取代肉桂酰甘氨酸甲酯的合成研究
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摘要
在N,N-二甲基乙酰胺(DMAC)促进下,取代肉桂酸(1a～1k)与二氯亚砜(SOCl_2)在25℃酰氯化反应0.5h,再加入甘氨酸甲酯盐酸盐在40℃下酰胺化反应3h,合成了11个取代肉桂酰甘氨酸甲酯(2a～2k),产率80.01%～91.12%,其结构经~1H NMR、~(13)C NMR、IR和EI-MS确证,并探讨了DMAC促进取代肉桂酰甘氨酸甲酯反应可能的机理。
Substituted cinnamyl glycinemethylester(2 a～2 k)were synthesized from the substituted cinnamyl acid(1a～1k)with SOCl_2 at 25 ℃ for 0.5 hunder the promotion of N,N-dimethylacetamide(DMAC),followed by the reaction with glycinemethylester hydrochloride at 40 ℃ for 3 h.The chemical structures were confirmed by ~1H NMR,~(13)C NMR,IR and EI-MS.The reaction mechanism of DMAC-promoted synthesis of substituted cinnamyl glycinemethylester was discussed.
Substituted cinnamyl glycinemethylester(2 a～2 k)were synthesized from the substituted cinnamyl acid(1a～1k)with SOCl_2 at 25 ℃ for 0.5 hunder the promotion of N,N-dimethylacetamide(DMAC),followed by the reaction with glycinemethylester hydrochloride at 40 ℃ for 3 h.The chemical structures were confirmed by ~1H NMR,~(13)C NMR,IR and EI-MS.The reaction mechanism of DMAC-promoted synthesis of substituted cinnamyl glycinemethylester was discussed.
引文
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[13]Zheng D G,Zhou A X,Zhu,X H,et al.An Efficient Dimethylacetamide-promoted Conversion of Alcohols to Alkyl Chlorides[J].Chin J Org Chem,2016,36(1):137-142(in Chinese).(郑大贵,周安西,祝显虹,等.DMAc高效促进由醇制备氯代烃[J].有机化学,2016,36(1):137-142.)
[2]Zhang C L,Song K K,Chen X R,et al.The Antibacterial and Antifungal Activity Studies of Cinnamic Acid and Its Derivants[J].J Xiamen Univ(Nat Sci),2006,(S1):16-18(in Chinese).(张春乐,宋康康,陈祥仁,等.肉桂酸及其衍生物的抑菌活性研究[J].厦门大学学报(自然科学版),2006,(S1):16-18.)
[3]Gunia A M,Waszkielewicz A,Cegla M,et al.Preliminary Evaluation of Anticonvulsant Activity of Some Aminoalkanol and Amino Acid Cinnamic Acid Derivatives[J].Lett Drug Des Discovery,2012,9(1):37-43.
[4]Gunia-Krzyzak A,Zeslawska E,Sloczynska K,et al.Anticonvulsant Activity,Crystal Structures,and Preliminary Safety Evaluation of N-Trans-cinnamoyl Derivatives of Selected(un)Modified Aminoalkanols[J].Eur J Med Chem,2015,107:26-37.
[5]Prakash S,Maji D,Samanta S,et al.Design,Synthesis and Antidiabetic,Cardiomyopathy Studies of Cinnamic Acid-amino Acid Hybrid Analogs[J].Med Chem,2014,4(2):345-350.
[6]Hardee D J,Kovalchuke L,Lambert T H.Nucleophilic Acyl Substitution via Aromatic Cation Activation of Carboxylic Acids:Rapid Generation of Acid Chlorides Under Mild Conditions[J].J Am Chem Soc,2010,41(32):5 002-5 003.
[7]Andrade C K Z,Rocha R O,Vercilo O E,et al.DCC/DMAP-mediated Coupling of Carboxylic Acids with Oxazolidinones and Thiazolidinethiones[J].Synlett,2003,15:2 351-2 352.
[8]Zambron B K,Dubbaka S R,Markovic D,et al.Amide Formation in One Pot From Carboxylic Acids and Amines via Carboxyl and Sulfinyl Mixed Anhydrides[J].Org Lett,2013,44(37):2 550-2 553.
[9]Zuo M M,Zhou J M,Hu G H,et al.Synthesis and Anti-tumor Activities In vitro of Cinnamic Amide Compounds[J].Chem world,2012,53(4):239-242(in Chinese).(左明明,周健民,胡国辉,等.肉桂酰胺类化合物的合成及其体外抗肿瘤活性[J].化学世界,2012,53(4):239-242.)
[10]Brochu J L,Prakesch M,Enrignt G D,et al.Reagent-based,Modular,Tandem Michael Approach for Obtaining Different Indoline Alkaloid-inspired Polycyclic Architectures[J].J Comb Chem,2008,10(3):405-420.
[11]Gillie A D,Raju J R,Davies P W.Efficient and Flexible Synthesis of Highly Functionalised 4-Aminooxazoles by a Gold-catalysed Intermolecular Formal[3+2]Dipolar Cycloaddition[J].Adv Synth Catal,2016,358(2):226-239.
[12]Kimura Y,Matsuura D.Novel Synthetic Method for the Vilsmeier-haack Reagent and Green Routes to Acid Chlorides,Alkyl Formates,And Alkyl Chlorides[J].Int J Org Chem,2013,3(3):1-7.
[13]Zheng D G,Zhou A X,Zhu,X H,et al.An Efficient Dimethylacetamide-promoted Conversion of Alcohols to Alkyl Chlorides[J].Chin J Org Chem,2016,36(1):137-142(in Chinese).(郑大贵,周安西,祝显虹,等.DMAc高效促进由醇制备氯代烃[J].有机化学,2016,36(1):137-142.)