Mannich反应合成3,6(8)-二取代-2,4-二氢-1,3-苯并噁嗪及其杀菌活性

doi:10.3724/SP.J.1095.2013.20507

摘要/Abstract

摘要： 以取代苯酚、多聚甲醛和取代苯胺为原料，在无催化剂的条件下，通过Mannich缩合反应合成了一系列新型3,6(8)-二取代-2,4-二氢-1,3-苯并噁嗪类化合物。结果表明，取代苯酚和取代苯胺的取代基为供电子基时，合成产物的产率高于吸电子取代基的。产物的结构用1H NMR、13C NMR、IR和MS等进行了表征。初步测试了目标化合物的杀菌活性，部分化合物具有较好的杀菌活性。当浓度为25 mg/L时，化合物4j和4d对菌核病菌的抑制率分别为86.1％和81.5％，化合物4i对灰霉病菌的抑制率为81.6％。

关键词: 二取代-二氢-苯并噁嗪, 合成, Mannich反应, 杀菌活性

Abstract: A series of novel 3,6(8)-disubstituted 2,4-dihydro-1,3-benzoxazines was synthesized by Mannich reactions of substituted anilines with paraformaldehyde and substituted phenols in the absence of catalyst. The results show that substituted phenols and anilines with electron-donating groups on the phenyl ring give higher yields than those with electron-withdrawing groups. The structures of the products were characterized by 1H NMR, 13C NMR, IR and MS. The fungicidal activity of the title compounds was preliminarily evaluated. Compounds 4j and 4d show 86.1％ and 81.5％ activity against Sclerotonia sclerotiorum at the concentration of 25 mg/L, respectively. Compound 4i exhibits 81.6％ activity against Botrytis cinerea.

Key words: disubstituted-dihydro-benzoxazines, synthesis, Sterilization Activity

中图分类号:

O646

唐子龙, 夏赞稳, 马红伟, 刘汉文, 欧晓明. Mannich反应合成3,6(8)-二取代-2,4-二氢-1,3-苯并噁嗪及其杀菌活性[J]. 应用化学, DOI: 10.3724/SP.J.1095.2013.20507.

TANG Zilong1,2,3*, XIA Zanwen1, MA Hongwei1, LIU Hanwen1,2,3, OU Xiaoming2,4. Synthesis of 3,6 (8)-Disubstituted -2,4-Dihydro-1,3-benzoxazines via Mannich Reaction and Their Fungicidal Activity[J]. Chinese Journal of Applied Chemistry, DOI: 10.3724/SP.J.1095.2013.20507.

参考文献

[1] Urbanski T. New Derivatives of Nitroparaffins and Their Antitubercular and Antirickettsial Properties[J]. Nature,1951,168:562-563.

[2] Kuehne M E,Konopka E A. Dihydro-1,3-oxazines as Antitumor Agents[J]. J Med Chem,1962,5(2):257-280.

[3] Kuehne M E,Konopka E A,Lambert B F. Steroidal Dihydro-1,3-oxazines as Antitumor Agents[J]. J Med Chem,1962,5(2):281-296.

[4] Bouaziz Z,Riondel J,Mey A,et al. Synthesis of Some Naphthoxazine Carbolactone Derivatives with in Vitro Cytotoxic and Antifungal Activities[J]. Eur J Med Chem,1991,26(4):469-472.

[5] Zhang P,Terefenko E A,Fensome A,et al. 6-Aryl-1,4-dihydro-benzo[d][1,3] oxazin-2-ones:a Novel Class of Potent, Selective, and Orally Active Nonsteroidal Progesterone Receptor Antagonists[J]. J Med Chem,2002,45(20):4379-4382.

[6] Wang S,Li Y,Liu Y,et al. Novel Hexacyclic Camptothecin Derivatives:Part 1.Synthesis and Cytotoxicity of Camptothecins with an a-Ring Fused 1,3-Oxazine Ring [J]. Bioorg Med Chem Lett,2008,18:4095-4097.

[7] Tang Z,Zhu Z,Xia Z,et al. Synthesis and Fungicidal Activity of Novel 2,3-Disubstituted-3-benzoxazines[J]. Molecules,2012,17:8174-8185.

[8] Tang Z,Chen W,Zhu Z,et al. Synthesis of 2,3-Diaryl-3,4-dihydro-2H-1,3-benzoxazines and Their Fungicidal Activities[J]. J Heterocycl Chem,2011,48:255-260.

[9] Kerdesky F A. A Novel and Efficient Method for the Conversion of a Trans-hexahydronaphthoxazine to a cis-Isomer Using Boron Tribromide[J]. Tetrahedron Lett,2005,46:1711-1712.

[10] Tomasulo M,Sortino S,White A,et al. Fast and Stable Photochromic Oxazines[J]. J Org Chem,2005,70:8180-8189.

[11] Deniz E,Tomasulo M,Sortino S,et al. Substituent Effects on the Photochromic of Bichromophoric Oxazines[J]. J Phys Chem C,2009,113:8491-8497.

[12] Jin L,Agag T,Yagci Y,et al. Methacryloyl-functional Benzoxazine:Photopolymerization and Thermally Activated Polymerization[J]. Macromolecules,2011,44:767-772.

[13] Baqar M,Agag T,Huang R,et al. Mechanistic Pathways for the Polymerization of Methylol-functional Enzoxazine Monomers[J]. Macromolecules,2012,45:8119-8125.

[14] Schimidt C,Straub T,Falabu D,et al. Selective Derivatisation of Resorcarenes,Mannich Reactions with Amino Alcohols[J]. Eur J Chem,2000:3937-3944.

[15] Kukharev V F,Stankevich V K,Tiumov M P,et al. A New Heterocyclic System-2,3,4,6,11b-pentahydro[1,3]-Oxazino[3,2-c][1,3]benzoxazine[J]. Chem Heterocycl Compd,2002,38(11):1434-1435.

[16] Tang Z,Chen W,Zhu Z ,et al. SnCl4-catalyzed Aza-acetalization of Aromatic Aldehydes:Synthesis of Aryl Substituted 3,4-dihydro-2H-benzoxazines[J]. Synth Commun,2012,42:1372-1383.

[17] TANG Zilong,CHANG Shuhong,YAN Lin,et al. Synthesis and Fungicidal Activity of 2-(1,3,4-Thiadiazolylaminomethyl) phenols[J]. Chinese J Appl Chem,2012,29(8):878-884(in Chinese).

唐子龙，常书红，颜林，等. 2-(1,3,4-噻二唑胺甲基)苯酚的合成及其杀菌活性[J]. 应用化学，2012,29(8):878-884.

[18] Liu A,Ou X,Huang M,et al. Synthesis and Insecticidal Activities of Novel Oxime Ether Pyrethroids[J]. Pest Manag Sci,2005,61:166-170.

[19] Mezheritskii V,Kagan E,Ardashev B. Synthesis of 2,5-Divinylpyridine by the Mannich Reaction[J]. Chem Heterocycl Compd,1967,3(4):677-678.

[20] XIAO Shangyou,ZENG Qingwen,CHEN Zhitao,et al. Mannich Reactions of Aromatic Aldehydes with Aromatic Amines and Aromatic Ketones[J]. J Chongqing Univ(Nat Sci Edn),2000,23(1):102-104,122(in Chinese).

肖尚友，曾庆文，陈志涛，等. 芳香醛与芳香酮及芳胺的曼尼希反应[J]. 重庆大学学报（自然科学版），2000,23(1):102-104,122.