7th International Electronic Conference on Synthetic Organic Chemistry (ECSOC-7), http://www.mdpi.net/ecsoc-7, 1-30 November 2003
[A033]
3-Formylchromones II.
♠A Simple Facile Route to Novel Pyrazolo[3,4-b]pyridines
Margita Lacova*1, Agnieszka Puchala2, Eva Solcanyova3, Jan Lac Jr.4, Pavol Kois1, Jarmila Chovancova1, Henrieta Stankovicová3 and Danuta Rasala2
1
Department of Organic Chemistry, 3Institute of Chemistry, Fac. of Natural Sciences, Comenius University, SK-842 15 Bratislava, Slovakia;2
Institute of Chemistry, Swietokrzyska Academy, Checinska 5, PL-25020 Kielce, Poland,4
European Media Laboratory Research, Villa-Bosch, Schloss-Wolfsbrunnenweg 33, D-69118, Heidelberg, Germany,*
Corresponding author: lacova@fns.uniba.sk #9; Tel. +421 2 60296-338Abstract:
We found a simple, one pot and facile route to 17-hydroxy-5-methyl-7-phenyl-3-phenyloxopyrazolo[3,4-b]pyridine derivatives 4a-e from 3-formylchromones 1a-e with 3-amino-N-phenylpyrazole 2 in ethanol. Intermediate 3 was isolated at low temperature (-15 oC). We found the new way to 3- and 4-substituted coumarine derivatives 6 by the condensation of compounds 4 with R-acetic acids. Acylation reaction of 4 formed 17-acyloxy-derivatives of pyrazolo[5,6-b]pyridines 5. At elevated temperature pyrazolo[5,6-b]pyridines 4 with 2,4dinitrophenyl hydrazine formed hydrazones 7. Synthesis under microwave irradiation was found to proceed significantly faster with high yields of pure products.Keywords:
3-formylchromone, coumarine, chromene, pyrazole, rearrangement, enamine, microwave irradiation
Introduction
Important role of 3-formylchromones 1 as versatile synthons in heterocyclic chemistry as well as their pharmaceutical importance is well known1-4. These compounds also have interesting photochemical properties5. In general, 3-formylchromones 1 readily react with primary amines in alcoholic medium yielding enamine-aduct which rarely continue to change into Schiff bases1,2.
The relevant theoretical and kinetic studies of the reaction paths9 of some chromone derivatives with amines we published elsewhere6-10. Microwave irradiation study of condensation reaction of various 3-formylchromones we also reported11,12.
In this article we report on a very convenient, smooth, one-pot method for the preparation of 17-hydroxy-5-methyl-7-phenyl-3-phenyloxopyrazolo[3,4-b]pyridine derivatives 4a-e. Reactions were performed under classical as well as microwave irradiation conditions.
Results and Discussion
Pyrazolo[3,4-b]pyridine derivatives 4a-e were obtained by refluxing of equimolar mixture of 3-formylchromones 1 and 3-amino-N-phenylpyrazole 2 in ethanol using the p-toluensulfonic acid as catalyst. The adduct - stable yellow enamine intermediate 3 - was isolated from the reaction mixture at low temperature (-15ºC), which after prolonged refluxing quickly changed into the final product 4. Synthesis under microwave irradiation proceeded significantly faster and offered clean products in high yields (Scheme 1.).
Scheme 1.
4a (R = H) 4b (R = Br) 4c (R = Cl) 4d (R = F) 4e (R = CH3)Ethanol as a solvent was found most suitable for the synthesis of compounds 4. Dioxan or toluene could be also used, but the reaction in ethanol is faster,with higher yields of better purity products.
The structure of compounds 4 was confirmed by 1H and 13C NMR spectra. The assignment of the 1H chemical shifts was deduced from the signal multiplicities and from the HH COSY spectra. The appropriate assignment of the 13C chemical shifts was based on the HMQC spectra for the C-H carbons and that of the quarternary carbons from the coupled 13C spectrum (compound R1=H, 4a).
All the NMR spectra indicate that the product of the reaction contains the pyridine ring. This conclusion is based on the observation of typical pyridine-ring shift values of 8.96(H-2) and of 8.46(H-4) respectively, and of their coupling constant J(2,4)=1.1Hz (compound R1=H). The presence of the doublet-doublets signal in 13C coupled spectrum at 151.5 Hz (C-4a), with the coupling constants 3J(C,H-2) = 13.4 Hz and 3J(C,H-4) = 6.8 Hz confirms that the pyrazole ring is connected with the pyridine ring in(3,4-b) position.
The final products 4 as bifunctional compounds are usefull in the synthesis of acyl- 5, or coumarine- 6 derivatives. Compounds 5 were prepared from the compound 4e by acylation with acylchlorides or acetylanhydride.
Very simple and successful deacylation proces of compounds 5 to 4 was achieved by an 1 hour reflux of 5 with formamide (Scheme2).
Scheme 2.
Keto-groups of compounds 4, 5 easily react with 2,4-dinitrophenylhydrazine to form hydrazones ( Scheme 3.).
Identity of compounds 5, 6 and 7 were also confirmed by the microanalyses and the 1HNMR spectra.
Scheme 3.
Experimental part
Melting points (uncorrected) of the synthesized compounds were determined on the Kofler block. The microanalyses (Carlo Erba Instrumentazione 1106) were in satisfactory agreement with the calculated values (the results for C, H, and N show an agreement within 0.30%).
Microwave assisted reactions were carried out in a Lavis–1000 MultiQuant microwave oven. The apparatus was adapted for laboratory application with magnetic stirring and an external reflux condenser.
1
H NMR spectra were measured at 300MHz, 13C NMR spectra at 75MHz in CDCl3 on a Varian Gemini 2000 spectrometer. The HHCOSY and HMQC analyses were performed using the manufacturer’s software. Chemical shifts are given in -scale, coupling constants in Hz. TMS was used as an internal standard2-Ethyloxy-6-methyl-3-(1-phenyl-3-methyl-5-pyrazolylaminomethylene) chroman-4-one (
enamine derivative) 3aThe equimolar mixture of 3-formylchromones 1 (20 mmol ) and 3-amino-N-phenylpyrazole 2 (20 mmol) in 30 ml of ethanol with 6 mg of 4-toluenesulfonic acid resulted in a yellow solid intermediate 3 after intensive stirring for 20 minutes at the low temperature (–15 C). The adduct must be removed quickly by sucking away the solvent and then washed with cold ethanol to eliminate catalyst. The residue was dried in vacuum at room temperature, yield about 40%.
Melting point is 162 - 164 C .
1
HNMR ( CDCl3): 1.24t, 3H (CH3); 2.17s, 3H (CH3), 2.49s, 3H (CH3); 3.71q, 2H (CH2); 6.25s, 1H. H-2; 7.37- 7.42m, 3H, H-18,19,20; 7.52dd ,2H , 3J =8.4 Hz, 4J =2 Hz,H-17,21; 7.56d ,1H , 3J =8.4 Hz,H-8; 7.65dd ,1H , 3J =8.4 Hz, 4J =2 Hz,H-7; 7.67d,1H , 4J =2 Hz,H-5; 8.08s, 1H,H-10; 8.67s, 1H,H-12; 8.99s ,1H,H-9;Preparation of pyrazolo[3,4-b]pyridine derivatives 4a-e
Classical condition
The mixture of equimolar amounts of 3-formylchromones (20 mmol ) and 3-amino-N-phenylpyrazole (20 mmol) in 30 ml of ethanol with 6 mg of 4-toluenesulfonic acid was refluxed for 2 hours. The pale-yellow crystal product was isolated and recrystallized from ethanol to give pure product in about 85% yield.
Microwave procedure
The mixture as above was irradiated at 800 W. To find an optimal conditions the irradiation time was varied between 6 and 10 minutes. The solid compounds were filtered off and recrystallized from ethanol. to obtain pure product in 90% yield.
17-hydroxy-5-methyl-7-phenyl-3-phenyloxopyrazolo[3,4-b]pyridine 4a
Melting point: 120 -121º C; Elemental analysis for C20H15N3O2; MW:329.4;
Calc.72.94 %C; 4.59 %H, 12.76%N; Found 73.12 %C; 4.54 %H, 12.87 %N;
1
H NMR(CDCl3):2.71s, 3H(H-8); 6.94ddd, 1H, J(20,21) = 8.0, J(19,20) = 8.2, J(18,20) = 1.1(H-20);7.13dd, 1H, J(18,19) = 8.2, J(18,20) = 1.1(H-18); 7.34tt, 1H, J(11,12) = 7.5, 3J(10,12) = 1.1(H-12); 7.55t, 2H, J(10,11) = J(11,12) = 7.5(H-11,13); 7.57td, 1H, J(18,19) = J(19,20) = 8.2, J(19,21) = 1.4(H-19); 7.63dd, 1H, J(20,21) = 8.0, J(19,21) = 1.4(H-21); 8.26dd, 2H, J(10,11) = 7.5, J(10,12)=1.1(H-10), 8.46d,1H, J(2,4) = 2.1(H-4); 8.96d, 1H, J(2,4)=2.1(H-4); 11.86s, 1H(OH).
13
C NMR:12.73q, J(C,H)=127.9(C-8); 116.57q, 3J(C,H)=2.9(C-4a); 118.98dt, J(C,H)=162.3, 3J(C,H)=7.3 (C-18); 119.23dd, J(C,H)=163.6, 3J(C,H)=9.2(C-20); 119.59dt, 3J(C,H)=4.7, 3J(C,H)=7.6(C-16); 121.45dt, J(C,H)=161.6, 3J(C,H)=7.5(C-10); 126.55dt, J(C,H)=162.9, 3J(C,H)=7.6(C-12); 127.54d, 3J(C,H-4)=8.0(C-3); 129.41dd, J(C,H)=161.5, 3J(C,H) = 8.3(C-11); 131.87dd, J(C,H)=166.1, 3J(C,H)=6.0(C-9); 133.27dd,J(C,H)=160.2, 3J(C,H)=9.0(C-21); 136.85dd, J(C,H)=159.8, 3J(C,H)=9.2(C-19); 139.24t, 3J(C,H)=8.0(C-9);144.50qd, 2J(C,H)=7.1, 3J(C,H)=2.5(C-5); 150.30dd, J(C,H)=183.3, 3J(C,H)=5.5(C-2); 151.54dd, 3J(C,H-2)=13.4, 3J(C,H-4)=6.8(C-7a); 163.43 dd, 3J(C,H) 7.5,6.8(C-17), 199.11 t, 3J(C,H) = 4.4(15).17-hydroxy-20-bromo 5 -methyl-7-phenyl-3-phenyloxopyrazolo[3,4-b]pyridine 4b
Melting point: 161 -162, Elemental analysis for C20H14 BrN3O2; MW:408.4;
Calc.58.82 %C; 3.43 %H, 10.21%N; Found :58.62 %C; 3.21 %H, 10.01%N;
1
H NMR: 2.73 s, 3H(H-8); 7.05d, 1H, J(18,19) = 8.8(H-18); 7.38 t, 1H, J(11,12) = 7.7(H-12);7.56 t, 2H, J(10,11) = J(11,13) = 7.7(H-13, 15); 7.64dd, 2H, J(18,19) = 8.8, J(19,21) = 2.5 (H-19,21);8.25d, 2H, J(10,11) = 7.7(H-10,14); 8.46 d, 1H, J(2,4) = 1.9(H-4); 8.94d, 1H, J(2,4) = 1.9(H-4);11.75s, 1H(OH).17-hydroxy-20-chloro-5-methyl-7-phenyl-3-phenyloxopyrazolo[3,4-b]pyridine 4c
Melting point: 160 - 162 C, Elemental analysis for C20H14ClN3O2; MW:363.2; Calc.65.97 %C; 3.84 %H, 11.54%N; 9.74%Cl, Found 66.22 %C; 3.88 %H, 11.34%N; 9.70%Cl
1
H NMR:2.73s, 3H(H-8); 7.10d, 1H, J(18,19)=9.0(H-18); 7.35t, 1H, J(11,12)=7.7(H-12); 7.51dd, 1H, J(18,19)=9, J(19,21)=2.5(H-19); 7.56t, 2H, J(10,11)=J(11,12)=7.7(H-11,13); 7.60d, 1H, J(19,21)=2.5(H-21); 8.25dd, 2H, J(10,11)=7.7, J(10,12)=1.1(H-10,14); 8.47d, 1H,J(2,4)=2.1(H-4); 8.95d, 1H, J(2,4)=2.1(H-2); 11.74s, 1H(OH).17-hydroxy-20-fluoro-5-methyl-7-phenyl-3-phenyloxopyrazolo[3,4-b]pyridine 4d
Melting point 155 - 156 C, C20H14FN3O2; MW:339.4;
1
H NMR:2.72s, 3H(H-8); 7.10dd, 1H, J(20,21)=10.2, 4J(20,F)=4.4(H-18); 7.2-7.4m, 3H(H-19,H-21,H-12); 7.55t, 2H, J(10,11)=J(11,12)=8.0; 8.25d, 2H, J(10,11)=8.0(H-10,14);8.45d, 1H, J( 2,4)=1.9(H-4); 8.95d, 1H, J(2,4)=1.9(H-2); 11.57s, 1H(OH).17-hydroxy-5,20-dimethyl-7-phenyl-3-phenyloxopyrazolo[3,4-b]pyridine 4e
Melting point: 125-127 C, Elemental analysis for C21H17N3O2; MW:343.4;
Calc.73.38 %C; 4.99 %H, 12.23%N; Found 73.26 %C; 5.09 %H, 12.28%N;
1
H NMR:2.28s, 3H(CH3 on C-20); 2.72s, 3H(H-8); 7.04d, 1H, J(18,19)=7.7(H-18); 7.34tt, 1H, J(11.12)=7.6, J(10,12)=1.1(H-12); 7.38dd, 1H, J(18,19)=7.7, J(19,21)=0.8(H-19); 7.39d,1H, J(19,21)=0.8(H-21); 7.55t, 2H, J(10,11)=7.6(H-11,13); 8.26dd, 2H, J(10,11)=7.6, J(10,12)=1.1(H-10,14); 8.47d, 1H, J(2,4)=1.9(H-4); 8.94d, 1H, J(2,4)=1.9(H-2).Preparation of compounds 5 (
acylation)Procedure for 5a,5b
3-Phenyloxopyrazolo[5,6-b]pyridine derivative (2mmol), anhydrous acetanhydride (10 ml) and freshly melted sodium acetate (2mmol) was stirred at 60 oC for 3 hours. Then the acetanhydride was removed in vacuum and the residuum was recrystalized from acetone or chloroform. The pure crystal products were obtained in 70% yields.
17-Acetyloxy-5 -methyl-7-phenyl-3-phenyloxopyrazolo[3,4-b]pyridine 5a
Melting point: 125-127 C, Elemental analysis for C21H17N3O2; MW:343.4;
Calc.73.38 %C; 4.99 %H, 12.23%N; Found 73.26 %C; 5.09 %H, 12.28%N;
1
H NMR:(CDCl3)1.99s, 3H(CH3CO); 2.40s, 3H,CH3; 2.67s, 3H CH3; 7.11d, 1H,3J=8.3(H-19); 7.30dd, 1H, 3J=7.3, 4J=2.1(H-18); 7.35d, 1H, 4J=2.2 H-16; 7.39m, 1H, H-11); 7.55t, 2H, 3J=7.6,H-10,12); 8.23dd, 2H, 3J=7.6, 4J=1.1,H-9,13; 8.49d, 1H, 4J(2,4)=1.9,H-4; .9.04d, 1H, 4J=1.9,H-2).17-Acetyloxy-5,20-dimethyl-7-phenyl-3-phenyloxopyrazolo[3,4-b]pyridine 5b
Melting point: 108- 110 o C, Elemental analysis for C21H17N3O2; MW:343.4;
Calc.73.38 %C; 4.99 %H, 12.23%N; Found 73.26 %C; 5.09 %H, 12.28%N;
1
H NMR:(CDCl3)1.99s, 3H(CH3CO); 2.40s, 3H,CH3; 2.67s, 3H CH3; 7.11d, 1H,3J=8.3(H-19); 7.30dd, 1H,3J=7.3, 4J=2.1(H-18); 7.35d, 1H, 4J=2.2 H-16; 7.39m, 1H, H-11); 7.55t, 2H, 3J=7.6,H-10,12); 8.23dd, 2H, 3J=7.6, 4J=1.1,H-9,13; 8.49d, 1H, 4J(2,4)=1.9,H-4; .9.04d, 1H, 4J=1.9,H-2).Procedure for 5c, 5d
The mixture of equimolar amounts of 3-phenyloxopyrazolo[5,6-b]pyridine derivative (2 mmol ) and KOH (2.4 mmol) in anhydrous acetone (20 ml) was heated under reflux for 1 hour. Subsequently the mixture was cooled down to -5 oC and then to this the solution of acylchloride (2.4mmol) in anhydrous acetone (15 ml) was added in small portions under vigorous stirring. Reaction mixture was stirred 2 more hours at room temperature, then solvent was removed in vacuum. The residue was treated with water, thn product was filtered and recrystallized from ethanol or acetone in about 70% yield.
17-Ethyloxycarbonyloxy-5,20-dimethyl-7-phenyl-3-phenyloxopyrazolo[5,6-b]pyridine 5c
Melting point: 154-156 o C (from ethanol), Elemental analysis for C24H21N3O4; MW= 415.4; Calc.69.39 %C; 5.09 %H, 10.11%N; Found 69.48 %C; 4.89 %H, 10.02%N;
1
H NMR:(CDCl3):1.07t(3H, 3J=7,3 Hz,CH3); 2.55s, 3H(CH3 on C20); 2.66s, (3H,CH3 -8); 4.09q(2H, 3J=7,5Hz ,CH2 ) ; 7.23t, 1H,3J=8.3Hz(H-18); 7.37d,1H,3J=8.3Hz(H-12);49tt,2H, 3J=7.6Hz(H-13,11); 8.24dd, 2H, 3J=8.8, 4J=1.1Hz,(H-10,14); 8.49d, 1H, 4J=2.3Hz(H-4); 9.04d,1H,4J=2.3Hz(H-2).17-Ethyloxycarbonyloxy-5,20-dimethyl-18-nitro-7-phenyl-3-phenyloxopyrazolo[3,4-b]pyridine 5d
Melting point: 140-142 o C (from ethanol), Elemental analysis for C24H20N4O6; MW:460.4; Calc.62.55 %C; 4.34 %H, 12.16%N; Found 62.48 %C; 4.22 %H, 12.19%N;
1
H NMR:(CDCl3):1.17t(3H, 3J=7,4 Hz,CH3); 2.14s, 3H(CH3 on C20); 2.66s, (3H,CH3 -8); 4.09q(2H, 3J=7,3Hz ,CH2 ) ; 7.23d, 1H,3J=7.3Hz(H-18); 7.51-7.56m,2H,(H19,21); 4H( H-10,11,13,14); 8.25dd, 2H, 3J=7.6, 4J=1.3Hz,(H-19,21); 8.48d, 1H, 4J=2.4Hz(H-4); 9.02d,1H,4J=2.4Hz(H-2).Preparation of coumarine derivatives 6a, 6b
3-Phenyloxopyrazolo[5,6-b]pyridine derivative (2 mmol ), anhydrous acetanhydride (20 ml), fresh melted sodium acetate (2mmol) and phenylacetic acid or phenylthioacetic acid (2,4 mmol) was stirred under reflux for 6 hours. Then the solvent was removed in vacuum and the residuum was crystallized from toluene. The pure crystal products were obtained at about 65% yields.
5,6'-dimethyl-3',7-diphenyl-3-(coumarin-4'-yl)pyrazolo[3,4-b]pyridine 6a
Melting point: 222-224 o C, Elemental analysis for C21H17N3O2; MW:343.4;
Calc.73.38 %C; 4.99 %H, 12.23%N; Found 73.26 %C; 5.09 %H, 12.28%N;
1
H NMR:(CDCl3) 2.29s, 3H,CH3; 2.59s, 3H CH3; 6.95s,1H,H-5' 7.1-7.2m,5H,Ph on 3'; 7.29t, 1H, 3J=7.3 Hz, 4J=1.9Hz,H-12; 7.38dd, 2H,3J=7.3Hz, 4J=1.9HHz11,13; 7.51d, 1H, 3J=7.4Hz H-8'; 7.54dd, 3J=7.4 Hz, 4J=1.9Hz,H-7'; 7.78d, 1H, 4J=2.1Hz,H-4; 8.23dd, 2H, 3J=7.6Hz, 4J=2.0Hz,H-10,14; 8.39d, 1H, 4J=1.9,H-2;5,6'-dimethyl-7-phenyl-3-(3'-phenylthiocoumarin-4'-yl)pyrazolo[3,4-b]pyridine 6b
Melting point: 319-321 o C, C, Elemental analysis for C21H17N3 O2S; MW:375.4;
Calc.67.12 %C; 4.52 %H, 11.18%N; Found 66.98.26 %C; 4.35 %H, 11.28%N;
1
H NMR:(DMSO-6d): 2.25s, (3H,CH3 ); 2.62s, (3H, CH3 ); 6.97s,(1H,H-5') 7.1-7.2s,(5H,Ph on 3'); 7.33t,(1H, 3J=7.5 Hz, 4J=1.9Hz,H-12); 7.48d,(1H, 3J=8.1 Hz,H-8'); 7.52-7.55m, (2H, H-11,13 ); 7.56dd, (1H, 3J=8.3 Hz, 4J=1.9Hz,H-7'); 8.26dd,(2H, 3J=8.6Hz, 4J=2.0Hz,H-10,14); 8.39d, (1H, 4J=1.9,H-4); 8.64d, (1H, 4J=1.9,H-2).Preparation of hydrazone derivatives 7
The mixture of equimolar amounts of pyrazolo[5,6-b]pyridine (4) (1 mmol ) and 2,4- dinitrophenylhydrazine 0.2g (1 mmol) in 10ml of acetic acid was heated and stirred for 15 minutes at 80 o C. The red crystal product was isolated after recrystallized from acetic acid in about 90% yield.
17-hydroxy-5-methyl-7-phenyl-3-phenyl-15-oxopyrazolo[3,4-b]pyridin-15-(2', 4'-dinitrophenyl)hydrazone (7a)
Melting point: 280-281 C, Elemental analysis for C26H19N7 O5; MW:509.5;
Calc.61.23 %C; 3.73 %H, 19.24%N; Found 61.45 %C; 3.40 %H, 19.02%N;
1
H NMR(CDCl3):2.72s, 3H,CH3; 6.82-6.86m, 2H, H-18,19, 7.13dd, 1H, 3J=8.3Hz, 4J=2 Hz H-21; 7.32-7.43m, 2H, H-12,20, 7.56t,2H, 3J=7.9Hz, 4J=2Hz, H-11,13; 8.17d, 1H, 4J=1.6Hz, H-4; 8.27d, 1H, 3J=8.9Hz, H-6'; 8.28dd, 2H, 3J=7.9Hz 4J=1.9Hz, H-10,14; 8.45dd, 1H, 3J=9 Hz 4J=2Hz,H-5'; 8.59d, 1H, 4J=1.6Hz, H-2; 9.09d, 1H, 4J=2, H-3'; 11.26s,(NH); 11.37s,(OH).17-hydroxy-5,20-dimethyl-7-phenyl-3-phenyl-15-oxopyrazolo[3,4-b]pyridin-15-(2', 4'-dinitrophenyl)hydrazone (7b)
Melting point: 290-292 C, , Elemental analysis for C27H21N7O5; MW:523.5;
Calc.61.89 %C; 4.01 %H, 18.72%N; Found 61.78 %C; 4.11 %H, 18.53%N;
1H NMR(CDCl3):2.26s, 3H (CH3); 2.75s, 3H (CH3); 6.58s (H-21); 7.05d, 1H, 3J=8.5Hz (H-18); 7.17dd, 1H, 3J=8.6Hz,4J=2.4Hz (H-19); 7.34tt, 1H,3J=7.6Hz, 4J=1.1Hz(H-20); 7.55dd, 2H, 3J=8.5Hz, 4J=2Hz,H-13,16; 7.75dd, 1H, 3J=8.4Hz; , 4J=2.5Hz, H-6'; 8.32dd, 2H, 3J=8.1Hz 4J=2Hz,H-10,14; 8.44dd, 1H, 3J=9.1Hz 4J=2.6Hz,H-5'; 8.15d, 1H, 4J=2.8 H-4; 8.57d, 1H, 4J=2.8 H-2; 9.07d, 1H, 4J=2.6 H-3'; 11.13s,(NH); 11.20s,(OH).
17-hydroxy-5-methyl-20-fluoro-7-phenyl-3-phenyl-15-oxopyrazolo[3,4-b]pyridin-15-(2', 4'-dinitrophenyl)hydrazone (7c)
Melting point = 290-291 C.,C26H18FN7O5 , MW:528.4, red compound with very low solubility in common organic solvents
1
H NMR(CDCl3):2.66s, 3H,(CH3); 6.94dd, 1H, 3J=8.8Hz,4J=2.4Hz(H-19); 7.12d, 1H, 3J=8.8Hz,(H-18); 7.51t, 1H, 3J=8.8Hz, 4J=2Hz,(H-12); 7.56d, 4J=2.4Hz (H-21); 8.14d, 1H, 4J=1.9Hz (H-4); 8.16dd, 2H, 3J=8.8Hz; 4J=2. Hz ( H-11,13); 8.39dd, 1H, 3J=9.1Hz 4J=2.6Hz (H-5'); 8.43dd, 2H, 3J=8.1Hz 4J=2 Hz (H-10,14); 9.07d, 1H, 4J=1.9Hz (H-2); 9.09d, 1H, 4J=2.6 Hz (H-3'); 11.06s (NH); 11.27s (OH).
Conclusion
A simple, one pot and facile synthetic route for preparation of new 17-hydroxy-5-methyl-7-phenyl-3-phenyloxopyrazolo[3,4-b]pyridine derivatives 4a-4e from 3-formylchromones 1a-e by classical and microwave irradiation heating was developed. These bifunctional derivatives are usefull as synthons for the preparation of additional interesting heterocycles, as we illustrated on the 3,4-substituted coumarines.
References:
♠
Previous part, the 3-Formylchromones I, was presented at the XXVIth Conference of Organic Chemists, September 1-5, 2002, Stara Lesna, Slovak Republic