Efficient Construction of Oxazole via Base-Promoted Tandem Cyclization Reaction of Amides and Propargyl Halides

doi:10.6023/cjoc202511012

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (5): 2010-2016.DOI: 10.6023/cjoc202511012 Previous Articles Next Articles

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碱促进的酰胺与炔丙基卤代物串联环化高效构建噁唑骨架

罗倩婷^a^,^b, 焦丽萍^c, 种雪兰^b, 张建欣^b, 王庆兵^b^,^*(), 何华锋^*()

^a 山东第一医科大学(山东省科学院)药学院(药物研究所) 济南 271016
^b 济宁医学院药学院山东日照 276826
^c 山东中医药大学药学院济南 250355

收稿日期:2025-12-30 修回日期:2026-03-05 发布日期:2026-03-20
基金资助:
日照市自然科学基金(RZ2021ZR27)

Efficient Construction of Oxazole via Base-Promoted Tandem Cyclization Reaction of Amides and Propargyl Halides

Qianting Luo^a^,^b, Liping Jiao^c, Xuelan Chong^b, Jianxin Zhang^b, Qingbing Wang^b^,^*(), Huafeng He^*()

^a School of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 271016
^b School of Pharmacy, Jining Medical University, Rizhao, Shandong 276826
^c School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355

Received:2025-12-30 Revised:2026-03-05 Published:2026-03-20
Contact: * E-mail: wangqb@mail.jnmc.edu.cn; captainhuafeng@mail.jnmc.edu.cn
Supported by:
Rizhao Natural Science Foundation(RZ2021ZR27)

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Abstract

Oxazole has a unique heterocyclic structure and is the parent nucleus in various natural active products and pharmaceutical molecules. It is important to develop an efficient approach to construct oxazole, as well as for new drug research and development. In this study, a series of 2-aryl-5-methyl oxazoles were obtained with high efficiency at 120 ℃ for 3 h, using potassium methoxide as the base, and benzamides and propargyl halides as the substrates. This base-driven strategy involves a cascade sequence: nucleophilic substitution between the propargyl halide and amide, enolization of the amide, and intramolecular nucleophilic addition to the unsaturated bond. This approach exhibits high compatibility with aromatic and aliphatic amides, producing 19 oxazole compounds with moderate yields (including 5 new compounds). This study provides a new approach for the efficient construction of oxazole skeleton with convenience and feasibility, laying a solid foundation for subsequent bioactivity selectivity of oxazole-based lead compounds and new drug development.

Key words: oxazole, tandem reactions, propynyl group, amide, green synthesis

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Qianting Luo, Liping Jiao, Xuelan Chong, Jianxin Zhang, Qingbing Wang, Huafeng He. Efficient Construction of Oxazole via Base-Promoted Tandem Cyclization Reaction of Amides and Propargyl Halides[J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2010-2016.

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References 35

[1]	Peng X.-M.; Cai G.-X.; Zhou C.-H. Curr. Top. Med. Chem. 2013, 13, 1963. doi: 10.2174/15680266113139990125
[2]	Yadav P.; Shah K. Med. Chem. 2025, 21, 1.
[3]	Zhang W.; Liu W.; Jiang X.; Jiang F.; Zhuang H.; Fu L. Eur. J. Med. Chem. 2011, 46, 3639. doi: 10.1016/j.ejmech.2011.05.028 pmid: 21641699
[4]	Kumar G.; Singh N. P. Bioorg. Chem. 2021, 107, 104608. doi: 10.1016/j.bioorg.2020.104608
[5]	Liu J. R.; Jiang E. Y.; Sukhbaatar O.; Zhang W. H.; Zhang M. Z.; Yang G. F.; Gu Y. C. Med. Res. Rev. 2025, 45, 97. doi: 10.1002/med.v45.1
[6]	Guerrero-Pepinosa N. Y.; Cardona-Trujillo M. C.; Garzon-Cas- tano S. C.; Veloza L. A.; Sepúlveda-Arias J. C. Biomed. Pharmacother. 2021, 138, 111495. doi: 10.1016/j.biopha.2021.111495 pmid: 33765586
[7]	Velluti F.; Mosconi N.; Acevedo A.; Borthagaray G.; Castiglioni J.; Faccio R.; Back D. F.; Moyna G.; Rizzotto M.; Torre M. H. J. Inorg. Biochem. 2014, 141, 58. doi: 10.1016/j.jinorgbio.2014.08.007
[8]	Wang B.; Hansen T. M.; Wang T.; Wu D.; Weyer L.; Ying L.; Engler M. M.; Sanville M.; Leitheiser C.; Christmann M.; Lu Y.; Chen J.; Zunker N.; Cink R. D.; Ahmed F.; Lee C.-S.; Forsyth C. J. J. Am. Chem. Soc. 2011, 133, 1484. doi: 10.1021/ja108906e pmid: 21190385
[9]	Yang R.; Cui L.; Xu S.; Zhong Y.; Xu T.; Liu J.; Guo Y. J. Med. Chem. 2024, 67, 16858. doi: 10.1021/acs.jmedchem.4c01860
[10]	Wasserman H. H.; McCarthy K. E.; Prowse K. S. Chem. Rev. 1986, 86, 845. doi: 10.1021/cr00075a008
[11]	Brooks D. A. Name Reactions in Heterocyclic Chemistry, Wiley- Interscience, Hoboken, 2005, pp. 220-224.
[12]	Evans D. A.; Nagorny P.; Xu R. Org. Lett. 2006, 8, 5669. doi: 10.1021/ol0624530
[13]	Beletskii E. V.; Kuznetsov M. A. Russ. J. Org. Chem. 2009, 45, 1229. doi: 10.1134/S107042800908020X
[14]	Corrao S. L.; Macielag M. J.; Turchi I. J. J. Org. Chem. 1990, 55, 4484. doi: 10.1021/jo00301a056
[15]	Lee C.-Y.; Chen Y.-C.; Lin H.-C.; Jhong Y.; Chang C.-W.; Tsai C.-H.; Kao C.-L.; Chien T.-C. Tetrahedron 2012, 68, 5898. doi: 10.1016/j.tet.2012.04.102
[16]	Shaw A. Y.; Xu Z.; Hulme C. Tetrahedron Lett. 2012, 53, 1998. doi: 10.1016/j.tetlet.2012.02.030
[17]	Zheng X.; Liu W.; Zhang D. Molecules 2020, 25, 1594. doi: 10.3390/molecules25071594
[18]	Tietze L. F. Domino Reactions in Organic Synthesis, Wiley-VCH, Weinheim, 2014, pp. 579-610.
[19]	Kaiser D.; Bauer A.; Lemmerer M.; Maulide N. Chem. Soc. Rev. 2018, 47, 7899. doi: 10.1039/C8CS00335A
[20]	Venkatesha N. J.; Bhat Y. S.; Prakash B. J. Appl. Catal. A: Gen. 2015, 496, 51. doi: 10.1016/j.apcata.2015.02.036
[21]	Schmidt E. Y.; Semenova N. V.; Ivanova E. E.; Ushakov I. A.; Bidusenko I. A.; Bobkov A. S.; Vitkovskaya N. M.; Trofimov B. A. Adv. Synth. Catal. 2025, 367, e202400953. doi: 10.1002/adsc.v367.2
[22]	Hashmi A. S. K.; Weyrauch J. P.; Frey W.; Bats J. W. Org. Lett. 2004, 6, 4391. doi: 10.1021/ol0480067
[23]	Jankowski N.; Dietrich J.; Krause N. Adv. Synth. Catal. 2022, 364, 3404. doi: 10.1002/adsc.v364.19
[24]	Zhou Z. H.; Chen K. H.; He L. N. Chin. J. Chem. 2019, 37, 1223. doi: 10.1002/cjoc.v37.12
[25]	Li M.; He Z.; Zhao W.; Yu Y.; Huang F.; Baell J. B. J. Org. Chem. 2023, 88, 8257. doi: 10.1021/acs.joc.3c00269
[26]	Bao L.; Liu C.; Li W.; Yu J.; Wang M.; Zhang Y. Org. Lett. 2022, 24, 5762. doi: 10.1021/acs.orglett.2c02252
[27]	Zhou Y.; Wang J.; Gu Z.; Wang S.; Zhu W.; Aceña J. L.; Soloshonok V. A.; Liu H. Chem. Rev. 2016, 116, 422. doi: 10.1021/acs.chemrev.5b00392 pmid: 26756377
[28]	Senadi G. C.; Hu W. P.; Hsiao J. S.; Vandavasi J. K.; Chen C. Y.; Wang J. J. Org. Lett. 2012, 14, 4478. doi: 10.1021/ol301980g
[29]	Zhang L.; Xiao K.; Qiao Y.; Li X.; Song C.; Chang J. Eur. J. Org. Chem. 2018, 2018, 6913. doi: 10.1002/ejoc.v2018.48
[30]	Mali J. K.; Takale B. S.; Telvekar V. N. RSC Adv. 2017, 7, 2231. doi: 10.1039/C6RA25857C
[31]	Yasmin N.; Ray J. K. Synlett 2009, 2009, 2825. doi: 10.1055/s-0029-1217995
[32]	Melen R. L.; Hansmann M. M.; Lough A. J.; Hashmi A. S. K.; Stephan D. W. Chem.-Eur. J. 2013, 19, 11928. doi: 10.1002/chem.v19.36
[33]	Safrygin A.; Dar'in D.; Lukin A.; Bakholdina A.; Sapegin A.; Krasavin M. Tetrahedron Lett. 2019, 60, 777. doi: 10.1016/j.tetlet.2019.02.011
[34]	Saltykova L. E.; Vasil'vitskii A. E.; Shostakovskii V. M.; Nefedov O. M. Bull. Acad. Sci. USSR, Div. Chem. Sci. 1988, 37, 2557. doi: 10.1007/BF00952639
[35]	Arcadi A.; Cacchi S.; Cascia L.; Fabrizi G.; Marinelli F. Org. Lett. 2001, 3, 2501. pmid: 11483045

碱促进的酰胺与炔丙基卤代物串联环化高效构建噁唑骨架

Efficient Construction of Oxazole via Base-Promoted Tandem Cyclization Reaction of Amides and Propargyl Halides

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Fig. & Tab. 6

References 35

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Entry	Base	Solvent	Temp./℃	Time/h	Yield^b/%
1	KOH	DMSO	50	12	51
2	KHCO₃	DMSO	50	12	N.R.
3	KOAc	DMSO	50	12	N.R.
4	K₂CO₃	DMSO	50	12	N.R.
5	CH₃OK	DMSO	50	12	64
6	t-BuOK	DMSO	50	12	51
7	DBU	DMSO	50	12	N.R.
8	CH₃OK	Acetone	50	12	55
9	CH₃OK	CH₃CN	50	12	55
10	CH₃OK	DMF	50	12	59
11	CH₃OK	NMP	50	12	54
12	CH₃OK	THF	50	12	N.R.
13	CH₃OK	1,4-Dioxane	50	12	N.R.
14	CH₃OK	CHCl₃	50	12	N.R.
15	CH₃OK	MeOH	50	12	N.R.
16	CH₃OK	DMSO	100	12	56
17	CH₃OK	DMSO	120	12	57
18	CH₃OK	DMSO	120	6	52
19	CH₃OK	DMSO	120	3	63
20^c	CH₃OK	DMF	50	12	52
21^d	CH₃OK	DMF	50	12	57
22^e	CH₃OK	DMF	50	12	58

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