3-Methyl-4-aryl-1-phenyl-1H -pyrazolo[3,4-d]-pyrimidine-6-thiols(
11)were synthesised by the raction of thiourea with 3-methyl-\u27
-1-phenyl-4-arylidene-2-pyrazolin-5-ones(1) in ethanolic solution of
potassium hydroxide. The mechanism of this reaction is discussed
and further transformation of the products with different reagents
(S-methylation, substitution of SR-group by arylamines, hydrazine,
and azide) was carried out

M. A. Metwally

Mansour T. Younes

Saoud A. Metwally

English

HRČAK - Portal of Croatian Scientific and Professional Journals

CROATICA CREMICA ACTA CCACAA 59 (2) 483-489 (1986)CCA-1661YU ISSN 0011-1643'UDC 547.772;853·OriginaL Scientific PaperSynthesis and SomeReactions of 3-Methyl-4-aryl-l-phenyl-lH-pyrazolo[3,4-dJpyrimidine-6-thiolsSaoud A. MetwalIya*, Mansour t. Younesb, and M. A. MetwalIyCaChemistry Department, FacuLty of Science, (Assiuta and Quenab), Assiut University,.Egypt. cChemistry Department, FacuLty of Science, Mansoura University, EgiptReceived July 22, 19853-Methyl-4-aryl-1-phenyl-1H -pyrazolo[3,4-d]-pyrimidine-6-thi-ols(11)were synthesised by the raction of thiourea with 3-methyl-'-1-phenyl-4-arylidene-2-pyrazolin-5-ones(1) in ethanolic solution ofpotassium hydroxide. The mechanism of this reaction is discussedand further transformation of the products with different reagents(S-methylation, substitution of SR-group by arylamines, hydrazine,and azide) was carried out.The literature reveals that the reactions of 3-metyl-l-phenyl-4-arylidene--2-pyrazolin-5-ones with thiourea':" have not been reported. This led us toattempt the above reactions in order to get the pyrazole nucleus fused witha pyrimidine ring, a combination which is expected to possess high biologicalactivities. Interaction of 3-methyl-l-phenyl-4-arylidene-2-pyrazolin-5-ones (I)with thiourea in ethanolic potassium hydroxide gives the corresponding3-methy 1-4-aryl-I-pheny I-IH -pyrazolo [3,4-d] pyrimidine-6- thiols(II). The react-ion proceeds by addition of thiourea on arylidene double bond, this process,also could be assigned as Michael type addition on a,/J-unsaturated amidev",followed by cyclisation of the intermediate 1 to 2. The latter undergoesdehydration and aromatisation to yield the final product (II). The force forsuch elimination reactions is the resonance stabilisation energy in (II). Wewere not able to isolate the intermediate and the reaction can be representedby Scheme 1.The structure of derivatives (II) was established using physical andchemical methods (cf. Table I).The IR spectra show the absorption band at 2700-2800 cm'" chara-cteristic of SR group and no absorption can be detected for thio carbonylgroup. These products can be alkylated or aminated using an appropriatereagent. Thus, the reaction with methyl iodide in dry acetone and in thepresence of basic catalyst yields S-methyl derivative (ef. Table II).* Author to whom all correspondence should be addressed. Chemistry De-partment, Faculty of Science, Assiut University, Assiut, Egypt.484 S. A. METWALLY ET AL.l(I)TABLE I3-Methyl-4-aryl-l-phenyl-1H-pyrazolo[3,4-d]pyrimidine-6-thiol(II)AnalysisCompd* Ar M.pFC'* Yield Molecular Calc'd.lFoundNo. (%) FormulaC H N SIla C6H5 142 68 ClsH14N4S 67.92 4.43 17.72 10.1268.20 4.30 17.4 10.3TIb p-ClC6H4 145 79 ClsH13N4SCl 61.27 3.68 15.88 9.0761.52 3.7 15.4 8.9Ile P-N02C6H4 162 62 ClsH13N502S 59.50 3.58 19.28 8.8159.50 3.70 18.95 8.5Ild P-CH30C6H4 118 84 C19H16N4S0 65.51 4.59 16.09 9.1965.3 4.90 15.9 9.4Ile P-CH3C6H4 192 93 C19H16N4S 68.67 4.81 16.86 9.6368.3 5.0 16.4 9.2* IR spectra exhibited the characteristic absorption bands for SH at 2700-2800 cm'and D C=N at - 1580.** Crystallised from benzene.rPYRAZOLO-PYRIMIDINE DERIVATIVES 485TABLE II6-Methylthio-3-methyl-4-aryl-l-phenyl-1H-pyrazolo[3,4-d]pyrimidine (III).o Analysis0.' Ar M. p.JOC'" Yield Molecular Calc'd.lFoundEl o (%) FormulaoZ C H N SUIlIa C6HS 125-1 78 C19H16N4S 68.67 4.81 16.86 9.6368.7 4.9 16.6 9.50IlIb p-ClC6H4 100-1 72 C19H15N4SCl 62.21 4.09 15.27 8.7361.8 4.1 14.9 8.45IIIe p-CHSOC6H4 110 80 C20H1SN40S 66.29 4.97 15.46 8.8365.9 5.2 15.2 8.70* Crystallised from benzene/Iight petroleum (40-60°C)Amination of (II) using aromatic amines or hydrazine resulted in sub-stitution of sulphydryl group, affording IV.The structural assignments of (IV) were based on elemental and spectralanalyses (cf. Table III).Treatment of 6-hydrazino-3-methyl-4-aryl-l-phenyl-lH-pyrazolo[3,4-d]py-rimidine (IV, X = NH2) with nitrous acid gave the corresponding tetrazoloderivatives (VI), which may take place via 6-azido intermediate (Va). Thereaction can be represented by Scheme 2.The angular tetrazolo derivative (VI) is more likely than the plannarone (VII) as it shows more conjugation and hence more aromatic character.This is supported by analogy with previously mentioned tetrazole syn-theses.9-14 The chemical structure of compounds (VI) was elucidated fromtheir analytical and spectral data (ef. Table IV).~~TABLEIIICO en6-SubstitutedAmino-3-methyl-4-aryl-l-phenyl-1H-pyrazolo[3,4-d]pyrimidine(IV)AnalysisCompd.*XArm.p.!°CandsolventYieldMolecularCalc'd.!Foundofcrysta1lisation(%)FormulaCHNIVaP-CH30C6H4C6H520274C25H21N5073.715.1517.19aqueousaceticacid73.605.317.40(1:1)IVbP-CH30C6H4p-Cl-C6H420868C25H20N50Cl67.954.5315.85ulaceticacid68.44.615.4?'IVeP-CH30C6H4P-N02C6H4222-177C25H20N60366.374.4218.58~aqueousaceticacid66.404.818.8l'j(1:1)t-3 :;::IVdP-CH30CGH4P-CH30CGH416781C26H23N50271.395.2616.01~ r-aqueousaceticacid71.705.4016.2t"' ><:(1:1)l'j t-3IVeNH2C6H513856ClsH16NG68.355.0626.58~aqueousmethanol(1:1)67.915.426.2r-IVjNH2P-N02C6H4145-168C1SH15N7062.503.3428.40ethanol62.724.528.72IVgNH2P-CH3C6H410522lightpetroleumC19H1SNG69.094.4525.45(60-80°)69.35.6025.40*IRspectraexhibitedthecharacteristicabsorptionbandsfor:::C=Nat-1580;NHat-3220;andNH2at3340--3450cm-loThePMRspectrumof(IVj)inDMSOshowedasingletat(52.45(3H,CH3);at(572-7.8(rn,9H,Ar-H);at(56.66(S,2H,NH2)andat(59.8(S,IH,NH).ThePMRspectrumof(IVg)inCDCrashowedat(51.29(S,3H,p-CH3-Ar);at(52.45(S,3H,CH3);at(57.2-7.7(m,9H,Ar-H);at(57.1(S,2H,NH2)andat(59.9(S,IH,NH).PYRAZOLO-PYRIMIDINE DERIVATIVES( IV, X = NH2 )487/ ( Va)( VI)EXPERIMENTALMelting point s are uncorrected. Nuclear magnetic resonance spectra were mea-sured on varian XL-100 spectrophotometer. Infrared spectra were measured on af'erkin-Elmer model 21 spectrophotometer.3-Methyl-1-phenyl-4-arylidine-2-pyrazolin-5-ones were prepared according tothe litrature procedure.w-?3-Methyl-4-aryl-l-phenyl-1H-pyrazolo[3,4-d]pyrimidine-6-thiol(IIJModeL procedureA mixture of (0.01 mole) of the 3-methyl-1-phenyl-4-arylidene-2-pyrazolin-5--ones (Ia-e); (0.011 mole) of thiourea and 1 g of potassium hydroxide in 30 ml ofethanol was ref1uxed for 3 hours then cooled and filtered off. The filtrate was aci-dified with dilute acetic acid and the solid formed was col1ected, washed with waterand crystallised (cf. Table I).Reaction of Methyl Iodide with II. Formatian of (III)3-Methyl-4-aryl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine-6-thiol (0.01 mole) andanhydrous potassium carbonate (2.07 g, 0.015 mole) were dissolved in dry acetone(30 ml) and heated under efficient reflux for 30 minutes. Methyl iodide (0.61 ml,0.01 mole) was added to the ref1uxing solution and the mixture heated for 5 hourson the water bath. The excess solvent was removed and the residue was crystallised(cf. Table II).5-A mino-3-methyl-4-aryl-l-pheny I-lH -pyrazolo[ 3,4-d ]pyrimidine (IVa-dJGeneral procedureA mixture of II (0.001 mole) and p-anisidine (0.0011 mole) was heated in an oilbath at 170-180oC for 4 hours. On cooling and tituration with ethanol the productseparated out and crystal1ised from the proper solvent. The results are summarizedin Table III.liA CO COTABLEIVTetrazoLoDerivatives(VI)Compd.*Arm.p./°CandsolventofcrystallizationYield(0/0)MolecularFormula!'JlAnalysis?>Calc'd.lFound;;:: M >-:lCHN:;: ;,.66.053.9729.96r< r<66.34.129.6>< M58.063.2230.10>-:l58.43.0229.8;,. r<VIaC6HS85benzene/methanol55C1SH1SN7VIeP-N02CoH4110aqueousethanol(1:1)62C1SH12NS02*IRspectraexhibitedthecharacteristicabsorptionbandsfor::;C=Nat1580;andtetrazoleringat1180-1220cm".PYRAZOLO-PYRIMIDINE DERIVATIVES 4896-Hydrazino-3<~ethyl-4-aryl-l-phenyl-1H-pyrazoloI3,4-dlpyrimidine (IVe-g)Model procedureA mixture of II (0.03 mole) and excess hydrazin hydrate (10 ml, 98%) washeated at 1000C for 5 hours, after which hydrogen sulfide ceased to evolve. Themixture was concentrated, 1eft at room temperature for one weak, whereby theproduct was formed, collected and crystallised (ef. Tab1e III).To a solution of IV, X==NH2 (0.02 mole s) in acetic acid (15 ml) was addedsodium nitrite solution (0.022mo1es in 3 ml water) at 0-5°C during 30 minute s withstirring. The mixture was kept over night at room temperature, diluted with waterand filtered. The product was crystallised from the proper solvent (ef. Table IV).REFERENCES1. M. Nomura, Y. Nagano, and K. Teramura, Yuki Gosei KagakuKyokai Shi 30 (1972) 971; C. A. 78 (1973) 84342.2. R. G. Ta b o r sky, J. Org. Chem. 23 (1958) 1779.3. K. Tak e m o to, H. Ta h ara, Y. I n a k i, and N. Ue d a, Chem. Lett.(1972) 767; C. A. 77 (1972) 139953.4. F. G. Bad dar, F. H. A 1- H a j jar, and N. R. E 1- Ray y es, J. Hetero-cyclic Chem. 13 (1976) 257.5. Y. Al - F ark h, F. H. Al - H aja r, F. S. Al - S ham ali, and H. S.Ham o u d, Chem. Pharm. eou., 27 (1979) 264.6. F. H. Al - H a j jar, Y. Al - F ark h, and H. S. Ham o u d, Can J. Chem.57 (1979) 2734.7. A. G. Ham m a m, Egypt. J. Chem. 25 (1982) 5.471.8. N. R. E 1- Ray y e s, J. Heterocyclic Chem. 19 (1982) 415.9. A. Me s s m e r, G. H aj o 's, J. T ama' s, and A. N e s z m e l y i, J. Org.Chem. 44 (1979) 1823.10. M. Ti s 1e r, Synthesis (1973) 123.11. K. C. J o s h i and P. C han d, J. Heterocyclic Chem. 17 (1980) 1783.12. A. M. V e g a, -I. Al dan a, M. M. Rab b a n i, and E. Fer n and e z -- A 1ver e z, J. Heterocyclic Chem. 17 (1980). 77.13. A. M. V e ga and I. AId ana, J. Heterocyclic Chem. 18 (1981) 1533.14. S. N i s h i g a k i, M. I c h i b a, and K. S eng a, J. Org. Chem. 48 (1983) 1628.15. V. L. K n o r r, Liebigs Ann. Chem. 238 (1887) 137.16. Ta m b o r, Chem. Ber. 33 (1900) 864.17. A. Heiduschka and O. Rothacker, J. Prakt. Chem. 84 (1911) 533.SAZETAKPriprava i neke reakcije 3-metil-4-aril-1-fenil-1H-pirazolo 3,4-dpirimidin-6-tiolaSaoud A. Metwally, Mansour I. Jounes i M. A. Metwally3-retil-4-aril-1-fenil-1H-pirazolo 3,4-d -pirimidin-6-tioli (II) pripravljeni sureakcijom tioureje s 3-metil-3-fenil-4-ariliden-2-pirazolin-5-onima (I) u etanolnojotopini kalijeva hidroksida. Diskutira se o mehanizmu te reakcije; dobiveni pro-dukti dalje su transformirani u reakcijama S-metilacije, supstitucije sulfhidrilneskupine arilaminima, hidrazinom i azid-ionom.r

Synthesis and SomeReactions of 3-Methyl-4-aryl-1-phenyl-1H- pyrazolo[3,4-dipyrimidine-6-thiols

Abstract

Similar works

Full text

Available Versions

HRČAK - Portal of Croatian Scientific and Professional Journals

Hrčak - Portal of scientific journals of Croatia