WO2011010524A1 - Procédé de production de chlorures d'alcoxybenzènesulfonyle - Google Patents

Procédé de production de chlorures d'alcoxybenzènesulfonyle Download PDF

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Publication number
WO2011010524A1
WO2011010524A1 PCT/JP2010/060747 JP2010060747W WO2011010524A1 WO 2011010524 A1 WO2011010524 A1 WO 2011010524A1 JP 2010060747 W JP2010060747 W JP 2010060747W WO 2011010524 A1 WO2011010524 A1 WO 2011010524A1
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WO
WIPO (PCT)
Prior art keywords
chloride
mol
reaction
dimethylformamide
alkoxybenzenesulfonyl
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PCT/JP2010/060747
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English (en)
Japanese (ja)
Inventor
秀三 佐竹
幹生 山本
宗明 田中
哲也 小林
Original Assignee
住友精化株式会社
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Application filed by 住友精化株式会社 filed Critical 住友精化株式会社
Publication of WO2011010524A1 publication Critical patent/WO2011010524A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
    • C07C303/04—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof by substitution of hydrogen atoms by sulfo or halosulfonyl groups
    • C07C303/10—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof by substitution of hydrogen atoms by sulfo or halosulfonyl groups by reaction with sulfur dioxide and halogen or by reaction with sulfuryl halides

Definitions

  • the present invention relates to a method for producing alkoxybenzenesulfonyl chloride useful as an intermediate for synthesis of pharmaceuticals and the like.
  • alkoxybenzene Since alkoxybenzene has an alkoxy group which is an electron donating group, it exhibits a large reaction activity with respect to an electrophile. Therefore, as described in Patent Document 1, when sulfonating 1,3-dialkoxybenzene with sulfuric acid or the like to obtain 2,4-dialkoxybenzenesulfonic acid, a relatively large amount of 4,6 -Dialkoxybenzene-1,3-disulfonic acid is by-produced.
  • 4,6-dialkoxybenzene-1,3-disulfonic acid is chlorinated in the same manner as 2,4-dialkoxybenzenesulfonic acid in the subsequent reaction with thionyl chloride. It becomes 1,3-disulfonyl chloride and is present as an impurity in the reaction product.
  • Patent Document 1 after obtaining 2,4-dialkoxybenzenesulfonic acid from 1,3-dialkoxybenzene, potassium 2,4-dialkoxybenzenesulfonate is obtained using a saturated potassium carbonate solution.
  • 2,4-dialkoxybenzenesulfonyl chloride obtained by reducing the content of the 4,6-dialkoxybenzene-1,3-disulfonyl chloride by subjecting it to isolation after filtration It is for improving the purity of.
  • the operation since the operation is complicated, it is desired to propose a more efficient method for producing 2,4-dialkoxybenzenesulfonyl chloride.
  • An object of the present invention is to provide a method capable of industrially easily and efficiently producing high-purity alkoxybenzenesulfonyl chloride.
  • the present invention relates to a reaction product of sulfuryl chloride and N, N-dimethylformamide, and a formula (1):
  • R 1 represents the same or different lower alkyl group having a carbon number of 1 - 4, R 1 of the adjacent two OR 1 is good .n be connected to each other to form a ring 2 ⁇
  • R 1 represents the same or different lower alkyl group having a carbon number of 1 - 4, R 1 of the adjacent two OR 1 is good .n be connected to each other to form a ring 2 ⁇ 5 represents an integer of 5).
  • the alkoxybenzene used in the present invention is a compound represented by the following formula (1).
  • R 1 represents the same or different lower alkyl group having a carbon number of 1 ⁇ 4, R 1 of the adjacent two OR 1 may be bonded to each other to form a ring.
  • n represents an integer of 2 to 5.
  • Examples of the alkyl group having 1 to 4 carbon atoms represented by R 1 include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a tert-butyl group, and an isobutyl group.
  • the group R 1 of the two adjacent OR 1 are linked to one another, such as 1,3-dioxole group. Of these, a methyl group and a 1,3-dioxole group are preferably used.
  • alkoxybenzene represented by the formula (1) include, for example, 1,2-dimethoxybenzene, 1,2-diethoxybenzene, 1,2-di n-propoxybenzene, 1,2-diisopropoxy.
  • the reaction product of sulfuryl chloride and N, N-dimethylformamide used in the present invention can be produced, for example, by dropping a predetermined amount of sulfuryl chloride into N, N-dimethylformamide in the absence of a solvent. This order of addition is not essential, and N, N-dimethylformamide may be added dropwise to the sulfuryl chloride.
  • the ratio of sulfuryl chloride to be used is not particularly limited, but is preferably 0.1 to 1.5 mol, preferably 0.5 to 1.2 mol with respect to 1 mol of N, N-dimethylformamide. More preferably. When the use ratio of sulfuryl chloride is less than 0.1 mol, the reaction efficiency may be lowered. On the other hand, when the use ratio of sulfuryl chloride exceeds 1.5 mol, a side reaction may occur when it is used as it is for the reaction with alkoxybenzene described later.
  • the reaction temperature for producing a reaction product of sulfuryl chloride and N, N-dimethylformamide is not particularly limited, but is preferably 0 to 180 ° C, more preferably 40 to 150 ° C. When it exceeds 180 degreeC, there exists a possibility that reaction efficiency may fall.
  • the reaction time varies depending on the reaction temperature, but is, for example, 10 minutes to 3 hours.
  • the specific operation method for reacting the reaction product of sulfuryl chloride and N, N-dimethylformamide with the alkoxybenzene is not particularly limited.
  • sulfuryl chloride and N, N-dimethylformamide Examples include a method in which alkoxybenzene is dropped into the reaction solution when the reaction product is produced.
  • the use ratio of the reaction product of sulfuryl chloride and N, N-dimethylformamide is not particularly limited, but is preferably 0.5 to 10 mol per mol of alkoxybenzene, and 0.7 to More preferably, it is 1.5 mol.
  • the number of moles of the reaction product of sulfuryl chloride and N, N-dimethylformamide is based on the amount of sulfuryl chloride and N, N-dimethylformamide used in the reaction product formation. If the ratio of the reaction product of sulfuryl chloride and N, N-dimethylformamide is less than 0.5 mol, the yield may decrease. On the other hand, when the use ratio of the reaction product of sulfuryl chloride and N, N-dimethylformamide exceeds 10 mol, there is a possibility that the effect corresponding to the use amount cannot be obtained.
  • a solvent is not necessarily used.
  • the solvent used include fats such as pentane, hexane, cyclohexane, and heptane.
  • Aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene; ethers such as methyl-tert-butyl ether, diethyl ether, tetrahydrofuran and dioxane.
  • toluene is preferably used.
  • the amount of the solvent used is not particularly limited, but is preferably 3000 parts by weight or less, more preferably 10 to 2000 parts by weight with respect to 100 parts by weight of alkoxybenzene.
  • the usage-amount of a solvent exceeds 3000 weight part, there exists a possibility that volumetric efficiency may deteriorate.
  • the temperature at which alkoxybenzene, the reaction product of sulfuryl chloride and N, N-dimethylformamide are reacted is not particularly limited, but is preferably 0 to 180 ° C, more preferably 40 to 150 ° C. When the reaction temperature exceeds 180 ° C., the reaction product of sulfuryl chloride and N, N-dimethylformamide may be decomposed.
  • the reaction time varies depending on the reaction temperature, but is, for example, 10 minutes to 5 hours.
  • the alkoxybenzenesulfonyl chloride thus obtained is represented by the following formula (2).
  • R 1 represents the same or different lower alkyl group having a carbon number of 1 ⁇ 4, R 1 of the adjacent two OR 1 may be bonded to each other to form a ring.
  • n represents an integer of 2 to 5.
  • alkoxybenzenesulfonyl chloride represented by the formula (2) examples include 3,4-dimethoxybenzenesulfonyl chloride, 3,4-diethoxybenzenesulfonyl chloride, 3,4-di-n-propoxybenzene, 3 , 4-Diisopropoxybenzenesulfonyl chloride, 3,4-di-n-butoxybenzenesulfonyl chloride, 3,4-ditert-butoxybenzenesulfonyl chloride, 3,4-diisobutoxybenzenesulfonyl chloride, 2,4-dimethoxybenzene Sulfonyl chloride, 2,4-diethoxybenzenesulfonyl chloride, 2,4-di-n-propyloxybenzenesulfonyl chloride, 2,4-diisopropyloxybenzenesulfonyl chloride, 2,4-di-n-buty
  • the alkoxybenzenesulfonyl chloride according to the present invention is prepared by adding a predetermined amount of water to the reaction solution after completion of the reaction, followed by liquid separation, cooling the resulting organic layer, and washing and drying the deposited crystals. Can be isolated.
  • alkoxybenzenesulfonyl chloride which is an intermediate for synthesis of pharmaceuticals and the like, can be easily produced with high purity without the need for an impurity removal step.
  • a 1 L four-necked flask equipped with a stirrer, a condenser, a thermometer and a dropping funnel was charged with 47.5 g (0.65 mol) of N, N-dimethylformamide and 87.7 g (0.65 mol) of sulfuryl chloride. Mol) was added dropwise at 25 ° C. over 20 minutes, followed by stirring for 1 hour while maintaining the same temperature.
  • the obtained crystal was confirmed to be 2,4-dimethoxybenzenesulfonyl chloride by the following analysis results.
  • a 1 L four-necked flask equipped with a stirrer, a condenser, a thermometer and a dropping funnel was charged with 47.5 g (0.65 mol) of N, N-dimethylformamide and 87.7 g (0.65 mol) of sulfuryl chloride. Mol) was added dropwise at 25 ° C. over 20 minutes, followed by stirring for 1 hour while maintaining the same temperature.
  • the purity of the obtained 1,3-benzodioxol-5-sulfonyl chloride was measured by HPLC (High Performance Liquid Chromatography) and found to be 99.0 area%. The yield was 78.0% with respect to 1,3-benzodioxole.
  • the entire amount of the reaction solution was dropped into 120 ml of a saturated aqueous potassium carbonate solution at 25 ° C. over 10 minutes, and then stirred for 2 hours while maintaining the same temperature.
  • the precipitated crystals were filtered at 25 ° C. and dried to obtain 15.1 g (0.059 mol) of potassium 2,4-dimethoxybenzenesulfonate.
  • the purity of the obtained potassium 2,4-dimethoxybenzenesulfonate was measured by HPLC (high performance liquid chromatography) and found to be 100.0 area%.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention a pour objet un procédé par lequel il est possible de produire au niveau industriel, facilement et efficacement, des chlorures d'alcoxybenzènesulfonyle de pureté élevée. Un procédé de production de chlorures d'alcoxybenzènesulfonyle représentés par la formule générale (2) [dans laquelle les R1 peuvent être identiques ou différents et représentent chacun un groupe alkyle inférieur en C1 à C4 ou les R1 des deux OR1 qui sont adjacents l'un à l'autre peuvent être unis pour former un cycle ; et n représente un nombre entier de 2 à 5], caractérisé par la soumission du produit réactionnel de chlorure de sulfuryle et de N,N-diméthylformamide à une réaction avec un alcoxybenzène représenté par la formule générale (1) [dans laquelle les R1 peuvent être identiques ou différents et représentent chacun un groupe alkyle inférieur en C1 à C4, ou les R1 des deux OR1 qui sont adjacents l'un à l'autre peuvent être unis pour former un cycle ; et n représente un nombre entier de 2 à 5].
PCT/JP2010/060747 2009-07-24 2010-06-24 Procédé de production de chlorures d'alcoxybenzènesulfonyle WO2011010524A1 (fr)

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JP2009173050 2009-07-24
JP2009-173050 2009-07-24

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106674065A (zh) * 2016-12-07 2017-05-17 贵州大学 一种5‑卤代‑2‑烷氧基‑4‑甲苯磺酰氯制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001513746A (ja) * 1995-03-10 2001-09-04 ジー．ディー．サール アンド カンパニー アミノ酸ヒドロキシエチルアミノスルホンアミド レトロウイルスプロテアーゼインヒビター

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001513746A (ja) * 1995-03-10 2001-09-04 ジー．ディー．サール アンド カンパニー アミノ酸ヒドロキシエチルアミノスルホンアミド レトロウイルスプロテアーゼインヒビター

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KOJTSCHEFF T. ET AL.: "Zur Reaktionsfahigkeit von Saureamid-Saurechlorid-Komplexen auf Basis Dimethylformamid und Sulfurylchlorid", ZEITSCHRIFT FUER CHEMIE, vol. 6, no. 4, 1966, pages 148 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106674065A (zh) * 2016-12-07 2017-05-17 贵州大学 一种5‑卤代‑2‑烷氧基‑4‑甲苯磺酰氯制备方法

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