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Contents Vol 68(2)

Reactions of Methyl Ketones and (Hetero)arylcarboxamides with N,N-Dimethylacetamide Dimethyl Acetal. A Simple Metal-Free Synthesis of 2,4,6-Trisubstituted Pyridines*

Benjamin Prek A B , Uroš Grošelj A , Marta Kasunič A , Silvo Zupančič C , Jurij Svete A B and Branko Stanovnik A B D
+ Author Affiliations
- Author Affiliations

A Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, PO Box 537, 1000 Ljubljana, Slovenia.

B EN-FIST Center of Excellence, Trg OF 13, 1000 Ljubljana, Slovenia.

C FARMA GRS, Seidlova cesta 70, 8000 Novo mesto, Slovenia.

D Corresponding author. Email: branko.stanovnik@fkkt.uni-lj.si

Australian Journal of Chemistry 68(2) 184-195 https://doi.org/10.1071/CH14349
Submitted: 30 May 2014  Accepted: 19 June 2014   Published: 3 September 2014

Abstract

Two metal-free syntheses of 2,4,6-trisubstituted pyridines 10a–m and 16a–j are described. N,N,6-Trimethyl-4-(substituted)pyridin-2-amines 10 were prepared from aryl or heteroaryl methyl ketones which were transformed with N,N-dimethylacetamide dimethyl acetal (DMADMA) into enaminones 4a–m, followed by treatment with ammonium acetate to give (Z)-3-amino-1-(substituted)but-2-en-1-ones 5a–m. These were treated with DMADMA under microwave irradiation in a closed vessel at 130°C, to give via intermediates 7–9 the final products 10a–m. N2,N2,N4,N4-Tetramethyl-6-(substituted) pyridine-2,4-diamines 16a–j were prepared in a one-pot synthesis from the corresponding carboxamides 11a–j by treatment with an excess of DMADMA in a closed vessel under microwave irradiation to give via intermediates 12a–j to 15a–j the final products 16a–j. X-Ray single crystal diffractometry studies of the enaminones 5c, 5g, 5i, 5j, and 5m and 2,4,6-trisubstituted pyridines 16a, 16b, 16g, 16i, and 16j were consistent with the expected structures.


References

[1]  J. S. Carey, D. Laffan, C. Thomson, M. T. Williams, Org. Biomol. Chem. 2006, 4, 2337.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XlsV2jtr8%3D&md5=965798f4047494e3ac2b264893f91cebCAS | 16763676PubMed |

[2]  J. Bosch, M.-L. Bennasar, Synlett 1995, 587.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXntFagtrs%3D&md5=1695630f87d72798e9804fd396f4e2c7CAS |

[3]  A. Sinclair, R. A. Stockman, Nat. Prod. Rep. 2007, 24, 298.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXlt1Oqsr0%3D&md5=4c28f89ea6e1047c22095d50f546f30cCAS | 17389999PubMed |

[4]  P. A. Keller, in Comprehensive Heterocyclic Chemistry III (Eds A. R. Katritzky, C. A. Ramsden, E. F. V. Scriven, R. J. K. Taylor) 2008, Vol. 7 (Ed. D. StC. Black), pp. 217–307 (Elsevier: Amsterdam).

[5]  D. Spitzner, in Science of Synthesis (Ed. D. StC. Black) 2006, Vol. 15, pp. 11–284 (Thieme Verlag: Stuttgart).

[6]  P. A. Keller, in Science of Synthesis (Ed. D. StC. Black) 2006, Vol. 15, pp. 285–387 (Thieme: Stuttgart).

[7]  J. J. Li, G. W. Gribble, Palladium in Heterocyclic Chemistry 2000 (Pergamon Press: New York, NY).

[8]  G. Zeni, R. C. Larock, Chem. Rev. 2006, 106, 4644.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVKitbzM&md5=c0d5ea9b62b673b77581f3d176457b10CAS | 17091931PubMed |

[9]  Metal-Catalysed Cross-Coupling Reactions (Eds F. Diederich, P. Stang) 1998 (Wiley-VCH: New York, NY).

[10]  C. Guetz, A. Luetzen, Synthesis 2010, 1, 85.

[11]  D. X. Yang, S. L. Colletti, K. Wu, M. Song, G. Y. Li, H. C. Shen, Org. Lett. 2009, 11, 381.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsFSjtbzE&md5=120c6e4edea5cf2676486c8b49b1d4d9CAS | 19072215PubMed |

[12]  D. M. Knapp, E. P. Gillis, M. D. Burke, J. Am. Chem. Soc. 2009, 131, 6961.and references cited therein.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXlt1Cls7s%3D&md5=cb2dcb34a9639ad86483d70e1f95c7a5CAS | 19405470PubMed |

[13]  M. R. Luzung, J. S. Patel, J. Yin, J. Org. Chem. 2010, 75, 8330.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlOqu7bO&md5=f8a67e1934e076935558737806d3eeecCAS | 21047088PubMed |

[14]  F. Zhang, X.-F. Duan, Org. Lett. 2011, 13, 6102.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlyjsr%2FE&md5=43415884f83a267d1ae79de589a373b6CAS | 22032274PubMed |

[15]  J. Wen, R.-Y. Zhang, S.-Y. Chen, J. Zhang, X.-Q. Yu, J. Org. Chem. 2012, 77, 766.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsFKktrbN&md5=a651301028c2eedd0cdf661f905ae92aCAS | 22136304PubMed |

[16]  B. Stanovnik, J. Heterocycl. Chem. 1999, 36, 1581.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXptl2gug%3D%3D&md5=eadb5a42e36bc7b8021423154dd17fa0CAS |

[17]  B. Stanovnik, J. Svete, Synlett 2000, 1077.
         | 1:CAS:528:DC%2BD3cXlvFWqsbo%3D&md5=adfd1ecbc7bfedc12eabf5ba5311c9adCAS |

[18]  B. Stanovnik, J. Svete, in Targets in Heterocyclic Systems, Synthesis, Reactions and Properties (Eds O. A. Attanasi, D. Spinelli) 2000, Vol. 4, pp. 105–137 (Italian Society of Chemistry: Rome).

[19]  B. Stanovnik, J. Svete, Chem. Rev. 2004, 104, 2433.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtFGjs7c%3D&md5=bcb5c35cdd50ef6eac68fbe807b5a1feCAS | 15137796PubMed |

[20]  J. Svete, J. Heterocycl. Chem. 2005, 42, 361.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXjs12ku7o%3D&md5=b9bf9a42c25d2cc60f8d49455e84b6b8CAS |

[21]  L. Selič, R. Jakše, K. Lampič, L. Golič, S. Golič-Grdadolnik, B. Stanovnik, Helv. Chim. Acta 2000, 83, 2802.
         | Crossref | GoogleScholarGoogle Scholar |

[22]  L. Selič, B. Stanovnik, Tetrahedron 2001, 57, 3159.
         | Crossref | GoogleScholarGoogle Scholar |

[23]  R. Jakše, J. Svete, B. Stanovnik, A. Golobič, Tetrahedron 2004, 60, 4601.
         | Crossref | GoogleScholarGoogle Scholar |

[24]  Z. Časar, D. Bevk, J. Svete, B. Stanovnik, Tetrahedron 2005, 61, 7508.
         | Crossref | GoogleScholarGoogle Scholar |

[25]  J. Wagger, D. Bevk, A. Meden, J. Svete, B. Stanovnik, Helv. Chim. Acta 2006, 89, 240.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XitlGmur4%3D&md5=f909b178f26df522522264c861ee0b7cCAS |

[26]  J. Wagger, S. Golič Grdadolnik, U. Grošelj, A. Meden, J. Svete, B. Stanovnik, Tetrahedron Asymmetry 2007, 18, 464.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjsVOjs7s%3D&md5=b7c4931ece6d48e161d96f2cd4611932CAS |

[27]  J. Wagger, U. Grošelj, A. Meden, J. Svete, B. Stanovnik, Tetrahedron 2008, 64, 2801.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXitlaltL8%3D&md5=63a16922914bc2360d5a1843862aaf84CAS |

[28]  J. Bezenšek, T. Koleša, U. Grošelj, A. Meden, K. Stare, J. Svete, B. Stanovnik, Curr. Org. Chem. 2011, 15, 2530.
         | Crossref | GoogleScholarGoogle Scholar |

[29]  J. Bezenšek, T. Koleša, U. Grošelj, J. Wagger, K. Stare, A. Meden, J. Svete, B. Stanovnik, Tetrahedron Lett. 2010, 51, 3392.
         | Crossref | GoogleScholarGoogle Scholar |

[30]  F. Bohlmann, D. Rahtz, Chem. Ber. 1957, 90, 2265.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaG1cXlsFyqug%3D%3D&md5=a383ab1e3a6c35e954f626f2675c25cdCAS |

[31]  M. C. Bagley, J. W. Dale, J. Bower, Synlett 2001, 1149.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXltVylt7c%3D&md5=10506b1be61916abb091cecdff9c56bfCAS |

[32]  J. Bezenšek, B. Prek, U. Grošelj, M. Kasunič, J. Svete, B. Stanovnik, Tetrahedron 2012, 68, 4719.
         | Crossref | GoogleScholarGoogle Scholar |

[33]  G. Maas, B. Singer, P. Wald, M. Gimmy, Chem. Ber. 1988, 121, 1847.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1cXmtlSnu78%3D&md5=e812348b202bb223a95f41e7e34ac079CAS |

[34]  R. Rahm, G. Maas, Chem. Ber. 1994, 127, 1295.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXltlCjt70%3D&md5=79a0ae31648e6346f915860826a4a959CAS |

[35]  K. Drandarov, I. Tiritiris, O. Wassiljew, H.-U. Siehl, W. Kantlehner, Chem. – Eur. J. 2012, 18, 7224.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XlvFentLg%3D&md5=23d819064d8826bb190a7cf42ebf6858CAS | 22527911PubMed |

[36]  J. Bezenšek, B. Prek, U. Grošelj, A. Golobič, K. Stare, J. Svete, W. Kantlehner, G. Maas, B. Stanovnik, Z. Naturforsch. 2014, 69b, 554.
         | Crossref | GoogleScholarGoogle Scholar |

[37]  B. Prek, J. Bezenšek, M. Kasunič, U. Grošelj, J. Svete, B. Stanovnik, Tetrahedron 2014, 70, 2359.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXjsVCqt70%3D&md5=f8db575d375352ecfea9fd6f7deb1acbCAS |

[38]  M. M. Abdel-Khalik, M. H. Elnagdi, Synth. Commun. 2002, 32, 159.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xhtlahtb8%3D&md5=301101abca6d371fc8a269f90124d46aCAS |

[39]  A. Z. A. Hassanien, S. A. S. Ghoslan, M. H. Elnagdi, J. Heterocycl. Chem. 2003, 40, 225.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXjsVamt7g%3D&md5=78bd5e9ae61b849f3f0d93bb2fba7b27CAS |

[40]  F. Eiden, K. Berndl, Arch. Pharm. (Weinheim, Ger.) 1986, 319, 338.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28XksValur8%3D&md5=928b589f62a35df54256e1282794378eCAS |

[41]  Y.-I. Lin, S. A. Lang, J. Heterocycl. Chem. 1977, 14, 345.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE2sXksFeisb0%3D&md5=abc24c43d1fe6e4e72d0f75e5e6099fcCAS |

[42]  H. Bredereck, F. Effenberger, H. Botsch, Chem. Ber. 1964, 97, 3397.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF2MXjs1GntQ%3D%3D&md5=1b3df3c5da90cf5b0832e2d962247d53CAS |

[43]  T. I. Mukhanova, L. M. Alekseyeva, Y. F. Kuleshova, Y. N. Sheinker, V. G. Granik, Khim. Farm. Zh. 1993, 27, 60.
         | 1:CAS:528:DyaK2cXntVSksrY%3D&md5=ea865288de954bc3362a5e690bc06027CAS |

[44]  P. G. Baraldi, D. Simoni, S. Manfredini, Synthesis 1983, 1983, 902.
         | Crossref | GoogleScholarGoogle Scholar |

[45]  S. Jain, R. Jain, J. Singh, N. Anand, Tetrahedron Lett. 1990, 1, 131.

[46]  F. Zhao, X. Lin, R. Qi, D. Zhang-Negrerie, J. Huang, Y. Du, K. Zhao, J. Org. Chem. 2011, 76, 10338.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsVCgtL3P&md5=fa4ecc6bbb8b1c4772f2cd63ac20a232CAS | 22066895PubMed |

[47]  B. Singh, G. Y. Lesher, J. Heterocycl. Chem. 1990, 27, 2085.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3MXkt12it7k%3D&md5=b59c6836ca85c403a14f0f32710b290fCAS |

[48]  L. Cao, J. Ding, M. Gao, Z. Wang, J. Li, A. Wu, Org. Lett. 2009, 11, 3810.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXps1ekur8%3D&md5=e6961c77332c85f601c3fb31cfb78012CAS | 19663463PubMed |

[49]  CrysAlis PRO 2011 (Oxford Diffraction Ltd: Yarnton, UK).

[50]  A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C. Giacovazzo, A. Guagliardi, A. G. G. Moliterni, G. Polidori, R. Spagna, J. Appl. Crystallogr. 1999, 32, 115.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXhsFOrsbo%3D&md5=50eb4e0e2e2b1ff525c9a58324a20359CAS |

[51]  L. Palatinus, G. Chapuis, J. Appl. Crystallogr. 2007, 40, 786.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXnslWqtrg%3D&md5=2df99aa27af3cc91ffa6b0fb5fe0c584CAS |

[52]  O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard, H. Puschmann, J. Appl. Crystallogr. 2009, 42, 339.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjsFSnsbg%3D&md5=aaca26860e75b3466b3e308b609249aeCAS |

[53]  G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, 64, 112.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsVGhurzO&md5=e60798290754f1a9dfe9beb4e8e0b93dCAS |

[54]  L. J. Farrugia, J. Appl. Crystallogr. 1997, 30, 565.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXnt1KgsLg%3D&md5=a7266c74c349b9b85af8754926af7bf6CAS |