TW201105620A - Process for production of alkoxybenzenesulfonyl chlorides - Google Patents
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- 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
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201105620 六、發明說明: 【發明戶斤屬之技術領域3 技術領域 本發明係有關於一種作為醫藥品等合成用中間產物有 用的烷氧苯磺醯氣之製造方法。 【先前技名好]1 背景技術 已知有各種方法可作為烷氧苯磺醯氣(其可作為醫藥 等重要的合成用中間產物而被使用)之製造方法,。 舉例而言,已知有將硫酸滴下至1,3-二烷氧苯中藉此將 其磺化而成為2,4-二烷氧苯磺酸,接著,於使用碳酸鉀飽和 水溶液而作成2,4-二烷氧苯磺酸鉀後,將亞硫醯氣滴下至二 曱基甲醯胺中的方法(請參照專利文獻1)等。 習知技術文獻 專利文獻 【專利文獻1】日本專利特開昭57-181053號公報 【發明内容】 發明概要 發明所欲解決之課題 烷氧苯由於具有可作為電子供予基的烷氧基,因此會 對親電子劑顯示高反應活性。因此,如專利文獻1所記載 般,在使用硫酸等來磺化1,3-二烷氧苯以得到2,4-二烷氧苯 磺酸時,會產生較多量的副產物4,6-二烷氧苯-1,3-二磺酸。 4,6-二烷氧苯-1,3-二磺酸在接下來進行之使用亞硫醯 201105620 氣的反應中,會與2,4-二烷氧苯磺酸相同地被氣化而成為 4,6-二烷氧苯-1,3-二磺醯氣,而會在反應生成物中作為不純 物存在。 2,4-二烷氧苯磺醯氣中存在的前述4,6-二烷氧苯-1,3-二 磺醯氣由於難以分離去除,因此特別是在使用2,4-二烷氧苯 磺醯氣作為醫藥合成用中間產物時會成為很大的問題。 於專利文獻1中,自1,3-二烷氧苯得到2,4-二烷氧苯磺 酸後,使用碳酸鉀飽和溶液作成2,4-二烷氧苯磺酸鉀,係為 了將其過濾分離後供以氣化反應,藉此減低前述4,6-二烷氧 苯-1,3-二磺醯氣之含量,而提升所得之2,4-二烷氧苯磺醯氣 的純度。然而,此作業很繁雜故希望有更有效率的2,4-二烷 氧苯磺醯氯之製造方法的提案。 本發明之課題在於提供在工業上可輕易且有效率地製 造高純度之烷氧苯磺醯氣的方法。 用於解決課題的方法 本發明係一種以式(2)所表示之烧氧苯續醯氣的製造方 法: 【化2】 (R1〇]^-^j4j —S02CI ⑵ (式中,R1表示相同或相異的碳數1〜4之低級烷基,且鄰接 的2個OR1之R1亦可五相連結而形成環。n表示2〜5之整數), 該方法的特徵在於: 使硫醯氣及Ν,Ν-二曱基甲酿胺之反應物’與以式(丨)所 201105620 表示的烷氧苯反應: 【化1】 (Rl〇)fr〇 (1) (式中,R1表示相同或相異的碳數卜4之低級烷基’且鄰接 的2個OR1之R1亦可互相連結而形成環。^表示2〜5之整數)。 I:實施方式3 以下將δ羊細說明本發明。 本發明所使用的烷氧苯係以下述式(1)所表示的化合 物。 【化3】 (1) 於式(1)中’R1表示相同或相異的碳數丨〜4之低級烧基, 且鄰接的2個OR1之R1亦可互相連結而形成環。η表示2〜5之 整數。 以R1所表示的碳數丨〜4之烷基可舉例如:甲基、乙基、 正丙基、異丙基、正丁基、第三丁基、異丁基等。又,鄰 接的2個OR之R互相連結而成的基可例舉1,3_二。夸嗤基 等。其等之中可適當地使用曱基及丨,3_二。号唑基。 以式(1)所表不的烷氧苯之具體例可舉例如:1,2-二甲 乳笨、1,2-二乙氧苯、二正丙氧笨、❻二異丙氧苯、 1’2-一正丁氧苯、ι,2-二第三丁氧笨、a-二異丁氧苯、13_ 二甲氧苯、1,3-二乙氧苯、二正内氧苯、υ-二異丙氧 201105620 苯、1,3-二正丁氧苯、ι,3_二第三丁氧苯、i,3_二異丁氧苯、 M-二曱氧苯、1,4-二乙氧苯、ι,4-二正丙氧苯、ι,4-二異丙 氧苯、1,4-二正丁氧苯' 丨,4_二第三丁氧苯、丨,4_二異丁氧 苯、1,3-苯并二噚唑、H4-三曱氧苯、三乙氧苯、12, 三正丙氧苯、1,2,4-三異丙氧苯、ι,2,4-三正丁氧苯、ι,2,4-三第三丁氧苯、1,2,4-三異丁氧苯、1,3,5-三曱氧苯、1,3,5-二乙氧苯、1,3,5-三正丙氧苯、1,3,5-三異丙氧苯、1,3,5-三 正丁氧苯、1,3,5-三第三丁氧苯 '丨,3,5_三異丁氧苯、m 三甲氧苯、1,2,3-三乙氧笨、ι,2,3-三正丙氧苯、i,2,3-三異 丙氧苯、1,2,3-三正丁氧笨、三第三丁氧苯、丨,2,3-三 異丁氧苯、1,2,3,4-四曱氧苯、四乙氧苯、1,2,3,4-四正丙氧苯、1,2,3,4-四異丙氧苯、12,3,4-四正丁氧苯、 1,2,3,4-四第三丁氧苯' 四異丁氧苯、i,2,4,5_四甲氧 苯、1,2,4,5-四乙氧苯、12,4,5-四正丙氧苯、ι,2,4,5-四異丙 氧苯、1,2,4,5-四正丁氧苯、^,尖^四第三丁氧苯、 四異丁氧苯、1,2,3,5-四甲氧苯、12,3,5-四乙氧苯、ms 四正丙氧苯、1,2,3,5-四異丙氧苯、12,3,5-四正丁氧苯、ι,2,3, -四第三丁氧苯、1,2,3,5-四異丁氧苯、12,3,4,5-五甲氧苯、 1,2,3,4,5-五乙氧苯、12,3,4,5-五正丙氧苯、nut五異 丙氧苯、1,2,3,4,5-五正丁氧苯、^七^五第三丁氧苯及 1,2,3,4,5-五異丁氧苯等。 本發明所使用的硫醯氣及N,N_二甲基甲醯胺之反應 物,可例如藉由在無溶劑下將預定量的硫醯氯滴下至N,N_ 一甲基甲醯胺而製造。此添加順序並非必須,而亦可將N,N_ 6 201105620 二曱基甲醢胺滴下至硫醯氣中。硫酿氣的使用比例雖無特[Technical Field] The present invention relates to a method for producing alkoxybenzene sulfonium gas which is useful as an intermediate product for synthesis such as pharmaceuticals. [Previous technical name] 1 Background Art Various methods are known as a method for producing alkoxybenzene sulfonium gas (which can be used as an important intermediate product for synthesis such as medicine). For example, it is known that sulfuric acid is dropped into 1,3-dioxylbenzene to sulfonate it to 2,4-dialkoxybenzenesulfonic acid, followed by using a saturated aqueous solution of potassium carbonate to prepare 2 After the potassium 4-dialkyloxybenzenesulfonate is added, a method of dropping arsenite into the dimercaptocarboxamide (see Patent Document 1) and the like. LIST OF INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION The alkoxybenzene has an alkoxy group which can serve as an electron donor group, and therefore It shows high reactivity to electrophilic agents. Therefore, as described in Patent Document 1, when 1,3-dialkyloxybenzene is sulfonated using sulfuric acid or the like to obtain 2,4-dialkoxybenzenesulfonic acid, a large amount of by-products 4, 6- are produced. Dialkoxybenzene-1,3-disulfonic acid. 4,6-dialkyloxybenzene-1,3-disulfonic acid is vaporized in the same manner as 2,4-dialkyloxybenzenesulfonic acid in the subsequent reaction using sulfoxide 201105620 gas. 4,6-Dialkyloxybenzene-1,3-disulfonium is present as an impurity in the reaction product. The aforementioned 4,6-dialkoxybenzene-1,3-disulfonium gas present in the 2,4-dialkoxybenzenesulfonium gas is particularly difficult to be separated and removed, and therefore, particularly, 2,4-dialkoxybenzene is used. Sulfonium gas is a big problem as an intermediate product for pharmaceutical synthesis. In Patent Document 1, after obtaining 2,4-dialkoxybenzenesulfonic acid from 1,3-dialkoxybenzene, a potassium carbonate saturated solution is used to prepare potassium 2,4-dialkoxybenzenesulfonate for the purpose of After filtration and separation, a gasification reaction is provided, thereby reducing the content of the aforementioned 4,6-dialkoxybenzene-1,3-disulfonium gas, thereby increasing the purity of the obtained 2,4-dialkoxybenzenesulfonate gas. . However, this operation is complicated and it is desired to have a more efficient proposal for a method for producing 2,4-dialkyloxybenzenesulfonyl chloride. SUMMARY OF THE INVENTION An object of the present invention is to provide a process for industrially producing a high purity alkoxybenzene sulfonium gas easily and efficiently. Means for Solving the Problems The present invention relates to a method for producing an oxygen-burning benzene-containing helium gas represented by the formula (2): [Chemical Formula 2] (R1〇]^-^j4j —S02CI (2) (wherein R1 represents the same Or a different lower alkyl group having 1 to 4 carbon atoms, and R1 of two adjacent OR1 groups may be connected in five phases to form a ring. n represents an integer of 2 to 5), and the method is characterized in that: And Ν, 反应-dimercaptoamine reactant ' reacts with alkoxybenzene represented by formula (丨) 201105620: 【化1】(Rl〇)fr〇(1) (wherein R1 represents the same Or a different carbon number of the lower alkyl group of 4 and R1 of two adjacent OR1 may be bonded to each other to form a ring. ^ represents an integer of 2 to 5.) I: Embodiment 3 Hereinafter, the δ sheep will be described in detail. The alkoxybenzene used in the present invention is a compound represented by the following formula (1). (1) In the formula (1), 'R1 represents the same or different carbon number 丨~4. Further, R1 of two adjacent OR1s may be bonded to each other to form a ring. η represents an integer of 2 to 5. The alkyl group having a carbon number of 44 represented by R1 may, for example, be a methyl group or an ethyl group. N-propyl And an isopropyl group, an n-butyl group, a tert-butyl group, an isobutyl group, etc. Further, the group in which the adjacent two ORs of R are linked to each other may be exemplified by 1,3_2, anthracene, etc. Among them, a mercapto group and an anthracene, a bis-oxazolyl group can be suitably used. Specific examples of the alkoxybenzene represented by the formula (1) include, for example, 1,2-dimethylemulsion, 1,2. -diethoxybenzene, di-n-propoxybenzene, bis-isopropoxybenzene, 1'2-monobutoxybenzene, ι,2-di-butoxide, a-diisobutoxybenzene, 13_ Methoxybenzene, 1,3-diethoxybenzene, di-n-ano-oxybenzene, hydrazine-diisopropyloxy 201105620 Benzene, 1,3-di-n-butoxybenzene, ι, 3_di-tert-butoxybenzene, i , 3_ diisobutoxybenzene, M-dioxabenzene, 1,4-diethoxybenzene, ι,4-di-n-propoxybenzene, ι,4-diisopropoxybenzene, 1,4-two n-Butoxybenzene' 丨, 4_2, 3rd butoxybenzene, hydrazine, 4_diisobutoxybenzene, 1,3-benzobisoxazole, H4-trioxobenzene, triethoxybenzene, 12, Tri-n-propoxybenzene, 1,2,4-triisopropoxybenzene, iota, 2,4-tri-n-butoxybenzene, iota, 2,4-tris-tert-butoxybenzene, 1,2,4-tri Isobutoxybenzene, 1,3,5-trioxabenzene, 1,3,5-diethoxybenzene, 1,3,5-tri-n-butyl Oxybenzene, 1,3,5-triisopropoxybenzene, 1,3,5-tri-n-butoxybenzene, 1,3,5-tris-tert-butoxybenzene', 3,5-triisobutoxy Benzene, m trimethoxybenzene, 1,2,3-triethoxybenzene, iota, 2,3-tri-n-propoxybenzene, i,2,3-triisopropoxybenzene, 1,2,3-tri-n-negative Butoxy-oxygen, tri-tert-butoxybenzene, hydrazine, 2,3-triisobutoxybenzene, 1,2,3,4-tetraoxabenzene, tetraethoxybenzene, 1,2,3,4-tetra n-Propoxybenzene, 1,2,3,4-tetraisopropoxybenzene, 12,3,4-tetra-n-butoxybenzene, 1,2,3,4-tetra-tert-butoxybenzene'tetraisobutoxy Benzene, i, 2,4,5-tetramethoxybenzene, 1,2,4,5-tetraethoxybenzene, 12,4,5-tetra-n-propoxybenzene, ι, 2,4,5-tetraiso Propoxybenzene, 1,2,4,5-tetra-n-butoxybenzene, ^, thixos, tetrabutoxybenzene, tetraisobutoxybenzene, 1,2,3,5-tetramethoxybenzene, 12, 3,5-tetraethoxybenzene, ms tetra-n-propoxybenzene, 1,2,3,5-tetraisopropoxybenzene, 12,3,5-tetra-n-butoxybenzene, ι, 2, 3, -4 Third butoxybenzene, 1,2,3,5-tetraisobutoxybenzene, 12,3,4,5-pentamethoxybenzene, 1,2,3,4,5-pentaethoxybenzene, 12, 3,4,5-penta-propoxybenzene, nut penta-isopropylbenzene, 1,2,3,4,5-penta-butoxybenzene, ^7^5-tert-butoxybenzene, and 1,2,3 , 4,5-pentaiso Benzene and the like. The reactants of sulfonium gas and N,N-dimethylformamide used in the present invention can be obtained, for example, by dropping a predetermined amount of thioxanthine chloride to N,N-methylformamide without a solvent. Manufacturing. This order of addition is not required, but N,N_ 6 201105620 dimercaptocarboxamide can also be dropped into the sulphur gas. The use ratio of sulfur brewing gas is not special.
為佳,且以〇.5~ι.2莫耳更佳。當石m氣的使用比例小於〇1 莫耳時,恐有反應效率降低之虞。另—方面,當硫酿氣的 使用比例大於1.5莫耳時,若在後述與院氧苯之反應中照原 樣使用時恐有發生副反應之虞。 在製造硫醯氣及N,N-二曱基甲醯胺之反應物時的反應 溫度雖無特別限定,但以0〜18〇r為佳,且以4〇〜15〇χ:更 佳。若大於18(TC ’恐會有反應效率降低之虞。又反應時間 雖因反應溫度而異,但可舉例如1〇分鐘〜3小時。 於本發明中,使硫醯氯及聯二甲基甲醯胺之反應物 與前述縣苯反應的㈣操作方法雖域職^,但可舉 例如將炫氧苯滴下至製造硫醯氣及N,N•二甲基甲醯胺之反It is better, and it is better to use 〇.5~ι.2. When the use ratio of the stone gas is less than 〇1 mole, there is a fear that the reaction efficiency is lowered. On the other hand, when the use ratio of sulfur-burning gas is more than 1.5 m, there is a fear of side reaction if it is used as it is in the reaction with oxybenzene. The reaction temperature in the case of producing a reaction product of sulfonium gas and N,N-dimercaptocarbamide is not particularly limited, but is preferably 0 to 18 Torr, and more preferably 4 Torr to 15 Torr. If it is greater than 18 (TC ' there is a fear that the reaction efficiency is lowered. The reaction time varies depending on the reaction temperature, but it may be, for example, 1 minute to 3 hours. In the present invention, thiopurine chloride and dimethyl group are made. The reaction method of the reaction of prostamine with the above-mentioned county benzene (IV) is a method of operation, but for example, the dropping of oxy-oxybenzene to the manufacture of sulphur and gas and the reverse of N,N-dimethylformamide
係以在該反應物生成時所用的硫醯 胺的反應物之莫耳數, 氯及Ν —The number of moles of the reactants of thioindole used in the formation of the reactants, chlorine and hydrazine -
甲基甲醯胺的反應物的使用比例小於Q5莫耳時恐有產率 降低之虞。另一方面,當硫醯氣及Ν,Ν_: 恐會無法得到與使用量相 應物的使用比例大於1〇莫耳時,恐會無法 稱的效果。 在硫醯氣及Ν,Ν·二甲基甲_的反應物歧氧苯之反 201105620 應中,溶劑雖不一定必須使用,但在使用情況下的溶劑可 舉例如戊烷、己烷、環己烷、庚烷等脂肪烴類;苯、甲苯、 二曱苯、氣苯等芳香烴類;甲基-第三丁基醚、二乙基醚、 四氫呋喃、二。号烷等醚類等。其等之中,可適當地使用甲 苯。 溶劑的使用量雖無特別限制,但以相對於烷氧苯100 重量份為3000重量份以下為佳,以10〜2000重量份更佳。當 溶劑的使用量大於3000重量份時,會有體積效率惡化之虞。 使烷氧苯及硫醯氣及Ν,Ν-二甲基甲醯胺的反應物反應 的溫度雖無特別限定,但以0〜180°C為佳,且以40〜150°C更 佳。若反應溫度大於180°C,則恐有硫醯氣及N,N-二曱基甲 醯胺的反應物會分解之虞。又,反應時間雖因反應溫度而 異,但可舉例如10分鐘〜5小時。 如此而得的烧氧苯續醯氣係以下述式(2)所表示。 【化4】 (Rl〇)fi^^J s〇2CI (2) 於式(2)中,R1表示相同或相異的碳數1〜4之低級烷基, 且鄰接的2個OR1之R1亦可互相連結而形成環。η表示2〜5之 整數。 以式(2)所表示的烷氧苯磺醯氣之具體例可舉例如: 3,4-二甲氧苯績醯氣、3,4-二乙氧苯績醯氯、3,4-二正丙氧 苯、3,4-二異丙氧苯績醯氣、3,4-二正丁氧苯續醯氣、3,4-二第三丁氧苯磺醯氣、3,4-二異丁氧苯磺醯氣、2,4-二甲氧 8 201105620 苯磺醯氣、2,4-二乙氧苯磺醯氣、2,4-二正丙氧苯磺醯氣、 2.4- 二異丙氧苯磺醯氣、2,4-二正丁氧苯磺醯氣、2,4-二第 二丁氧苯續酿氯、2,4-二異丁乳本叾寅酿乳、1,3-苯并二号β坐 -5-磺醯氯、2,5-二曱氧苯磺醯氣、2,5-二乙氧苯磺醯氣、2,5-二正丙氧苯、2,5-二異丙氧苯績醯氣、2,5-二正丁氧苯續醯 氯、2,5-二第三丁氧苯磺醯氣、2,5-二異丁氧苯磺醯氣、2,4,6-三曱氧苯磺醯氣、2,4,6-三乙氧苯磺醯氣、2,4,6-三正丙氧 苯、2,4,6-三異丙氧苯磺醯氣、2,4,6-三正丁氧苯磺醯氣、 2.4.6- 三第三丁氧苯磺醯氣、2,4,6-三異丁氧笨磺醯氯、2,3,6-三甲氧苯磺醯氣、2,3,6-三乙氧苯磺醯氣、2,3,6-三正丙氧 苯、2,3,6-三異丙氧苯磺醯氣、2,3,6-三正丁氧笨磺醯氣、 2.3.6- 三第三丁氧苯磺醢氣、2,3,6-三異丁氧苯磺醯氯、2,4,5-三甲氧苯磺醯氣、2,4,5-三乙氧苯磺醯氣、2,4,5-三正丙氧 苯、2,4,5-三異丙氧苯磺醯氣、2,4,5-三正丁氧苯磺醯氣、 2,4,5-三第三丁氧苯磺醯氯、2,4,5-三異丁氧苯磺醯氣、2,3,4-三曱氧苯磺醯氣、2,3,4-三乙氧苯磺醯氣、2,3,4-三正丙氧 苯、2,3,4-三異丙氧苯磺醯氯、2,3,4-三正丁氧苯磺醯氣、 2.3.4- 三第三丁氧苯磺醯氣、2,3,4-三異丁氧苯磺醯氣、 2.3.4.6- 四甲氧苯磺醯氯、2,3,4,6-四乙氧苯磺醯氣、2,3,4,6-四正丙氧苯、2,3,4,6-四異丙氧苯磺醯氣、2,3,4,6-四正丁氧 苯磺醯氯、2,3,4,6-四第三丁氧苯磺醯氣、2,3,4,6-四異丁氧 笨磺醯氯、2,3,5,6-四曱氧苯磺醯氣、2,3,5,6-四乙氧苯磺醯 氣、2,3,5,6-四正丙氧苯、2,3,5,6-四異丙氧苯磺醯氯、2,3,5,6-四正丁氧苯磺醯氯、2,3,5,6-四第三丁氧苯磺醯氣、2,3,5,6- 201105620 四異丁氧苯磺醯氣、2,3,4,5-四甲氧苯磺醯氣、2,3,4,5-四乙 氧苯磺醯氣、2,3,4,5-四正丙氧苯、2,3,4,5-四異丙氧苯磺醯 氣、2,3,4,5-四正丁氧苯磺醯氣、2,3,4,5-四第三丁氧苯磺醯 氯、2,3,4,5-四異丁氧苯磺醯氣、2,3,4,5,6-五甲氧苯磺醯氣、 2,3,4,5,6-五乙氧苯磺醯氯、2,3,4,5,6-五正丙氧苯、2,3,4,5,6- 五異丙氧苯磺醯氯、2,3,4,5,6-五正丁氧苯磺醯氣、2,3,4,5,6-五第三丁氧苯磺醯氣、2,3,4,5,6-五異丁氧苯磺醯氣等。 與本發明有關的烷氧苯磺醯氣可藉由例如:添加預定 里的水至前述反應結束後的反應液中並分液,且冷卻所得 到的有機層並洗淨、乾燥析出的結晶而分離。 發明之效果 若依據本發明,則可不需要不純物的去除步驟,而輕 易地以高純度製造作為醫藥品等合成用中間產物之烷氧苯 磺醯氣。 用以實施發明的形態 以下雖例舉實施例及比較例以具體說明本發明,但本 發明絕不為該等實施例所限定。 實施例1 將Ν,Ν-二甲基甲醯胺47, •5g(0.65莫耳)饋送至設置有攪When the proportion of the reactant of methylcarbamide is less than that of Q5 mole, there is a fear that the yield is lowered. On the other hand, when sulphur and sputum, Ν _: may not be able to obtain a ratio of use of the corresponding amount of use of more than 1 〇 Mo, it may not be able to claim the effect. In the reaction of thioxanthene and hydrazine, hydrazine dimethyl ketone, oxybenzene benzene, 201105620, although the solvent does not necessarily have to be used, the solvent in the case of use may, for example, be pentane, hexane or ring. An aliphatic hydrocarbon such as hexane or heptane; an aromatic hydrocarbon such as benzene, toluene, diphenylbenzene or benzene; methyl-tert-butyl ether, diethyl ether, tetrahydrofuran or two. An ether such as an alkyl group. Among them, toluene can be suitably used. The amount of the solvent to be used is not particularly limited, but is preferably 3,000 parts by weight or less based on 100 parts by weight of the alkoxybenzene, more preferably from 10 to 2,000 parts by weight. When the amount of the solvent used is more than 3,000 parts by weight, there is a possibility that the volume efficiency is deteriorated. The temperature at which the reaction of the alkoxybenzene and sulfonium gas and the reaction product of hydrazine and hydrazine-dimethylformamide is not particularly limited, but is preferably 0 to 180 ° C and more preferably 40 to 150 ° C. If the reaction temperature is more than 180 ° C, there is a fear that the reactants of sulphur and gas and N,N-dimercaptocarbamide will decompose. Further, the reaction time varies depending on the reaction temperature, and is, for example, 10 minutes to 5 hours. The thus produced oxygen-burning benzene continued gas system is represented by the following formula (2). (Rl〇)fi^^J s〇2CI (2) In the formula (2), R1 represents the same or different lower alkyl group having 1 to 4 carbon atoms, and adjacent R1 of two OR1 They can also be connected to each other to form a ring. η represents an integer of 2 to 5. Specific examples of the alkoxybenzenesulfonium represented by the formula (2) include, for example, 3,4-dimethoxybenzophenone, 3,4-diethoxybenzene, and 3,4-di. N-propoxybenzene, 3,4-diisopropoxybenzene, helium, 3,4-di-n-butoxybenzene, helium, 3,4-di-butoxide, helium, 3,4-di Isobutoxybenzene sulfonate, 2,4-dimethoxy 8 201105620 Benzene sulfonium, 2,4-diethoxybenzene sulfonium, 2,4-di-n-propoxybenzene sulfonium, 2.4- II Isopropoxybenzene sulfonium, 2,4-di-n-butoxybenzene sulfonium, 2,4-di-2-butoxybenzene, chlorinated, 2,4-diisobutyl milk, 1 , 3-Benzene II β--5-sulfonium chloride, 2,5-dioxabenzenesulfonate, 2,5-diethoxybenzenesulfonate, 2,5-di-n-propoxybenzene, 2,5-diisopropyloxybenzene, helium, 2,5-di-n-butoxybenzene, continuous chlorine, 2,5-di-tert-butoxybenzenesulfonate, 2,5-diisobutoxybenzenesulfonate Helium, 2,4,6-trioxoxabenzenesulfonium, 2,4,6-triethoxybenzenesulfonate, 2,4,6-tri-n-propoxybenzene, 2,4,6-three Isopropoxybenzene sulfonium, 2,4,6-tri-n-butoxybenzenesulfonate, 2.4.6-tris-tert-butoxybenzenesulfonate, 2,4,6-triisobutoxysulfonate Chlorine, 2,3,6-trimethoxybenzenesulfonate , 2,3,6-triethoxybenzenesulfonate, 2,3,6-tri-n-propoxybenzene, 2,3,6-triisopropoxybenzenesulfonate, 2,3,6-tri-positive Butoxy-oxygen sulfonate, 2.3.6-tris-tert-butoxybenzene sulfonium, 2,3,6-triisobutoxybenzenesulfonium chloride, 2,4,5-trimethoxybenzenesulfonate, 2 , 4,5-triethoxybenzenesulfonate, 2,4,5-tri-n-propoxybenzene, 2,4,5-triisopropoxybenzenesulfonate, 2,4,5-tri-n-butoxy Phenylsulfonium, 2,4,5-tris-tert-butoxybenzenesulfonium chloride, 2,4,5-triisobutoxybenzenesulfonate, 2,3,4-trioxabenzenesulfonate, 2,3,4-triethoxybenzenesulfonate, 2,3,4-tri-n-propoxybenzene, 2,3,4-triisopropoxybenzenesulfonyl chloride, 2,3,4-tri-n-butyl Oxybenzene sulfonate, 2.3.4-tris-tert-butoxybenzene sulfonium, 2,3,4-triisobutoxybenzene sulfonium, 2.3.4.6-tetramethoxybenzene sulfonium chloride, 2,3 , 4,6-tetraethoxybenzenesulfonate, 2,3,4,6-tetra-n-propoxybenzene, 2,3,4,6-tetraisopropoxybenzenesulfonate, 2,3,4, 6-tetra-n-butoxybenzenesulfonium chloride, 2,3,4,6-tetra-tert-butoxybenzenesulfonium, 2,3,4,6-tetraisobutoxysulfonyl chloride, 2,3, 5,6-tetraoxabenzenesulfonium, 2,3,5,6-tetraethoxybenzenesulfonate, 2,3,5,6-tetra-n-propoxybenzene, 2,3,5,6- Tetrapropoxybenzene sulfonium chloride , 2,3,5,6-tetra-n-butoxybenzenesulfonium chloride, 2,3,5,6-tetra-tert-butoxybenzenesulfonate, 2,3,5,6- 201105620 tetraisobutoxybenzene Sulfonium, 2,3,4,5-tetramethoxybenzenesulfonate, 2,3,4,5-tetraethoxybenzenesulfonate, 2,3,4,5-tetra-n-propoxybenzene, 2,3,4,5-tetraisopropoxybenzenesulfonate, 2,3,4,5-tetra-n-butoxybenzenesulfonate, 2,3,4,5-tetra-butoxybenzenesulfonate Chlorine, 2,3,4,5-tetraisobutoxybenzenesulfonate, 2,3,4,5,6-pentamethoxybenzenesulfonate, 2,3,4,5,6-pentaethoxy Phenylsulfonium chloride, 2,3,4,5,6-penta-propoxybenzene, 2,3,4,5,6-pentaisopropoxybenzenesulfonyl chloride, 2,3,4,5,6- Penta-n-butoxybenzenesulfonate, 2,3,4,5,6-penta-butoxybenzenesulfonate, 2,3,4,5,6-pentaisobutoxybenzenesulfonate. The alkoxybenzenesulfonium gas according to the present invention can be obtained by, for example, adding a predetermined amount of water to the reaction liquid after the completion of the reaction, and separating the liquid, and cooling the obtained organic layer to wash and dry the precipitated crystal. Separation. According to the present invention, the alkoxybenzene sulfonium gas which is an intermediate product for synthesis such as a pharmaceutical product can be easily produced in a high purity without the step of removing the impurities. MODE FOR CARRYING OUT THE INVENTION The present invention will be specifically described below by way of examples and comparative examples, but the present invention is by no means limited by the examples. Example 1 Feeding Ν, Ν-dimethylformamide 47, • 5g (0.65 mol) to the setting
持同溫度一邊攪拌1小時。Stir for 1 hour while holding the same temperature.
分鐘滴下1,3-二甲氧苯69.1g(〇.5莫耳), 邊維持同溫度,一邊費時40 5莫耳)’再於同溫度攪拌2小 10 201105620 時。反應結束後,將反應液冷卻至25°C ’並添加甲苯ii6g 及水191g而進行分液。將所得到的有機層冷卻至〇°C,且過 濾所析出的結晶後,以甲苯167g洗淨並乾燥,藉此得到2,4_ 二甲氧苯磺醯氣66.6g(以濕重換算為0.28莫耳)。以HPLC(高 效能液相層析)法測量所得到的2,4-二曱氧苯磺醯氣之純 度,結果為99.3面積%。又,產率相對於1,3-二甲氧苯為 56.4%。 再者,依據下述分析結果確認所得到的結晶為2,4-二甲 氧苯磺醯氣。In a minute, 69.1 g (〇.5 mol) of 1,3-dimethoxybenzene was dropped, while maintaining the same temperature, which took 40 5 m) while stirring at the same temperature for 2 small 10 201105620. After completion of the reaction, the reaction solution was cooled to 25 ° C ', and 6 g of toluene ii and 191 g of water were added to carry out liquid separation. The obtained organic layer was cooled to 〇 ° C, and the precipitated crystal was filtered, washed with 167 g of toluene and dried to obtain 66.6 g of 2,4-dimethoxybenzenesulfonate (0.28 in terms of wet weight). Moore). The purity of the obtained 2,4-dioxanthenesulfonate gas was measured by HPLC (High Performance Liquid Chromatography), and as a result, it was 99.3 area%. Further, the yield was 56.4% based on 1,3-dimethoxybenzene. Further, it was confirmed from the analysis results below that the obtained crystal was 2,4-dimethylbenzenesulfonate.
分子量:236.67 熔點:69-70°C Η-核磁共振光譜(CDCI3、以TMS為基準)§(ppm). 7.89(d、1H)、6.55(d、1H)、6.53(s、1H)、4.01(s、3H)、3 89(s、 3H) 實施例2 將N,N-二曱基甲醯胺47.5g(0.65莫耳)饋送至設置有搜 拌機、冷卻管、溫度計及滴液漏斗的1L體積之四頸燒瓶, 並於25°C費時20分鐘滴下硫醯氣87.7g(0.65莫耳)後,一邊維 持同溫度一邊攪拌1小時。 其後,昇溫至60°C,一邊維持同溫度,—邊費時卯分 鐘滴下U-苯并二㈣61.lg(0.5莫耳),再於同溫度㈣ 時。反應結束後’將反應液冷卻至25t:,添加甲苯丨丨^及 水191g並進行分液。將所得到的有機層冷卻至〇它,且過濾 析出的結晶後,以甲苯167g洗淨並乾燥,藉此得到丨,3苯^ 201105620Molecular weight: 236.67 Melting point: 69-70 ° C Η-NMR spectrum (CDCI3, based on TMS) § (ppm). 7.89 (d, 1H), 6.55 (d, 1H), 6.53 (s, 1H), 4.01 (s, 3H), 3 89 (s, 3H) Example 2 47.5 g (0.65 mol) of N,N-dimercaptocarbamide was fed to a mixer, a cooling tube, a thermometer and a dropping funnel After a four-necked flask of a 1 L volume, 87.7 g (0.65 mol) of sulphur gas was dropped at 20 ° C for 20 minutes, and the mixture was stirred for 1 hour while maintaining the same temperature. Thereafter, the temperature was raised to 60 ° C while maintaining the same temperature, and it took time and time to drip U-benzo bis (four) 61. lg (0.5 m), and then at the same temperature (four). After the completion of the reaction, the reaction liquid was cooled to 25 t: and toluene hydrazine and 191 g of water were added and liquid separation was carried out. The obtained organic layer was cooled to dryness, and the precipitated crystals were filtered, washed with 167 g of toluene and dried to obtain hydrazine, 3 benzene ^ 201105620
riSP I 一 5_〜醯氣86.0g(以濕重換算為〇 39莫耳)、 HPLC(高效驗相層析)法測量所得到…以 碏酼菡々开-'气唑_5_ 、,、一”,,屯度’結果為99.0面積%。又,產率相對於4 并二。号唑為78.0%。 、,-本 ^者,依據下述分析結果確認所得到的結晶為^ 二噚唑-5-磺醯氣。 , 开 分子量:220.6 炼點:51t: lH_核磁共振光譜(CDa3、m^ 準)❿㈣:7.66(d、1H)、7 43(s、1H)、6 _、ih)、6 叫土、 2H) 比較例1 以專利文獻1所記載之製造方法為基準製造2,4•二曱氧 苯石黃醯氣。 ,首先,將丨,3·二甲氧苯13.8g(0.1莫耳)饋送至設置有攪 拌機、冷卻管、溫度計及滴液漏斗<1〇〇mL體積的四頸燒 瓶中,並於lOt費時13分鐘滴下硫酸15 2g(〇 15莫耳)後,— 邊維持同溫度一邊攪拌1小時。以HPLc(高效能液相層析) 法對該反應液進行測量,結果2,4-二甲氧笨磺酸之純度為 88.0面積。/。,而副產物4,6·二曱氧苯Μ,、二磺酸則為12 〇面 積%。 接著’於25 C費時10分鐘將上述反應液之全量滴下至 碳酸钟飽和水溶液120ml中後,一邊維持同溫度一邊檀拌2 小時。反應結束後’於25°C過濾所析出的結晶後進行乾燥, 藉此得到2,4-二曱氧苯磺酸鉀15.1§(0_059莫耳)。以1^1(:(高 12 201105620 效能液相層析)法測量所得到的2,4-二曱氧苯磺酸鉀之純 度,結果為100.0面積%。 再者,將所得到的2,4-二甲氧苯磺酸鉀10.25g(0.04莫耳) 與N,N-二曱基曱醯胺40g饋送至設置有攪拌機、冷卻管、溫 度計及滴液漏斗之100mL體積的四頸燒瓶中,並於25°C費 時10分滴下亞硫醯氯5.7g(0.048莫耳)後,一邊維持同溫度一 邊攪拌1小時。 接著,在約25°C費時10分將該反應液的全量滴下至水 l〇〇g後,一邊維持同溫度一邊攪拌1小時。於同溫度過濾所 析出的結晶後並進行乾燥,藉此得到2,4-二甲氧苯磺醯氣 8.62g(以濕重換算為0.036莫耳)。以HPLC(高效能液相層析) 法測量所得到的2,4-二曱氧苯磺醯氣之純度,結果為98.8面 積%。又,產率相對於1,3-二甲氧苯為53.8%。 【圖式簡單說明】 (無) 【主要元件符號說明】 (無) 13riSP I -5_~ helium 86.0g (calculated as wet weight to 〇39 moles), HPLC (high-performance phase contrast chromatography) method to obtain ... to open - 'oxazole _5_,,, a The results of the "twisting degree" were 99.0 area%. Further, the yield was 78.0% with respect to 4 and 2. The azole was confirmed to be bisoxazole according to the following analysis. -5-sulfonate gas., molecular weight: 220.6 refining point: 51t: lH_ nuclear magnetic resonance spectrum (CDa3, m^ quasi) ❿ (four): 7.66 (d, 1H), 7 43 (s, 1H), 6 _, ih ), 6 is called soil, and 2H) Comparative Example 1 2,4 • dioxobenzoxanthine gas is produced based on the production method described in Patent Document 1. First, yttrium, 3·dimethoxybenzene is 13.8 g. (0.1 mol) was fed to a four-necked flask equipped with a stirrer, a cooling tube, a thermometer, and a dropping funnel < 1 mL volume, and after dropping 15 2 g (〇15 mol) of sulfuric acid at 13 minutes for 10 minutes, - stirring for 1 hour while maintaining the same temperature. The reaction liquid was measured by HPLc (high performance liquid chromatography), and the purity of 2,4-dimethoxy sulfonic acid was 88.0 area. Product 4,6·two The oxybenzone and the disulfonic acid were 12% by area. Then, the whole amount of the above reaction liquid was dropped into 120 ml of a saturated aqueous solution of the carbonic acid clock at 10 C for 10 minutes, and then the mixture was mixed for 2 hours while maintaining the same temperature. After completion, the precipitated crystals were filtered at 25 ° C and then dried to obtain potassium 2,4-dioxabenzenesulfonate 15.1 § (0-059 mol). To 1 ^ 1 (: (high 12 201105620 potent liquid) The purity of the obtained potassium 2,4-dioxabenzenesulfonate was measured by a phase chromatography method, and it was 100.0 area%. Further, the obtained potassium 2,4-dimethoxybenzenesulfonate was 10.25 g ( 0.04 mol) and 40 g of N,N-dimethyl decylamine were fed into a 100 mL volume four-necked flask equipped with a stirrer, a cooling tube, a thermometer and a dropping funnel, and the sulfite was dropped at 10 ° C for 10 minutes. After 5.7 g (0.048 mol) of ruthenium chloride, the mixture was stirred for 1 hour while maintaining the same temperature. Then, the total amount of the reaction liquid was dropped to 10 g after 10 minutes at about 25 ° C, while maintaining the same temperature. After stirring for 1 hour, the precipitated crystals were filtered at the same temperature and dried to obtain 2,4-dimethoxybenzenesulfonate gas 8.62 g. (In terms of wet weight, it was 0.036 mol). The purity of the obtained 2,4-dioxanthenesulfonate gas was measured by HPLC (High Performance Liquid Chromatography) method, and as a result, it was 98.8 area%. It is 53.8% relative to 1,3-dimethoxybenzene. [Simple description of the diagram] (none) [Explanation of main component symbols] (none) 13
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