RU2691736C1 - Method of producing 1,2,4,5-tetrakis(4-r-phenylsulfanyl)benzenes - Google Patents
Method of producing 1,2,4,5-tetrakis(4-r-phenylsulfanyl)benzenes Download PDFInfo
- Publication number
- RU2691736C1 RU2691736C1 RU2018146632A RU2018146632A RU2691736C1 RU 2691736 C1 RU2691736 C1 RU 2691736C1 RU 2018146632 A RU2018146632 A RU 2018146632A RU 2018146632 A RU2018146632 A RU 2018146632A RU 2691736 C1 RU2691736 C1 RU 2691736C1
- Authority
- RU
- Russia
- Prior art keywords
- dinitrobenzene
- tetrakis
- benzenes
- phenylsulfanyl
- dichloro
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 10
- 150000001555 benzenes Chemical class 0.000 title claims abstract description 6
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims abstract description 12
- ZPXDNSYFDIHPOJ-UHFFFAOYSA-N 1,5-dichloro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=C(Cl)C=C1Cl ZPXDNSYFDIHPOJ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims description 3
- 230000003993 interaction Effects 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 abstract 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 230000007717 exclusion Effects 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 229910000027 potassium carbonate Inorganic materials 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- YPFCYPZKFQPCOC-UHFFFAOYSA-N 1,2,3,5-tetrabromobenzene Chemical compound BrC1=CC(Br)=C(Br)C(Br)=C1 YPFCYPZKFQPCOC-UHFFFAOYSA-N 0.000 description 2
- ACTOMNCGVDCBDK-UHFFFAOYSA-N 1,2,4,5-tetrakis(phenylsulfanyl)benzene Chemical compound C=1C(SC=2C=CC=CC=2)=C(SC=2C=CC=CC=2)C=C(SC=2C=CC=CC=2)C=1SC1=CC=CC=C1 ACTOMNCGVDCBDK-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 description 1
- MQMOHVHKSPHBJQ-UHFFFAOYSA-N ClC1=CC=C(C=C1)SC1=C(C=C(C(=C1)SC1=CC=C(C=C1)Cl)SC1=CC=C(C=C1)Cl)SC1=CC=C(C=C1)Cl Chemical compound ClC1=CC=C(C=C1)SC1=C(C=C(C(=C1)SC1=CC=C(C=C1)Cl)SC1=CC=C(C=C1)Cl)SC1=CC=C(C=C1)Cl MQMOHVHKSPHBJQ-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical class Br* 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C15/00—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts
- C07C15/02—Monocyclic hydrocarbons
- C07C15/04—Benzene
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Изобретение относится к способу синтеза тетразамещенных бензоловThe invention relates to a method for the synthesis of tetrasubstituted benzenes
где R = Cl, H,where R = Cl, H,
которые могут быть использованы в качестве полупродуктов для получения эффективных лигандов (G.D. Martino, M.C. Edler, G. L. Regina, A. Coluccia, M. C. Barbera, D. Barrow, R. I. Nicholson, G. Chiosis, A. Brancale, E. Hamel, M. Artico, R. Silvestri // J Med Chem 2006, Vol. 49, pp. 947), обладающих повышенной способностью связывать различные низкомолекулярные соединения (L.J. Farrugia, J.H. Gall, D.D.MacNicol // ChemComm. - 2012. - Vol. 48. - pp. 10600). Инкапсуляция оказывает сильное влияние на физико-химические свойства встраиваемых молекул: улучшение растворимости, повышение стойкости к окислению, световым и термическим воздействиям (D. Samanta, P.S. Mukherjee. // Chem. Commun. - 2014. - Vol .50. - pp. 159; D. Song, S. Wang // Eur. J. Inorg. Chem. - 2003. - pp. 3774). Подобные лиганды используют для контроля выделения лекарственных средств, а также летучести и сублимации, устранения запахов (L.J. Farrugia, J.H. Gall, D.D.MacNicol // ChemComm. - 2012. - Vol. 48. - pp. 10600). which can be used as intermediates for efficient ligands (GD Martino, MC Edler, GL Regina, A. Coluccia, MC Barbera, D. Barrow, RI Nicholson, G. Chiosis, A. Brancale, E. Hamel, M. Artico , R. Silvestri // J Med Chem 2006, Vol. 49, pp. 947), which have an increased ability to bind various low-molecular compounds (LJ Farrugia, JH Gall, DDMacNicol // ChemComm. - 2012. - Vol. 48. - pp .10600). Encapsulation has a strong influence on the physicochemical properties of embedded molecules: improved solubility, increased resistance to oxidation, light and thermal effects (D. Samanta, PS Mukherjee. // Chem. Commun. - 2014. - Vol .50. - pp. 159 ; D. Song, S. Wang // Eur. J. Inorg. Chem. - 2003. - pp. 3774). Such ligands are used to control drug release, as well as volatility and sublimation, odor removal (L.J. Farrugia, J.H. Gall, D.D.MacNicol // ChemComm. - 2012. - Vol. 48. - pp. 10600).
Известен способ синтеза 1,2,4,5-тетракис(фенилсульфанил)бензола, заключающийся в замещении атомов брома в 1,2,3,5-тетрабромбензоле. Реакцию проводили с In(SPh)3, в присутствие палладиевого катализатора, диизопропилэтиламина в ДМФА при 100°C в течение 4 ч (P.H Lee, Y. Park, S.Park, E. Lee, S. Kim // J.Org.Chem.-2011.-Vol. 76.-pp. 760).A known method for the synthesis of 1,2,4,5-tetrakis (phenylsulfanyl) benzene, which consists in the substitution of bromine atoms in 1,2,3,5-tetrabromobenzene. The reaction was carried out with In (SPh) 3 , in the presence of a palladium catalyst, diisopropylethylamine in DMF at 100 ° C for 4 h (PH Lee, Y. Park, S. Park, E. Lee, S. Kim // J. Org. Chem.-2011.-Vol. 76.-pp. 760).
Недостатками известного способа получения является использование дорогостоящих реагентов три(арилтиолата) индия, палладиевого катализатора и длительное время реакции.The disadvantages of this method of obtaining is the use of expensive reagents tri (arylthiolate) indium, palladium catalyst and a long reaction time.
Цель изобретения - снижение стоимости синтеза 1,2,4,5-тетракис(4-R-фенилсульфанил)бензолов и уменьшение времени реакции ароматического нуклеофильного замещения.The purpose of the invention is to reduce the cost of synthesizing 1,2,4,5-tetrakis (4-R-phenylsulfanyl) benzenes and reducing the reaction time of an aromatic nucleophilic substitution.
Поставленная цель достигается тем, что вместо малоактивного в реакции ароматического нуклеофильного замещения 1,2,3,5-тетрабромбензола применяется более активный 1,5-дихлор-2,4-динитробензол, использование которого позволяет употреблять в качестве нуклеофила вместо дорогостоящего три(арилтиолата) индия легкодоступный тиофенол или его производные. Применение катализатора не требуется.. Причем процесс взаимодействия 4-R-тиофенолов с 1,5-дихлор-2,4-динитробензолом проводят в ДМФА в присутствии К2СО3 при температуре 140°С в течение 2 часов при молярном соотношении 1,5-дихлор-2,4-динитробензол : 4-R-тиофенол = 1 : 4.This goal is achieved by the fact that instead of inactive in the reaction of aromatic nucleophilic substitution of 1,2,3,5-tetrabromobenzene used more active 1,5-dichloro-2,4-dinitrobenzene, the use of which allows you to use as a nucleophile instead of expensive three (arylthiolate) Indium readily available thiophenol or its derivatives. The use of a catalyst is not required. Moreover, the interaction of 4-R-thiophenols with 1,5-dichloro-2,4-dinitrobenzene is carried out in DMF in the presence of K 2 CO 3 at a temperature of 140 ° C for 2 hours at a molar ratio of 1.5 dichloro-2,4-dinitrobenzene: 4-R-thiophenol = 1: 4.
Реализация предложенной схемы синтеза 1,2,4,5-тетракис(4-R-фенилсульфанил)бензолов, позволяет значительно удешевить процесс их синтеза, уменьшить время реакции с 4 до 2 ч и получить целевые продукты с выходом 95-97%.The implementation of the proposed scheme for the synthesis of 1,2,4,5-tetrakis (4-R-phenylsulfanyl) benzenes makes it possible to significantly reduce the cost of their synthesis, reduce the reaction time from 4 to 2 hours, and obtain the desired products with a yield of 95-97%.
Строение и чистоту продукта анализировали методами 1Н ЯМР спектроскопии, масс-спектрометрии, определением температуры плавления и элементного состава.The structure and purity of the product were analyzed by 1 H NMR spectroscopy, mass spectrometry, determination of the melting temperature and elemental composition.
Изобретение иллюстрируется следующим примерами.The invention is illustrated by the following examples.
Пример 1. 1,2,4,5-тетракис(4-хлорфенилсульфанил)бензолExample 1. 1,2,4,5-tetrakis (4-chlorophenylsulfanyl) benzene
К 2.37 г (16.88 ммоль) 4-хлортиофенола, 3.49 г (25.32 ммоль) K2CO3 в 10 мл ДМФА вносится раствор 1 г (4.22 ммоль) 1,5-дихлор-2,4–динитробензола в 10 мл ДМФА. Реакционная смесь перемешивается при 140 ºС в течение 2 часов. После охлаждения реакционная масса выливается в воду. Выпавший осадок отфильтровывается и кристаллизуется из смеси изопранол : ДМФА = 5:1. Выход: 2.64 г (97%) Т. пл 263.5-266.5ºC.To 2.37 g (16.88 mmol) of 4-chlorothiophenol, 3.49 g (25.32 mmol) K 2 CO 3 in 10 ml of DMF is added a solution of 1 g (4.22 mmol) of 1,5-dichloro-2,4 – dinitrobenzene in 10 ml of DMF. The reaction mixture is stirred at 140 ° C for 2 hours. After cooling, the reaction mass is poured into water. The precipitate formed is filtered and crystallized from isopranol: DMF = 5: 1. Yield: 2.64 g (97%), m.p. 263.5-266.5ºC.
Найдено %: C 53.61; H 32.13; S 7.18; Cl 7.08;. C30H18S4Cl4. Found%: C 53.61; H 32.13; S 7.18; Cl 7.08; C 30 H 18 S 4 Cl 4.
Вычислено %: C 53.57; H 32.14; S 7.14; Cl 7.14Calculated%: C 53.57; H 32.14; S 7.14; Cl 7.14
Спектр 1H ЯМР (ДМСО-d6, δ, м.д., J/Гц): 7.25-7.60 (м, 18H).1H NMR spectrum (DMSO-d6, δ, ppm, J / Hz): 7.25-7.60 (m, 18H).
MS, Найдено, m/z: 648.9077 [M + H]+. С30H19Cl4S4. Вычислено [M + H] 648.9095MS, Found, m / z: 648.9077 [M + H] +. C 30 H 19 Cl 4 S 4 . Calculated [M + H] 648.9095
Пример 2. 1,2,4,5-тетракис(фенилсульфанил)бензол получают аналогично примеру 1Example 2. 1,2,4,5-tetrakis (phenylsulfanyl) benzene is prepared analogously to example 1
Выход: 2.04 г (95%) Т. пл = 135.5-137.5 ºC.Yield: 2.04 g (95%), mp = 135.5-137.5 ºC.
Найдено %: C 53.60; H 39.34; S 7.06;. C30H22S4 Found%: C 53.60; H 39.34; S 7.06; C 30 H 22 S 4
Вычислено %: C 53.57; H 39.29; S 7.14; Calculated%: C 53.57; H 39.29; S 7.14;
Спектр 1H ЯМР (ДМСО-d6, δ, м.д., J/Гц): 6.70 (с, 2H, H6, Н3); 7.20-7.25 (м, 8H); 7.30-7.32 (м, 12H).1H NMR spectrum (DMSO-d6, δ, ppm, J / Hz): 6.70 (s, 2H, H6, H3); 7.20-7.25 (m, 8H); 7.30-7.32 (m, 12H).
Найдено, m/z: 511.0669 [M + H]+. С30H23S4. Вычислено [M + H] 511.0683.Found m / z: 511.0669 [M + H] +. C 30 H 23 S 4 . Calculated by [M + H] 511.0683.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2018146632A RU2691736C1 (en) | 2018-12-25 | 2018-12-25 | Method of producing 1,2,4,5-tetrakis(4-r-phenylsulfanyl)benzenes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2018146632A RU2691736C1 (en) | 2018-12-25 | 2018-12-25 | Method of producing 1,2,4,5-tetrakis(4-r-phenylsulfanyl)benzenes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2691736C1 true RU2691736C1 (en) | 2019-06-18 |
Family
ID=66947801
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2018146632A RU2691736C1 (en) | 2018-12-25 | 2018-12-25 | Method of producing 1,2,4,5-tetrakis(4-r-phenylsulfanyl)benzenes |
Country Status (1)
| Country | Link |
|---|---|
| RU (1) | RU2691736C1 (en) |
-
2018
- 2018-12-25 RU RU2018146632A patent/RU2691736C1/en active
Non-Patent Citations (4)
| Title |
|---|
| Lee, P. H., Park, Y., Park, S., Lee, E., & Kim, S. (2011). Synthesis of Di-, Tri-, and Tetrasulfides through Multifold Carbon−Sulfur Cross-Coupling Reactions with Indium Tri(organothiolates) in a One-Pot Procedure. The Journal of Organic Chemistry, 76(3), 760-765. doi:10.1021/jo102441t. * |
| Pastor, S. D., & Hessell, E. T. (1985). Substitution of unactivated aryl halides by thiolate anions in polyglymes. The Journal of Organic Chemistry, 50(24), 4812-4815. doi:10.1021/jo00224a032. * |
| Соколов А.А., Бегунов Р.С., Гопанюк П.Д., Сакулина В.О. "РЕАКЦИЯ Ar 1,3-ДИХЛОР-4,6-ДИНИТРОБЕНЗОЛА С S-, O- И N-НУКЛЕОФИЛАМИ " Журнал органической химии, Выпуск 6, 2018, Том 54, 938-940. * |
| Соколов А.А., Бегунов Р.С., Гопанюк П.Д., Сакулина В.О. "РЕАКЦИЯ Ar 1,3-ДИХЛОР-4,6-ДИНИТРОБЕНЗОЛА С S-, O- И N-НУКЛЕОФИЛАМИ " Журнал органической химии, Выпуск 6, 2018, Том 54, 938-940. Lee, P. H., Park, Y., Park, S., Lee, E., & Kim, S. (2011). Synthesis of Di-, Tri-, and Tetrasulfides through Multifold Carbon−Sulfur Cross-Coupling Reactions with Indium Tri(organothiolates) in a One-Pot Procedure. The Journal of Organic Chemistry, 76(3), 760-765. doi:10.1021/jo102441t. Pastor, S. D., & Hessell, E. T. (1985). Substitution of unactivated aryl halides by thiolate anions in polyglymes. The Journal of Organic Chemistry, 50(24), 4812-4815. doi:10.1021/jo00224a032. * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Rassukana et al. | Fluorinated NH-iminophosphonates and iminocarboxylates: novel synthons for the preparation of biorelevant α-aminophosphonates and carboxylates | |
| RU2324678C2 (en) | Method of phenylmalonic acid dinitriles production | |
| CN102076656B (en) | Unsymmetrical oxine compound and its preparation method | |
| Oswald et al. | Negishi cross-coupling reactions of α-amino acid-derived organozinc reagents and aromatic bromides | |
| RU2691736C1 (en) | Method of producing 1,2,4,5-tetrakis(4-r-phenylsulfanyl)benzenes | |
| CA3058686C (en) | Method for preparing 2-aryl malonamide and applications thereof | |
| Liu et al. | Diastereoselective Synthesis of Arylidene Bis (3‐arylaminoacrylates) via One‐pot Domino Reactions | |
| CN105949118A (en) | Preparation method of 2-aryl quinoline derivatives | |
| Muzalevskiy et al. | New approach to the synthesis of trifluoromethylvinyl sulfides | |
| JP6027910B2 (en) | Method for producing catalyst and method for producing optically active anti-1,2-nitroalkanol compound | |
| CN108689874B (en) | A kind of method for preparing 2-arylmalonamide and application thereof | |
| KR102299990B1 (en) | METHOD FOR PREPARATION OF 4-((3-amino-2-hydroxypropyl)-aminocarbony)-pheylboronic acid | |
| CN105085472B (en) | The preparation method and application of 1,3 dithiane class compound of β chlorine α, β unsaturation | |
| JP5186115B2 (en) | 2-Substituted benzyl-3,3-difluoroacrylic acid ester derivatives and process for producing them | |
| CN104693213A (en) | Synthesis method of flavonoid natural compounds Frutinones A, B and C | |
| RU2522553C1 (en) | Method of obtaining 1,1-dichloro-2,2-bis(3-nitro-4-n, n-dimethylaminophenyl)ethylene | |
| JP4956088B2 (en) | Method for producing ω-bromo long chain carboxylic acid | |
| KR101574719B1 (en) | C5 sulfone compound, method for preparing the same, method for preparing crocetin dinitrile using the same, and use thereof | |
| EP2855422B1 (en) | Synthesis of diamido gellants by using dane salts of amino acids | |
| CN104945350A (en) | Novel simple method for synthesizing high-optical-purity thiazolyl amino acid | |
| Alikarami et al. | Regioselective iodination of aryl amines using 1, 4-dibenzyl-1, 4-diazoniabicyclo [2.2. 2] octane dichloroiodate in solution and under solvent-free conditions | |
| JP5243303B2 (en) | Process for producing bis (3-nitro-4-hydroxyphenyl) s | |
| JP4853911B2 (en) | Method for producing isothiazolopyridin-3-one compound | |
| KR20110007741A (en) | Process for preparing 5- (substituted phenylalkyl) -2-alkoxy-5-amino-benzoic acid compound | |
| RU2316558C1 (en) | Method for preparing 8-nitro-1,3,6-triazahomoadamantane |