www.elsevier.com/locate/catcom
a
Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran
b
Department of Chemistry, School of Sciences, Payame nour University, Delijan, Iran
c
Department of Chemistry, Islamic Azad University – Mashhad Branch, Mashhad, Iran
Received 18 June 2006; received in revised form 12 December 2006; accepted 12 December 2006
Available online 21 December 2006
Abstract
1566-7367/$ - see front matter 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2006.12.012
1468 M.M. Heravi et al. / Catalysis Communications 8 (2007) 1467–1471
in solution [8]. They are used as industrial catalysts for sev- The product was dissolved in warm water and upon cooling
eral liquid-phase reactions such as esterification, etherifica- to room temperature yellow crystals formed. Acidic form of
tion, hydration and dehydration, de-esterification, and molybdenum substituted heteropolyacid was prepared by
condensation reactions [9–20]. passage of a solution of the potassium salt in water through
Herein we present synthesis of some derivatives of a column (50 · 1 cm) of Dowex 50 w · 8 in the H+ form and
1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones 4 that are impor- evaporation of the elute to dryness under vacuum.
tant in medicine, by a Keggin-type, H3[PMo12O40] and a IR (cm 1): 1165(vs), 1085(s), 1060(m), 960(vs), 920(vs),
Preyssler-type, H14[NaP5W29MoO110] heteropolyacids as 700–800(b).
solid acid catalysts. Our findings indicate that both HPA These catalysts fully characterized in the literature
catalysts are effective for synthesis of 1H-pyrazolo[3,4- [21,22].
d]pyrimidin-4(5H)-ones with high yields.
The major aim described in this work is the design and 2.2. General procedure for the synthesis 6-substituted-
development of applications for HPAs with exclusive prop- pyrazolo[3,4-d]pyrimidin-4(5H)-ones(4a–n)
erties surpassing the mineral acids in synthesis of heterocy-
clic systems. A solution of 1 (0.9 mmol) and appropriate aromatic
aldehyde 2 (0.9 mmol) and an appropriate heteropolyacid
2. Experimental (0.04 mmol) in acetic acid (10 mL) was refluxed for 1 h.
The catalyst was removed by filtering and washed with
2.1. Catalyst preparation warmed acetic acid (the catalyst is not soluble in acetic
acid). The catalyst was washed with diethyl ether after fil-
H3PMo12O40 was prepared as follows: To 420 mL of a tration. It could be reused and subjected to a second run
2.85 M aqueous solution of Na2Mo4 were added succes- of reaction. The yields of products were almost identical
sively 6.8 mL of 85% H3PO4 and 284 mL of 70% HClO4. to yields obtained by using fresh catalyst. The filtrate was
The disodium salt precipitated from the yellow solution. cooled and the solid was filtered, washed with water, dried
After filtering the mixture, the obtained powder was air- and re-crystalized from ethanol to give pure product 4
dried. Recrystallization in a mixture of Et2O/H2O gave (Table 1). All compounds were characterized by mass, IR
greenish microcrystals. An aqueous solution of the greenish and 1H NMR spectra (Table 2).
microcrystals, acidified by HCl, and extracted by Et2O. To
heavy layer, was added water and yellow crystals of 3. Result and discussions
H3PMo12O40 precipitated.
IR (cm 1): 1067(s), 975(sh), 963(vs), 870(s), 810(sh), Recently, we described synthesis of some new derivatives
785(vs), 593(w). of 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones 4 by HPAs
H14[NaP5W29MoO110] was prepared as follow: 2.8 g including W such as H3[PW12O40] and H14[NaP5W30O110]
(0.169 mol) Na2WO4 Æ 2H2O and 2 g (0.008 mol) as acidic catalysts instead of mineral acids like HCl
Na2MoO4 Æ 2H2O were dissolved in 35 mL water and mixed or polyphosphoric acid as a more eco-friendly and suitable
at 60 C for 30 min. Then this solution was cooled to room method [23]. Therefore, it is great interest to know,
temperature, and 25 mL concentrated phosphoric acid was what occurs if the other HPAs have been used in these
added. The resulted yellow solution was refluxed for 18 h. reactions.
The solution was brought to room temperature, diluted In continuation with our works using heteropolyacids
with water and then during stirring, 10 g KCl was added. [24] which are low in toxicity, highly stable towards humid-
The mixture was stirred and then heated up to dryness. ity, being recyclable, air stable, and very important in green
Table 1
Catalytic synthesis of 6-substituted-pyrazolo[3,4-d]pyrimidin-4(5H)-ones 4
Compound R R1 Reaction time (min) Yield (%) using H3[PMo12O40] Yield (%) using H14[NaP5W29MoO110] Mp (C) [23]
4a CH3 Ph 60 70 92 300–301
4b CH3 4-MeC6H4 60 76 98 275–277
4c CH3 3-MeC6H4 60 79 85 279–281
4d CH3 4-NO2C6H4 60 76 96 308–310
4e CH3 3-NO2C6H4 60 76 95 293–295
4f CH3 4-ClC6H4 60 88 98 316–318
4g CH3 4-BrC6H4 60 76 91 310–311
4h H Ph 60 73 90 288–290
4i H 4-MeC6H4 60 76 83 253–255
4j H 3-MeC6H4 60 88 86 262–264
4k H 4-NO2C6H4 60 75 94 278–280
4l H 3-NO2C6H4 60 74 94 285–287
4m H 4-ClC6H4 60 73 88 235–237
4n H 4-BrC6H4 60 91 84 338–340
M.M. Heravi et al. / Catalysis Communications 8 (2007) 1467–1471 1469
Table 2
H1 NMR, mass and IR Spectral data for 4
Compound m/z IR Vmax cm 1
H1 NMR d(ppm)
(KBr)
4a 302(M+) 3308(NH), (CDCl3), 3.05(3H, s, CH3), 7.2–7.6(5H, m, Ph), 7.6–7.8(5H, m, Ph), 10.6(1H, bs, NH)
1692(C@O)
4b 316(M+) 3470(NH), (DMSO), 3.06(3H, s, CH3), 2.45(3H, s, CH3), 7.25(2H, d, J = 11.7, Ar), 7.36(2H, d, J = 11.7,
1655(C@O) Ar), 7.5–7.7(5H, m, Ph), 10.2(1H, s, NH)
4c 316(M+) 3447(NH), (DMSO), 3.06(3H, s, CH3), 2.47(3H, s, CH3), 7.4–7.8(9H, m, Ph), 10.83(1H, s, NH)
1683(C@O)
4d 348(M+ + H+) 3266(NH), (DMSO), 3.1(3H, s, CH3), 7.3–7.67(5H, m, Ph), 8.25(2H, d, J = 10.2, Ph), 8.35(2H, d, J = 10.2,
1680(C@O) Ph), 11.02(1H, bs, NH)
4e 347(M+) 3177(NH), (DMSO), 3.12(3H, s, CH3), 7.3–7.69(5H, m, Ph), 8.01–8.21(4H,m, Ph), 11.04(1H, bs, NH)
1689(C@O)
4f 336(M+), 3459(NH), (DMSO), 3.08(3H, s, CH3), 7.3–7.7(5H, m, Ph), 7.89(2H, d, J = 8.5, Ph), 8.06(2H, d, J = 8.5,
338(M+ + 2) 1691(C@O) Ph), 11.9(1H, bs, NH)
4g 380(M+), 3389(NH), (DMSO), 3.06(3H, s, CH3), 7.34–7.68(5H, m, Ph), 7.80(2H, d, J = 7.5, Ph), 7.9(2H, d, J = 7.5,
382(M+ + 2) 1697(C@O) Ph), 11.5(1H, s, NH)
4h 288(M+) 3240(NH), (DMSO), 7.4–7.6(5H, m, Ph), 7.65–7.83(5H, m, Ph), 8.23(1H, s, C3H), 12.5(1H, bs, NH)
1723(C@O)
4i 302(M+) 3447(NH), (DMSO), 2.45(3H, s, CH3), 7.30(2H, d, J = 11.9, Ar), 7.48(2H, d, J = 11.9, Ar), 7.6–7.8(5H, m,
1655(C@O) Ph), 8.02(1H, s, C3H), 11.8(1H, s, NH)
4j 302(M+) 3325(NH), (DMSO), 2.48(3H, s, CH3), 7.5–7.8(9H, m, Ph), 8.0(1H, s, C3H), 11.2(1H, s, NH)
1641(C@O)
4k 333(M+) 3323(NH), (DMSO), 7.3–7.7(5H, m, Ph), 8.3(1H, s, C3H), 8.35 (2H, d, J = 10.2, Ph), 8.4(2H, d, J = 10.2,
1692(C@O) Ph), 11.1 (1H, bs, NH)
4l 333(M+) 3442(NH), (CDCl3), 7.3–7.8(5H, m, Ph), 8.1–8.3(5H, m, Ph, C3H), 11.02(1H, bs, NH)
1690(C@O)
4m 322(M+), 3322(NH), (DMSO), 7.3–7.6(5H, m, Ph), 8.1(2H, d, J = 8.6, Ar), 8.2(2H, d, J = 8.6, Ar), 8.23(1H, s, C3H),
324(M+ + 2) 1697(C@O) 11.8(1H, s, NH)
4n 366(M+), 3399(NH), (DMSO), 7.35–7.7(5H, m, Ph), 7.85(2H, d, J = 7.6, Ar), 7.96(2H, d, J = 7.6, Ar), 8.20(1H, s,
368(M+ + 2) 1707(C@O) C3H), 11.7(1H, s, NH)
chemistry, we studied this reaction with heteropolyacid tungsten (VI) ion by Mo (VI). Interestingly, these catalysts,
catalysts including Mo, such as H3[PMo12O40] and not only catalyzed this reaction, but also showed higher
H14[NaP5W29MoO110]. yields than the H3[PW12O40] and H14[NaP5W30O110] in
When the mixture of 5-amino-1-phenyl-1H-pyrazolo-4- our earlier work (55–87% yields) [23]. In study of reaction
carboxamide 1 and aromatic aldehyde 2 in acetic acid were progress with TLC, we found that conversion rates were
refluxed in the presence of catalytic amounts of mentioned affected by catalyst structure. In all cases the conversion
heteropolyacids for 1 h, 6-aryl-1H-pyrazolo[3,4-d]pyrimi- rates was higher with H14-P5Mo. This result is agreement
din-4[5H]-ones 4 were obtained (Scheme 1). No other by with expectation and earlier works on Biginelli reaction
products was recognized. In spite of obtaining good to [24a,24b].
moderate yields of products, we believe that the selectivity In acid-catalyzed reactions by heteropolyacids, several
towards obtained 6-aryl-1H-pyrazolo[3,4-d]pyrimidin- types of acid sites are present [25–28]. They are including:
4[5H]-ones remains 100% in all cases. On TLC only one proton sites in bulk heteropolyacids, Lewis acid sites in
spot, for the assigned products are observed and few other salts of them (metal counteractions), proton sites in acidic
inseparable minor spots are assumed impurities. The salts, proton sites generated by dissociation of coordinated
results are shown in Table 1. Mixed addenda Preyssler water and reduction of salts, and proton generated by par-
and Keggin catalysts are formed by the substitution of tial hydrolysis of polyanions. Generally reactions catalyzed
by heteropolyacids may be represented by the conventional
mechanisms of Bronsted acid catalysis. The mechanism
O O may include the protonation of the substrate followed by
R
R the conversion of the ionic intermediate to yield the reac-
NH2
NH tion product [27,28].
+ R1CHO N Misono and co-workers advanced two types of catalysis
N 2a-g
N
NH2 N
N R1
for heterogeneous acid catalysis by heteropolyacids as sur-
Ph
face type and bulk type [25,26]. In surface type catalysis,
Ph 4 the reactions occur on the surface of bulk or supported het-
R=CH3 1a eropoly compounds and the catalytic activity usually
R=H 1b
depends on the surface acidity of heteropolyacid. In this
Scheme 1. case, the reaction rate and yield is parallel to the number
1470 M.M. Heravi et al. / Catalysis Communications 8 (2007) 1467–1471
Yield %
50
3-MeC6H4
lytic reaction. Due to the flexible nature of the solid struc- 40 4-ClC6H4
ture of some heteropolyacids, reactant molecules having 30
4-BrC6H4
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