RU2788745C1 - Method of producing 2-[(alkyl(phenyl)sulfanyl)methyl]benzamides - Google Patents
Method of producing 2-[(alkyl(phenyl)sulfanyl)methyl]benzamides Download PDFInfo
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- phenyl
- alkyl
- methyl
- sulfanyl
- benzamides
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- 125000000217 alkyl group Chemical group 0.000 title claims abstract description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 title claims abstract description 15
- 125000003396 thiol group Chemical group [H]S* 0.000 title claims abstract description 14
- 229940054066 Benzamide antipsychotics Drugs 0.000 title claims abstract description 13
- 150000003936 benzamides Chemical class 0.000 title claims abstract description 13
- -1 heptyl- Chemical class 0.000 claims abstract description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000003573 thiols Chemical class 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- LKYXEULZVGJVTG-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH] LKYXEULZVGJVTG-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- RMVRSNDYEFQCLF-UHFFFAOYSA-N Thiophenol Chemical class SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims abstract description 4
- WMXCDAVJEZZYLT-UHFFFAOYSA-N Tert-Butylthiol Chemical class CC(C)(C)S WMXCDAVJEZZYLT-UHFFFAOYSA-N 0.000 claims abstract description 3
- YTNNYKSXJIDJBI-UHFFFAOYSA-N 2-[(2-carbamoylanilino)methylamino]benzamide Chemical compound NC(=O)C1=CC=CC=C1NCNC1=CC=CC=C1C(N)=O YTNNYKSXJIDJBI-UHFFFAOYSA-N 0.000 claims abstract 4
- 230000003993 interaction Effects 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract 1
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical class NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 6
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 229960004676 ANTITHROMBOTIC AGENTS Drugs 0.000 description 2
- 229940042795 Hydrazides for tuberculosis treatment Drugs 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drugs Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- VPIAKHNXCOTPAY-UHFFFAOYSA-N heptane-1-thiol Chemical compound CCCCCCCS VPIAKHNXCOTPAY-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 2
- 229940121372 histone deacetylase inhibitors Drugs 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing Effects 0.000 description 2
- WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical class C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 description 1
- TXJUTRJFNRYTHH-UHFFFAOYSA-N 1H-3,1-benzoxazine-2,4-dione Chemical compound C1=CC=C2C(=O)OC(=O)NC2=C1 TXJUTRJFNRYTHH-UHFFFAOYSA-N 0.000 description 1
- KLGQWSOYKYFBTR-UHFFFAOYSA-N 2-nitrobenzamide Chemical class NC(=O)C1=CC=CC=C1[N+]([O-])=O KLGQWSOYKYFBTR-UHFFFAOYSA-N 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000000845 anti-microbial Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 230000000259 anti-tumor Effects 0.000 description 1
- 239000000611 antibody drug conjugate Substances 0.000 description 1
- 108091008116 antibody drug conjugates Proteins 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005241 heteroarylamino group Chemical group 0.000 description 1
- 239000008079 hexane Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- KJRCEJOSASVSRA-UHFFFAOYSA-N propane-2-thiol Chemical compound CC(C)S KJRCEJOSASVSRA-UHFFFAOYSA-N 0.000 description 1
- 230000003595 spectral Effects 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 230000001549 tubercolostatic Effects 0.000 description 1
Abstract
Description
Предлагаемое изобретение относится к области органической химии, конкретно к способу получения 2-[(алкил(фенил)сульфанил)метил]бензамидов общей формулы (1):The present invention relates to the field of organic chemistry, specifically to a method for producing 2 -[(alkyl(phenyl)sulfanyl)methyl]benzamides of the general formula (1) :
Ациклические азотсодержащие производные амидов кислот обладают противомикробными [Ya. N. Mabkhot, A. M. Al-Majid, A. Barakat, S. S. Al-Showiman, M. S. Al-Har, S. Radi, M. M. Naseer, T. B. Hadda. Synthesis and Biological Evaluation of 2-Aminobenzamide Derivatives as Antimicrobial Agents: Opening/Closing Pharmacophore Site. Int. J. Mol. Sci. 2014, 15, p. 5115 - 5127], антитромботическими [A. Verma, R. Giridhar, A. Kanhed, A. Sinha, P. Modh, M. R. Yadav. Novel 2-Aminobenzamides as Potential Orally Active Antithrombotic Agents. ACS Med. Chem. Lett., 2013, 4, p. 32 - 36], противоопухолевыми [Sh. Kiyokawa, Yo. Hirata, Ya. Nagaoka, M. Shibano, M. Taniguchi, M. Yasuda, K. Baba, Sh. Uesato. New orally bioavailable 2-aminobenzamide-type histone deacetylase inhibitor possessing a (2-hydroxyethyl)(4-(thiophen-2-yl)benzyl)amino group. Bioorganic & Medicinal Chemistry, 2010, 18, p. 3925-3933] свойствами, близки по структуре к азаподандам, которые обеспечивают адресную доставку формакофора [L. R. Staben, S. G. Koenig, S. Lehar, R. Vandlen, D. Zhang, J. Chuh, Sh.-F. Yu, C. Ng, J. Guo, Ya. Liu, A. Fourie-O’Donohue, M. Go, X. Linghu, N. L. Segraves, T. Wang, J. Chen, B. Wei, G. D. L. Phillips, K. Xu, K. R. Kozak, S. Mariathasan, J. A. Flygare, T. H. Pillow. Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody-drug conjugates. Nature Chem., 2016, 8, p. 1112 - 1119; X. Chen, L. Liu, Ch. Jiang. Charge-reversal nanoparticles: novel targeted drug delivery carriers. Acta Pharm. Sinica B, 2016, 6(4), p. 261 - 267; Е. С. Переяславская, В. А. Потемкин, Е. В. Барташевич, М. А. Гришина, Г. Л. Русинов, О. В. Федорова, М. С. Жидовинова, И. Г. Овчинникова. Теоретическое исследование туберкулостатической активности соединений дигидропиримидинового ряда. Хим.-фарм. журн., 2008, 42(11), 18 - 21].Acyclic nitrogen-containing derivatives of acid amides have antimicrobial [Ya. N. Mabkhot, AM Al-Majid, A. Barakat, SS Al-Showiman, MS Al-Har, S. Radi, MM Naseer, TB Hadda. Synthesis and Biological Evaluation of 2-Aminobenzamide Derivatives as Antimicrobial Agents: Opening/Closing Pharmacophore Site. Int. J. Mol. sci. 2014, 15 , p. 5115 - 5127], antithrombotic [A. Verma, R. Giridhar, A. Kanhed, A. Sinha, P. Modh, MR Yadav. Novel 2-Aminobenzamides as Potential Orally Active Antithrombotic Agents. ACS Med. Chem. Lett., 2013, 4 , p. 32 - 36], antitumor [Sh. Kiyokawa, Yo. Hirata, Ya. Nagaoka, M. Shibano, M. Taniguchi, M. Yasuda, K. Baba, Sh. Uesato. New orally bioavailable 2-aminobenzamide-type histone deacetylase inhibitor possessing a (2-hydroxyethyl)(4-(thiophen-2-yl)benzyl)amino group. Bioorganic & Medicinal Chemistry, 2010, 18 , p. 3925-3933] with properties similar in structure to azapodands that provide targeted delivery of formacophore [LR Staben, SG Koenig, S. Lehar, R. Vandlen, D. Zhang, J. Chuh, Sh.-F. Yu, C. Ng, J. Guo, Ya. Liu, A. Fourie-O'Donohue, M. Go, X. Linghu, NL Segraves, T. Wang, J. Chen, B. Wei, GDL Phillips, K. Xu, KR Kozak, S. Mariathasan, JA Flygare, T.H. Pillow. Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody-drug conjugates. Nature Chem ., 2016, 8 , p. 1112 - 1119; X. Chen, L. Liu, Ch. Jiang. Charge-reversal nanoparticles: novel targeted drug delivery carriers. Acta Pharm. Sinica B , 2016, 6(4), p. 261 - 267; E. S. Pereyaslavskaya, V. A. Potemkin, E. V. Bartashevich, M. A. Grishina, G. L. Rusinov, O. V. Fedorova, M. S. Zhidovinova, I. G. Ovchinnikova. Theoretical study of the tuberculostatic activity of dihydropyrimidine compounds. Chem.-farm. magazine , 2008, 42 (11), 18 - 21].
Известен способ [Ya. N. Mabkhot, A. M. Al-Majid, A. Barakat, S. S. Al-Showiman, M. S. Al-Har, S. Radi, M. M. Naseer, T. B. Hadda. Synthesis and Biological Evaluation of 2-Aminobenzamide Derivatives as Antimicrobial Agents: Opening/Closing Pharmacophore Site. Int. J. Mol. Sci. 2014, 15, p. 5115-5127; A. Verma, R. Giridhar, A. Kanhed, A. Sinha, P. Modh, M. R. Yadav. Novel 2-Aminobenzamides as Potential Orally Active Antithrombotic Agents. ACS Med. Chem. Lett., 2013, 4, p. 32 - 36] получения N-замещенных производных 2-аминобензамида (2) взаимодействием изатоового ангидрида (2H 3,1-бензоксацин-2,4(1H)-дион) с алкил- или ариламинами при нагревании с выходами 65-99% соответственно.The known method [Ya. N. Mabkhot, AM Al-Majid, A. Barakat, SS Al-Showiman, MS Al-Har, S. Radi, MM Naseer, TB Hadda. Synthesis and Biological Evaluation of 2-Aminobenzamide Derivatives as Antimicrobial Agents: Opening/Closing Pharmacophore Site. Int. J. Mol. sci. 2014, 15 , p. 5115-5127; A. Verma, R. Giridhar, A. Kanhed, A. Sinha, P. Modh, MR Yadav. Novel 2-Aminobenzamides as Potential Orally Active Antithrombotic Agents. ACS Med. Chem. Lett., 2013, 4 , p. 32 - 36] obtaining N-substituted derivatives of 2-aminobenzamide ( 2 ) by the interaction of isatoic anhydride (2H 3,1-benzoxacin-2,4(1H)-dione) with alkyl- or arylamines on heating in 65-99% yields, respectively.
Известный способ не позволяет получать 2-[(алкил(фенил)сульфанил)метил]бензамиды общей формулы (1).The known method does not allow to obtain 2 -[(alkyl(phenyl)sulfanyl)methyl]benzamides of the General formula ( 1 ).
Известен способ [Sh. Kiyokawa, Yo. Hirata, Ya. Nagaoka, M. Shibano, M. Taniguchi, M. Yasuda, K. Baba, Sh. Uesato. New orally bioavailable 2-aminobenzamide-type histone deacetylase inhibitor possessing a (2-hydroxyethyl)(4-(thiophen-2-yl)benzyl)amino group. Bioorganic & Medicinal Chemistry, 2010, 18, p. 3925-3933] получения N-замещенных производных 2-аминобензамида (3) взаимодействием 2-нитробензамидов с альдегидами и галогенидами с последующим восстановлением NaBH(OAc)3 и SnCl2 с выходами 19-45% соответственно.The known method [Sh. Kiyokawa, Yo. Hirata, Ya. Nagaoka, M. Shibano, M. Taniguchi, M. Yasuda, K. Baba, Sh. Uesato. New orally bioavailable 2-aminobenzamide-type histone deacetylase inhibitor possessing a (2-hydroxyethyl)(4-(thiophen-2-yl)benzyl)amino group. Bioorganic & Medicinal Chemistry, 2010, 18 , p. 3925-3933] obtaining N-substituted derivatives of 2-aminobenzamide ( 3 ) by the interaction of 2-nitrobenzamides with aldehydes and halides, followed by reduction of NaBH(OAc) 3 and SnCl 2 in 19-45% yields, respectively.
Известный способ не позволяет получать 2-[(алкил(фенил)сульфанил)метил]бензамиды общей формулы (1).The known method does not allow to obtain 2 -[(alkyl(phenyl)sulfanyl)methyl]benzamides of the General formula ( 1 ).
Известен способ [Хайруллина Р.Р., Акманов Б.Ф., Кунакова Р.В., Ибрагимов А.Г., Джемилев У.М. эффективное каталитическое тиометилирование гидразидов карбоновых кислот. Изв. АН. Сер.Хим.- 2013.- 1. –с. 98-103] получения N,N-бис[(алкил(фенил)сульфанил)метил] арилгидразидов (4) взаимодействием гидразидов кислот с 1,3-аминосульфидами в присутствии SmCl3·6H2O с выходами 68 - 98% соответственно.There is a method [Khairullina R.R., Akmanov B.F., Kunakova R.V., Ibragimov A.G., Dzhemilev U.M. efficient catalytic thiomethylation of carboxylic acid hydrazides. Izv . AN. Ser.Chem.- 2013.- 1 . -With. 98-103] obtaining N,N-bis[(alkyl(phenyl)sulfanyl)methyl]arylhydrazides ( 4 ) by the interaction of acid hydrazides with 1,3-aminosulfides in the presence of SmCl 3 ·6H 2 O with yields of 68 - 98%, respectively.
Известный способ не позволяет получать 2-[(алкил(фенил)сульфанил)метил]бензамиды общей формулы (1).The known method does not allow to obtain 2 -[(alkyl(phenyl)sulfanyl)methyl]benzamides of the General formula ( 1 ).
Таким образом, в литературе отсутствуют сведения о способе получения 2-[(алкил(фенил)сульфанил)метил]бензамидов общей формулы (1).Thus, there is no information in the literature about the method of obtaining 2 -[(alkyl(phenyl)sulfanyl)methyl]benzamides of the general formula ( 1 ).
Предлагается новый способ селективного получения 2-[(алкил(фенил)сульфанил)метил]бензамидов общей формулы (1).A new method for the selective preparation of 2 -[(alkyl(phenyl)sulfanyl)methyl]benzamides of the general formula ( 1 ) is proposed.
Сущность способа заключается во взаимодействии 2-[({[2-(аминокарбонил)фенил]амино}метиламино]бензамида (диамида) с алкил(фенил)тиолами, выбранных из ряда гептил-, или изопропил-, или трет-бутил-, или фенилтиолами в присутствии в качестве катализатора SmCl3⋅6H2O, взятых в мольном соотношении 2-[({[2-(аминокарбонил)фенил]амино}метиламино]-бензамид : тиол : [SmCl3⋅6H2O] = 1:(0.5-1.5):(0.01-0.1), предпочтительно 1:1:0.05, при температуре 60-80°С, предпочтительно 70°С, в течение 7 - 9 ч, предпочтительно 8 ч, в смеси растворителей EtOH : CHCl3 (1:1, обьемные). Выход 2-[(алкил(фенил)сульфанил)метил]бензамидов общей формулы (1) составляет 29-81%. Реакция проходит по схеме:The essence of the method consists in the interaction of 2-[({[2-(aminocarbonyl)phenyl]amino}methylamino]benzamide (diamide) with alkyl(phenyl)thiols selected from the range of heptyl-, or isopropyl-, or tert-butyl-, or phenylthiols in the presence of SmCl 3 ⋅6H 2 O as a catalyst, taken in a molar ratio of 2-[({[2-(aminocarbonyl)phenyl]amino}methylamino]-benzamide : thiol : [SmCl 3 ⋅6H 2 O] = 1: (0.5-1.5):(0.01-0.1), preferably 1:1:0.05, at a temperature of 60-80°C, preferably 70°C, for 7-9 hours, preferably 8 hours, in a mixture of solvents EtOH : CHCl 3 (1:1, vol.) The yield of 2 -[(alkyl(phenyl)sulfanyl)methyl]benzamides of general formula ( 1 ) is 29-81%. The reaction proceeds according to the scheme:
Проведение указанной реакции в присутствии катализатора SmCl3⋅6H2O больше 0.1 ммолей не приводит к существенному увеличению выхода целевого продукта (1). Без катализатора целевой продукт (1) не образуется.Carrying out this reaction in the presence of a SmCl 3 ⋅6H 2 O catalyst greater than 0.1 mmol does not lead to a significant increase in the yield of the target product ( 1 ). Without a catalyst, the target product ( 1 ) is not formed.
Способ поясняется примерами.The method is illustrated with examples.
Пример 1. В стеклянный реактор помещали 1 ммоль 2-[({[2-(аминокарбонил)фенил]амино}метиламино]бензамида (диамида) (0.284 г), 1 ммоль гептилтиола (0.132 г), 0.05 ммоль катализатора (SmCl3⋅6H2O, 0.02 г), 7 мл растворителя (EtOH : CHCl3, 1:1) и перемешивали в течение 8 часов при температуре 70°С. Затем методом колоночной хроматографии на SiO2 выделяли 2-{[(гептилтио)метил]амино}бензамид (1a). Элюент гексан : этилацетат = 2 : 1. Другие примеры, подтверждающие способ, приведены в таблице. Example 1. 1 mmol of 2-[({[2-(aminocarbonyl)phenyl]amino}methylamino]benzamide (diamide) (0.284 g), 1 mmol of heptylthiol (0.132 g), 0.05 mmol of catalyst (SmCl 3 ⋅ 6H 2 O, 0.02 g), 7 ml of solvent (EtOH : CHCl 3 , 1:1) and stirred for 8 hours at 70° C. Then, 2-{[(heptylthio)methyl] was isolated by column chromatography on SiO 2 amino}benzamide ( 1a ) Eluent hexane : ethyl acetate = 2 : 1 Other examples supporting the method are given in the table.
п/п№№
p/p
тиолoriginal
thiol
диамид : тиол : [SmCl3·6H2O], ммольRatio
diamide : thiol : [SmCl 3 6H 2 O], mmol
(1), %Output
(1), %
Реакции проводились в смеси растворителей (EtOH : CHCl3, 1:1, объемные).The reactions were carried out in a mixture of solvents (EtOH : CHCl 3 , 1:1, by volume).
Спектральные характеристики 2-[(алкил(фенил)сульфанил)метил]бензамидов общей формулы (1)Spectral characteristics of 2-[(alkyl(phenyl)sulfanyl)methyl]benzamides of general formula (1)
2-{[(Гептилтио)метил]амино}бензамид (1a).2-{[(Heptylthio)methyl]amino}benzamide (1a).
Выход 0.20 г (71%), кристаллы, т. пл. 110-112°С. Спектр ЯМР 1Н (CDCl3, δ, м.д., J/Гц): 0.89 (т, 3H, -CH 3, 3 J = 8.0); 1.27-1.39 (м, 8H, -CH 2-); 1.61 (п, 2H, -CH 2-); 2.59 (т, 2H, -CH 2S-, 3 J = 8.0); 4.48 (с, 2H, -HNCH 2S-); 5.84 (уш.с, 2H, -NH 2); 6.70 (т, 1H, -CH Ar-, 3 J = 8.0); 6.91 (д, 1H, -CH Ar-, 3 J = 8.0); 7.38-7.44 (м, 2H, -CH Ar-); 8.48 (уш.с, 1H, -NH). Спектр ЯМР 13С (CDCl3, δ, м.д.): 14.10 (-CH3); 22.61, 28.92, 29.72, 30.53, 31.73 (-CH2-); 45.58 (-HNCH2S-); 113.32 (-CH); 114.14 (-C(CONH2)); 115.95, 128.24, 133.38 (-CH); 148.24 (-C(NHCH2)); 171.92 (-C(CONH2)). Масс-спектр HRMS: найдено, m/z: 303.1468 [M+Na]+; вычислено для C15H24N2NaOS+, 303.1507.Yield 0.20 g (71%), crystals, mp. 110-112°C. 1Н NMR spectrum (CDCl 3 , δ, ppm , J /Hz): 0.89 (t, 3H, -C H 3 , 3 J = 8.0); 1.27-1.39 (m, 8H, -C H 2 -); 1.61 (n, 2H, -C H 2 -); 2.59 (t, 2H, -C H 2 S-, 3 J = 8.0); 4.48 (s, 2H, -HNC H 2 S-); 5.84 (br. s, 2H, -N H 2 ); 6.70 (t, 1H, -C H Ar -, 3 J = 8.0); 6.91 (d, 1H, -C H Ar -, 3 J = 8.0); 7.38-7.44 (m, 2H, -C H Ar -); 8.48 (br. s, 1H, -N H ). 13 C NMR spectrum (CDCl 3 , δ, ppm): 14.10 ( -C H 3 ); 22.61, 28.92, 29.72, 30.53, 31.73 (- C H 2 -); 45.58 (-HN C H 2 S-); 113.32 (-CH); 114.14 (- C (CONH 2 )); 115.95 , 128.24, 133.38 (-CH); 148.24 (- C (NHCH 2 )); 171.92 (-C( C ONH 2 )). HRMS mass spectrum: found, m/z : 303.1468 [M+Na] + ; calculated for C 15 H 24 N 2 NaOS + , 303.1507.
2-{[(Изопропилтио)метил]амино}бензамид2-{[(Isopropylthio)methyl]amino}benzamide (1b).(1b).
Выход 0.14 г (60%), кристаллы, т. пл. 140-142°С. Спектр ЯМР 1Н (ДМСО-d 6, δ, м.д., J/Гц): 1.21 (д, 6H, -CH 3, 3 J = 7.0); 2.97 (п, 1H, (CH3)2CHS-, 3 J = 7.0); 4.52 (д, 2H, -HNCH 2S-, 3 J = 7.0); 6.62 (т, 1H, CH Ar, 3 J = 8.0); 6.82 (д, 1H, CH Ar, 3 J = 8.0); 7.21 (уш.с, 1H, NH 2); 7.30 (т, 1H, CH Ar, 3 J = 8.0); 7.64 (д, 1H, CH Ar, 3 J = 8.0); 7.88 (уш.с, 1H, NH 2); 8.68 (т, 1H, NH, 3 J = 8.0). Спектр ЯМР 13С (ДМСО-d 6, δ, м.д.): 24.15 (CH3); 33.99 ((CH3)2 CHS-); 44.40 (-HNCH2S-); 113.19 (CH); 115.60 (CH, -C(CONH2)); 129.45, 132.66 (CH); 148.32 (-C(NHCH2)); 171.91 (-C(CONH2)). Масс-спектр: найдено: m/z 247.0866 [M+Na]+; вычислено для C11H16N2NaOS+, 247.0881.Yield 0.14 g (60%), crystals, mp. 140-142°C. 1H NMR spectrum (DMSO- d 6 , δ, ppm , J /Hz): 1.21 (d, 6H, -C H 3 , 3 J = 7.0); 2.97 (p, 1H, (CH 3 ) 2 C H S-, 3 J = 7.0); 4.52 (d, 2H, -HNC H 2 S-, 3 J = 7.0); 6.62 (t, 1H, C H Ar , 3 J = 8.0); 6.82 (d, 1H, C H Ar , 3 J = 8.0); 7.21 (br. s, 1H, N H 2 ); 7.30 (t, 1H, C H Ar , 3 J = 8.0); 7.64 (d, 1H, C H Ar , 3 J = 8.0); 7.88 (br. s, 1H, N H 2 ); 8.68 (t, 1H, N H , 3J = 8.0). 13C NMR spectrum ( DMSO- d 6 , δ, ppm): 24.15 ( C H 3 ); 33.99 ((CH 3 ) 2 C HS-); 44.40 (-HN C H 2 S-); 113.19 (CH); 115.60 (CH, -C ( CONH 2 )); 129.45 , 132.66(CH); 148.32 (- C (NHCH 2 )); 171.91 (-C( C ONH 2 )). Mass spectrum: found: m/z 247.0866 [M+Na] + ; calculated for C 11 H 16 N 2 NaOS + , 247.0881.
2-{[(Трет-бутилтио)метил]амино}бензамид (1c).2-{[(T-butylthio)methyl]amino}benzamide (1c).
Выход 0.12 г (53%), кристаллы, т. пл. 141-143°С. Спектр ЯМР 1Н (ДМСО-d 6, δ, м.д., J/Гц): 1.31 (с, 9H, -CH 3); 4.53 (д, 2H, -HNCH 2S-, 3 J = 8.0); 6.60 (т, 1H, CH, 3 J = 8.0); 6.77 (д, 1H, CH Ar, 3 J = 8.0); 7.17 (уш.с, 1H, NH 2); 7.30 (т, 1H, CH Ar, 3 J = 8.0); 7.62 (д, 1H, CH Ar, 3 J = 8.0); 7.85 (уш.с, 1H, NH 2); 8.60 (т, 1H, NH, 3 J = 8.0). Спектр ЯМР 13С (ДМСО-d 6, δ, м.д.): 31.72 (-CH3); 42.85 (-HNCH2S-); 42.99 (-C(СH3)3); 112.81, 115.40 (CH); 115.34 (-C(CONH2)); 129.44, 132.72 (CH); 148.42 (-C(NHCH2)); 171.90 (-C(CONH2)). Масс-спектр: найдено: m/z 261.1007 [M+Na]+; вычислено для C12H18N2NaOS+, 261.1037.Yield 0.12 g (53%), crystals, mp. 141-143°C. 1 H NMR spectrum (DMSO- d 6 , δ, ppm, J /Hz): 1.31 (s, 9H, -C H 3 ); 4.53 (d, 2H, -HNC H 2 S-, 3 J = 8.0); 6.60 (t, 1H, CH , 3J = 8.0); 6.77 (d, 1H, C H Ar , 3 J = 8.0); 7.17 (br. s, 1H, N H 2 ); 7.30 (t, 1H, C H Ar , 3 J = 8.0); 7.62 (d, 1H, C H Ar , 3 J = 8.0); 7.85 (br. s, 1H, N H 2 ); 8.60 (t, 1H, N H , 3J = 8.0). 13 C NMR spectrum (DMSO- d 6 , δ, ppm): 31.72 (- C H 3 ); 42.85 (-HN C H 2 S-); 42.99 (- C (CH 3 ) 3 ); 112.81 , 115.40(CH); 115.34 (- C (CONH 2 )); 129.44 , 132.72(CH); 148.42 (- C (NHCH 2 )); 171.90 (-C( C ONH 2 )). Mass spectrum: found: m/z 261.1007 [M+Na] + ; calculated for C 12 H 18 N 2 NaOS + , 261.1037.
2-{[(Фенилтио)метил]амино}бензамид (1d).2-{[(Phenylthio)methyl]amino}benzamide (1d).
Выход 0.16 г (65%), кристаллы, т. пл. 102-104°С. Спектр ЯМР 1Н (ДМСО-d 6, δ, м.д., J/Гц): 4.94 (д, 2H, -HNCH 2S-, 3 J = 8.0); 6.67 (т, 1H, CH Ar, 3 J = 8.0); 6.94 (д, 1H, CH Ar, 3 J = 8.0); 7.22-7.39 (м, 7H, CH Ar, NH); 7.64 (д, 1H, CH Ar, 3 J = 8.0); 7.89 (уш.с, 1H, NH 2); 8.83 (т, 1H, NH, 3 J = 8.0). Спектр ЯМР 13С (ДМСО-d 6, δ, м.д.): 48.58 (-HNCH2S-); 113.39 (CH); 115.93 (C(CONH2)); 116.20 (CH); 126.94, 129.49, 130.98, 132.75, 135.66 (CH); 147.73 (-C(NHCH2)); 171.70 (-C(CONH2)). Масс-спектр: найдено: m/z 281.0717 [M+Na]+; вычислено для C14H14N2NaOS+, 281.07245.Yield 0.16 g (65%), crystals, mp. 102-104°C. 1Н NMR spectrum (DMSO- d 6 , δ, ppm, J /Hz): 4.94 (d, 2H, -HNC H 2 S-, 3 J = 8.0); 6.67 (t, 1H, C H Ar , 3 J = 8.0); 6.94 (d, 1H, C H Ar , 3 J = 8.0); 7.22-7.39 (m, 7H, C H Ar , NH); 7.64 (d, 1H, C H Ar , 3 J = 8.0); 7.89 (br. s, 1H, N H 2 ); 8.83 (t, 1H, N H , 3J = 8.0). 13 C NMR spectrum (DMSO- d 6 , δ, ppm): 48.58 (-HN C H 2 S-); 113.39 (CH); 115.93 ( C ( CONH2 )); 116.20 (CH); 126.94, 129.49, 130.98, 132.75 , 135.66 (CH); 147.73 (- C (NHCH 2 )); 171.70 (-C( C ONH 2 )). Mass spectrum: found: m/z 281.0717 [M+Na] + ; calculated for C 14 H 14 N 2 NaOS + , 281.07245.
Claims (3)
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2788745C1 true RU2788745C1 (en) | 2023-01-24 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4221730A (en) * | 1979-07-26 | 1980-09-09 | Morton-Norwich Products, Inc. | 3-[[(4-Aminophenyl)sulfonyl]amino]-N-[diaminophosphinyl]-benzamide |
| RU2504537C2 (en) * | 2012-01-10 | 2014-01-20 | Учреждение Российской Академии Наук Институт Нефтехимии И Катализа Ран | Method of producing n',n'-bis{[alkyl(phenyl)sulphanyl]methyl}arylhydrazides |
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4221730A (en) * | 1979-07-26 | 1980-09-09 | Morton-Norwich Products, Inc. | 3-[[(4-Aminophenyl)sulfonyl]amino]-N-[diaminophosphinyl]-benzamide |
| RU2504537C2 (en) * | 2012-01-10 | 2014-01-20 | Учреждение Российской Академии Наук Институт Нефтехимии И Катализа Ран | Method of producing n',n'-bis{[alkyl(phenyl)sulphanyl]methyl}arylhydrazides |
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| MABKHOT Y. et al., Synthesis and Biological Evaluation of 2-Aminobenzamide Derivatives as Antimicrobial Agents: Opening/Closing Pharmacophore Site, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2014, 15(3), 5115-5127. ТРИФИЛЕНКОВ А., Синтез замещенных бензамидов, бензотиазинов и хиноксалинов с использованием галогензамещенных бензойных кислот и их ближайших структурных аналогов, АВТОРЕФЕРАТ ДИССЕРТАЦИИ НА СОИСКАНИЕ УЧЕНОЙ СТЕПЕНИ КХН, Москва, 2006, стр. 19. KHAIRULLINA R.R. et al., Catalytic thiomethylation of regioisomeric aminobenzamides using bis(N,N-dimethylamino)methane and α,ω-alkanedithiols, RUSSIAN CHEMICAL BULLETIN, 2021, 70(4), pp. 757-762. * |
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