摘要:

Oxidative Deprotection of TetrahydropyranylEthers to Carbonyl Compounds with4-(Dimethylamino)pyridinium and 2,2'-BipyridiniumChlorochromates under Non-aqueous Conditions$Iraj Mohammadpoor-Baltork* and Bahram KharameshDepartment of Chemistry, Esfahan University, Esfahan 81744, IranAn efcient oxidation of tetrahydropyranyl ethers to their carbonyl compounds using 4-(dimethylamino)pyridinium and2,2'-bipyridinium chlorochromates is described.The tetrahydropyranyl group is one of the most usefulprotective groups for alcohols in multi-step organic syn-theses.1 Many catalysts have already been proposed forthe tetrahydropyranylation of alcohols and deprotectionof tetrahydropyranyl ethers to the parent alcohols.2¡Ó17But there are only a few reports dealing with the directoxidation of tetrahydropyranyl ethers to their carbonyl com-pounds.18,19 Consequently, there is a need to develop andintroduce new methods and reagents for such functionalgroup transformations.We now report a new and ecient oxidative deprotectionof tetrahydropyranyl ethers to their carbonyl compoundsin high yields using 4-(dimethylamino)pyridinium and 2,2'-bipyridinium chlorochromates.20,21 As shown in Table 1these reagents are able to convert primary and secondarytetrahydropyranyl ethers 1 to their corresponding aldehydesand ketones 2 eciently in reuxing acetonitrile.Oxidationof THP ethers in which a conjugated benzylic doublebond exists, in addition to the desired product is usuallyaccompanied with cleavage of the double bond to producethe corresponding carbonyl compounds in 20¡Ó25% yield(entries 9 and 10).In order to investigate whether THP ethers are directlyoxidized or initially cleaved to the corresponding alcoholsand then oxidized to carbonyl compounds, we attempted tooxidize some corresponding alcohols under the same reac-tion conditions.We found that the oxidation of alcohols isvery fast compared to THP ethers. Therefore, it was notfeasible to observe such alcohol intermediates in the oxi-dation.It is worth mentioning that such intermediates werenot observed by TLC or GLC. It is possible that THPethers are rst cleaved to alcohols and then converted, viavery fast reactions, to the nal products.In summary, the present methodology oers an attractiveand ecient method for the direct oxidation of tetrahydro-pyranyl ethers to their carbonyl compounds.Experimental4-(Dimethylamino)pyridinium and 2,2'-bipyridinium chloro-chromates were prepared by reported methods.20,21 Yields refer toisolated products.All oxidation products were identied by com-parison of their physical data, IR and NMR spectra with those ofauthentic samples. THP ethers were prepared according to describedprocedures.3,12General Procedure for the Oxidative Deprotection of THP Etherswith 4-(Dimethylamino)pyridinium Chlorochromate.In a round-bottomed ask (50 ml) equipped with a condenser and a magneticstirrer, a solution of THP ether (1 mmol) in MeCN (15 ml) wasprepared, 4-(Dimethylamino)pyridinium chlorochromate (0.775 g,3 mmol) was added to this solution and reuxed for 25¡Ó50 min.Theprogress of the reaction was monitored by GLC or TLC (eluent:n-hexane¡Óethyl acetate, 20:1). After completion of the reaction,silica gel (2 g) was added and the mixture was stirred at roomtemperature for 5 min. The reaction mixture was ltered and thesolid material was washed with MeCN (15 ml). The ltrates werecombined and evaporated.The resulting crude material was puriedon a silica-gel plate or silica-gel column with appropriate eluent.J. Chem. Research (S),1998, 146¡Ó147$Evaporation of the solvent aorded pure carbonyl compound; yield65¡Ó96% (Table 1).General Procedure for the Oxidative Deprotection of THP Etherswith 2,2'-Bipyridinium Chlorochromate.To a solution of THP etherTable 1 Oxidative deprotection of THP ethers with DMAPHCrO3Cl and Bipy HCrO3ClYield (%) (t/min) Mp/8C [bp/8C/Torr]Entry Substrate Product DMAPHCrO3Cl Bipy HCrO3Cl Found Reported1 PhCH2OTHP (1a) PhCHO (2a) 90 (25) 93 (20) 176¡Ó178 178¡Ó1792 3-MeOC6H4CH2OTHP (1b) 3-MeOC6H4CHO (2b) 92 (30) 94 (25) 141¡Ó143/50 143/503 4-MeOC6H4CH2OTHP (1c) 4-MeOC6H4CHO (2c) 90 (30) 90 (15) 247¡Ó248 2484 3-O2NC6H4CH2OTHP (1d) 3-O2NC6H4CHO (2d) 72 (50) 85 (35) 57¡Ó59 57¡Ó595 4-O2NC6H4CH2OTHP (1e) 4-O2NC6H4CHO (2e) 90 (40) 93 (35) 106¡Ó108 105¡Ó1086 PhCH2CH2CH2OTHP (1f) PhCH2CH2CHO (2f) 93 (30) 91 (25) 96¡Ó98/12 97¡Ó98/127 PhCH(Me)OTHP (1g) PhCOMe (2g) 94 (30) 92 (30) 200¡Ó202 2028 4-CIC6H4CH(Me)OTHP (1h) 4-ClC6H4COMe (2h) 95 (30) 95 (30) 231¡Ó232 2329 PhCH1CHCH2OTHP (1i) PhCH1CHCHO (2i) 68 (30) 70 (20) 246¡Ó248 248PhCHO (2a) 23 2010 3-O2NC6H4CH1CHCH(Ph)OTHP (1j) 3-O2NC6H4CH1CHCOPh (2j) 65 (30) 68 (30) 145¡Ó146 144¡Ó1463-O2NC6H4CHO (2d) 25 25 106¡Ó108 105¡Ó10811 4-PhC6H4CH(Me)OTHP (1k) 4-PhC6H4COMe (2k) 96 (35) 98 (30) 117¡Ó118 116¡Ó11812 a-Tetralol tetrahydropyranyl ether (1 l) a-Tetralone (2 l) 90 (40) 96 (25) 114¡Ó116 113¡Ó116/613 Cyclohexanol tetrahydropyranyl ether (1m) Cyclohexanone (2m) 80 (30) 85 (30) 153¡Ó155 15514 (£¾)-Menthol tetrahydropyrany l ether (1n) (£¾)-Menthone (2n) 85 (40) 87 (30) 208¡Ó210 207¡Ó21015 Cholesterol tetrahydropyranyl ether (1o) Cholest-5-en-3-one (2o) 80 (40) 83 (30) 124¡Ó126 125¡Ó127$This is a Short Paper as dened in the Instructions for Authors,Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there-fore no corresponding material in J.Chem. Research (M).*To receive any correspondence.146 J. CHEM. RESEARCH (S), 1998(1 mmol) in MeCN (15 ml) was added 2,2'-bipyridinium chloro- chromate (0.438 g, 1.5 mmol) and the mixture was stirred magneti- cally under re�Pux conditions for 15�}35 min. The progress of the reaction was monitored by GLC or TLC (eluent: n-hexane-ethyl acetate, 20:1). After completion of the reaction, silica gel (2 g) was added and the mixture was stirred at room temperature for 5 min.The reaction mixture was Rltered and the solid material was washed with MeCN (15 ml). The combined Rltrates were evaporated on a rotary evaporator and the resulting crude material was puriRed on a silica-gel plate or silica-gel column with appropriate eluent. Evaporation of the solvent a€orded pure carbonyl compound; yield 68�}98% (Table 1). We are thankful to Esfahan University Research Council for partial support of this work. Received, 4th August 1997; Accepted, 3rd December 1997 Paper E/7/05637K References 1 T.W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley, New York, 2nd edn., 1991. 2 F. Chavez and R. Godinez, Synth. Commun., 1992, 22, 159. 3 K. Tanemura, T. Horguchi and T. Suzuki, Bull. Chem. Soc. Jpn., 1992, 65, 304. 4 P. Kumar, C. U. Dinesh, R. S. Reddy and B. Pandey, Synthesis, 1993, 1069. 5 M. L. Kantam and P. L. Santhi, Synth. Commun., 1993, 23, 2225. 6 J. M. Campelo, A.Garcia, F. Lafont, D. Luna and J. M. Marinas, Synth Commun, 1992, 22, 2335. 7 F. M. Menger and C. H. Chu, J. Org. Chem., 1981, 46, 5044. 8 M. Miyashita, A. Yoshikoshi and P. A. Grieco, J. Org. Chem., 1977, 42, 3772. 9 A. Srikrishna, J. A. Sattigeri, R. Viswajanani and C. V. Yelamaggad, J. Org. Chem., 1995, 60, 2260. 10 G. M. Caballero and E. G. Gros, Synth. Commun., 1995, 25, 395. 11 S. Raina and V. K. Singh, Synth. Commun., 1995, 25, 2395. 12 G. Maity and S. C. Roy, Synth. Commun., 1993, 23, 1667. 13 S. Kim and J. Park, Tetrahedron Lett, 1987, 35, 3036. 14 K. P. Nambiar and A. Mitra, Tetrahedron Lett., 1994, 35, 3036. 15 N. Iranpoor and P. Salehi, J. Chem. and Chem. Eng., 1996, 15, 8. 16 G. Maiti and S. C. Roy, J. Org. Chem., 1996, 61, 6038. 17 R. Ballini, F. Bigi, S. Carloni, R. Maggi and G. Sartori, Tetrahedron Lett., 1997, 28, 4169. 18 E. J. Parish, S. A. Kizito and R. W. Heideprien, Synth. Commun., 1993, 23, 223. 19 P. E. Sonnet, Org. Prep. Proced. Int., 1978, 10, 9F. S. Guziec and F. A. Luzzio, J. Org. Chem., 1982, 47, 1787. 21 F. S. Guziec and F. A. Luzzio, Synthesis, 1980, 691. 22 Aldrich Catalogue/Handbook of Fine Chemicals, 1990�}1991. J. CHEM. RESEARCH (S), 1998 1

ISSN:0308-2342    

DOI:10.1039/a705637k

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

A Novel Synthesis of Allyl SulAdes by Organosamarium Reagents$ Zhuangping Zhan and Yongmin Zhang* Department of Chemistry, Hangzhou University, Hangzhou 310028, P.R. China Organosamarium reagents react with sodium alkyl thiosulfates to afford allyl sulAdes; a reaction mechanism involving organosamarium(II) and organosamarium (III) intermediates is suggested. Intensive studies have been carried out on the role of SmI2 in organic synthesis.1�}3 In general, the reactivity of samarium(II) iodide is characterized by the single electron transfer (SET) from samarium(II) to a suitable substrate.Recently, the use of samarium metal in organic synthesis has stimulated great interest.4�}7 Curran Rrst reported the Grignard reaction of alkylsamarium(III) reagents.8 S. H. Wu et al. reported the Barbier-type allylation of ketones9 and carboxylic esters10 with samarium metal and allyl bromide and an allylsamarium(II) intermediate reaction mechanism has been suggested.Our group have studied the reaction of allylsamarium(II) with imine,11 the synthesis of allyl selenides by allylsamarium(II) reagents12 and homoallyl- amines by the addition of allylsamarium(II) reagents to nitriles,13 and the synthesis of allyl sulRdes by treating allylsamarium(II) reagents with disulRdes.14 Up until now, no reaction mechanism involving both the organosamarium(III) and the organosamarium(II) inter- mediate has been suggested. The organosamarium(III) intermediate is more stable than the corresponding organosamarium(II) intermediate.In some reactions, the organosamarium(II) intermediate may act as a reductive reagent rather than a general organometallic reagent. Recently, there has been an increase in the interest on the application of organosamarium reagents in organic synthesis which prompted us to investigate the reaction mechanism of organosamarium intermediates. Here we report the reaction of allylsamarium(II) reagents with sodium alkyl thiosulfates to a€ord allyl sulRdes.In our experiments, mixtures of sodium alkyl thiosulfates and allylsamarium(II) reagent, prepared as described in the Experimental section, were stirred for 0.5 h at room temperature. Only alkyl disulRdes (no allyl sulRdes) were obtained. However, allyl sulRdes were obtained when the reaction was carried out at 60 8C. Considering the experimental facts mentioned above and according to our previous work that samarium diiodide reductively cleaves the S0S bond of sodium alkyl thio- sulfates to give the corresponding disulRdes,15 we suggest that the reaction may occur via single electron transfer from the allylsamarium(II) intermediate to the sodium alkyl thiosulfates to yield an allylsamarium(III) intermediate and alkyl disulRde, which further react to form allyl sulRdes at 60 8C.SulRdes are a class of useful synthetic intermediates, and many syntheses have been reported for their preparation, for example, the alkylation of thiols,16 the reaction of alkyl halide with sodium sulRde,17 addition of hydrogen sulRde to alkene,18 reduction of disulRdes with copper in the presence of halide,19 reduction of sulfoxides with titanium(II) chlor- ide,20 deoxygenation of sulfoxides with triphenylphosphine�} iodide�}sodium iodide,21 and the synthesis of allyl sulRdes via allyldialkyltelluronium salts.22 The advantages of this present method are readily available starting materials, simple operation, mild and neutral conditions, as well as good yield. The results are summarized in Table 1.Experimental Typical procedure.DSamarium (0.33 g, 2.2 mmol), THF (20 ml) and allyl bromide (0.30 g, 2.5 mmol) were added to a three necked �Pask with stirring at room temperature under nitrogen. When the mixture turned purple, the stirring was continued for 1 h until the samarium powder disappeared. Sodium alkyl thiosulfates were then added to the solution. The solution turned brownish red within a few seconds and the mixture was further stirred for 2.5 h at room temperature under nitrogen and then at 60 8C for a given time.Water (10 ml) was then added and the resulting mixture extracted with diethyl ether (340 ml) and the ether layer separated. The ethereal solution was washed with water (340 ml) and the organic layer dried (MgSO4). The solvent was removed by evaporation under reduced pressure and the crude product obtained puriRed by preparative TLC on silica gel (cyclohexane and ethyl acetate as J.Chem. Research (S), 1998, 148�}149$ $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 148 J. CHEM. RESEARCH (S), 1998eluent). The products were characterized by 1H NMR, MS and IR. We thank the National Natural Science Foundation of China and the Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences for ®nancial support.Received, 16th September 1997; Accepted, 3rd December 1997 Paper E/7/06725I References 1 P. Girard, J. L. Namy and H. B. Kagan, J. Am. Chem. Soc., 1980, 102, 2693. 2 G. A. Molender, Chem. Rev., 1992, 92, 29. 3 G. A. Molender and C. R. Harris, Chem. Rev., 1996, 96, 307. 4 S. Fukuzawa and S. Fujinami, J. Chem. Soc., Chem. Commun., 1986, 475. 5 M. Lautens and Y. Ren, J. Org. Chem., 1996, 61, 2210. 6 M. Hojo, H. Aihara and A. Hosomi, J. Am. Chem. Soc., 1996, 118, 3533. 7 T. H. Chuang, J. M. Fang, W. T. Jiang and Y. H. Tsai, J. Org. Chem., 1996, 61, 1794. 8 D. P. Curran and M. J. Totleben, J. Am. Chem. Soc., 1992, 114, 6050. 9 X. Gao, X. Wang, R. F. Car, J. D. Wei and S. H. Wu, Acta Chim. Sin. (Engl. Ed.), 1993, 51, 1139. 10 X. Gao, J. Zeng, J. Y. Zhou and S. H. Wu, Acta Chim. Sin. (Engl. Ed.), 1993, 51, 1191. 11 J. Q. Wang and Y.M. Zhang, Synth. Commun., 1996, 26, 2473. 12 M. X. Yu, Y. M. Zhang and W. L. Bao, Synth. Commun., 1997, 27, 609. 13 M. X. Yu, Y. M. Zhang and H. Y. Guo, Synth. Commun., 1997, 27, 1495. 14 M. X. Yu and Y. M. Zhang, Synth. Commun., 1997, 27, 2743. 15 X. Jia, Y. Zhang and X. Zhou, Synth. Commun, 1994, 24, 2893. 16 R. Adams and W. Reifschneider, Org. Synth., 1973, Coll. Vol. V, 107. 17 E. S. Cook and C. W. Kroke, J. Am. Chem. Soc., 1939, 61, 2971. 18 E. A. Fehnel and M. Carmack, Org. Synth., 1963, Coll. Vol. IV, 669. 19 J. R. Campbell, J. Org. Chem., 1962, 27, 2207. 20 J. Drabowicz and M. Mikolajezyk, Synthesis, 1978, 138. 21 G. A. Olah and B. G. Balaram Gupta, Synthesis, 1978, 137. 22 S. M. Lu, C. D. Xu and X. Huang, Youji Huaxue, 1994, 14, 545. Table 1 Reaction conditions, products and yields Reaction conditions Entry Products t/h T/8C Yield (%)a 1 PhCH2SCH2CH1CH2 1.5 60 86 2 p-ClC6H4CH2SCH2CH1CH2 1.5 60 84 3 n-C16H33SCH2CH1CH2 2 60 80 4 n-C12H25SCH2CH1CH2 2 60 84 5 n-C10H21SCH2CH1CH2 2 60 80 6 n-C8H17SCH2CH1CH2 2 60 81 7 n-C7H15SCH2CH1CH2 2 60 78 8 n-C6H13SCH2CH1CH2 2 60 76 aYield of isolated product. J. CHEM. RESEARCH (

ISSN:0308-2342    

DOI:10.1039/a706725i

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

A Novel Synthesis of Allyl and Prop-2-ynyl SelenidesPromoted by Tin in the Presence of Water$Puhong Liao, Weiliang Bao and Yongmin Zhang*Department of Chemistry, Hangzhou University, Hangzhou, 310028, P.R. ChinaAllylic and prop-2-ynyl (propargyl) bromides react with diorganyl diselenides in the presence of water to give allylic andprop-2-ynyl selenides in moderate to good yields; the reaction rate is faster than for the same reaction in anhydrous organicmedia.Metal-mediated reactions in aqueous media have recentlyfound considerable applications in organic synthesis.1,2Such aqueous organometallic reactions oer a number ofadvantages over conventional organometallic reactions,including their simple operation through obviating the needfor anhydrous organic solvents and an inert atmosphere,and there is no need to protect `reactive' hydroxy functionalgroups etc.Although tin has been one of the mostcommonly used metals in aqueous organometallic reactions,tin-mediated reactions in aqueous media have only focusedon the allylation reaction of carbonyl compounds, crossedaldol and Reformastasky-type reactions.1a It is expected thatthe scope of the reactions will be extended.We report here a novel synthesis of allyl and prop-2-ynyl(propargyl) selenides via reactions, promoted by tin, ofallyl and pro-2-ynyl bromides with diselenides in aqueousmedia.Allylic selenides are useful intermediates in organicsynthesis.In allylic selenides, the allylic anions are stabilizedby the seleno group and can be attacked by nucleophilesregioselectively.3 Allylic selenides can be prepared by severalmethods, e.g.by the displacement of allylic halide byselenide anions,4 dehydroxysilylation of 2-hydroxy-3-trimethylsilypropylselenide catalysed by SnCl2,5 and thereaction of allylic acetates with diphenyl diselenide inducedby samarium diiodide in the presence of a palladiumcatalyst.3 Some of the methods suer from disadvantages,e.g.a strong base (EtONa) and poisonous starting material(PhSeH) were used.4 Here we provide a very simple andeasy alternative method for the synthesis of allylic andprop-2-ynyl selenides in moderate to good yields.As can be seen from Table 1, when the reaction takesplace in the presence of water it is faster than the samereaction in anhydrous organic media (entries 1, 2 and 3).Compared with the dialkyl diselenide, diphenyl diselenide ismore suitable as a substrate (entries 5 and 6).J. Chem.Research (S),1998, 150¡Ó151$Table 1 Reaction conditions and yieldsEntry Products Solventsa Temp. (T/ 8C) Time (t/h) Yield (%)15 PhSeCH2CH1CH2 A 50 24 75B 50 12 8026 p-CH3C6H4SeCH2CH1CH2 A 50 30 73B 50 20 7836 p-ClC6H4SeCH2CH1CH2 A 65 30 70B 50 24 7447 B 60 24 5553 B 50 20 7267 B 60 24 4377 CH3(CH2)5SeCH2CH1CH2 B 60 24 45aSolvent A is THF (20 ml) and solvent B is THF¡ÓH2O(20 ml 1 ml).Experimental1H NMR spectra were recorded in CCl4 on a JEOL PMX 60sispectrometer using TMS as internal standard.IR spectra wereobtained on a Perkin Elmer 683 spectrometer.General Procedure.In a 50 ml three-necked ask tted witha reux condenser and a magnetic stirrer were placed 1.5 mmolmetallic tin powder, 1.5 mmol diorganyl diselenide, 4 mmol allylicbromide and the solvent (as listed in Table 1). The mixture is stirredvigorously at a specied temperature for a given time, until thepowdered tin is almost consumed. The mixture is extracted withdiethyl ether twice (30 ml2).The extracts are washed with brine,dried (Na2SO4) and concentrated in vacuo. The product is obtainedfrom the residue through preparative TLC (silica gel) with lightpetroleum (bp 30-60 8C)¡Ódiethyl ether as eluent.Allyl phenyl selenide (1).Oil5; max/cm£¾1, 3090, 3075, 2940,1645, 1590, 1485, 1445, 1075, 1065, 1020, 1000, 985, 730, 685;H 3.32 (2 H, d, J 7 Hz), 4.65¡Ó4.92 (2 H, m), 5.45¡Ó6.15 (1 H, m),7.06¡Ó7.58 (5 H, m).Butyl cyclohex-2-enyl selenide (4).Oil7; max/cm£¾1, 3045, 2980,2950, 2880, 1650, 1590, 1450, 1382, 1260, 1180, 1000, 985, 862, 730;$This is a Short Paper as dened in the Instructions for Authors,Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there-fore no corresponding material in J. Chem. Research (M).*To receive any correspondence.150 J. CHEM. RESEARCH (S), 1998 H 0.83 (3 H, t, J 5.4 Hz), 1.12¡¾2.14 (10 H, m), 2.43 (2 H, t, J 6.4 Hz), 3.43 (1 H, m), 5.30¡¾5.82 (2 H, m). Cyclohex-2-enyl phenyl selenide (5).�¢Oil3; max/cm¢§1, 3090, 3080, 3045, 2950, 2880, 1648, 1585, 1480, 1445, 1020, 1000, 880, 865, 735, 685; H 1.59¡¾1.93 (6 H, m), 3.82 (1 H, m), 5.30¡¾5.91 (2 H, m), 7.00¡¾7.60 (5 H, m).Phenyl prop-2-ynyl selenide (6).�¢Oil7; max/cm¢§1, 3320, 3090, 3080, 2940, 2870, 1700, 1590, 1485, 1445, 1070, 1025, 1000, 860, 735, 685; H 1.95 (1 H, t, J 2.6 Hz), 3.25 (2 H, d, J 2.6 Hz), 7.00¡¾7.53 (5 H, m). We thank the National Natural Science Foundation of China for ¢çnancial support. Received, 8th July 1997; Accepted, 31st October 1997 Paper E/7/04857B References 1 For reviews, see (a) C. J. Li, Chem. Rev., 1993, 93, 2023; (b) A. Lubineau, J. Auge and Y. Quenean, Synthesis, 1994, 741. 2 (a) M. E. Isaac and T. H. Chan, J. Chem. Soc., Chem. Commun., 1995, 1003; (b) C. J. Li, and Y. Q. Lu, Tetrahedron Lett., 1995, 36, 2721; (c) L. A. Paquette and T. M. Mitzel, Tetrahedron Lett., 1995, 36, 6863. 3 S. Sakai Fukuzawa and T. S. Fujinami, Chem. Lett., 1990, 927. 4 J. N. Fitzner, R. G. Shea, J. E. Fankhauser and P. B. Hopkins, J. Org. Chem., 1985, 50, 417. 5 G. E. Kataev, L. M. Kataev and G. A. Chmutova, Zh. Org. Khim., 1966, 2244. 6 E. G. Kataev and G. A. Chmutova, Zh. Org. Khim., 1967, 2192. 7 (a) W. Bao, Y. Zheng, Y. Zhang and J. Zhou, Tetrahedron Lett., 1996, 37, 9333; (b) Y. Zheng, W. Bao and Y. Zhang, Synth. Commun., 1997, 27, 79. J. CHEM. RESEARCH (S), 1998

ISSN:0308-2342    

DOI:10.1039/a704857b

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

A Simple and Efficient Procedure for Deprotection of Tetrahydropyranyl Ethers Catalysed by Expansive Graphite$ Zhan-Hui Zhang, Tong-Shuang Li,* Tong-Shou Jin and Jian-Xin Wang Department of Chemistry, Hebei University, Baoding 071002, Hebei Province, P.R. China A variety of tetrahydropyranyl ethers of alcohols and phenols are easily deprotected in excellent yield under catalysis by expansive graphite. Selective introduction and removal of protective groups is of great signiRcance in organic synthesis.1 The tetrahydro- pyran-2-yl ether (THPE) functions are one of the most common protecting groups for hydroxy functions owing to their easy installation and remarkable stability towards basic media, Grignard reagents and reactions involving oxidation and reduction by inorganic hydrides.2 Tetrahydropyran-2-yl ethers are usually transformed into their parent alcohols or phenols under acid-catalysed conditions.A wide variety of catalysts have been already used for this conversion, including the use of protic acids3 (acetic acid, toluene-p-sulfonic acid, boric acid), Lewis acids4 (magnesium bromide in diethyl ether, dimethylalumi- nium chloride), electrogenerated acid,5 pyridinium toluene- p-sulfonate,6 ion-exchange resins7 (amberlyst H-15, Dowex 50W-X8, NaRon-H), bis(trimethylsilyl)sulfate,8 distann- oxane,9 organotin phosphate condensates10 and triphenyl- phosphine dibromide (PPh3Br2).11 More recently, 2,3- dichloro-5,6-dicyano-p-benzoquinone (DDQ),12 mesoporous H-MCM-41 molecular sieve13 and heteropoly acid14 have been applied to this reaction. However, some of these procedures su€er from using expensive reagents, strongly acidic conditions and/or necessitate aqueous work-up.Consequently, there is still a demand to develop a mild and ecient alternative procedure for this conversion. The surface acid character of expansive graphite has been used as an ecient catalyst for organic reactions.15 Previously we have developed ecient and convenient methods for the preparation16 and cleavage17 of 1,1-di- acetates and the protection of alcohols by formation of methoxymethyl ethers18 catalysed by expansive graphite.In connection with our ongoing work on expansive graphite catalysis, herein we wish to report an ecient deprotection of THPEs under catalysis by expansive graphite under mild conditions (Scheme 1). As summarised in Table 1, in the presence of expansive graphite the deprotection of THPEs could be carried out rapidly in methanol to a€ord the corresponding parent hydroxy compounds (2) at 40�}50; 8C in high yields.The present procedure for deprotection of THPEs is quite general as a wide range of THPEs of primary (1a�}c and 1 h), secondary (1d�}i) and benzylic alcohols (1c, 1g and 1i) as well as phenols and naphthols (1j�}1q) were cleaved in excellent yield. The acid-sensitive functionalities such as methoxy (11) are safe in this procedure. Betulin (1 h) was not converted into allobetulin under these conditions.The reaction proceeds cleanly and the work-up is simple, involving only the Rltration of the catalyst and the removal of solvent to obtain the product in high purity. The reaction rate is markedly dependent on temperature. We found that at room temperature the reaction proceeds much more slowly; for example, complete conversion of J. Chem. Research (S), 1998, 152�}153$ Scheme 1 Table 1 Deprotection of THPE of alcohols and phenols catalysed by expansive graphite Substrate Product Time (t/h) Yield (%)a n-C8H17-OTHP (1a) n-C8H17OH (2a) 0.70 94 n-C10H21-OTHP (1b) n-C10H21OH (2b) 0.80 96 PhCH2-OTHP (1c) PhCH2OH (2c) 0.50 96 n-C6H13CH(OTHP)CH3 (1d) n-C6H13CH(OH)CH3 (2d) 1.0 97 Cholesteryl-OTHP (1e) Cholesterol(2e) 0.60 95 b-Sitosteryl-OTHP (1f) b-Sitosterol (2f) 0.50 97 Ph2CH-OTHP (1g) PhCHOH (2g) 0.70 92 Lup-20(29)-ene-3b,28-diyl-diOTHP (1h) Betulin (2h) 1.0 95 PhCH(OTHP)COPh (1i) Benzoin (2i) 0.50 94 PhOTHP (1j) PhOH (2j) 0.35 96 p-CH3C6H4OTHP (1k) p-CH3C6H4OTHP (2k) 0.50 96 p-CH3OC6H4OTHP (1l) p-CH3OC6H4OH (2l) 0.50 96 Resorcinyl-(OTHP)2 (m) Resorcinol (2m) 0.50 96 a-Naphthyl-OTHP (1n) a-Naphthol (2n) 0.30 97 b-Naphthyl-OTHP (1o) b-Naphthol (2o) 0.65 92 m-O2NC6H4OTHP (1p) m-O2NC6H4OH (2p) 0.35 98 p-O2NC6H4OTHP (1q) p-O2NC6H4OH (2q) 0.35 97 aYields refer to isolated pure products.cholesteryl THPE (1e) into cholesterol (2e) needed 6 h in methanol under catalysis of expansive graphite.The catalyst was easily regenerated by washing with ethanol followed by drying at 120 8C for 1 h. The catalyst could be reused four $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence (e-mail: orgsyn@hbu.edu.cn). 152 J. CHEM. RESEARCH (S), 1998times for the deprotection of cholesteryl THPE (1e) without any loss of catalytic activity.In conclusion, the present procedure provides a general methodology for the deprotection of THPE from a variety of primary, secondary and benzylic alcohols and phenols. The operational simplicity, use of an inexpensive, non- corrosive and reusable catalyst, high yields and short reac- tion time can make this procedure a useful and attractive alternative to the currently available methods. Experimental The expansive graphite catalyst was prepared according to the literature.16,19 THPEs were synthesised according to our recent report.20 The products were characterised by IR and 1H NMR spectra and by comparison of their TLC and mps or bps with authentic samples.General Procedure for Deprotection of THPE.�A mixture of THPE (2 mmol), methanol (5 ml) and expansive graphite (100 mg) was stirred at 40±50 8C for the length of time indicated in Table 1. The progress of the reaction was monitored by TLC.After completion of the reaction, the catalyst was removed by ®ltration and washed with CH2Cl2 (5 ml). Evaporation of the solvent gave, essentially pure, the corresponding parent hydroxy compound (2). Further puri®cation was performed by �ash column chromatog- raphy on silica gel with light petroleum±diethyl ether as eluent wherever necessary. The project was supported by NSFC (29572039), Education Commission of Hebei Province and Science and Technology Commission of Hebei Province.Received, 6th October 1997; Accepted, 3rd November 1997 Paper E/7/07188D References 1 (a) T. W. Green and P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley, New York, 2nd edn. 1991, p. 31; (b) P. J. Kocienski, Protective Groups, Georg Thieme Verlag, Stuttgart, 1994, p. 83. 2 S. Hoyer and P. Laszlo, Synthesis, 1986, 655 and references cited therein. 3 (a) E. J. Corey, R. L. Danheiser, S. Chandrasekaran, P. Siret, G. E. Kelk and J.-L. Cras, J. Am.Chem. Soc., 1978, 100, 8031; (b) K. F. Bernady, M. Brawner, J. F. Poletto and M. J. Weiss, J. Org. Chem., 1979, 44, 1438; (c) E. J. Corey, H. Niwa and J. Knolle, J. Am. Chem. Soc., 1978, 100, 1942; (d) A. B. Shenvi and H. Gerlach, Helv. Chim. Acta, 1980, 63, 2426; (e) J. Gigg and G. Gigg, J. Chem. Soc. C, 1967, 431. 4 (a) S. Kim and J. H. Park, Tetrahedron Lett., 1987, 28, 439; (b) Y. Ogawa and M. Shibasaki, Tetrahedron Lett., 1984, 25, 663. 5 S. Torii, T. Inokuchi, K. Kondo and H.Ito, Bull. Chem. Soc. Jpn., 1985, 58, 1347. 6 N. Miyasita, A. Yoshikoshi and P. A. Grieco, J. Org. Chem., 1977, 42, 3772. 7 (a) A. Bongini, G. Cardillo, M. Orena and S. Sandri, Synthesis, 1979, 618; (b) R. Beier and B. P. Mundy, Synth. Commun., 1979, 9, 271; (c) G. A. Olah, A. Husain and B. P. Singh, Synthesis, 1983, 892. 8 Y. Morizawa, I. Mori, T. Hiyama and H. Nozaki, Synthesis, 1981, 899. 9 J. Otera and H. Nozaki, Tetrahedron Lett., 1986, 27, 5743. 10 J. Otera, Y. Niibo, S. Chikada and H. Nozaki, Synthesis, 1988, 328. 11 A. Wagner, M.-P. Heitz and C. Mioskowski, J. Chem. Soc., Chem. Commun., 1989, 1619. 12 S. Raina and V. K. Singh, Synth. Commun., 1995, 25, 2395. 13 K. R. Kloetstra and H. van Bekkum, J. Chem. Res. (S), 1995, 26. 14 A. Molnar and T. Beregszaszi, Tetrahedron Lett., 1996, 37, 8597. 15 (a) S. Tsuchiya, K. Fujii, T. Mitsuno, Y. Sakata and H. Imamara, Bull. Chem. Soc. Jpn., 1991, 64, 1011; (b) J. Bertin, H. B. Kage and R. Setton, J. Am. Chem. Soc., 1974, 96, 8113. 16 T.-S. Jin, G.-Y. Du, Z.-H. Zhang and T.-S. Li, Synth. Commun., 1997, 27, 2261. 17 T.-S. Jin, Y.-R. Ma, Z.-H. Zhang and T.-S. Li, Synth. Commun., 1997, 27, 3379. 18 T.-S. Jin, T.-S. Li and G.-B. Duan, Synth. Commun., 1998, 28, in the press. 19 T.-S. Jin, Y.-R. Ma and Q. Li, Chin. J. Inorg. Chem., 1997, 13, 231. 20 T.-S. Li, Z.-H. Zhang, T.-S. Jin and Y.-L. Li, Chin. Chem., 1998, 9, in the press. J. CHEM. RESEARCH (S), 1998 153

ISSN:0308-2342    

DOI:10.1039/a707188d

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Hexamethylenetetramine�}Bromine: A Novel Reagent for Selective Regeneration of Carbonyl Compounds from Oximes and Tosylhydrazones$% Babasaheb P. Bandgar,*a Shivaji B. Admaneb and Sandip S. Jareb aOrganic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Dnyanteerth, Vishnupuri, Nanded-431 602, PO Box 87, Maharashtra, India bDepartment of Chemistry R.B.N.B. College, Shrirampur-413709, Dist. Ahmadnagar, India Hexamethylenetetramine�}bromine (HMTAB) has been found to be an efficient and selective reagent for the mild oxidative cleavage of the C1N of oximes and tosylhydrazones to yield their corresponding carbonyl compounds in good to excellent yields under mild conditions.There has been considerable growth in interest in the development of mild methods for the regeneration of car- bonyl compounds from stable and readily prepared oximes and tosylhydrazones.1 This is because such derivatives of carbonyl compounds serve as e€ective protecting groups for aldehydes and ketones in organic synthesis.2 Oximes are also extensively used for the puriRcation and character- ization of carbonyl compounds.Since oximes can be pre- pared from non-carbonyl compounds,3 the regeneration of carbonyl compounds from oximes provides an alter- native method for the preparation of aldehydes and ketones. Most of the known methods of regenerating carbonyl compounds from their nitrogen derivatives have several limitations.4�}11 It is most important to note that most of the reported methods are suitable for the regeneration of ketones but not for aldehydes from their oximes and tosylhydrazones, and that yields are low owing to the over oxidation of regenerated aldehydes to acids.Therefore it is desirable that a method which leads to high recoveries of a wide range aldehydes and ketones should be available. We now report an ecient and general method for the e€ective and selective cleavage of the C1N of oximes and tosylhydrazones with HMTAB under neutral and mild conditions (Scheme 1).Hexamethylenetetramine�}bromine complex could be readily prepared by adding bromine to a chloroform solution of hexamethylenetetramine and it has been used successfully for the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively.12 This yellow�}orange, non-hygroscopic, homogenous solid is very stable at room temperature and is not a€ected by ordinary exposure to light, air or water and has no o€ensive odour of bromine or amine.Ease of work-up and the stability of the reagent make it a safe and convenient source of active bromine.13 The reagent is transformed during reaction into easily removable products and presents a convenient alternative to other N-halogenoamines.14�}17 Table 1 summarizes the results of various oximes which underwent oxidative cleavage with HMTAB to form corre- sponding carbonyl compounds in good yields under mild conditions.The rate of oxidative cleavage of benzophenone oximes (entries 12�}14) was fast. Even the sterically hindered ketone oximes (entries 15, 16) successfully underwent oxidative deoximation with HMTAB to give ketones in good yields. J. Chem. Research (S), 1998, 154�}155$ Table 1 Oxidative cleavage of oximes with HMTAB in CCl4 Reaction conditions Entry Substrate Temp. (T/ 8C) Time (t/h) Producta Yieldb (%) 1 4-Chlorobenzaldoxime 60 7 4-Chlorobenzandehyde 76 2 4-N,N-Dimethylaminobenzaldoxime 25 3 4-N,N-Dimethylaminobenzaldehyde 77 3 2-Nitrobenzaldoxime 60 5.3 2-Nitrobenzaldehyde 98 4 3-Nitrobenzaldoximes 60 7 3-Nitrobenzaldehyde 87 5 4-Nitrobenzaldoximes 60 6 4-Nitrobenzaldehyde 69 6 Salicylaldehyde oxime 25 4 Salicylaldehyde 40 7 Cyclopentanone oxime 25 4 Cyclopentanone 86 8 Cyclohexanone oxime 25 4 Cyclohexanone 85 9 Acetophenone oxime 25 3 Acetophenone 88 10 4-Chloracetophenone oxime 60 4 4-Chloracetophenone 84 11 4-Methylacetophenone oxime 25 2.5 4-Methylacetophenone 77 12 Benzophenone oxime 25 1.5 Benzophenone 78 13 4-Bromobenzophenone oxime 25 2 4-Bromobenzophenone 90 14 4-Chlorobenzophenone oxime 25 2 4-Chlorobenzophenone 76 15 Camphor oxime 25 2 Camphor 80 16 Menthone oxime 25 2 Menthone 87 aCharacterized by IR, 1H NMR and comparison with authentic samples. bIsolated yields.The most remarkable advantage of this methodology is that it is a general method for oxidative cleavage of a variety of aldoximes and ketone oximes with HMTAB to give the corresponding carbonyl compounds in good yields under neutral, and mild conditions, and no trace of Scheme 1 $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). %Dedicated to Professor M. S. Wadia on the occasion of his 60th birthday. *To receive any correspondence. 154 J. CHEM. RESEARCH (S), 1998acid was formed owing to over oxidation of regeneratedaldehyde. This procedure is also useful for chemoselectiveoxidative deoximation of ketone oximes in preference toaldoximes.When a mixture of 2,4-dichlorobenzaldoxime andcyclopentanone oxime or 4-nitrobenzaldoxime and aceto-phenone oxime or 4-chlorobenzaldoxime and 4-bromo-benzophenone oxime in CCl4 was allowed to react withHMTAB at room temperature (25 8C) for a period of4, 3 and 2 h, respectively, the ketoximes cyclopentanoneoxime, acetophenone oxime and 4-bromobenzophenoneoxime underwent chemoselectively oxidative deoximationgiving cyclopentanone (80%), acetophenone (86%) andbromobenzophenone (89%) whereas the aldoximes 2,4-dichlorobenzaldoxime, 4-nitrobenzaldoxime and 4-chloro-benzaldoxime were recovered unchanged.Table 2 shows the oxidative cleavage of tosylhydrazoneswith HMTAB in CCl4 to give the corresponding carbonylcompounds in good yields.The aliphatic ketone tosylhydra-zone shown in entry 1 underwent oxidative cleavage withHMTAB to give the a-bromoketone due to subsequentbromination of the regenerated ketone.The present pro-cedure is general for the oxidative cleavage of aliphatic,aromatic, heteroaromatic and cyclic tosylhydrazones andno trace of acid was formed owing to over oxidation ofregenerated aldehyde. In contrast recently reported method-ology, involving the use of 70% TBHP, is suitable only forthe deprotection of ketone tosylhydrazones and failedfor aliphatic and heteroaromatic tosylhydrazones.In thisconnection, the present methodology is important andnoteworthy.In conclusion, we hope that the present deprotectionmethodology of oximes and tosylhydrazones nds wideapplication in organic systhesis because of the simplicity ofwork-up and use of readily prepared oxidant (HMTAB)under neutral and mild conditions.ExperimentalPreparation of the Hexamethylenetetramine¡ÓBromine Complex.A solution of bromine (20.0 g, 125 mmol) in CHCl3 (100 ml) wasadded dropwise with stirring to a solution of hexamethylene-tetramine (8.5 g, 60 mmol) in chloroform (100 ml).A yellow solidseparated out as the bromine was taken up. The mixture was stirredfor an additional 30 min, then the yellow solid was collected byvacuum ltration. Yield: 25.5 g (92%), mp=170¡Ó175 8C (dec.);max/cm£¾1 (KBr) 1460, 1360, 1325, 1045, 840 and 782 (Found: C,15.9; H, 2.7; N, 12.8. C6H12Br4N4 requires C, 15.87; H, 2.63; N,12.68%).The active bromine content of this complex is 1.5 mol Br2per mol of the complex, as determined by thiosulfate titrations.Oximes or tosylhydrazones in CCl4, when stirred at room tem-perature (25 8C) or boiled under reux with HMTAB, gave thecorresponding carbonyl compounds in good yields.A Typical Procedure.A mixture of 4-bromobenzophenoneoxime (3 mmol) and HMTAB (3.1 mmol) in CCl4 (10 ml) and 1 mlwater was stirred at room temperature (25 8C) for 2 h. After thereaction was complete (TLC), insoluble hexamethylenetetraminewas removed by ltration and washed with CCl4 (210 ml);the CCl4 layer was dried over anhdrous Na2SO4.Removal of thesolvent under reduced pressure gave the product in good yield andin almost pure form.Received, 23rd September 1997; Accepted, 14th November 1997Paper E/7/06884KReferences1 Y. H. Kim, J. C. Jung and K. S. Kim, Chem. Ind., 1992, 31 andreferences cited thedler and W. Karo, Organic Functional GroupPreparations, Academic Press, London, 1989, p. 430; T. W.Greene and P. G. M. Wuts, Protective Groups in OrganicSynthesis, Wiley, New York, 1991.3 G. W. Kabalka, R. D. Pace and P. P. Wadgaonkar, Synth.Commun., 1990, 20, 2453 and references cited therein.4 R. E. Donaldson, J. C. Saddler, S. Byrn, A. T. Mckenzie andP. L. Fuch, J. Org. Chem., 1983, 48, 2167 and references citedtherein.5 J. C. Lee, K. H. Kwak, J. P. Hwang, Tetrahedron Lett., 1990,31, 6677; B. Tamani, and N. Goudarizian, Eur.Polym. J., 1992,28, 1035.6 D. P. Curran, J. F. Brill and D. M. Rakiewicz, J. Org. Chem.,1984, 49, 1654; J. Drabowicz, Synthesis, 1990, 125; E. J. Corey,P. B. Hopkines, S. Kim, S. Yoo, K. P. Nambiar and J. R. Falk,J. Am. Chem. Soc., 1979, 101, 7131.7 P. Laszlo and E. Polla, Synthesis, 1985, 439.8 G. A. Olah, Q. Liao, C. S. Lee and G. K. Suryaprakash,Synlett, 1993, 427.9 R. Joseph, A. Sudalai and T. Ravindranthan, Tetrahedron Lett.,1994, 35, 5493; P. Kumar, V. R.Hegde, B. Pandey andT. Ravindranathan, J. Chem. Soc., Chem. Commun., 1993, 1553.10 N. B. Barhate, A. S. Gajare, R. D. Wakharkar and A. Sudalai,Tetrahedron Lett., 1997, 38, 635.11 D. H. R. Barton, D. J. Lester and S. V. Ley, J. Chem. Soc.,Perkin Trans. 1, 1980, 1212.12 I. Yavari and A. Shaabani, J. Chem. Res. (S), 1994, 274.13 For a review of positive halogens, see A. Foucaud, Chem.Halides, Pseudo-halides, Azides, 1983, 1, 441.14 S. Kondo, M. Ohira, S. Kawasoe, H. Kunisada and Y.Yuki,J. Org. Chem., 1993, 58, 5003.15 F. Minisci, E. Vismara, F. Fontana, E. Platone and J. Faraci,J. Chem. Soc., Perkin Trans. 2, 1989, 123.16 L. K. Blair, S. Hobbs, N. Bagnoli, L. Husband and N. Badika,J. Org. Chem., 1992, 57, 1600.17 R. E. Banks, S. N. Mohialdin-Khaaf, G. S. Lal, I. Sharif andR. G. Syvert, J. Chem. Soc., Chem. Commun., 1992, 595.Table 2 Oxidative cleavage of tosylhydrazones with HMTAB in CCl4 at 25 8CEntry Substrate Reaction time (t/h) Producta Yieldb (%)1 Butanone tosylhydrazone 0.5 a-Bromobutanone 742 4-Chlorobenzaldehyde tosylhydrazone 2 4-Chlorobenzandehyde 693 2,4-Dichlorobenzaldehyde tosylhydrazone 1.5 2,4-Dichlorobenzaldehyde 874 Furfuraldehyde tosylhydrazone 2 Furfuraldehyde 605 2-Nitrobenzaldehyde tosylhydrazone 1.5 2-Nitrobenzaldehyde 886 3-Nitrobenzaldehyde tosylhydrazone 5 3-Nitrobenzaldehyde 897 4-Nitrobenzaldehyde tosylhydrazone 6 4-Nitrobenzaldehyde 988 Salicylaldehyde tosylhydrazone 2 Salicyladehyde 409 Cyclopentanone tosylhydrazone 2 Cyclopentanone 5010 Cyclohexanone tosylhydrazone 2.5 Cyclohexanone 8111 4-Chloroacetophenone tosylhydrazone 0.5 4-Chloroacetophenone 6912 Benzophenone tosylhydrazone 0.5 Benzophenone 90aCharacterized by IR, 1H NMR and comparision with authentic samples. bIsolated product.J. CHEM. RESEARCH (S), 1998 155

ISSN:0308-2342    

DOI:10.1039/a706884k

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Correlations of 13C¡¾H Coupling Constants JC¡¾H and Bond Angles and Bond Force Angles in Strained Organic Molecules$ Cun-Yuan Zhao,*a,b Wen-Shan Duan,a Yong Zhangb and Xiao-Zeng Youb aDepartment of Chemistry, Northwest Normal University, Lanzhou 730070, P.R. China bCoordination Chemistry Institute, Nanjing University, Nanjing 210093, P.R. China The incorporation of the sum of interatomic angle distortion , the sum of bond force angle distortion , the C¡¾C¡¾C bond angle ccc and the s-character of C¡¾H bonds has improved the prediction of 13C¡¾H coupling constants, JCH, of strained organic molecules to average deviations of less than 2.0 Hz from experimental values.The theoretical calculation of spin¡¾spin coupling constants is important in the study and interpretation of molecular structure and chemical bonding.1 Unfortunately, the coupling constants obtained from theoretical calculations deviate greatly from experimental values. Generally, the coupling constants can be empirically evaluated by di€erent structural parameters (such as bond length and angles, etc.).The e€ect of valence bond angles on hybridization and thereby on the 13C¡¾H coupling constants, JC¡¾H has been well studied.3¡¾5 With a small data set of cyclic compounds, Foote found3 a linear relationship between JC¡¾H and the C¡¾C¡¾C interatomic angle. Mislow has presented4,5 some relationships between JC¡¾H and the fractional s-character (rH) of the central carbon atomic orbital and interorbital C¡¾C¡¾C bond angle for some hydrocarbons.Szalontai obtained6 a quadratic expression between JC¡¾H and the sum of the interatomic angle distortions in saturated hydro- carbons. However, all the calculated JC¡¾H values in three- membered rings di€er somewhat from the experimental values, even though the methylene hydrogens of cyclo- propane and bicyclobutane were treated separately as special cases. However, it may be expected that strain-related par- ameters could be useful in describing JC¡¾H values in strained molecules.Recently, we presented a new approach7,8 to evaluating the molecular strain and bonding behaviour of strained organic molecules. In this model, the bond force angle (b), de¢çned as the angle subtended at a nucleus by the overlap force vectors to two bonded atoms, is found to be important in quantifying the concept of bond strain. In most strained organic molecules,7,8 b has a preference for the tetrahedral angle 109.5 8.Thus, it may be regarded as the valence bond angle or interorbital angle. As Foote3 pointed out, the hybridization would be expected to be more closely connected with the interorbital angle. In an e€ort to ¢çnd a general solution for the above-mentioned problems, we found that good correlations exist between the JC¡¾H values and the sum of interatomic angle distortion, SDy, and the sum of bond force angle distortion SDb for a wide range of strained organic molecules, including cyclic, J.Chem. Research (S), 1998, 156¡¾157$ Table 1 13C¡¾H coupling constants JC¡¾H (Hz) and sum of bond angles SDy and bond force angles SDba JC¡¾H JC¡¾H JC¡¾H H SDy SDb expt. (calcd.) H SDy SDb expt. (calcd.) H SDy SDb expt. (calcd.) 1 5 11.64 2.89 133.6(134.3) 6 11 ¢§1.15 0.37 125.7(128.1) 11 4 32.08 5.41 161.0(161.6) 2 6 0.86 1.12 128.5(129.5) 7 39.04 11.68 150.5(151.6) 12 5 110.86 14.45 205.0(204.8) 3 7 ¢§2.28 ¢§0.49 125.0(126.8) 7 10 10.15 3.19 135.1(134.3) 7 36.26 5.97 170.0(163.6) 4 6 10.58 2.36 134.7(133.4) 9 4.78 2.63 132.5(132.3) 8 29.80 7.33 152.0(152.2) 5 8 17.15 7.38 140.1(141.0) 8 6 67.92 14.79 164.0(162.5) 13 6 32.54 4.69 160.0(164.8) 9 7.89 3.60 131.3(134.2) 8 20.23 5.34 144.0(139.3) 14 6 125.42 16.53 212.0(211.2) 12 0.69 1.31 130.3(129.7) 9 11 40.50 9.38 148.1(149.2) 15 7 88.50 14.90 180.0(181.2) 6 9 0.81 1.92 134.7(130.4) 10 9 58.50 11.82 155.0(156.6) 16 8 115.84 15.30 206.0(206.5) aThe coupling constants JC¡¾H were calculated with eqns. (3) and (6) for molecules 1¡¾10 and 11¡¾16, respectively.The summations and are summed with and , which are from ref. 8. bicyclic and polyhedral hydrocarbons. In addition, we have also found excellent correlations between the JC¡¾H values and the C¡¾C¡¾C interatomic angle yCCC and the s-character in C¡¾H bonds for the local C2v type R2CH2. $This is a Short Paper as de¢çned in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 156 J. CHEM. RESEARCH (S), 1998Because any distortion in the valence bond angles can a€ect the hybridization state of a C¡¾H bond, we should take into account at least three bonds of the central carbon atom. The extent of angle distortion can be characterized by the departure of interatomic and bond force angles from the methane interatomic angle, 109.5 8 (Dy = 109.5 8 ¢§ y, Db =109.5 8 ¢§ b).In highly strained organic molecules, Dy and Db can be large positive or negative numbers.7,8 As it is well known that JC¡¾H is 125 Hz for the standard angle, 109.5 8 in methane, when the angle is smaller or larger than 109.5 8 JC¡¾H will be increased or decreased. Thus, the summation (SDy and SDb) of these positive and negative distortions could be used for the evaluation of JC¡¾H values. In view of the great degree of bend (with angles ranging from 22 to 33 8)8 and much higher JC¡¾H values of three- membered rings, the treatments have been performed on the compounds containing three-membered rings (11¡¾16) and compounds (1¡¾10) that don't contain three-membered rings.For compounds (1¡¾10) with 16 data sets, both JC¡¾H vis, SDy and JC¡¾H vs. SDb can be best described by linear regression eqns. (1) and (2) (Fig. 1). With both SDy and SDb it is easy to obtain the binary least-square ¢çtting eqn.(3) with a coe.cient of 0.981 and mean deviation of 1.68 Hz. For compounds (11¡¾16), JC¡¾H vs. SDy and JC¡¾H vs. SDb can also be approximated, by the linear regression eqns. (4) and (5) (Fig. 2). Although the linear relationship between JC¡¾H and SDb of eqn. (5) is not very good, it is of interest to note that JC¡¾H can be best ¢çtted by the binary linear regression given in eqn. (6). The coe.cient is as high as 0.992. The mean deviation is only 1.84 Hz.For all the ¢çtting equations, the average deviation (A.D.), standard deviation (S.D.) and correlation coe.cients are listed in Table 2. The experimental and calculated JC¡¾H values from eqns. (3) and (6) are shown in Table 1. It can be seen that the proposed equations can produce JC¡¾H values that are in excellent agreement with the experimental data. Their validity is not restricted to certain symmetry classes. They can be applied to any kind of strained organic molecules, such as cyclic, bicyclic, spiro and polyhedral hydrocarbons. Szalontai's treatment6 gave an average deviation of 3.22 Hz for the JC¡¾H values, which is almost two times higher than the same ¢çgure of eqns.(3) and (6). Using eqns. (3) and (6), it is possible to predict JC¡¾H values any known structure, e.g. we expect about 142.2, 132.9 and 245.6 Hz for hexaprismane, dodecahedrane and tetrahedrane, respectively. For structures of the type R2CH2 with local C2v symmetry, we have found that the experimental JC¡¾H values have excellent quadratic relationships both with the C¡¾C¡¾C interatomic angle yCCC and the per cent s-characters in C¡¾H bonds [12 data set, see Fig. 2 and eqns. (7) and (8), respectively, in Table 2]. The coe.cients are as high as 0.990 and 0.991 and the mean deviation is as small as 1.26 and 1.34 Hz, respectively. Therefore, the percent s-character in C¡¾H bonds also crucially a€ects JC¡¾H, which is consistent with previous studies on this kind of relation.2,4 In summary, consideration of a strain-related parameter, the bond force angle b, has improved the calculations for 13C¡¾H coupling constants in strained molecules.The best-¢çt eqns. (3) and (6) can be used to accurately predict JC¡¾H values for the larger rings and three-membered rings, respectively. The other two best-¢çt equations, eqns. (7) and (8) derived from yCCC and s%(C¡¾H), can also be used to predict JC¡¾H values for compounds of the type R2CH2 with local C2v symmetry.Speci¢çcally, the y-derived eqn. (7) should be recommended to predict JC¡¾H values because y values are more generally accessible than b values for these species. Received, 17th September 1997; Accepted, 13th November 1997 Paper E/7/06761E References 1 A. D. C. Towl and K. Schaumberg, Mol. Phys., 1971, 22, 49. 2 N. Muller and D. E. Pritchard, J. Chem. Phys., 1959, 31, 768, 1471. 3 C. S. Foote, Tetrahedron Lett., 1963, 579. 4 K. Mislow, Tetrahedron Lett., 1963, 1415. 5 M. W. Baum, A. Guenzi, C. A. Johnson and K. Mislow, Tetrahedron Lett., 1982, 23, 31. 6 G. Szalontai, Tetrahedron, 1983, 39, 1783. 7 C.-Y. Zhao, Y. Zhang and X. Z. You, J. Phys. Chem. A, 1997, 101, 5174. 8 C.-Y. Zhao, W.-Y. Qiu, X.-F. Xu, C.-Y. Zhang, W.-H. Fang and X.-Z. You, Gaodeng Xuexiao Huaxue Xuebao, 1995, 16, 1783. Table 2 Fitting equations, average deviation (A.D.), standard deviation (S.D.) and coefficients (R)a No. Fitting equation A.D. S.D. R (1) JC¡¾H a 129.43 a 0.49SDy 2.03 2.63 0.974 (2) JC¡¾H a 126.77 a 2.33SDb 1.95 2.64 0.973 (3) JC¡¾H a 127.94 a 0.25SDy a 1.18SDb 1.68 2.32 0.981 (4) JC¡¾H a 142.08 a 0.54SDy 4.06 6.11 0.971 (5) JC¡¾H a 137.04 a 4.13SDb 8.49 11.6 0.890 (6) JC¡¾H a 150.49 a 0.98SDy ¢§ 3.733SDb 1.84 3.64 0.992 (7) JC¡¾H a 268.97 ¢§ 2.46 a 0.011y2 1.26 1.85 0.990 (8) JC¡¾H a 323.71 ¢§ 19.27S a 0.46S2 1.34 1.81 0.991 aEqns. (4)¡¾(6) for three-membered rings. Fig. 2 Plots of JC¡¾H vs. yCCC and s% Fig. 1 Plots of JC¡¾H vs. SDy and SDb J. CHEM. RESEARCH (S), 1998 157

ISSN:0308-2342    

DOI:10.1039/a706761e

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Regioselective Metallation of Propylbenzene withSuperbase: a Convenient Route to StilbeneDerivatives$Angelika Thurner, BeÈÍ la AÈÍ gai and Ferenc Faigl*Department of Organic Chemical Technology, Technical University of Budapest, H-1521,Budapest, HungaryThe benzylic metallation of propylbenzene has been elaborated with LIC¡ÓKOR superbase; the method has been appliedin a new synthesis of stilbene derivatives.Ecient methods have been published for the regioselectivemetallation of toluene1 and ethylbenzene2 with the super-basic LIC¡ÓKOR (butyllithium¡Ópotassium tert-butoxide)mixture.3 The benzyl-type organometallics formed are stableenough (even at 60 8C in hexane2), thus their syntheticapplication does not require special conditions.In contrast,the benzylic metallation of propylbenzene has not beenpublished. Previously, a-ethylbenzylalkali compounds wereonly prepared by the reductive cleavage of 1-methoxy-1-phenylpropane with alkali metals at low temperature4because these compounds underwent decomposition4 whenthe temperature of the reaction mixture was higher than£¾20 8C.Trace amounts of a-ethylbenzyllithium formed inthe reaction of propylbenzene with benzyllithium5 (theequilibrium constant K is 1.110£¾4).We now report an ecient method for the benzylic metal-lation of propylbenzene and the application of this reactionin the synthesis of several stilbene derivatives. The targetmolecules have practical importance because of theiranticancer activity.6Detailed investigation of the reaction of propylbenzene(1) with LIC¡ÓKOR has shown that clean benzylicmetallation can be achieved in neat tetrahydrofuran as wellas in tetrahydrofuran¡Óhexanes at £¾50 8C (Scheme 1).Theorganometallic product (2) was stable at £¾50 8C for severalhours but it decomposed if the temperature rose above£¾20 8C (alkalihydride elimination followed by polymeriz-ation occurred within 2 h in neat hexane). However,addition of tertiary amine to the reaction mixture increasesthe thermal stability of 2.Thus, the reaction could also beaccomplished at 0 8C (5 h) in hexane in the presence oftriethylamine.The eciency and regioselectivity of the metallations weremonitored by trapping 2 with dierent electrophiles(Table 1). All of the products were isolated and character-ized by their physical constants and spectra, which wereidentical with those of authentic samples known from theliterature. Though the hydroxymethyl derivative 3b was pre-pared with low eciency, the ethyl (3a) and the carboxylicacid (3c) derivatives as well as the benzophenone adduct(3d) were obtained with satisfactory to good yields.We observed that water elimination from 3d partiallyoccurred during the acidic work-up and puricationprocedure on silica gel.Therefore, we used the crudeaddition products (4, Scheme 2) for the preparation ofstilbene derivatives (5). The elimination reaction was practi-cally quantitative when it was accomplished in a boilingethanol¡Óhydrochloric acid mixture. The pure products wereisolated as a Z/E mixture by column chromatography(Table 2).In the case of 4a (R1=H, R2=phenyl) a ca. 1:1mixture of the erythro and threo isomers was formed.The water elimination resulted in a 1:1 mixture of the Z-and E-stilbenes (5a) together with some isomer product(1,2-diphenylbut-2-ene, Z:E =2:1.5).The overall yield of the reaction sequence (metallation,addition, elimination) was excellent when the benzo-phenone-type oxo compound contained a uoro ordimethylaminoethoxy substituent in the para position.(1-Phenylpropylmagnesium chloride failed to react with thebenzophenone bearing a dimethylaminoethoxy side chainin the para position.)Consequently, our new method for the clean, benzylicmetallation of propylbenzene is a synthetically useful routeto a-ethylbenzylpotassium, which can serve as a keyintermediate of an ecient and convenient synthesis ofJ.Chem.Research (S),1998, 158¡Ó159$Scheme 1Scheme 2Table 1 Reaction of 2 with different electrophilesElX Product Yield (%) Ref.Et 39 8CH2O 20 9CO2 48 10Ph2CO 68 11$This is a Short Paper as dened in the Instructions for Authors,Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-fore no corresponding material in J. Chem. Research (M).*To receive any correspondence.158 J. CHEM. RESEARCH (S), 1998(Z/E)-stilbene derivatives such as 5d (Tamoxifen,7 a drugagainst mammary cancer).ExperimentalStarting materials were purchased from Fluka AG.Butyllithiumsolution was delivered by Chemetall GmbH, Frankfurt. Allcommercial reagents were used without further purication. Air-and moisture-sensitive materials were stored and handled inSchlenk tubes or Schlenk burettes under dry, pure nitrogen.Tetrahydrofuran was dried by distillation after the characteristicblue colour of the in situ generated sodium diphenylketyl was foundto persist.Metallation and Derivatization of Propylbenzene (General Pro-cedure).Potassium tert-butoxide (1.3 g, 12 mmol) was added to aprecooled (£¾50 8C) mixture of dry tetrahydrofuran (15 ml), propyl-benzene (1.7 ml, 1.4 g, 12 mmol) and a 1.5 M solution of butyllithium(8.4 ml, 13 mmol) in hexane.The reaction mixture was stirred at£¾50 8C for 5 h. The corresponding electrophile reagent (10 mmol,Table 1) was added before the cooling bath was removed. Water(15 ml) was poured into the mixture at 20 8C; the phases producedwere then separated and the crude products were isolated from theorganic solutions by standard methods, except for compound 3cwhich was obtained from the aqueous phase by acidication.Preparation of 1,1,2-Triphenylpropene (Typical Example).Thecrude oily product of 3d obtained by the above described procedure(using benzophenone as electrophile) was dissolved in a mixture ofEtOH (17 ml) and 10 M solution of HCl in H2O (2.5 ml).Thesolution was boiled under reux for 2 h then concentrated in vacuo.The residue was puried by column chromatography (Kieselgel,eluent hexane) to yield pure product (5b, Table 2).This work was supported by the National ResearchFoundation of Hungary (OTKA Grant T-014397).Received, 26th August 1997; Accepted, 19th November 1997Paper E/7/06203FReferences1 M.Schlosser, J. Organomet. Chem., 1967, 8, 9; Pure Appl.Chem., 1988, 60, 1627.2 Y. Guggisberg, F. Faigl and M. Schlosser, J. Organomet. Chem.,1991, 415, 1; F.Faigl and M. Schlosser, Tetrahedron, 1991, 32,3369.3 A. Mordini, Advances in Carbanionic Chemistry, ed. V. Snieckus,Jai Press, Greenwich, CT, 1992, ch. 1.4 K. Matswaki, Y. Shinohara and T. Kanai, Makromol. Chem.,1980, 181, 1923.5 A. Maercker and R. Sto tzel, J. Organomet. Chem., 1983, 254, 1.6 F. Angerer, J. Prekajac and J. Strohmeier, J. Med. Chem., 1984,27, 1439.7 R. Bedford, Nature (London), 1966, 212, 733; Br. Pat. GB1,064,629 (Chem. Abstr. 1967, 67, 90515).8 P. Maslak, J. N. Narvaez, J. Kula and D. S. Malinski, J. Org.Chem., 1990, 55, 4550.9 C. Berk and S. L. Buchwald, J. Org. Chem., 1992, 57, 3751.10 S. Wislicenus, Liebigs Ann. Chem., 1924, 424.11 D. Dodds, Proc. R. Soc. B (London), 1945, 132, 83.12 G. Guanti, L. Ba n and R. Riva, Tetrahedron, 1995, 51, 10343.13 R. Schneider, E. Angerer, H. Schoenenberger, R. T. Michel andH. P. Fortmeyer, J. Med. Chem., 1982, 25, 1070.14 Ger. Pat. DE 2,704,690 (Chem. Abstr., 1977, 87, 167689).15 A. F. Casy, A. Parulkar and P. Pocha, Tetrahedron, 1968, 24,3031.Table 2 Preparation of (Z)/(E)-stilbene derivativesYield (%)R1 R2 Product (Z/E) Ref.H 5a 66 (1:1)a 12, 155b 84 11, 135c 89 (1:1) 145d 85 (1:1) 7aThe crude product contained 1,2-diphenylbut-2-ene (20%).J. CHEM. RESEARCH (S), 1998 159

ISSN:0308-2342    

DOI:10.1039/a706203f

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Palladium-catalysed Transfer Hydrogenation of Azobenzenes and Oximes using Ammonium Formate$ G. K. Jnaneshwara, A. Sudalai* and V. H. Deshpande* Organic Chemistry: Technology Division, National Chemical Laboratory, Pune 411 008, India The reductive cleavage of azobenzenes, including the reduction of oximes to their corresponding amines, has been achieved with Pd0 using ammonium formate as hydrogen source. The reduction of aromatic azo and azoxy compounds has received a good deal of attention, both preparatively and analytically.1 It proceeds via the hydrazo derivative to the amine or a mixture of two amines when the original azo compound is unsymmetric.Azobenzene undergoes reductive cleavage to aniline with a number of reagents, such as metal�}acid combinations and on transfer hydrogenation over Pd.2 Reductive cleavage of azo- and azoxy-benzenes continues to be used in connection with structural determi- nations of azo dyes. More recently, Cp2TiBH4 has been reported to reduce azobenzenes to the corresponding amines.3 Catalytic transfer hydrogenation with Pd/C as catalyst and ammonium formate as hydrogen source has found widespread use in the reduction of various functionalities.4 This forms a safe alternative to the use of hydrogen gas.We have recently reported the regiospeciRc reductive ring opening of epoxides and glycidic esters under transfer hydrogenation using ammonium formate.5 In this paper, we wish to report that Pd/C catalyses the reductive cleavage of various azobenzenes as well as the reduction of various oximes to the corresponding amines in moderate yields, using ammonium formate as H2 source. Table 1 summarizes the results of the reductive cleavage of the N1N of azobenzenes to give the corresponding amines, using 4 equiv.of ammonium formate at ambient temperature. It is to be noted that reducible groups such as Cl and NO2 also underwent facile reduction under the reaction conditions employed.However, it is remarkable that selective reduction of a C�}Cl bond over a C�}F or a C�}N (debenzylation) bond6 has been achieved with the present system (Scheme 1). The reduction of various carbon�}nitrogen systems to saturated derivatives with various reducing agents provides highly useful processes for the preparation of amines and related functionalities.7 The reduction of oximes and sub- sequent cleavage of the N�}O bond to a€ord primary amines occurs with a variety of potent hydride reagents, including LiAlH4.8 Table 2 gives the various oximes that underwent reduction with 2 equiv.of ammonium formate at the re�Pux temperature to produce the corresponding amines in moderate yields. Further, it is to be noted that C1N has been reduced preferentially over C1C (entries 4 and 5, Table 2). The yield in the case of oxime reduction is only moderate owing to the instability of the amines under the reaction conditions, possibly giving other side products.In conclusion, we have shown that the ammonium formate�} Pd/C system is a versatile, selective and rapid method for catalytic hydrogenation of N1N and C1N functionalities. Experimental All mps reported are uncorrected. IR spectra were recorded neat or as Nujol mulls (in case of solid samples) on a Perkin Elmer Infrared model 137-E. The 1H NMR spectra were recorded on Varian FT 80A and Bruker 200MHz instruments. 13C NMR were obtained on a Bruker 200MHz instrument.The chemical shifts (ppm) were reported with Me4Si as the internal standard. The mass spectra (MS) were recorded on an automated Finnigan-MAT 1020 C mass spectrometer using an ionization energy of 70 eV. General Experimental Procedure for the Reduction of Azobenzene. DA mixture of azobenzene (1.82 g, 0.01 mol), ammonium formate (2.52 g, 0.04 mol) and 10% Pd/C (180 mg) in MeOH (20 ml) was stirred at room temperature for 5 h. The progress of the reaction was monitored by TLC.After the reaction was complete, the J. Chem. Research (S), 1998, 160�}161$ Table 1 Pd-catalysed transfer hydrogenation of azobenzenes using ammonium formate as H2 source Entry Substrate Productsa (% yield)b 1 Azobenzene Aniline (63) 2 4-Aminoazobenzene Aniline (31) a 1,4-diaminobenzene (64) 3 4-Hydroxyazobenzene Aniline (29) a 4-aminophenol (54) 4 4-Methyl-4'-hydroxyazobenzene p-Toluidine (31) a 4-aminophenol (47) 5 4-Chloro-4'-hydroxyazobenzene Aniline (25) a 4-aminophenol (48) 6 4-Nitro-4'-hydroxyazobenzene 1,4-Diaminobenzene (49) a 4-aminophenol (34) 7 2-Methoxy-4'-hydroxyazobenzene o-Anisidine (30) a 4-aminophenol (64) 8 2-Nitro-4-methoxy-4'-hydroxyazobenzene 3,4-Diaminoanisole (21) a 4-aminophenol (55) 9 Acetophenone azine a-Methylbenzylamine (30) aCharacterized by IR, 1H and 13C NMR and MS.bIsolated after chromatographic purification. catalyst was Rltered o€ and the crude product was puriRed by �Pash chromatography. Yield: 63%. General Experimental Procedure for the Reduction of Oximes.D A mixture of acetophenone oxime (1.35 g, 0.01 mol), ammonium Scheme 1 i, HCO2NH4 (2 mol), 10% Pd/C (cat.), MeOH, heat, 5�}6 h $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 160 J. CHEM. RESEARCH (S), 1998formate (1.26 g, 0.02 mol) and 10% Pd/C (135 mg) in MeOH (20 ml)was boiled under reux for 5 h.The progress of the reaction wasmonitored by TLC. After the reaction was complete, the catalystwas ltered o and the crude product was puried by ash chroma-tography. Yield: 41%.2-Phenylglycine methyl ester. max/cm£¾1 3500¡Ó3300, 1740, 1600,1450, 1400, 1250, 1180, 1100, 1000, 740; dH (200 MHz, CDCl3) 2.7(2 H, br, s, NH2), 3.70 (3 H, s, OMe), 4.6 (1 H, s>CH), 7.35 (5 H,s, Ar-H); m/z 165 (M+, 100%), 150 (13%), 135 (4%), 121 (6%),105 (8%), 91 (6%), 77 (8%).a-Methylbenzylamine.max/cm£¾1 2500¡Ó3500, 1600, 1450, 1300,1000, 700; dH (200 MHz, CDCl3) 1.45 (3 H, s, Me), 1.5 (3 H, s,Me), 3.1¡Ó3.5 (2 H, br s, NH2), 4.1¡Ó4.25 (1 H, q, J 3.5 Hz, 7CH, 7.4(5 H, s, Ar-H); m/z 121 (M+, 4%), 120 (M £¾ 1, 12%), 106 (100%),79 (52%), 66 (35%).4-Methoxyphenylglycine ethyl ester. max/cm£¾1 3500¡Ó3300, 1740,1600, 1250, 1050, 820; dH (200 MHz, CDCl3) 1.3¡Ó1.4 (3 H, t, J3 Hz, CH3), 4.3 (3 H, s, OMe), 4.2¡Ó4.4 ( H, q, J 4 Hz, CH2), 4.45(1 H, s, >CH), 6.9¡Ó6.95 (2 H, d, J 8 Hz, ArH), 7.3¡Ó7.35 (2 H, d, J8 Hz, Ar-H); m/z 209 (M+, 2%) 208 (M-1, 33%), 164 (4%), 145(5%), 136 (12%), 111 (12%), 97 (25%), 83 (35%), 77 (12%), 57(100%).1-Amino-2-methyl-5-(1-methylethenyl)cyclohex-2-ene. max/cm£¾12500¡Ó3500, 1610, 1450, 1390, 950, 500; dH (200 MHz, CDCl3)1.2¡Ó1.35 (1 H, m, CH), 1.75 (3 H, s, CH3), 1.9 (3 H, s, CH3), 2.05¡Ó2.4 (4 H, M, 2>CH2), 3.2¡Ó3.3 (1 H, dd, J 3 and 5 Hz, >CH0),4.65 (2 H, m 1CH2), 6.0¡Ó6.1 (1 H, m 1CH0), 10.1 (2 H, br, s,NH2); m/z 151 (M+, 2%), 150 (M £¾ 1, 9%), 135 (5%), 124 (5%),109 (5%), 99 (9%), 93 (9%), 84 (29%), 69 (100%).2-Amino-4-(2,6,6-trimethylcyclohex-1-en-1-yl)but-3-ene. max/cm£¾13000¡Ó3500, 1600, 1450, 940, 500; dH (90 MHz, CDCl3): 0.7¡Ó0.85(4 H, m, CH2), 1.6¡Ó1.7 (9 H, s, 3Me), 2¡Ó2.1 (3 H, m, CH2), 2.3¡Ó2.9(3 H, m, CH3), 4.6 (2 H, s, CH2), 5.8 (2 H, dd, J 3 and 5 Hz,1CH0), 8.9¡Ó9.0 (2 H, br, s, NH2 ); m/z 193 (M+, 12%), 192(M £¾ 1, 100%), 160 (40%), 146 (5%), 134 (8%), 120 (5%), 105(10%), 91 (15%), 77 (12%).GKJ thanks CSIR (New Delhi) for the award of a SeniorResearch Fellowship.Received, 14th August 1997; Accepted, 17th November 1997Paper E/7/05957DReferences1 H.Zollinger, Azo and Diazo Chemistry: Aliphatic and AromaticCompounds, Interscience, New York, 1989; B. T. Newbold in TheChemistry of the Hydrazo, Azo and Azoxy Groups (ed. S. Patai),Wiley, London, 1975, p. 599.2 T. L. Ho and G. A. Olah, Synthesis, 1977, 169.3 P. Dosa, I.Kronish, J. McCallum, J. Schwartz and M. C.Barden, J. Org. 4 (a) S. Ram and R. E. Ehrenkaufer, Synthesis, 1988, 91;(b) R. A. W. Johnstone, A. H. Willby and I. D. Entwistle, Chem.Rev., 1985, 85, 129.5 J. P. Varghese, A. Sudalai S. and S. Iyer, Synth. Commun., 1995,25, 2267.6 B. M. Adger, C. O. Farrell, N. J. Lewis and M. B. Mitchell,Synthesis, 1987, 53.7 R. O. Hutchins and M. K. Hutchins, Comprehensive OrganicSynthesis, eds. B. M. Trost and I. Fleming, Pergamon Press,Oxford, 1991, vol. 8, p. 25.8 T. L. Girchrist, Comprehensive Organic Synthesis, eds. B. M.Trost and I. Fleming, Pergamon Press, Oxford, 1991, vol. 8,p. 381.Table 2 Pd-catalysed transfer hydrogenation of oximes using ammonium formateEntry Substrate Producta Yield (%)1 Benzaldoxime Benzylamine 422 Acetophenone oxime a-Methylbenzylamine 413 Cyclohexanone oxime Cyclohexylamine 424 b-Ionone oxime 2-Amino-4-(2,6,6-trimethylcyclohex-1-en-1-yl)but-3-ene 295 Carvone oxime 1-Amino-2-methyl-5-(1-methylethenyl)cyclohex-2-ene 226 Methylphenylglyoxalate oxime 2-Phenylglycine methyl ester 457 Ethyl (4-methoxyphenyl)glyoxalate oxime 4-Methoxyphenylglycine ethyl ester 55aCharacterized by IR, 1H and 13C NMR and MS. bIsolated after chromatographic purification.J. CHEM. RESEARCH (S), 1998 161

ISSN:0308-2342    

DOI:10.1039/a705957d

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Novel Synthesis of Thioguanine and SulfanylpurineAnalogues: Reaction of Heterocyclic KeteneDithioacetals with Nucleophiles{Galal H. Elgemeie,*a Ahmed H. Elghandour,b Ali M. Elzanateb andSayed A. AhmedcaChemistry Department, Faculty of Science, Helwan University, Cairo, Helwan, EgyptbChemistry Department, Faculty of Science, Cairo University (Bani Suef Branch), Bani Suef, EgyptA novel synthesis of thioguanine and sulfanylpurine analogues via the reaction of heterocyclic ketone dithioacetals with nucleo-philes is reported and the synthetic potential of themethod is demonstrated.Synthetic analogues of purines are widely used in medicalscience and clinical medicine.The purine analogues of pur-ines are widely used in medical science and clinical medicine.The purine analogue 4-hydroxypyrazolopyrimidine (allo-purinol), used in treatment of hyperuricemia and gout,inhibits de novo purine biosynthesis and xanthine oxidaseactivity. Both 6-thioguanine and 6-sulfanylpurine, in whichthiol groups replace the hydroxy groups at the 6-position,are widely used clinically.As part of our programme ofresearch on the synthesis of purine analogues and otherantimetabolites1¡Ó7 we have recently reported an interestingsynthesis of 7-methylsulfanylpyrazolo[1,5-a]pyrimidines and7-methylsulfanylpyrazolo[1,2-c]imidazolones via the reactionof cyanoketene dithioacetals with 5-aminopyrazoles and 2-sulfanylhydantoins, respectively.8¡Ó10 We report here a noveland convenient method for the synthesis of fused pyrazolescarrying a methysulfanyl group.Derivatives of these ringsystems are interesting because they are sulfanylpurineanalogues and as such they may have useful propertiesas antimetabolites in purine biochemical reactions. Theheterocyclic ketone dithioacetals 2 were chosen as thekey intermediate and were prepared by the reaction ofpyrazolin-5-ones 1 with sodium ethoxide and carbon disul-de, followed by methyl iodide treatment in a one-pot reac-tion (Scheme 1).The structure of 2 was established on thebasis of elemental analysis and spectral data. Thus, the massspectrum of 2a was compatible with the molecular formulaC7H10N2OS2 (M+ 202) and its 1H NMR spectrum con-tained two singlets at d 2.52 and 2.63 ppm, which areassignable to two methylsulfanyl groups, and a broad bandat 12.22 ppm assignable to an NH group.The 13C NMR spectrum was characterized by two signals,at 18.20 and 18.70 ppm corresponding to two SMe carbons.Compounds 2 reacted with aromatic amines in reuxingethanol containing catalytic amounts of piperidine to aordthe corresponding anilino derivates 3.The structures ofcompound 3 were established on the basis of elementalanalysis and spectral data. Thus, the mass spectrum of 3awas compatible with the molecular formula C12H13N3OS(M+ 247) and its 1H NMR spectrum contained a bandat 2.52 ppm, assigned to the SMe group, and two broadbands at 10.17 and 11.00 ppm assignable to two NHgroups.Compounds 2 bearing latent functional substituentswere found useful for the synthesis of fused pyrazole deriva-tives. Thus, it has been found that the reaction of ketonedithioacetals 2 with hydrazine hydrate in reuxing ethanolcontaining catalytic amounts of piperidine gives thecorresponding 4-methylsulfanylpyrazolo[3,4-c]pyrazoles (5)in good yields. The structures of 5 were established andconrmed for the reaction products on the basis of theirelemental analysis and spectral data (MS, IR and 1HNMR).The analytical data for 5a indicated a molecularformula C6H8N4S (M+ 168) and 1H NMR revealed a bandat d 2.74 ppm, assignable to a SMe group. When compounds2 were subjected to reaction with cyanoacetohydrazide 6a orcyanothioacetamide 6b in reuxing ethanol containing cata-lytic amounts of piperidine, the corresponding 4-methyl-sulfanylpyrazolo[3,4-b]pyridine derivatives 7 were obtainedand their structures were established on the basis of elemen-tal analysis and spectral data. Thus, for 7b the IR spectrumrevealed the presence of a cyano group at 2220 cm£¾1, andthe 1H NMR spectrum revealed a band at d 2.56 ppm,assignable to the SMe group, a multiplet at d 6.91¡Ó8.70ppm, assigned for aromatic protons, and a broad singlet atd 3.35 ppm assigned to the amino group.The formationJ. Chem. Research (S),1998, 162¡Ó163$NN NNMe MeR1 RNNOMe R NNOMe RMeSSMeNNOMe RMeSNHPhR1NHNH24a R1 = Hb R1 = Ph EtOH¡VpipheatEtOH¡VpipheatEtONa¡VEtOHCS2¡VMeI PhNH2+ ¡Va R = Hb R = Ph1 a R = Hb R = Ph3 a R = Hb R = Ph2N NMeSMeNCXR3 REtOH¡Vpipheat6a R2 = CONHNH2b R2 = CSNH2CNR2HNN NNMeSMeZRabcHPhHNH2NH2HOOSR R3 X 7HHPhHPhNHOOSSR Z 9abcdeNN NNMeSMeHZRYH2N NH28a Y = NHb Y = Oc Y = SEtONa¡VEtOH, heat+ ¡V2HHPhPhHPhHPhR R1 5abcdScheme1$This is a Short Paper as dened in the Instructions for Authors,Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there-fore no corresponding material in J. Chem.Research (M).*To receive any correspondence.162 J. CHEM. RESEARCH (S), 1998of 7 from the reaction of dithioacetals 2 and cyanoaceto-hydrazide 6a is assumed to proceed via the intermediacy ofMichael adducts, which cyclize to yield the nal 4-methyl-sulfanypyrazolo[3,4-b]pyridin-6-one 7. Direct treatment of 2with guanidine, urea or thiourea aorded the corresponding4-methylsulfanylpyrazolo[3,4-d]pyrimidine derivatives 9. Thestructures of compounds 9 were established on the basis oftheir elemental analysis and spectral data.The 1H NMRspectrum of 9a showed a broad band at d 6.80 ppm assign-able to an amino group. The mass spectrum was compatiblewith the molecular formula C7H9N5S (M+ 196).In summary, we have achieved a regiospecic synthesisof interesting non-classical sulfanylpurine and thioguanineanalogues and other antimetabolites by the reaction ofheterocyclic ketone dithioacetals with hydrazine derivativesand active methylene compounds. The compounds obtainedseem promising for further chemical transformations andbiological evaluation studies.ExperimentalAll mps are uncorrected.The IR spectra were obtained (KBrdisk) on a Perkin Elmer/1650 FT-IR instrument. The 1H NMRspectra were measured on a Varian 400MHz spectrometer forsolutions in (CD3)2SO using SiMe4 as an internal standard. Massspectra were recorded on a Varian MAT 112 spectrometer.Analytical data were obtained from the Microanalytical DataCenter at Cairo University.4-Bis(methylsulfanyl)methylidene-3-methylpyrazolin-5-ones (2a,b).General procedure.A mixture of 3-methylpyrazolin-5-ones (1)(0.01 mol) and a solution of sodium ethoxide (0.02 mol) was boiledunder reux for 20 min, then cooled and carbon disulde (0.01 mol)was added.The reaction mixture was warmed at 30 8C for 20 min.After cooling, methyl iodide (0.02 mol) was added. The mixture waspoured over an ice¡Ówater mixture and neutralized with dil. hydro-chloric acid. The precipitated product was collected by ltrationand recrystallized from ethanol 2a.Yellow crystals, from EtOH,yield 95%, mp 202 8C; max/cm£¾1 (KBr) 1655 (CO), 1525 (C1N);H [(CD3)2SO] 2.51 (s. 3 H, CH3), 2.52 (s, 3 H, SCH3), 2.63 (s, 3 H,SCH3), 12.22 (s, br, 1 H, NH), C 11.51 (CH3), 18.22 (SCH3), 18.70(SCH3), 113.10 (C-6), 143.00 (C-4), 160.00 (C-3), 183.00 (C-5); m/z202 (Found: C, 41.8; H, 4.5; N, 13.6. C7H10N2OS2 requires C, 41.6;H, 4.9; N, 13.8%). 2b: Yellow crystals, from EtOH, yield 95%, mp94 8C; max/cm£¾1 (KBr) 1655 (CO), 1525 (C1N); m/z 278 (Found:C, 56.4; H, 5.1; N, 10.3.C7H10N2OS2 requires C, 56.1; H, 5.0; N,10.0%).4-Substituted-3-methylpyrazolin-5-one derivatives (3a,b). Generalprocedure.A mixture of pyrazolinones 2a,b (0.01 mol) and aniline(0.01 mol) was boiled under reux in ethanol (30 ml), containing acatalytic amount of piperidine for 3 h. The product was isolatedafter cooling, and recrystallized from ethanol. 3a: Yellow crystals,from EtOH, yield 80%, mp 235 8C; max/cm£¾1 (KBr) 3426 (NH),1657 (CO), H [(CD3)2SO] 2.40 (s, 3 H, CH3), 2.52 (s, 3 H, SCH3);7.1¡Ó7.8 (m, 5 H, C6H5), 10.17 (s, br, 1 H, NH), 11.00 (s, br, 1 H,NH); m/z 247 (Found: C, 58.6; H, 4.9; N, 17.2.C12H13N3OSrequires C, 58.3; H, 5.2; N, 17.0). 3b: Yellow crystals, from EtOH,yield 55%, mp >300 8C; max/cm£¾1 (KBr) 3178 (NH), 1668 (CO),1536 (C1N) (Found: C, 66.5; H, 5.1; N, 13.4. C18H17N3OS requiresC, 66.8; H, 5.3; N, 13.0%).3-Methyl-4-methylsulfanylpyrazolo[4,3-c] pyrazoles (3a,b).Generalprocedure.A solution of pyrazolinones 2a,b (0.01 mol) and hydra-zine hydrate or phenylhydrazine (0.01 mol) in ethanol (30 ml) con-taining a catalytic amount of piperidine was boiled under reux for3 h. The solution mixture was left to cool, and the product whichseparated was collected and recrystallized from the appropriatesolvent. 5a: Bu crystals, from DMF, yield 75%, mp >300 8C;max/cm£¾1 (KBr) 3341, 3310, 3270 (NH), 1538 (C1N); H[(CD3)2SO] 2.51 (s, 3 H, CH3), 2.74 (s, 3 H, SCH3), 7.96 (s, br, 1 H,NH), 9.78 (s, br, 1 H, NH); m/z 168 (Found: C, 42.5; H, 4.5; N,33.6.C6H8N4S requires C, 42.8; H, 4.7; N, 33.3%). 5b: Greencrystals, from EtOH, yield 60%, mp 190 8C; max/cm£¾1 (KBr) 3384,3182 (NH), 1623 (C1N); (Found: C, 59.4; H, 5.1; N, 23.2.C12H12N4S: requires C, 59.0; H, 4.9; N, 22.9%). 5c: Bu crystals,from DMF, yield 60%, mp >300 8C; max/cm£¾1 (KBr) 3404, 3240,3035 (NH), 1594 (C1N); H [(CD3)2SO] 2.36 (s, 3 H, CH3), 2.53 (s,3 H, SCH3), 7.08¡Ó8.00 (m, 5 H, C6H5), 9.52 (s, br, 1 H, NH)(Found: C, 59.2; H, 5.2; N, 22.7.C12H12N4S requires C, 59.0; H,4.9; N, 22.9%). 5d: Black crystals, from EtOH, yield 75%, mp203 8C; max/cm£¾1 (KBr) 1628 (C1N) (Found: C, 67.1; H, 4.8; N,17.3. C18H16N4S requires C, 67.5; H, 5.0; N, 17.5%).5-Cyano-3-methyl-4-methylsulfanylpyrazolo[3,4-b] pyridines (7a¡Óc).A mixture of pyrazolinones 2 (0.01 mol) and cyanoacetohydrazideor cyanothioacetamide (0.01 mol) was boiled under reux in ethanol(20 ml) containing a catalytic amount of piperidine for 6 h.The pro-duct was collected and recrystallized from the appropriate solvent.7a: Yellow crystals, from EtOH¡ÓDMF, yield 55% mp >300 8C;max/cm£¾1 (KBr) 3300, 3230 (NH2, NH), 2201 (CN), 1660 (CO),1583 (C1N); m/z 235 (Found: C, 45.5; H, 4.1; N, 29.5. C9H9N5OSrequires C, 45.9; H, 3.8; N, 29.8%). 7b: Yellow crystals, fromEtOH, yield 55%, mp 165 8C; max/cm£¾1 (KBr) 3204, 3008 (NH2,NH), 2220 (CN), 1726 (CO), 1569 (C1N); H [(CD3)2SO] 2.40 (s, 3H, CH3), 2.56 (s, 3 H, SCH3), 3.35 (s, 2 H, N-NH2), 6.91¡Ó8.70 (m,5 H, C6H5) (Found: C, 57.6; H, 4.2; N, 22.8.C15H13N5OS requiresC, 57.9; H, 4.2; N, 22.5%). 7c: Brown crystals, from EtOH¡ÓDMF,yield 50%, mp >300 8C; max/cm£¾1 (KBr) 3328, 3140 (NH), 2201(CN); m/z 236 (Found: C, 45.4; H, 3.6; N, 23.3. C9H8N4S2 requiresC, 45.8; H, 3.4; N, 23.7%).3-Methyl-4-methylsulfanylpyrazolo[3,4-d ] pyrimidines (9a¡Óe).Method (A): Guanidine hydrochloride (0.01 mol) was heated insodium ethoxide (0.01 mol) in EtOH (30 ml) for 30 min, then anequivalent amount of pyrazolinone 2a (0.01 mol) was added.Thereaction mixture was boiled under reux for 3 h. The product wasobtained after treatment with dil. HCl and recrystallized fromethanol. 9a: Yellow crystals from EtOH, yield 55%, mp >300 8C;max/cm£¾1 (KBr) 3637, 3443, 3302 (NH2, NH), 1553 (C1N); H{(CD3)2SO] 2.38 (s, 3 H, CH3), 2.51 (s, 3 H, SCH3), 6.80 (s, 2 H,NH2), 10.85 (s, br, 1 H, NH); m/z 196 (Found: C, 43.4; H, 4.5; N,35.5.C7H9N5S requires C, 43.0; H, 4.1; N, 35.9%). Method (B):Equivalent amounts of pyrazolinones 2a,b (0.01 mol) and thioureaor urea (0.01 mol) were mixed together and heated to 190 8C for30 min. The solidied product was collected and recrystallized fromethanol. 9b: Yellow crystals, from EtOH, yield 55%, mp >300 8C;max/cm£¾1 (KBr) 3493, 3181 (NH), 1700 (CO) (Found: C, 42.4; H,4.4; N, 28.1. C7H8N4OS requires C, 42.8; H, 4.0; N, 28.5%). 9c:Yellow crystals, from EtOH, yield 60%, mp >300 8C; max/cm£¾1(KBr) 3366 (NH), 1734 (CO), 1561 (C1N) (Found: C, 57.1; H, 4.6;N, 20.2. C13H12N4OS requires C, 57.3; H, 4.4; N, 20.5%). 9d:Yellow crystals, from EtOH, yield 60%, mp >300 8C; max/cm£¾1(KBr) 3708, 3356 (NH), 1556 (C1N) (Found: C, 39.1; H, 4.2; N,26.2. C7H8N4S2 requires C, 39.6; H, 3.7; N, 26.4%). 9e: Yellowcrystals, from EtOH yield 55%, mp >300 8C; max/cm£¾1 (KBr)3100 (NH), 1593 (C1N); H [(CD3)2SO] 2.31 (s, 3 H, CH3); 2.65(s, 3 H, SCH3); 7.38¡Ó7.71 (m, 5 H, C6H5) (Found: C, 54.4; H, 4.4;N, 19.1. C13H12N4S2 requires C, 54.1; H, 4.2; N, 19.4%).Received, 1st July 1997; Accepted, 22nd October 1997Paper E/7/04612JReferences1 G. E. H. Elgemeie, A. M. Attia, A. M. Elzanaty and A. K.Mansour, Bull. Chem. Soc. Jn., 1994, 67, 1627.2 G. E. H. Elgemeie, A. M. Attia, H. A. Ali and A. K. Mansour,J. Chem. Res. (S), 1994, 78.3 G. E. H. Elgemeie, A. M. Attia, D. S. Farag and S. M. Sherif,J. Chem. Soc., Perkin Trans. 1, 1994, 285.4 G. E. H. Elgemeie and B. A. W. Hussain, Tetrahedron, 1994, 50,199.5 G. E. H. Elgemeie, A. M. Attia and N. M. Fathy, Liebigs Ann.Chem., 1994, 955.6 G. E. H. Elgemeie and A. M. Attia, Carbohydr. Res., 1995, 268,295.7 G. E. H. Elgemeie and N. M. Fathy, Tetrahedron, 1995, 51,3345.8 G. E. H. Elgemeie, S. E. Elezbawy, H. A. Ali and A. K.Monsour, Bull. Chem. Soc. Jpn., 1994, 67, 738.9 G. E. H. Elgemeie, H. A. Ali and A. K. Mansour, Phosphorus,Sulfur Silicon, 1994, 90, 143.10 G. E. H. Elgemeie, H. A. Ali and A. M. Elzanaty, J. Chem.Res. (S), 1996, 340.J. CHEM. RESEARCH (S), 1998 163

ISSN:0308-2342    

DOI:10.1039/a704612j

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Novel N-Substituted Amino-4-methylsulfanyl-2- pyridones and Deazapurine Analogues from Ketene Dithioacetals{ Galal H. Elgemeie,*a Ahmed H. Elghandour,b Ali M. Elzanateb and Wafaa A. Masoudb aChemistry Department, Faculty of Science, Helwan University, Cairo, Helwan, Egypt bChemistry Department, Faculty of Science, Cairo University (bani Suef Branch), Bani Suef, Egypt A novel synthesis of N-substituted amino-4-methylsulfanyl-2-pyridones and deazapurine analogues via the reaction of ketene dithioacetals with substituted semi- and thio-semicarbazide derivatives is reported and the synthetic potential of the method is demonstrated. Synthetic analogues of purines are widely used in the medi- cal sciences and in clinical medicine.Examples include the 6-sulfanylguanine and 6-sulfanylpurine which are widely used clinically. The purine analogue 4-hydroxypyrazolo- pyrimidine (allopurine), used in the treatment of hyper- uricemia and gout, inhibits de novo purine biosynthesis and xanthine oxidase.Azathiopurine, which is catabolized to 6-sulfanylpurine, is employed in organ transplantation to supress events involved in immunologic rejection. As a part of our program directed towards the development of new simple and e.cient procedures for the synthesis of antimetabolities,1 we have recently reported di€erent successful approaches for the synthesis of sulfanylpurine, 5-deazafolic acid and deazapyrimidine nucleosides.2,3 Derivatives of these ring systems are interesting because they have useful properties as antimetabolites in biochemical reactions.4 The present research deals with a novel synthesis of N-substituted amino-4-methylsulfanyl-2-pyridones and deazapurine analogues using ketene dithioacetals. Thus, it has been found that compounds 1 reacted with 4-substituted 1-cyanoacetylthiosemicarbazide 3a,b at room temperature in the presence of pulverized potassium hydroxide in 1,4- dioxane to give the corresponding N-(4-methylsulfanyl-2- oxo-1-pyridyl)thiourea derivatives 4.The structures of com- pounds 4 were established on the basis of their elemental analysis and spectral data (MS, 1H NMR, 13C NMR and IR). Thus, structure 4a is supported by its mass spectrum which showed a molecular ion corresponding to the formula C15H12N6S2O (M+=356). The 1H NMR spectrum revealed a band at d 2.78 assignable to the SCH3 group, a multiplet at d 7.21¡¾7.60 assigned to aromatic protons, a broad singlet at d 8.78 assignable to an amino group and two broad singlets at d 9.85 and 10.69 assigned to the NH protons.The 13C NMR spectrum was characterized by a signal at d 19.81 attributed to the SCH3 carbon and two signals at d 113.17 and 115.52 attributed to the two CN carbons. Moreover, signals appeared at d 124.32, 127.56, 146.34, 149.12 and 161.93 corresponding to C-5, C-3, C-4, C-6 and C-2, respectively. The formation of 4 from the reaction of 1 with 3 is assumed to proceed via Michael addition of the active methylene of 3 to the double bond in 1.The formed Michael adducts then cyclized smoothly via MeSH elimin- ation and addition to the cyano group. In a typical exper- iment, when the ketene dithioacetals 1a,b reacted with cyanoacetohydrazide 2 at room temperature in the presence of KOH¡¾1,4-dioxane, the N-amino-4-methylsulfanyl-2- pyridones 5a,b were obtained in good yield. In related work, Peseke et al.5 has reported the synthesis of compound 6 by the reaction of 1 with cyanoacetohydrazide 2 in unreported conditions.The structures of 5 were established and con- ¢çrmed on the basis of their elemental analysis and spectral data (MS, 1H NMR, 13C NMR and IR). The analytical data for 5a revealed a molecular formula C8H7N5SO (M+=221) and 1H NMR spectroscopy was used to con¢çrm J. Chem. Research (S), 1998, 164¡¾165$ N SMe NC CN O HN Y C S NH R N N N EtO2C SMe H2N O 6 RNCS 1,4-dioxane, heat 5 a bc d NH2 OH NH2 OH Ph Ph COPh COPh 4 Y R 4 NC X MeS SMe NC NH HN HN R S O a X = CN b X = CO2Et 1 a R = Ph b R = COPh 3 KOH.1,4-dioxane NC NH N Ar H O 7 N SMe CN NC Y O N CHAr 8 a bc d NH2 NH2 OH OH 8 Y R C6H4-4-Cl C6H4-4-Me C6H5 C6H4-4-Me N SMe CN NC Y O NH2 a Y = NH2 b Y = OH 5 N NH CN Y O N CHAr 9 a bc d NH2 NH2 OH OH 9 Y R C6H4-4-Cl C6H4-4-Me C6H5 C6H4-4-Me N H2N NC NH NH2 O 2 KOH.1,4-dioxane room temp.in case of 1b NH2NH2 EtOH, heat ArCHO 1,4-dioxane, heat KOH.1,4-dioxane room temp. Scheme1 $This is a Short Paper as de¢çned in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 164 J. CHEM. RESEARCH (S), 1998the structure. Thus, 1H NMR revealed a band at d 2.68assignable to the SMe group and two broad singlets atd 5.52 and 8.42 assignable to two amino groups. The 13CNMR spectrum revealed a signal at d 18.93 assigned to theSMe group and signals appeared at d 120.32, 122.90, 147.14,149.17 and 160.96 corresponding to C-5, C-3, C-4, C-6 andC-2, respectively.The formation of 5 from the reaction of 1and cyanoacetohydrazide 2 is assumed to proceed via theintermediacy of Michael adducts, which cyclized to yield thenal N-amino-2-pyridones . The reaction of ketene dithio-acetals with Schi bases was also examined. Thus, when1a,b were reacted with 1-cyanoacetyl-4-arylmethylidene-semicarbazide 6 in the presence of KOH¡Ó1,4-dioxane, the 2-pyridone-N-Schi bases 8 were obtained.The structures of 8were established on the basis of elemental analysis and spec-tral data (MS, 1H NMR, 13C NMR and IR). The analyticaldata for 8c revealed a molecular formula C16H13N5SO(M+=323). The 13C NMR showed a signal at d 18.15 dueto the SMe carbon and a signal at d 160.17 attributed toa 2-pyridone carbonyl carbon. Compounds 4 and 8 canalso be prepared by the reaction of the corresponding N-amino-2-pyridones 5 with substituted isothiocyanates andaldehydes, respectively, in reuxing 1,4-dioxane for 2 h.Compounds 8 reacted with hydrazine in reuxing ethanol togive the corresponding pyrazolo[3,4-c]pyridines 9.The struc-tures of each of the compounds 9 were established on thebasis of elemental analysis and spectral data.In summary, we have achieved a regiospecic synthesisof interesting N-substituted amino-4-methylsulfanyl-2-pyridones and deazapurine analogues via the reaction ofketene dithioacetals with semi- and thio-semicarbazide-derivatives. The products obtained are currently underbiological evaluation studies.ExperimentalAll melting points are uncorrected.IR spectra were obtained(KBr) on a Pye Unicam instrument. 1H- and 13C-NMR spectrawere measured on a Varian 400 or Wilmad 270MHz spectrometerfor (CD3)2SO solutions using SiMe4 as internal standard. Massspectra were recorded on a Varian MAT 112 spectrometer.Analytical data were obtained from the Microanalytical DataCentre at Cairo University.N-(4-Methylsulfanyl-2-oxo-1-pyridyl)thiourea Derivatives 4a,b.Method A.A mixture of [bis(methylsulfanyl)methylene]malono-nitriles 1a or ethyl 2-cyano-3,3-bis(methylsulfanyl)acrylate 1b(0.01 mol), 4-substituted cyanoacetythiosemicarbazide 3a,b(0.01 mol), potassium hydroxide (0.012 mol) and dry 1,4-dioxane(50 ml) were stirred at room temperature for 24 h.The reactionmixture was acidied with hydrochloric acid and the formed precipi-tate was collected by ltration, dried and then crystallized from theappropriate solvent.Method B.To a solution of N-amino-2-pyridones 5 (0.01 mol)in 1,4-dioxane (50 ml), phenyl isothiocyanate or benzoyl isothio-cyanate (0.01 mol) was added.The resulting mixture was reuxedfor 2 h and the solid product collected by ltration and crystallizedfrom the appropriate solvent.4a: yield 52%, mp 280¡Ó282 8C (from EtOH); max (KBr)/cm£¾13391 (NH, NH2), 2217 (CN), 1655 (CO) (Found: C, 50.3; H, 3.6;N, 23.5%. C15H12N6S2O requires C, 50.7; H, 3.4; N, 23.6%).4b: yield 52%, mp 242¡Ó244 8C (from 1,4-dioxane); max (KBr)/cm£¾1 3600, 3380, 3320¡Ó3100 (OH, NH), 2212 (CN), 1655 (CO)(Found: C, 50.7; H, 3.0; N, 19.4%.C15H11N5S2O2 requires C, 50.4;H, 3.1; N, 19.6%).4c: yield 53%, mp >300 8C (from EtOH); max (KBr)/cm£¾1 3312,3280 (NH, NH2, 2211 (CN), 1650 (CO); dH (DMSO) 2.69 (s, 3 H,SMe), 6.92 (m, 2 H, NH2), 7.19¡Ó7.77 (m, 5 H, Ph), 9.60 (s, br, 1 H,NH), 10.53 (s, br, 1 H, NH) (Found: C, 49.7; H, 3.2; N, 21.9%.C16H13N6S2O2 requires C, 50.0; H, 3.0; N, 21.6%).4d: yield 55%, mp 290¡Ó293 8C (from MeOH); max (KBr)/cm£¾13454, 3350 (OH, NH), 2213 (CN), 1634 (CO). 2.82 (s, 3 H, SMe),7.18¡Ó7.81 (m, 5 H, Ph), 11.35 (s, br, 1 H, NH), 13.50 (s, br, 1 H,NH) (Found: C, 49.5; H, 3.0; N, 18.4%. C16H11N5S2O3 requires C,49.9; H, 2.9; N, 18.2%).N-Amino-4-methylsulfanyl-2-pyridone Derivatives 5a,bGeneralProcedure.A mixture of [bis(methylsulfanyl)methylene]malono-nitriles 1a or ethyl 2-cyano-3,3-bis(methylsulfanyl)acrylate 1b(0.01 mol), cyanoacetohydrazide 2 (0.01 mol), and potassium hy-droxide (0.012 mol) in dry 1,4-dioxane (50 ml) was stirred at roomtemperature for 24 h.The reaction mixture was acidied with hydro-chloric acid and the formed precipitate was collected by ltration,dried and then recrystallized from the appropriate solvent.5a: yield 40%, mp >300 8C (from MeOH), max (KBr)/cm£¾13549, 3292 (NH2), 2216 (CN), 1734 (CO) (Found: C, 43.6; H, 3.3;N, 31.5%.C8H7N5SO requires C, 43.4; H, 3.2; N, 31.6%).5b: yield 35%; mp 150¡Ó151 8C (from MeOH); max (KBr)/cm£¾13609, 3316 (OH, NH2), 2213 (CN), 1734 (CO) (Found: C, 43.4; H,2.9; N, 25.0%. C8H6N4SO2 requires C, 43.2; H, 2.7; N, 25.5%).1-(N-Substituted )arylmethylideneamino-4-methylsulfanyl-2-pyridoneDerivatives 8a¡Óf. Method A.A mixture of [bis(methylsulfanyl)-methylene]malononitriles 1a or ethyl 2-cyano-3,3-bis(methyl-sulfanyl)acrylate 1b (0.01 mol), 1-cyanoacetyl-4-arylidenesemicarba-zide (0.01 mol), potassium hydroxide (0.012 mol) and 1,4-dioxane(50 ml) were stirred at room temperature for 24 h.The reactionmixture was acidied with hydrochloric acid and the precipitateformed was collected by ltration, dried and then recrystallizedfrom the appropriate solvent.Method B. To a solution of N-amino-2-pyridones 5 (0.01 mol)in 1,4-dioxane (50 ml), aromatic aldehyde (0.01 mol) was added.The resulting mixture was reuxed for 2 h and the solid productcollected by ltration and crystallized from the appropriate solvent.8a: yield 51%; mp >300 8C (from 1,4-dioxane); max (KBr)/cm£¾13425 (NH2), 2211 (CN), 1634 (CO) (Found: C, 52.7; H, 3.1; N,20.2%.C15H10ClN5SO requires C, 52.4; H, 2.9; N, 20.4%).8b: yield 83%; mp >300 (from 1,4-dioxane); max (KBr)/cm£¾13446 (NH2), 2220 (CN), 1685 (CO) (Found: C, 59.0; H, 4.2; N,21.5%. C16H13N5SO requires C, 59.4; H, 4.0; N, 21.7%).8c: yield 76%; mp 285¡Ó287 8C (from MeOH); max(KBr)/cm£¾13506¡Ó3345 (OH), 2209 (CN), 1654 (CO) (Found: C, 58.2; H, 3.3; N,17.8%.C15H10N4SO2 requires C, 58.0; H, 3.2; N, 18.0%).8d: yield 62%; mp 210¡Ó211 8C (from EtOH); max/cm£¾1 3498,3381 (NH2), 2206 (CN), 1687 (CO) (Found: C, 59.0; H, 3.9; N,17.3%. C16H12N4SO2 requires C, 59.3; H, 3.7; N, 17.3%).6-Amino-3-cyanopyrazolo[3,4-c]pyridin-2(1H)-one Derivatives 9a¡Ód.General Procedure.A mixture of equivalent amounts of 5b,c,e,f(0.01 mol) and hydrazine hydrate (0.01 mol) was heated in ethanol(30 ml) for 4 h.The solid product formed was collected by ltrationand crystallized from the appropriate solvent.9a: yield 53%; mp >300 8C (from DMF); max (KBr)/cm£¾1 3479,3315 (NH, NH2), 2210 (CN), 1655 (CO); dH (DMSO) 5.68 (s, br, 2H, NH2), 6.87¡Ó7.89 (m, 4 H, C6H4), 8.12 (s, 1 H, ylidic CH), 8.28(s, br, 2 H, NH2), 11.85 (s, br, 1 H, NH) (Found: C, 51.5; H, 2.9;N, 30.2%. C14H10ClN7O requires C, 51.3; H, 3.1; N, 29.9%).9b: yield 55%; mp >300 8C (from EtOH); max (KBr)/cm£¾13600¡Ó3182 (NH, NH2), 2206 (CN), 1639 (CO) (Found: C, 58.2; H,4.3; N, 32.2%. C15H13N7O requires C, 58.6; H, 4.2; N, 31.9%).9c: yield 54%; mp >300 8C (from 1,4-dioxane); max (KBr)/cm£¾13450, 3350 (OH, NH, NH2), 2205 (CN), 1702 (CO) (Found: C,57.4; H, 3.5; N, 28.3%. C14H10N6O2 requires C, 57.1; H, 3.4; N,28.6%).9d: yield 54%; mp >300 8C (from MeOH); max (KBr)/cm£¾13451, 3352 (OH, NH, NH2), 2205 (CN), 1703 (CO) (Found: C,58.0; H, 4.0; N, 27.5%. C15H12N6O2 requires C, 58.4; H, 3.9; N,27.3%).Received, 18th March 1997; Accepted, 13th August 1997Paper E/7/01889DReferences1 G. H. Elgemeie and B. A. Hussain, Tetrahedron, 1994, 50, 199.2 G. H. Elgemeie, A. M. Attia, D. S. Farag and S. M. Sherif,J. Chem. Soc., Perkin Trans. 1, 1994, 1285.3 G. H. Elgemeie, S. E. El-Ezbawy, H. A. Ali and A. K. Mansour,Bull. Chem. Soc. Jpn, 1994, 67, 738.4 T. Tsukamoto, W. H. Haile, J. J. McGuire and J. K. Coward,J. Med. Chem., 1996, 39, 2536.5 K. Peseke, J. Q. Suarez, F. Napoies and M. Basilia, Ger. (East)DD 294 943 (Cl. C07D 487/04) (Chem. Abstr., 1992, 116, 128960u).J. CHEM. RESEARCH (S), 1998 165

ISSN:0308-2342    

DOI:10.1039/a701889d

出版商:RSC    

年代:1998

数据来源: RSC