A new laccase-catalyzed domino process and its application to the efficient synthesis of 2-aryl-1 H-benzimidazoles

The laccase-catalyzed domino reaction of o-phenylenediamine and benzaldehydes with aerial oxygen as the oxidant exclusively yields 2-aryl-1H-benzimidazoles in good to very good yields. It is easy to perform under very mild reaction conditions.
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   A new laccase-catalyzed domino process and its applicationto the efficient synthesis of 2-aryl-1  H  -benzimidazoles Heiko Leutbecher, Mihaela-Anca Constantin, Sabine Mika, Jürgen Conrad, Uwe Beifuss ⇑ Bioorganische Chemie, Institut für Chemie, Universität Hohenheim, Garbenstraße 30, D-70599 Stuttgart, Germany a r t i c l e i n f o  Article history: Received 28 October 2010Accepted 26 November 2010Available online 4 December 2010 Keywords: LaccaseAerobic oxidationDomino reactions N  -Heterocycles a b s t r a c t The laccase-catalyzed domino reaction of   o -phenylenediamine and benzaldehydes with aerial oxygen asthe oxidant exclusively yields 2-aryl-1 H  -benzimidazoles in good to very good yields. It is easy to performunder very mild reaction conditions.   2010 Elsevier Ltd. All rights reserved. Laccases are multicopper oxidases which are able to catalyzethe selective oxidation of a number of substrates using oxygen asan oxidant under mild reaction conditions. The oxidation of thesubstrate is accompanied by the reduction of oxygen to give wateras the only side product. 1 Over the last few years the interest inlaccase-catalyzed transformations has increased. 2 It has been dem-onstrated that laccases can be used for the oxidation of aromaticmethyl groups, 3a benzylic, allylic, and aliphatic alcohols, 3b ethers, 3c benzyl amines and hydroxylamines. 3d Laccases have also beenemployed for the oxidation of catechols and hydroquinones tothe corresponding benzoquinones and related transformations. 4 Also, there is ample evidence that laccases catalyze the oxidativecoupling of several phenolics using oxygen as the oxidant. 5 In anumber of contributions we have reported that laccase initiateddomino reactions between catechols and several 1,3-dicarbonylscan be employed for the synthesis of a number of heterocyclicsystems, including 1 H  -pyrano[4,3- b ]benzofuran-1-ones, 6b,c 3,4-dihy-drodibenzofuran-1(2 H  )-ones, 6b and benzofuro[3,2- c  ]pyridin-1(2 H  )-ones. 6a As part of our studies of the laccase-catalyzed domino processeswe have observed that the oxidative transformation of   o -phenyl-enediamine ( 1a ) with air as the oxidant in the presence of catalyticamounts of laccase from  Agaricus bisporus  exclusively delivers 2,3-diaminophenazine ( 2 ) in 90% yield (Scheme 1).It is assumed that the oxidative dimerization of   1a  starts withthe laccase-catalyzed oxidation of one molecule of the substrateto the corresponding diimine  3 , which reacts with a secondmolecule  o -phenylenediamine ( 1a ) by means of an inter- and anintramolecular 1,4-addition to yield a tetrahydrophenazine  4 . Thelast step is the oxidation of this intermediate to afford the 2,3-dia-minophenazine ( 2 ). On an analytical scale this reaction has beenemployed for determining the activity of laccases. 7c Alternatively,this transformation can also be performed on a preparative scaleusing either FeCl 37a or hydrogen peroxide in the presence of cata-lytical amounts of peroxidases. 7b The oxidative dimerization of   1a  has caught our attention fortwo reasons: (a) it allows the preparation of   2  with very highyields, and (b) during the course of the reaction a laccase-catalyzedaerobic oxidation of a C–N-single bond to a C @ N-double bondtakes place. Since transformations of this type play a centralrole in heterocyclic chemistry we have studied whether the NH 2 NH 2 air, laccase (  A. bisporus )buffer, pH = 6.0r.t., 6 h 1a 2 90%NN NH 2 NH 2 2NHNH 1a  + 4 NHHN NH 2 NH 2 3 HH[O] [O]1,4 Scheme 1.  Preparation of 2,3-diaminophenazine ( 2 ) by laccase-catalyzed aerobicdimerization of   1a .0040-4039/$ - see front matter    2010 Elsevier Ltd. All rights reserved.doi:10.1016/j.tetlet.2010.11.145 ⇑ Corresponding author. Tel.: +49 711 459 22171; fax: +49 711 459 22951. E-mail address:  ubeifuss@uni-hohenheim.de (U. Beifuss).Tetrahedron Letters 52 (2011) 604–607 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet  laccase-catalyzed imine formation can be applied to the synthesisof other heterocycles as well.No doubt, substituted benzimidazoles and structurally relatedcompounds occupy a pivotal position in medicinal chemistry. 8 These compounds have been studied in great detail because manyof them exhibit remarkable biological activities, resulting in theiruse as anti-ulcerative, antitumor, antihypertensive, antifungal,and antihistaminic agents in therapy. This is why the efficient syn-thesis of 2-aryl-1 H  -benzimidazoles  5  and their derivatives is ahighly important and rewarding target for synthetic organic chem-ists. 9 R 2 5 R 1  NHN One of the standard methods for the preparation of 2-aryl-1 H  -benzimidazoles  5  starts with the condensation of an  o -phenylene-diamine  1  with an aromatic aldehyde  6  to yield a Schiff base  7 .Cyclizationof  7 yieldsabenzimidazolinederivative 8 ,whichisthenoxidized to give the corresponding benzimidazole  5  (Scheme 2).Numerous oxidants have been used for this transformation,includingnitrobenzene, 10a 1,4-benzoquinone, 10b H 2 O 2 /cericammo-nium nitrate, 10c (bromodimethyl)sulfonium bromide, 10d oxone, 10e iodine, 10f  and cupric acetate. 10g Meanwhile a number of methodshavebeendevelopedbymakinguseofthehighlyattractiveoxidantoxygen. 11 However, most of these methods require organic sol-vents, high reaction temperatures, or the presence of additionalreagents,considerably limitingtheir attractiveness.It hasalso beenestablished that the synthesis of 2-aryl-1 H  -benzimidazoles  5  byreaction of an  o -phenylenediamine  1  and an aromatic aldehyde  6 can also be accomplished in aqueous solvent systems. 10f,g,11b,e With a number of these methods the formation of the required2-aryl-1 H  -benzimidazole  5  is accompanied by the occurrence of 1-benzylated 2-aryl-1 H  -benzimidazoles  9  as side products, 11g and sometimes this type of compounds has been isolated as themain product. 12 R 2 9 R 1  NNR 2 Therefore,we felt thatitwas worthto study whether2-aryl-1 H  -benzimidazoles  5  can be obtained by a laccase-catalyzed dominoreaction of   o -phenylenediamine ( 1a ) with aromatic aldehydes  6 using air as the oxidant. The model reaction chosen was the trans-formation of   o -phenylenediamine ( 1a ) and benzaldehyde ( 6a ). Wefound that the laccase-catalyzed reaction of   1a  and  6a  affords the2-phenyl-1 H  -benzimidazole ( 5a ) (Fig. 1) in 74% yield when performed under aerobic conditions at pH 6.0 (0.2 M phosphatebuffer) and at room temperature (Scheme 3, Table 1, entry 1). A commercially available laccase from  Agaricus bisporus  was usedas the catalyst. 13 The selectivity of this reaction is quite remarkablefor its exclusive formation of the 1 H  -benzimidazole ring system.The dimerization of   o -phenylenediamine ( 1a ) to the 2,3-diamino-phenazine ( 2 ) does not take place under the reaction conditionschosen.These encouraging findings prompted us to conduct a newbenzimidazole synthesis with a number of substituted benzalde-hydes ( 6b–g  ). In all cases the laccase-catalyzed domino processwas achieved using equimolar amounts of   o -phenylenediamine( 1a ) and benzaldehydes  6a–g   at room temperature. 14 The 2-aryl-1 H  -benzimidazoles  5b–g   (Fig. 1) were isolated with yields rangingfrom 50% to 99% (Scheme 3, Table 1, entries 2–7). 15 Due to their limited solubility in water the reactions with thealdehydes  6b–d  required the addition of some methanol to thephosphate buffer. All reactions could be performed in a most sim-ple manner by shaking the reaction mixture using a liquid phasesynthesis system ‘Synthesis 1’. Using this experimental setup suffi-cient aeration was ensured. The reactions could also be performedusing a magnetic stirrer at high stirring speed. The workup of the NHN R 2 NH 2 NH 2 OHC 1 6 5 + R 2 NH 2 N R 2 7 NHHN R 2 8 -H 2 O [O]R 1 R 1 R 1 R 1 Scheme 2.  Reaction of   o -phenylenediamines  1  with aromatic aldehydes  6  to yieldbenzimidazoles  5 . 5a NHN 5b NHN 5c NHN 5d NHN 5e NHHN 5f  NHHN 5g NHHNClOMeOMeOMeOMeO 2 C O 2 C OMeOMeO 3 S Figure 1.  Products  5a – g   of the laccase-catalyzed domino reaction between  1a  and 6a – g  . NHN RNH 2 NH 2 OHC 1a 6a-g 5a-g + Rair, laccase(  A. bisporus )buffer, pH = 6.0r.t., 3-18 h50-99% Scheme 3.  Laccase-catalyzed aerobic synthesis of 2-aryl-1 H  -benzimidazoles  5 . H. Leutbecher et al./Tetrahedron Letters 52 (2011) 604–607   605  reaction mixtures proved to be extremely simple as well. The prod-ucts were precipitated by simple salting out using NaCl. After fil-tration followed by washing with 15% aqueous sodium chloridesolution and then water, heterocycles  5a–g   were obtained. In noneof the reactions the formation of the 2,3-diaminophenazine ( 2 ) orany other side product was observed.Concerning the mechanism it is assumed that the reactionstarts with the formation of the Schiff base  7  followed by an intra-molecular ring closure to produce the  N  , N  -acetal  8 . The laccase-catalyzed oxidation of   8  finally yields the benzimidazole  5  (Scheme2).In order to elucidate the role of the laccase in the domino reac-tion a number of additional experiments were conducted. Whenthe laccase-catalyzed transformation of   o -phenylenediamine ( 1a )and benzaldehyde ( 6a ) was run in a 9:1 mixture of phosphate buf-fer (0.2 M, pH 6.0) and methanol  5a  was isolated in 64% yield. Thismeans that the yield obtained in the phosphate buffer/methanolmixture is only slightly lower (10%) than the one achieved withthe pure phosphate buffer (Table 1, entry 1). Under these condi-tions, however, the reaction can be more easily performed sincethe benzaldehyde completely dissolves in the phosphate buffer/methanol mixture. When the model reaction was run in the ab-sence of the laccase from  Agaricus bisporus  but under otherwiseidentical reaction conditions an inseparable mixture of a numberof compounds was formed. The composition of this mixture wasnot studied in more detail.When the phosphate buffer was replaced by a 9:1 mixture of acetate buffer (0.2 M, pH 4.4) and methanol and the reaction wasagainperformedintheabsenceof laccaseonly18%of a9:1 mixtureof 2-phenyl-1 H  -benzimidazole ( 5a ) and the N-benzylated product 9a  (R = H) was isolated (Scheme 4). In the presence of 2 equiv of benzaldehyde ( 6a ) the formation of 34% of a 20:3 mixture of   5a and  9a  was observed (Scheme 4, Table 2, entry 1). This clearly indi- cates that the laccase-catalyzed reaction between  1a  and  6a  pro-ceeds with much better selectivity and higher yield of   5a  (Table 1,entry 1) than the reaction in the absence of the enzyme.Despite these findings, the reactions of   1a  with the substitutedbenzaldehydes  6b–g   were also run in the absence of laccase(Scheme 4, Table 2, entries 2–7). In all cases 1 equiv of   1a  was reacted with 2 equiv of the respec-tive benzaldehyde under air in either acetate buffer or a mixture of acetate buffer/methanol and in the absence of laccase. It was foundthat the reaction with the aldehydes  6c  und  6d  delivered mixturesof  5 and 9 (Scheme 4, Table2, entries 3 and4). The crudeproduct of  the reaction with  6g   could not be analyzed in detail, but  6g   wasclearly present among the other compounds. The benzimidazole 5g  , though, could not be detected (NMR). The transformations with 6b ,  6e , and  6f   were the only ones where the benzimidazoles  5b ,  5e ,and  5f   were obtained as the sole products (Table 2, entries 2, 5 and 6)—but in yields considerably lower than those obtained in the lac-case-catalyzed reactions (Table 1, entries 2, 5 and 6) and less purecrude products.These results unambiguously demonstrate that the laccase-catalyzed oxidative transformation of   1a  and  6  is superior to thenon-enzymatic version with respect to yield and purity of the2-aryl-1 H  -benzimidazoles.To summarize, a new application for the laccase-catalyzed aer-obic oxidation of a C–N-single bond to a C @ N-double bond hasbeen discovered, namely the efficient synthesis of 2-aryl-1 H  -benz-imidazoles  5  by the reaction of   o -phenylenediamine ( 1a ) withbenzaldehydes  6  under mild conditions. References and notes 1. (a) Morozova, O. V.; Shumakovich, G. P.; Gorbacheva, M. A.; Shleev, S. V.;Yaropolov, A. I.  Biochemistry (Moscow)  2007 ,  72 , 1136; (b) Claus, H.  Micron 2004 ,  35 , 93; (c) Mayer, A. M.; Staples, R. C.  Phytochemistry  2002 ,  60 , 551.2. (a) Witayakran, S.; Ragauskas, A. J.  Adv. Synth. Catal.  2009 ,  351 , 1187; (b)Mikolasch, A.; Schauer, F.  Appl. Microbiol. Biotechnol.  2009 ,  82 , 605; (c)Kunamneni, A.; Camarero, S.; García-Burgos, C.; Plou, F. J.; Ballesteros, A.;Alcalde, M.  Microb. Cell Factories  2008 ,  7  , 32.3. (a) Potthast, A.; Rosenau, T.; Chen, C.-L.; Gratzl, J. S.  J. Org. Chem.  1995 ,  60 , 4320;(b) Astolfi, P.; Brandi, P.; Galli, C.; Gentili, P.; Gerini, M. F.; Greci, L.; Lanzalunga,O.  New J. Chem.  2005 ,  29 , 1308; (c) d‘Acunzo, F.; Baiocco, P.; Galli, C.  New J.Chem.  2003 ,  27  , 329; (d) Wells, A.; Teria, M.; Eve, T.  Biochem. Soc. Trans.  2006 ,  34 , 304.4. (a) Mikolasch, A.; Niedermeyer, T. H. J.; Lalk, M.; Witt, S.; Seefeldt, S.; Hammer,E.; Schauer, F.; Gesell Salazar, M.; Hessel, S.; Jülich, W.-D.; Lindequist, U.  Chem.Pharm. Bull.  2007 ,  55 , 412; (b) Witayakran, S.; Ragauskas, A. J.  Green Chem. 2007 ,  9 , 475; (c) Niedermeyer, T. H. J.; Mikolasch, A.; Lalk, M.  J. Org. Chem.  2005 , 70 , 2002.5. (a) Pickel, B.; Constantin, M.-A.; Pfannstiel, J.; Conrad, J.; Beifuss, U.; Schaller, A.  Angew. Chem., Int. Ed.  2010 ,  49 , 202; (b) Ponzoni, C.; Beneventi, E.; Cramarossa,M. R.; Raimondi, S.; Trevisi, G.; Pagnoni, U. M.; Riva, S.; Forti, L.  Adv. Synth. Catal. 2007 ,  349 , 1497; (c) Nicotra, S.; Intra, A.; Ottolina, G.; Riva, S.; Danieli, B. Tetrahedron: Asymmetry  2004 ,  15 , 2927; (d) Nicotra, S.; Cramarossa, M. R.;Mucci, A.; Pagnoni, U. M.; Riva, S.; Forti, L.  Tetrahedron  2004 ,  60 , 595.6. (a) Hajdok, S.; Conrad, J.; Leutbecher, H.; Strobel, S.; Schleid, T.; Beifuss, U.  J.Org. Chem.  2009 ,  74 , 7230; (b) Leutbecher, H.; Hajdok, S.; Braunberger, C.;Neumann, M.; Mika, S.; Conrad, J.; Beifuss, U.  Green Chem.  2009 ,  11 , 676; (c)Leutbecher, H.; Conrad, J.; Klaiber, I.; Beifuss, U.  Synlett   2005 , 3126.7. (a) Chauhan, S. M. S.; Bisht, T.; Garg, B.  Tetrahedron Lett.  2008 ,  49 , 6646; (b) Niu,S. Y.; Zhang, S. S.; Ma, L. B.; Jiao, K.  Bull. Korean Chem. Soc.  2004 ,  25 , 829; (c)Zuyun, H.; Houping, H.; Ruxiu, C.; Yun’e, Z.  Anal. Chim. Acta  1998 ,  374 , 99.  Table 1 Synthesis of 2-aryl-1 H  -benzimidazoles  5  by reaction of equimolar amounts of  o -phenylenediamine ( 1a ) and benzaldehydes  6a – g   under aerobic conditions usinglaccase from  A. bisporus  as a catalyst Entry  6  Buffer/MeOH (v:v) Time (h)  5  Yield (%)1  a  1:0 18  a  742  b  5:2 5  b  733  c  5:2 5  c  504  d  8:2 4  d  625  e  1:0 3  e  996  f   1:0 5  f   827  g   1:0 3  g   80 NHN RNH 2 NH 2 OHC 1a 65 + Rair buffer, pH = 4.4r.t., 20 hR 9 NNR + Scheme 4.  Reaction of   1a  and  6  under aerobic conditions in acetate buffer (pH 4.4)in the absence of laccase.  Table 2 Reaction of 1 equiv  o -phenylenediamine ( 1a ) with 2 equiv of benzaldehydes  6a – g  under air in acetate buffer (pH 4.4) and in the absence of laccase Entry  6  Buffer/MeOH (v:v) Product(s) a Total yield (%)1  a  9:1  5a / 9a  (20:3) 342  b  5:2  5b  313  c  5:2  5c / 9c  (2:1) 77 b 4  d  8:2  5d / 9d  (10:3) 995  e  1:0  5e  826  f   1:0  5f   157  g   1:0 — — ca All reactions were vigorously stirred using a magnetic stirrer for 20 h in acetatebuffer (0.2 M, pH 4.4) at rt under air. b In addition, the product also contains a side product of unknown structure. c The crude product is a mixture of   6g   and products of unknown structure.606  H. Leutbecher et al./Tetrahedron Letters 52 (2011) 604–607   8. (a) Alamgir, M.; Black, D. St. C.; Kumar, N.  Top. Heterocycl. Chem.  2007 ,  9 , 87; (b)Spasov, A. A.; Yozhitsa, I. N.; Bugaeva, L. I.; Anisimova, V. A.  Pharm. Chem. J. 1999 ,  33 , 232.9. (a) Grimmett, M. R.  Imidazole and Benzimidazole Synthesis ; Academic Press:London, 1997; (b) Grimmett, M. R. In  Comprehensive Heterocyclic Chemistry ;Katritzky, A. R., Rees, C. W., Eds.; Pergamon: London, 1984; Vol. 5, p 457; (c)Preston, P. N.  Chem. Rev.  1974 ,  74 , 279.10. (a) Blettner, C. G.; König, W. A.; Rühter, G.; Stenzel, W.; Schotten, T.  Synlett  1999 , 307; (b) Hopkins, K. T.; Wilson, W. D.; Bender, B. C.; McCurdy, D. R.; Hall, J. E.; Tidwell, R. R.; Kumar, A.; Bajic, M.; Boykin, D. W.  J. Med. Chem.  1998 ,  41 ,3872; (c) Bahrami, K.; Khodaei, M. M.; Naali, F.  J. Org. Chem.  2008 ,  73 , 6835; (d)Das, B.; Holla, H.; Srinivas, Y.  Tetrahedron Lett.  2007 ,  48 , 61; (e) Beaulieu, P. L.;Haché, B.; von Moos, E.  Synthesis  2003 , 1683; (f) Gogoi, P.; Konwar, D. Tetrahedron Lett.  2006 ,  47  , 79; (g) Denny, W. A.; Rewcastle, G. W.; Baguley, B. C.  J. Med. Chem.  1990 ,  33 , 814.11. (a) Raju, B. C.; Theja, N. D.; Kumar, J. A.  Synth. Commun.  2009 ,  39 , 175; (b)Rostamizadeh, S.; Amani, A. M.; Aryan, R.; Ghaieni, H. R.; Norouzi, L.  Monatsh.Chem.  2009 ,  140 , 547; (c) Chen, Y.-X.; Qian, L.-F.; Zhang, W.; Han, B.  Angew.Chem.  2008 ,  120 , 9470; (d) Sharghi, H.; Beyzavi, M. H.; Doroodmand, M. M.  Eur. J. Org. Chem.  2008 , 4126; (e) Mukhopadhyay, C.; Tapaswi, P. K.  Catal. Commun. 2008 ,  9 , 2392; (f) Trivedi, R.; De, S. K.; Gibbs, R. A.  J. Mol. Catal. A: Chem.  2006 ,  245 , 8; (g) Itoh, T.; Nagata, K.; Ishikawa, H.; Ohsawa, A.  Heterocycles  2004 ,  63 ,2769; (h) Curini, M.; Epifano, F.; Montanari, F.; Rosati, O.; Taccone, S.  Synlett  2004 , 1832.12. (a) Jacob, R. G.; Dutra, L. G.; Radatz, C. S.; Mendes, S. R.; Perin, G.; Lenardão, E. J. Tetrahedron Lett.  2009 ,  50 , 1495; (b) Sharma, S. D.; Konwar, D.  Synth. Commun. 2009 ,  39 , 980; (c) Salehi, P.; Dabiri, M.; Zolfigol, M. A.; Otokesh, S.;Baghbanzadeh, M.  Tetrahedron Lett.  2006 ,  47  , 2557.13. For all experiments commercially available laccase (EC from  A.bisporus  (Fluka) was used. Laccase activity was determined according to (a)Land, E. J.  J. Chem. Soc., Faraday Trans.  1993 ,  89 , 803; (b) Felici, M.; Artemi, F.;Luna, M.; Speranza, M.  J. Chromatogr., A  1985 ,  320 , 435.14.  General procedure for synthesis of   5a – g  : 1.0 equiv  6  (0.2 mmol) [ 6b  (0.13 mmol), 6c  (0.18 mmol),  6d  (0.11 mmol), respectively] and 1.0 equiv  o -phenylenedi-amine ( 1a ) were dissolved in phosphate buffer (14 mL, 0.2 M, pH 6.0) or aphosphate buffer/methanol mixture (see Table 1). 31 U laccase from  Agaricusbisporus  were added. The reaction mixture was shaken with a shakingfrequency of 850 rpm using a liquid phase synthesis system ‘Synthesis 1’(Heidolph) for 3–18 h (see Table 1) at room temperature under air until thesubstrates had been fully consumed. Alternatively, the reaction could beperformed using a magnetic stirrer at high stirring speed. The reaction mixturewas saturated with sodium chloride and filtered through a Büchner funnel. Forisolation of products  5a – d  2 M KOH (1 mL) was added before filtration. Thefilter cake was washed with 15% sodium chloride solution (20 mL) and water(2 mL) and dried at room temperature to yield pure heterocycles  5a – g   (NMR).Analytically pure compounds could be obtained via recrystallization.15.  Selected data for   5g  : IR (ATR)  ~ m  2652 (NH), 1626, 1563 and 1454 (C @ C), 1196(SO 3 ), 753 cm  1 ( @ C–H); UV–vis (MeOH)  k max  (log  e ) 202 (4.47), 238 (3.96),278 nm (4.07);  1 H NMR (300 MHz, CD 3 OD)  d  7.52–7.57 (m, 2H, 5-H and 6-H),7.63–7.73 (m, 1H, 5 0 -H), 7.71–7.75 (m, 1H, 4 0 -H), 7.74–7.78 (m, 2H, 4-H and 7-H), 7.77–7.82 (m, 1H, 6 0 -H), 8.13 (d,  3  J  3 0 -H, 4 0 -H  = 7.6 Hz, 1H, 3 0 -H);  13 C NMR (75 MHz, CD 3 OD)  d  115.47 (C-4 and C-7), 122.38 (C-1 0 ), 127.94 (C-5 and C-6),129.75(C-3 0 ),132.14(C-5 0 ),132.75(C-6 0 ),133.04(C-3aandC-7a),134.28(C-4 0 ),146.88 (C-2 0 ), 150.48 (C-2); MS (EI, 70 eV)  m /  z   274 [M + ] (15%), 256 [M +  H 2 O](3), 224 (2), 210 (8), 194 [M +  SO 3 ] (100), 166 (4), 91 (4), 44 (17); HRMS (EI,70 eV)  m /  z   calculated for C 13 H 10 N 2 O 3 S [M + ] 274.0412; found 274.0416. H. Leutbecher et al./Tetrahedron Letters 52 (2011) 604–607   607

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Jun 2, 2018
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