1-氯甲基磺酰胺类化合物的合成
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摘要
以吡啶为催化剂,实现了氯甲基磺酰氯和芳香伯胺的磺酰化反应。考察了催化剂、溶剂、物料比、反应温度等条件对反应产率的影响。结果表明,最优反应条件为:n(胺)∶n(磺酰氯)=1∶1.3,吡啶为催化剂,二氯甲烷为溶剂,先0℃再室温下反应,反应时间为4～8h。在最优条件下,以42%～95%的产率合成了9种具有不同取代基的磺酰胺类化合物。利用IR、~1HNMR、~(13)CNMR对目标产物的结构进行了确证。
Sulfonylation was accomplished between chloromethanesulfonyl chloride and aromatic primary amine in the presence of pyridine in this article. The effects of catalyst, solvent, molar ratio of raw materials and reaction temperature on the reation were investigated. The results indicated that the optimized reaction conditions were determined as follows: n(amine)∶n(chloromethanesulfonyl chloride) = 1∶1.3, pyridine as catalyst, dichloromethane as solvent, reaction temperature from 0 ℃ to room temperature, reaction time4～8 h. Under the optimized reaction conditions, nine chloromethyl sulfonamides were obtained in42%～95% yields. The structures of newly synthesized compounds were determined by IR, ~1 HNMR and~(13)CNMR.
Sulfonylation was accomplished between chloromethanesulfonyl chloride and aromatic primary amine in the presence of pyridine in this article. The effects of catalyst, solvent, molar ratio of raw materials and reaction temperature on the reation were investigated. The results indicated that the optimized reaction conditions were determined as follows: n(amine)∶n(chloromethanesulfonyl chloride) = 1∶1.3, pyridine as catalyst, dichloromethane as solvent, reaction temperature from 0 ℃ to room temperature, reaction time4～8 h. Under the optimized reaction conditions, nine chloromethyl sulfonamides were obtained in42%～95% yields. The structures of newly synthesized compounds were determined by IR, ~1 HNMR and~(13)CNMR.
引文
[1]Zhou Chenghe(周成合).Basic pharmaceutical chemistry(基础药物化学):No.1[M].Beijing:Science Press(科学出版社),2014,326-330.
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[13]Salahuddin A,Inam A,van Zyl R L,et al.Synthesis and evaluation of 7-chloro-4-(piperazin-1-yl)quinoline-sulfonamide as hybrid antiprotozoal agents[J].Bioorg Med Chem,2013,21(11):3080-3089.
[14]Wimum J Y,Dogn J M,Casin I A,et al.Carbonic anhydrase inhibitors:Synthesis andinhibition of cytosolic/membrane-associated carbonic anhydrase isozymesⅠ,Ⅱ,andⅨwith sulfonamides incorporating hydrazino moieties[J].J Med Chem,2005,48(6):2121-2125.
[15]Sun L,Wu Y,Liu Y,et al.Novel carbazole sulfonamide derivatives of antitumor agent:Synthesis,antiproliferative activity and aqueous solubility[J].Bioorg Med Chem Lett,2016,27(2):261-265.
[16]Chandak N,Ceruso M,Supuran C T,et al.Novel sulfonamide bearing coumarin scaffolds as selective inhibitors of tumor associated carbonic anhydrase isoformsⅨandⅫ[J].Bioorg Med Chem,2016,24(13):2882-2886.
[17]Yoon J,Yoo E A,Kim J Y,et al.Preparation of piperazine derivatives as 5-HT7 receptor antagonists[J].Bioorg Med Chem,2008,16(10):5405-5412.
[18]de Oliveira K N,Costa P,Santin J R,et al.Synthesis and antidepressant-like activity evaluation of sulphonamides and sulphonyl-hydrazones[J].Bioorg Med Chem,2011,19(14):4295-4306.
[19]Li Y Y,Hu B,Dong W H,et al.Visible light-induced radical rearrangement to construct C-C bonds via an intramolecular aryl migration/desulfonylation process[J].J Org Chem,2016,81(16):7036-7041.
[20]Jagadalea M,Khanapurea S,Salunkhea R,et al.Sustainable synthesis of sulfonamides using supported ionic liquid phase catalyst containing Keggin-type anion[J].Appl Organometal Chem,2016,30(3):125-131.
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[24]Buslova I,Hua X L.Transition metal-free intermolecularα-C-Hamination of ethers at room temperature[J].Adv Synth Catal,2014,356(16):3325-3330.
[25]Venning A R O,Bohan P T,Alexanian E J.Palladium-catalyzed,ring-forming aromatic C-H alkylations with unactivated alkyl halides[J].J Am Chem Soc,2015,137(11):3731-3734.
[26]Laha J K,Dayal N,Jain R,et al.Palladium-catalyzed regiocontrolled domino synthesis of N-sulfonyl dihydrophenanthridines and dihydrodibenzo[c,e]azepines:control over the formation of biaryl sultams in the intramolecular direct arylation[J].J Org Chem,2014,79(22):10899-10907.
[27]Laha J K,Jethava K P,Dayal N.Palladium-catalyzed intramolecular oxidative coupling involving double C(sp2)-H bonds for the synthesis of annulated biaryl sultams[J].J Org Chem,2014,79(17):8010-8019.
[28]Woolven H,Gonzálezrodríguez C,Marco I,et al.DABCO-bis(sulfur dioxide),DABSO,as a convenient source of sulfur dioxide for organic synthesis:utility in sulfonamide and sulfamide preparation[J].Org Lett,2011,13(18):4876-4878.
[29]Caddick S,Wilden J D,Judd D B.Direct synthesis of sulfonamides and activated sulfonate esters from sulfonic acids[J].J Am Chem Soc,2004,126(4):1024-1025.
[30]Grombein C M,Hu Q-Z,Rau S,et al.Heteroatom insertion into3,4-dihydro-1H-quinolin-2-ones leads to potent and selective inhibitors of human and rat aldosterone synthase[J].Eur J Med Chem,2015,90:788-796.
[2]Ilardi E A,Vitaku E,Njardarson J T.Data-mining for sulfur and fluorine:An evaluation of pharmaceuticals to reveal opportunities for drug design and discovery[J].J Med Chem,2014,57(7):2832-2842.
[3]Brown E D,Wright G D.Antibacterial drug discovery in the resistance era[J].Nature,2016,529(7586):336-343.
[4]Alanazi A M,El-Azab A S,Al-Suwaidan I A,et al.Structure-based design of phthalimide derivatives as potential cyclooxygenase-2(COX-2)inhibitors:Anti-inflammatory and analgesic activities[J].Eur J Med Chem,2015,92:115-123.
[5]Laev S S,Salakhutdinov N F.Anti-arthritic agents:Progress and potential[J].Bioorg Med Chem,2015,23(13):3059-3080.
[6]Srivastava N,Kumar A.Synthesis and study of 1-ethyl-3-carbohydrazide and 3-[1-oxo-2-hydrazino-3-{p-toluenesulfon}quinolone derivatives against bacterial infections[J].Eur J Med Chem,2013,67:464-468.
[7]Lal J,Gupta S K,Thavaselvam D,et al.Biological activity,design,synthesis and structure activity relationship of some novel derivatives of curcumin containing sulfonamides[J].Eur J Med Chem,2013,64:579-588.
[8]Nagarajan S R,De Crescenzo G A,Getman D P,et al.Discovery of novel benzothiazolesulfonamides as potent inhibitors of HIV-1protease[J].Bioorg Med Chem,2003,11(22):4769-4777.
[9]Benmansour F,Trist I,Coutard B,et al.Discovery of novel dengue virus NS5 methyltransferase non-nucleoside inhibitors by fragmentbased drug design[J].Eur J Med Chem,2016,125:865-880.
[10]Patel D,Jain M,Shah S R,et al.Discovery of potent,selective and orally bioavailable triaryl-sulfonamide based PTP1B inhibitors[J].Bioorg Med Chem Lett,2012,22(2):1111-1117.
[11]Frkic R L,He Y H,Rodriguez B B,et al.Structure-activity relationship of 2,4-dichloro-N-(3,5-dichloro-4-(quinolin-3-yloxy)phenyl)benzenesulfonamide(INT131)analogs for PPARγ-targeted antidiabetics[J].J Med Chem,2017,60(11):4584-4593.
[12]Krungkrai J,Krungkrai S R,Supuran C T.Carbonic anhydrase inhibitors:Inhibition of plasmodium falciparum carbonic anhydrase with aromatic/heterocyclic sulfonamides-in vitro and in vivo studies[J].Bioorg Med Chem Lett,2008,18(20):5466-5471.
[13]Salahuddin A,Inam A,van Zyl R L,et al.Synthesis and evaluation of 7-chloro-4-(piperazin-1-yl)quinoline-sulfonamide as hybrid antiprotozoal agents[J].Bioorg Med Chem,2013,21(11):3080-3089.
[14]Wimum J Y,Dogn J M,Casin I A,et al.Carbonic anhydrase inhibitors:Synthesis andinhibition of cytosolic/membrane-associated carbonic anhydrase isozymesⅠ,Ⅱ,andⅨwith sulfonamides incorporating hydrazino moieties[J].J Med Chem,2005,48(6):2121-2125.
[15]Sun L,Wu Y,Liu Y,et al.Novel carbazole sulfonamide derivatives of antitumor agent:Synthesis,antiproliferative activity and aqueous solubility[J].Bioorg Med Chem Lett,2016,27(2):261-265.
[16]Chandak N,Ceruso M,Supuran C T,et al.Novel sulfonamide bearing coumarin scaffolds as selective inhibitors of tumor associated carbonic anhydrase isoformsⅨandⅫ[J].Bioorg Med Chem,2016,24(13):2882-2886.
[17]Yoon J,Yoo E A,Kim J Y,et al.Preparation of piperazine derivatives as 5-HT7 receptor antagonists[J].Bioorg Med Chem,2008,16(10):5405-5412.
[18]de Oliveira K N,Costa P,Santin J R,et al.Synthesis and antidepressant-like activity evaluation of sulphonamides and sulphonyl-hydrazones[J].Bioorg Med Chem,2011,19(14):4295-4306.
[19]Li Y Y,Hu B,Dong W H,et al.Visible light-induced radical rearrangement to construct C-C bonds via an intramolecular aryl migration/desulfonylation process[J].J Org Chem,2016,81(16):7036-7041.
[20]Jagadalea M,Khanapurea S,Salunkhea R,et al.Sustainable synthesis of sulfonamides using supported ionic liquid phase catalyst containing Keggin-type anion[J].Appl Organometal Chem,2016,30(3):125-131.
[21]Sridhar R,Srinivas B,Pavan Kumar V,et al.β-Cyclodextrincatalyzed monosulfonylation of amines and amino acids in water[J].Adv Synth Catal,2007,349(11/12):1873-1876.
[22]Lis R,Marisca A J.Methanesulfonanilides and the Mannich reaction[J].J Org Chem,1987,52(19):4377-4379.
[23]Lakrout S,K'tir H,Amira A,et al.A simple and eco-sustainable method for the sulfonylation of amines under microwave-assisted solvent-free conditions[J].RSC Adv,2014,4:16027-16032.
[24]Buslova I,Hua X L.Transition metal-free intermolecularα-C-Hamination of ethers at room temperature[J].Adv Synth Catal,2014,356(16):3325-3330.
[25]Venning A R O,Bohan P T,Alexanian E J.Palladium-catalyzed,ring-forming aromatic C-H alkylations with unactivated alkyl halides[J].J Am Chem Soc,2015,137(11):3731-3734.
[26]Laha J K,Dayal N,Jain R,et al.Palladium-catalyzed regiocontrolled domino synthesis of N-sulfonyl dihydrophenanthridines and dihydrodibenzo[c,e]azepines:control over the formation of biaryl sultams in the intramolecular direct arylation[J].J Org Chem,2014,79(22):10899-10907.
[27]Laha J K,Jethava K P,Dayal N.Palladium-catalyzed intramolecular oxidative coupling involving double C(sp2)-H bonds for the synthesis of annulated biaryl sultams[J].J Org Chem,2014,79(17):8010-8019.
[28]Woolven H,Gonzálezrodríguez C,Marco I,et al.DABCO-bis(sulfur dioxide),DABSO,as a convenient source of sulfur dioxide for organic synthesis:utility in sulfonamide and sulfamide preparation[J].Org Lett,2011,13(18):4876-4878.
[29]Caddick S,Wilden J D,Judd D B.Direct synthesis of sulfonamides and activated sulfonate esters from sulfonic acids[J].J Am Chem Soc,2004,126(4):1024-1025.
[30]Grombein C M,Hu Q-Z,Rau S,et al.Heteroatom insertion into3,4-dihydro-1H-quinolin-2-ones leads to potent and selective inhibitors of human and rat aldosterone synthase[J].Eur J Med Chem,2015,90:788-796.