized reaction conditions.

The products 4(a–u) are stable solids and were characterized by

using IR, 1H NMR, 13C NMR and ESI-MS spectra and elemental

analysis data. An appropriate mechanistic rationale portraying

the probable sequence of events is indicated in Scheme 3. Firstly, it

involves the protonation of the carbonyl group of the aldehyde

2(a–o) followed by attack of the enolate form of the cyclic

b-diketone. The hydrogen ion donated by sulfamic acid helps in

the enolization of 1,3-dicarbonyl compounds to form the enolate

intermediate. Then, the formation of the heterodiene (5) takes

Scheme 1 Model reaction for the synthesis of triazole[1,2-a]indazole-

triones.

Table 1 Compared performances of various acid catalysts for the modelreactiona

Entry Catalyst (x mol%) Time (min) Yieldb (%)

1 Uncatalyzed 900 Nil2 L -proline (10) 530 Trace

3 H2NSO3H (10) 70 824 Amberlyst-15 (10) 180 765 PMA–SiO2 (2) 300 656 PMA–SiO2 (5) 280 707 PMA–SiO2 (10) 250 788 HClO4–SiO2 (2) 200 629 HClO4–SiO2 (5) 180 68

10 HClO4–SiO2 (10) 140 7811 pTSA (5) 220 5812 pTSA (10) 180 6613 pTSA (20) 150 7214 pTSA (30) 90 8015 Montmorillonite K-10 (10) 320 5516 I2 (10) 650 4817 InCl3 (30) 220 56a Reaction conditions: urazole 1 (1 mmol), benzaldehyde 2a (1.2mmol), cyclohexane-1,3-dione 3a (1 mmol); catalyst: (x mol%); temp:50 uC; solvent: water (10 ml). b Isolated yields.

Table 2 Catalytic activity evaluation of SA for the synthesis oftriazolo[1,2-a]indazole-trionesa

Entry SA (mol%) Time (min) Yieldb (%)

1 0 900 Nil2 2 280 ,303 5 200 624 10 70 825 15 60 876 20 40 927 25 35 928 30 35 92a Reaction conditions: urazole 1 (1 mmol), benzaldehyde 2a (1.2mmol), cyclohexane-1,3-dione 3a (1 mmol); catalyst: H2NSO3H(mol%); temp: 50 uC; solvent: water (10 ml). b Isolated yields.

Fig. 1 Effect of temperature on the model reaction.a

Scheme 2 Synthesis of library of triazole[1,2-a]indazole-trione derivatives.

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place by Knoevenagel condensation of enolate 3(a–b) and

aldehyde 2(a–o) in the presence of sulfamic acid. This step is

followed by subsequent Michael addition of urazole (1) to

heterodiene (5) followed by concerted cyclization via the

condensation of amino and carbonyl group of the intermediate

(6) to furnish the corresponding products 4(a–u) along with water

as the by-product. In this whole process, sulfamic acid is

regenerated and is reused for the next run.

The recycling potential of the sulfamic acid catalyst was

investigated for the model reaction (Scheme 1) at 50 uC in water

as the solvent and the results obtained are summarized in Table 4. As

sulfamic acid is insoluble in most of the common organic solvents,

upon completion of the reaction, ethyl acetate was added to extract

the product formed and the water extract containing the catalyst was

reused for consecutive reactions with fresh substrates. Furthermore,

to rule out the possibility of catalyst leaching, we also tried the

following procedure for the model reaction (Scheme 1) up to the

fourth run. After completion of the reaction, the water extract that

was left was subjected to evaporation under reduced pressure and the

solid catalyst that was recovered was weighed, which came out to be

approximately 0.1950 g, nearly 20 mol% catalyst. The experimental

results revealed that SA could be reused four times with only a slight

decrease in the yield. Loss of the weight of SA is attributed to

handling.

Experimental

General

Chemicals were purchased from Sigma-Aldrich and Sisco Research

Laboratories and were used without further purification. All

reactions and purity of triazole[1,2-a]indazole-trione derivatives were

monitored by thin-layer chromatography (TLC) using aluminium

plates coated with silica gel F254 plates (Merck) using 30% ethyl

acetate and 70% hexane as an eluent. The spots were detected either

under ultraviolet (UV) light or by placing them in an iodine

chamber. Melting points were determined in open capillary tubes

using Thomas Hoover melting point apparatus and are uncorrected.

Infrared (IR) spectra were recorded on a Perkin-Elmer FTIR-1710

spectrophotometer using nujol film. 1H and 13C nuclear magnetic

resonance (NMR) spectra were recorded on a JEOL JNM-ECX

400P FT NMR spectrometer using tetramethylsilane (TMS) as an

internal standard and the value of chemical shift values are recorded

on the d scale and coupling constants (J) values are in hertz (Hz).

Mass spectra were recorded on a Waters LCT Micromass spectro-

meter. Elemental analysis was performed on a Hereaus CHN rapid

analyzer. The temperature of the reaction mixture was measured

through a non-contact infrared mini gun thermometer (AZ minigun

type, model 8868).

General procedure for the synthesis of triazole[1,2-a]indazole-

trione derivatives

A mixture of urazole 1 (1 mmol), aldehyde RCHO 2(a–o)

(1.2 mmol), cyclic b-diketone 3a (C6H8O2) or 3b (C8H12O2) (1

mmol) and sulfamic acid (20 mol%) were stirred in water (10 ml) at

50 uC until the TLC indicated the completion of the reaction. After

the completion of the reaction, the reaction mixture was cooled to

room temperature and ethyl acetate (5 ml 6 3) was added to the

reaction mixture to extract the product. The combined organic layers

were washed with water, dried over anhydrous sodium sulphate and

concentrated under reduced pressure to obtain the neat product.

Table 3 Sulfamic acid mediated synthesis of triazole[1,2-a]indazole-trione derivativesa

S. no. R R1 4 Time (min) Yieldb (%)

1 C6H5 (2a) H (3a) 4a 40 922 4-Cl-C6H4 (2b) H 4b 45 873 4-MeO-C6H4 (2c) H 4c 40 884 4-Me-C6H4 (2d) H 4d 45 925 3-HO-C6H4 (2e) H 4e 50 906 3-NO2-C6H4 (2f) H 4f 60 887 4-NO2-C6H4 (2g) H 4g 70 908 Piperonyl (2h) H 4h 50 869 C6H5 Me (3b) 4i 40 92

10 4-Br-C6H4 (2i) Me 4j 50 9011 4-MeO-C6H4 Me 4k 45 8712 4-Me-C6H4 Me 4l 40 9113 3-HO-C6H4 Me 4m 45 9014 3-NO2-C6H4 Me 4n 50 9015 4-NO2-C6H4 Me 4o 60 8716 2-HO-C6H4 (2j) Me 4p 50 8817 2-Thienyl (2k) Me 4q 60 8518 Propyl (2l) Me 4r 90 6519 Ethyl (2m) H 4s 90 6820 Isobutyl (2n) H 4t 90 6521 Hexyl (2o) H 4u 90 62a Reaction conditions: urazole 1 (1 mmol), aldehyde 2(a–o) (1.2 mmol),cyclohexane-1,3-dione 3a or dimedone 3b (1 mmol); catalyst:H2NSO3H (20 mol%); temp: 50 uC; solvent: water (10 ml). b Isolatedyields.

Scheme 3 Suitable mechanism for the formation of triazole[1,2-a]indazole-

triones.

Table 4 Recyclability of the catalysta

No. of cyclesa Fresh Run 1 Run 2 Run 3 Run 4

Yieldb (%) 92 92 92 91 90Time (min) 40 40 40 40 40a Reaction conditions: urazole 1 (1 mmol), benzaldehyde 2a (1.2mmol), cyclohexane-1,3-dione 3a (1 mmol); catalyst: H2NSO3H (20mol%); temp: 50 uC; solvent: water (10 ml). b Isolated yields.

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Products thus obtained were subjected to purification either by

recrystallization from absolute ethanol or column chromatography

on silica gel (100–200 mesh size) using hexane–ethyl acetate in

varying proportions as eluent, which afforded the respective

triazole[1,2-a]indazole-trione derivatives, 4(a–u). All the synthesized

products were stable solids and their authenticity was established on

the basis of their spectral analysis (IR, 1H NMR, 13C NMR, ESI-

MS) and elemental analysis data. The spectral data for synthesized

compounds are listed below.

Recycling and reusability of sulfamic acid

One of the unique features of sulfamic acid is its immiscibility with

common organic solvents. Thus, upon completion of the reaction,

the product was extracted using ethyl acetate, dried over anhydrous

sodium sulphate and evaporated under reduced pressure to obtain

the product. The water extract that remained contained the sulfamic

acid catalyst which was used as such for the consecutive runs without

any appreciable loss in its catalytic activity, for up to four runs.

Spectral data for the synthesized derivatives 4(a–u)

5,6,7,9-Tetrahydro-9-(phenyl)-[1,2,4]-triazolo[1,2-a]indazole-

1,3,8(2H,5H,9H)-trione (4a). M.Pt.: 246–250 uC; IR (film, nmax

cm21): 3250, 2956, 1782, 1731, 1655; 1H NMR (CDCl3, 400 MHz): d

1.93–2.04 (m, 2H, CH2), 2.25–2.38 (m, 2H, CH2), 2.47–2.66 (m, 2H,

CH2), 6.08 (s, 1H, CH-Ar), 7.06–7.39 (m, 5H, Ar-H), 10.10 (br s, 1H,

NH); 13C NMR (CDCl3, 100 MHz): d 19.6, 27.4, 34.4, 52.7, 116.8,

126.6, 127.4, 127.7, 128.7, 136.4, 139.3, 149.8, 153.6, 192.8; ESI-MS:

282.98 (M+); Anal calcd. for C15H13N3O3: C, 63.60; H, 4.63; N,

14.83; Found: C, 63.28; H, 4.49; N, 14.66.

5,6,7,9-Tetrahydro-9-(4-chlorophenyl)-[1,2,4]-triazolo[1,2-

a]indazole-1,3,8(2H,5H,9H)-trione (4b). M.Pt.: 182–186 uC; IR

(film, nmax cm21): 3199, 2954, 1782, 1738, 1664; 1H NMR (CDCl3,

400 MHz): d 2.01–2.30 (m, 2H, CH2), 2.41–2.63 (m, 2H, CH2), 2.77–

2.92 (m, 2H, CH2), 4.70 (br s, 1H, NH), 6.00 (s, 1H, CH-Ar), 7.30–

7.94 (m, 4H, Ar-H); 13C NMR (CDCl3, 100 MHz): d 19.6, 28.3, 34.3,

52.8, 119.6, 126.5, 127.3, 129.4, 137.1, 139.4, 148.8, 150.6, 191.7; ESI-

MS: 316.97 (M+); Anal calcd. for C15H12ClN3O3: C, 56.70; H, 3.81;

N, 13.23; Found: C, 56.54; H, 3.65; N, 13.08.

5,6,7,9-Tetrahydro-9-(4-methoxyphenyl)-[1,2,4]-triazolo[1,2-

a]indazole-1,3,8(2H,5H,9H)-trione (4c). M.Pt.: 176–180 uC; IR

(film, nmax cm21): 3299, 2956, 2365, 1858, 1740, 1665; 1H NMR

(CDCl3, 400 MHz): d 1.95–2.07 (m, 2H, CH2), 2.26–2.41 (m, 2H,

CH2), 2.55–2.68 (m, 2H, CH2), 3.73 (s, 3H, OCH3), 4.75 (br s, 1H,

NH), 6.03 (s, 1H, CH-Ar), 6.73–7.22 (m, 4H, Ar-H); 13C NMR

(CDCl3, 100 MHz): d 20.3, 28.2, 37.7, 52.9, 55.8, 115.6, 118.8, 127.8,

133.6, 140.7, 149.3, 154.6, 157.9, 194.5; ESI-MS: 313.05 (M+); Anal

calcd. for C16H15N3O4: C, 61.34; H, 4.83; N, 13.41; Found: C, 61.20;

H, 4.68; N, 13.25.

5,6,7,9-Tetrahydro-9-(4-methylphenyl)-[1,2,4]-triazolo[1,2-

a]indazole-1,3,8(2H,5H,9H)-trione (4d). M.Pt.: 220–224 uC; IR

(film, nmax cm21): 3303, 2953, 1782, 1735, 1670; 1H NMR (CDCl3,

400 MHz): d 1.93–2.02 (m, 2H, CH2), 2.23 (s, 3H, CH3), 2.29–2.42

(m, 2H, CH2), 2.53–2.64 (m, 2H, CH2), 6.28 (s, 1H, CH-Ar), 6.99–

7.77 (m, 4H, Ar-H), 9.94 (br s, 1H, NH); 13C NMR (CDCl3, 100

MHz): d 20.2, 21.0, 36.9, 37.1, 116.9, 128.6, 128.8, 135.9, 141.4, 143.8,

149.8, 163.8, 196.6; ESI-MS: 297.04 (M+); Anal calcd. for

C16H15N3O3: C, 64.64; H, 5.09; N, 14.13; Found: C, 64.50; H,

4.94; N, 13.91.

5,6,7,9-Tetrahydro-9-(3-hydroxyphenyl)-[1,2,4]-triazolo[1,2-

a]indazole-1,3,8(2H,5H,9H)-trione (4e). M.Pt.: 238–240 uC; IR

(film, nmax cm21): 3327, 2917, 1768, 1719, 1685; 1H NMR (CDCl3,

400 MHz): d 1.89–2.05 (m, 2H, CH2), 2.29–2.41 (m, 2H, CH2), 2.50–

2.68 (m, 2H, CH2), 4.75 (br s, 1H, NH), 6.04 (s, 1H, CH-Ar), 7.11–

7.42 (m, 4H, Ar-H), 9.91 (br s, 1H, OH); 13C NMR (CDCl3, 100

MHz): d 19.7, 27.6, 38.8, 54.5, 114.8, 116.6, 118.3, 121.2, 127.5, 137.7,

141.8, 148.6, 153.4, 155.7, 193.6; ESI-MS: 299.0 (M+); Anal calcd. for

C15H13N3O4: C, 60.20; H, 4.38; N, 14.04; Found: C, 60.00; H, 4.16;

N, 13.90.

5,6,7,9-Tetrahydro-9-(3-nitrophenyl)-[1,2,4]-triazolo[1,2-a]inda-

zole-1,3,8(2H,5H,9H)-trione (4f). M.Pt.: 146–150 uC; IR (film, nmax

cm21): 3089, 2933, 1784, 1735, 1654; 1H NMR (CDCl3, 400 MHz): d

1.88–1.94 (m, 2H, CH2), 2.25–2.31 (m, 2H, CH2), 2.34–2.38 (m, 2H,

CH2), 6.14 (s, 1H, CH-Ar), 7.30–8.19 (m, 4H, Ar-H), 10.10 (br s, 1H,

NH); 13C NMR (CDCl3, 100 MHz): d 19.5, 26.8, 33.4, 53.8, 117.7,

120.8, 121.3, 128.6, 130.5, 136.7, 138.9, 145.4, 150.8, 154.6, 196.7;

ESI-MS: 328.03 (M+); Anal calcd. for C15H12N4O5: C 54.88; H 3.68;

N 17.07; Found: C, 54.64; H, 3.53; N, 16.92.

5,6,7,9-Tetrahydro-9-(4-nitrophenyl)-[1,2,4]-triazolo[1,2-a]inda-

zole-1,3,8(2H,5H,9H)-trione (4g). M.Pt.: 152–156 uC; IR (film,

nmax cm21): 3402, 3082, 2924, 1762, 1711, 1605; 1H NMR (CDCl3,

400 MHz): d 1.88–2.16 (m, 2H, CH2), 2.27–2.55 (m, 2H, CH2), 2.60–

2.94 (m, 2H, CH2), 4.77 (br s, 1H, NH), 6.12 (s, 1H, CH-Ar), 7.55–

8.33 (m, 4H, Ar-H); 13C NMR (CDCl3, 100 MHz): d 20.2, 28.1, 37.6,

55.4, 118.7, 122.8, 127.7, 139.2, 139.8, 144.6, 148.3, 153.7, 195.2; ESI-

MS: 328.02 (M+); Anal calcd. for C15H12N4O5: C, 54.88; H, 3.68; N,

17.07; Found: C, 54.65; H, 3.44; N, 16.87.

5,6,7,9-Tetrahydro-9-(benzo[1,3]-dioxo-5-yl)-[1,2,4]-tria-

zolo[1,2-a]indazole-1,3,8(2H,5H,9H)-trione (4h). M.Pt.: 262–266

uC; IR (film, nmax cm21): 3401, 2953, 2127, 1788, 1739, 1647; 1H

NMR (CDCl3, 400 MHz): d 1.60–1.75 (m, 2H, CH2), 1.94–2.04 (m,

2H, CH2), 2.18–2.38 (m, 2H, CH2), 5.58 (s, 1H, CH-Ar), 5.80 (s, 2H,

CH2-piperonyl), 6.26–6.75 (m, 3H, Ar-H), 8.56 (br s, 1H, NH); 13C

NMR (CDCl3, 100 MHz): d 19.3, 27.6, 36.8, 53.8, 100.2, 116.5,

118.8, 120.4, 121.3, 137.8, 140.8, 145.6, 149.8, 151.7, 156.5, 194.7;

ESI-MS: 327.03 (M+); Anal calcd. for C16H13N3O5: C, 58.72; H,

4.00; N, 12.84; Found: C, 58.60; H, 3.84; N, 12.71.

5,6,7,9-Tetrahydro-6,6-dimethyl-9-(phenyl)-[1,2,4]-triazolo[1,2-

a]indazole-1,3,8(2H,5H,9H)-trione (4i). M.Pt.: 150–154 uC; IR

(film, nmax cm21): 3200, 2958, 1781, 1735, 1596; 1H NMR (CDCl3,

400 MHz): d 1.05 (s, 3H, CH3), 1.09 (s, 3H, CH3), 2.36 (s, 2H, CH2),

2.81 (2H, AB system 2JHH = 16.9 Hz, CH2), 6.41 (s, 1H, CH-Ar),

7.14–7.65 (m, 5H, Ar-H), 10.00 (br s, 1H, NH); 13C NMR (CDCl3,

100 MHz): d 28.4, 28.7, 39.6, 53.4, 59.7, 118.7, 126.5, 127.9, 136.8,

148.7, 150.6, 154.6, 194.2; ESI-MS: 311.07 (M+); Anal calcd. for

C17H17N3O3: C, 65.58; H, 5.50; N, 13.50; Found: C, 65.43; H, 5.35;

N, 13.37.

5,6,7,9-Tetrahydro-6,6-dimethyl-9-(4-bromophenyl)-[1,2,4]-tria-

zolo[1,2-a]indazole-1,3,8(2H,5H,9H)-trione (4j). M.Pt.: 192–196 uC;

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IR (film, nmax cm21): 3016, 2962, 1765, 1701, 1648; 1H NMR (CDCl3,

400 MHz): d 0.94 (s, 6H, 2 6 CH3), 2.08 (s, 2H, CH2), 2.70 (2H, AB

system 2JHH = 19.1 Hz, CH2), 5.93 (s, 1H, CH-Ar), 6.82–7.61 (m, 4H,

Ar-H), 9.84 (br s, 1H, NH); 13C NMR (CDCl3, 100 MHz): d 27.2, 28.4,

38.7, 52.4, 60.7, 120.7, 125.2, 127.6, 128.7, 143.7, 146.1, 152.4, 156.2,

192.7; ESI-MS: 388.97 (M+); Anal calcd. for C17H16BrN3O3: C, 52.32;

H, 4.13; N, 10.77; Found: C, 52.18; H, 3.97; N, 10.62.

5,6,7,9-Tetrahydro-6,6-dimethyl-9-(4-methoxyphenyl)-[1,2,4]-

triazolo[1,2-a]indazole-1,3,8(2H,5H,9H)-trione (4k). M.Pt.: 176–

180 uC; IR (film, nmax cm21): 3015, 2931, 1895, 1697, 1599; 1H NMR

(CDCl3, 400 MHz): d 1.05 (s, 6H, 2 6 CH3), 2.41 (s, 2H, CH2), 2.86

(2H, AB system 2JHH = 21.2 Hz, CH2), 3.72 (s, 3H, OCH3), 5.45 (s,

1H, CH-Ar), 6.70–6.96 (m, 4H, Ar-H), 9.83 (br s, 1H, NH); 13C

NMR (CDCl3, 100 MHz): d 26.4, 27.3, 38.4, 53.5, 58.9, 60.3, 117.7,

119.2, 127.4, 138.1, 141.7, 148.5, 151.6, 155.4, 194.7; ESI-MS: 341.05

(M+); Anal calcd. for C18H19N3O4: C, 63.33; H, 5.61; N, 12.31;

Found: C, 63.20; H, 5.48; N, 12.17.

5,6,7,9-Tetrahydro-6,6-dimethyl-9-(4-methylphenyl)-[1,2,4]-

triazolo[1,2-a]indazole-1,3,8(2H,5H,9H)-trione (4l). M.Pt.: 170–

174 uC; IR (film, nmax cm21): 3019, 2929, 1897, 1666, 1598; 1H NMR

(CDCl3, 400 MHz): d 0.99 (s, 3H, CH3), 1.12 (s, 3H, CH3), 2.28 (s,

3H, CH3), 2.36 (s, 2H, CH2), 2.96 (2H, AB system 2JHH = 19.0 Hz,

CH2), 5.41 (s, 1H, CH-Ar), 6.88–7.22 (m, 4H, Ar-H), 9.84 (br s, 1H,

NH); 13C NMR (CDCl3, 100 MHz): d 20.6, 27.8, 28.4, 36.2, 52.8,

57.3, 118.6, 126.8, 128.2, 135.9, 140.7, 143.2, 147.5, 156.7, 196.7; ESI-

MS: 325.10 (M+); Anal calcd. for C18H19N3O3 : C, 66.45; H, 5.89; N,

12.91; Found : C, 66.31; H, 5.72; N, 12.76.

5,6,7,9-Tetrahydro-6,6-dimethyl-9-(3-hydroxyphenyl)-[1,2,4]-

triazolo[1,2-a]indazole-1,3,8(2H,5H,9H)-trione (4m). M.Pt.: 122–

126 uC; IR (film, nmax cm21): 3413, 2961, 1778, 1734, 1654; 1H NMR

(CDCl3, 400 MHz): d 0.97 (s, 3H, CH3), 1.00 (s, 3H, CH3), 2.29 (s,

2H, CH2), 2.63 (2H, AB system 2JHH = 16.2 Hz, CH2), 5.80 (s, 1H,

CH-Ar), 6.78–6.98 (m, 4H, Ar-H), 8.12 (br s, 1H, NH), 9.80 (br s,

1H, OH); 13C NMR (CDCl3, 100 MHz): d 26.5, 27.4, 34.2, 50.7,

54.7, 116.2, 117.3, 120.3, 121.5, 128.6, 139.4, 141.6, 149.7, 152.2,

158.3, 195.8; ESI-MS: 327.06 (M+); Anal calcd. for C17H17N3O4: C,

62.38; H, 5.23; N, 12.84; Found: C, 62.15; H, 5.10; N, 12.67.

5,6,7,9-Tetrahydro-6,6-dimethyl-9-(3-nitrophenyl)-[1,2,4]-tria-

zolo[1,2-a]indazole-1,3,8(2H,5H,9H)-trione (4n). M.Pt.: 134–138

uC; IR (film, nmax cm21): 3210, 2927, 1762, 1732, 1668; 1H NMR

(CDCl3, 400 MHz): d 1.09 (s, 3H, CH3), 1.25 (s, 3H, CH3), 2.42 (s,

2H, CH2), 2.83 (2H, AB system 2JHH = 17.6 Hz, CH2), 5.51 (s, 1H,

CH-Ar), 7.37–8.22 (m, 4H, Ar-H), 10.10 (br s, 1H, NH); 13C NMR

(CDCl3, 100 MHz): d 29.2, 29.7, 36.4, 53.8, 58.4, 120.8, 122.8, 124.7,

129.6, 133.8, 137.4, 142.7, 149.5, 149.8, 159.7, 194.2; ESI-MS: 356.04

(M+); Anal calcd. for C17H16N4O5: C, 57.30; H, 4.53; N, 15.72;

Found: C, 57.10; H, 4.36; N, 15.54.

5,6,7,9-Tetrahydro-6,6-dimethyl-9-(4-nitrophenyl)-[1,2,4]-tria-

zolo[1,2-a]indazole-1,3,8(2H,5H,9H)-trione (4o). M.Pt.: 224–228

uC; IR (film, nmax cm21): 3110, 2960, 1775, 1708, 1654; 1H NMR

(CDCl3, 400 MHz): d 0.97 (s, 6H, 2 6 CH3), 2.18 (s, 2H, CH2), 2.76

(2H, AB system 2JHH = 17.6 Hz, CH2), 6.10 (s, 1H, CH-Ar), 7.53–

8.15 (m, 4H, Ar-H), 10.10 (br s, 1H, NH); 13C NMR (CDCl3, 100

MHz): d 28.7, 29.3, 35.2, 52.4, 57.4, 118.8, 122.6, 129.3, 139.7, 146.7,

147.4, 150.8, 154.8, 191.6; ESI-MS: 356.05 (M+); Anal calcd. for

C17H16N4O5: C, 57.30; H, 4.53; N, 15.72; Found: C, 57.08; H, 4.37;

N, 15.58.

5,6,7,9-Tetrahydro-6,6-dimethyl-9-(2-hydroxyphenyl)-[1,2,4]-

triazolo[1,2-a]indazole-1,3,8(2H,5H,9H)-trione (4p). M.Pt.: 110–

114 uC; IR (film, nmax cm21): 3064, 2958, 1764, 1712, 1643; 1H NMR

(CDCl3, 400 MHz): d 1.00 (s, 3H, CH3), 1.10 (s, 3H, CH3), 2.30 (s,

2H, CH2), 2.51 (2H, AB system 2JHH = 17.6 Hz, CH2), 4.64 (br s,

1H, NH), 6.02 (s, 1H, CH-Ar), 6.89–7.54 (m, 4H, Ar-H), 10.46 (br s,

1H, OH); 13C NMR (CDCl3, 100 MHz): d 27.4, 28.2, 37.9, 51.8,

53.3, 116.7, 117.4, 121.8, 126.4, 126.8, 128.7, 129.2, 138.4, 149.9,

153.6, 192.7; ESI-MS: 327.05 (M+); Anal calcd. for C17H17N3O4: C,

62.38; H, 5.23; N, 12.84; Found: C, 62.21; H, 5.10; N, 12.70.

5,6,7,9-Tetrahydro-6,6-dimethyl-9-(2-thienyl)-[1,2,4]-tria-

zolo[1,2-a]indazole-1,3,8(2H,5H,9H)-trione (4q). M.Pt.: 136–140 uC;

IR (film, nmax cm21): 3086, 2959, 1786, 1732, 1668; 1H NMR

(CDCl3, 400 MHz): d 0.95 (s, 6H, 2 6 CH3), 2.35 (s, 2H, CH2),

2.92 (2H, AB system 2JHH = 16.9 Hz, CH2), 6.26 (s, 1H, CH-

Ar), 6.68–7.11 (m, 3H, Ar-H), 9.81 (br s, 1H, NH); 13C NMR

(CDCl3, 100 MHz): d 26.5, 27.3, 35.7, 49.2, 54.8, 118.6, 120.2,

126.7, 127.2, 137.4, 140.8, 147.8, 153.6, 193.8; ESI-MS: 316.98

(M+); Anal calcd. for C15H15N3O3S: C, 56.77; H, 4.76; N, 13.24;

Found: C, 56.58; H, 4.62; N, 13.06.

5,6,7,9-Tetrahydro-6,6-dimethyl-9-(propyl)-[1,2,4]-triazolo[1,2-

a]indazole-1,3,8(2H,5H,9H)-trione (4r). M.Pt.: 184–186 uC; IR

(film, nmax cm21): 3196, 2959, 2734, 1725, 1601; 1H NMR (CDCl3,

400 MHz): d 0.86 (t, 3H, *CH3CH2), 0.99 (s, 6H, 2 6 CH3), 1.29 (m,

2H, *CH2CH3), 2.16 (m, 2H, CH*CH2CH2), 2.46 (s, 2H, CH2), 2.94

(2H, AB system 2JHH = 17.8 Hz, CH2), 5.28 (m, 1H, CHN), 8.20 (br

s, 1H, NH); 13C NMR (CDCl3, 100 MHz): d 15.3, 17.8, 26.8, 27.4,

31.2, 36.4, 39.4, 52.7, 121.8, 140.8, 151.7, 156.4, 195.8; ESI-MS:

277.08 (M+); Anal calcd. for C14H19N3O3: C, 60.63; H, 6.91; N,

15.15; Found: C, 60.46; H, 6.73; N, 14.98.

5,6,7,9-Tetrahydro-9-(ethyl)-[1,2,4]-triazolo[1,2-a]indazole-

1,3,8(2H,5H,9H)-trione (4s). M.Pt.: 132–134 uC; IR (film, nmax

cm21): 3206, 2962, 2737, 1714, 1667; 1H NMR (CDCl3, 400 MHz): d

0.56 (t, 3H, *CH3CH2), 1.39–1.45 (m, 2H, *CH2CH3), 1.92–2.00 (m,

2H, CH2), 2.23–2.30 (m, 2H, CH2), 2.37–2.48 (m, 2H, CH2), 4.76 (m,

1H, CHN), 6.12 (br s, 1H, NH); 13C NMR (CDCl3, 100 MHz): d

11.2, 20.8, 22.3, 33.4, 38.4, 46.7, 11.6, 139.8, 147.2, 152.2, 193.6; ESI-

MS: 235.03 (M+); Anal calcd. for C11H13N3O3: C, 56.16; H, 5.57; N,

17.86; Found: C, 56.03; H, 5.42; N, 17.70.

5,6,7,9-Tetrahydro-9-(isobutyl)-[1,2,4]-triazolo[1,2-a]indazole-

1,3,8(2H,5H,9H)-trione (4t). M.Pt.: 120–124 uC; IR (film, nmax

cm21): 3276, 3192, 2952, 1734, 1622; 1H NMR (CDCl3, 400 MHz): d

0.85 (d, 6H, 2 6 CH3), 1.22 (m, 2H, CH-CH2), 1.65 (m, 1H,

CH(CH3)2), 1.94–2.02 (m, 2H, CH2), 2.42–2.46 (m, 2H, CH2), 2.48–2.52

(m, 2H, CH2), 4.08 (m, 1H, CHN), 7.78 (br s, 1H, NH); 13C NMR

(CDCl3, 100 MHz): d 18.6, 22.7, 24.2, 31.8, 40.6, 44.5, 49.3, 119.6, 138.6,

148.6, 152.4, 192.7; ESI-MS: 263.06 (M+); Anal calcd. for C13H17N3O3:

C, 59.30; H, 6.51; N, 15.96; Found: C, 59.13; H, 6.36; N, 15.80.

5,6,7,9-Tetrahydro-9-(hexyl)-[1,2,4]-triazolo[1,2-a]indazole-

1,3,8(2H,5H,9H)-trione (4u). M.Pt.: 166–168 uC; IR (film, nmax

7664 | RSC Adv., 2012, 2, 7660–7665 This journal is � The Royal Society of Chemistry 2012

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cm21): 3086, 2959, 1786, 1732, 1668; 1H NMR (CDCl3, 400 MHz): d

0.76 (t, 3H, *CH3CH2), 1.36 (m, 2H, *CH2CH3), 1.68 (m, 2H, CH-

*CH2–CH2), 1.84 (m, 6H, 3 6 CH2), 1.92–1.98 (m, 2H, CH2), 2.23–

2.30 (m, 2H, CH2), 2.37–2.44 (m, 2H, CH2), 6.38 (m, 1H, CHN),

8.33 (br s, 1H, NH); 13C NMR (CDCl3, 100 MHz): d 14.8, 19.2, 24.7,

25.2, 28.7, 29.6, 31.8, 33.2, 38.4, 49.6, 119.7, 137.8, 146.6, 151.8,

192.7; ESI-MS: 291.10 (M+); Anal calcd. for C15H21N3O3: C, 61.84;

H, 7.27; N, 14.42; Found: C, 61.52; H, 7.12; N, 14.28.

Conclusion

In summary, we have developed a green and efficient multi-

component reaction protocol for the synthesis of triazolo[1,2-

a]indazolones using sulfamic acid as a recyclable and cost-effective

catalyst. Simple work up procedure, general applicability, ambient

conditions and use of water as a reaction medium makes this

protocol eco-friendly and distinctly superior to many other methods

reported earlier. Moreover, it is noteworthy to mention that the

catalyst could be reused for the four successive runs without any

significant change in its activity.

Acknowledgements

Author (R. Chauhan) thanks UGC (University Grants

Commission) for providing a Junior Research Fellowship and

also to the Director of University Science and Instrumentation

Centre, University of Delhi, Delhi for providing the instrumen-

tation facilities.

References

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This journal is � The Royal Society of Chemistry 2012 RSC Adv., 2012, 2, 7660–7665 | 7665

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