WO2019044814A1 - Method for producing pentafluorosulfanyl aromatic compound - Google Patents
Method for producing pentafluorosulfanyl aromatic compound Download PDFInfo
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- X to Y includes X and Y which are the end values. Also, “X or Y” includes either X or Y or both.
- X or Y includes either X or Y or both.
- the present invention comprises the following reaction steps. Ar- (SF 4 Hal) k + specific silver salt ⁇ Ar- (SF 5 ) k
- the electron withdrawing group is a group having a property of attracting electrons more easily than hydrogen, and in the present invention, a group having a positive value of the substituent constant ⁇ preferably determined according to the Hammett rule.
- fluorine-containing groups are preferred.
- Example 2 The following target compounds were produced in the same manner as in Example 1 except that the reaction temperature was changed to 40 ° C. The results are shown below.
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Abstract
Description
本発明は、ペンタフルオロスルファニル芳香族化合物の製造方法に関する。 The present invention relates to a process for the preparation of pentafluorosulfanyl aromatic compounds.
医薬の設計および開発においてフッ素原子は非常に重要な要素となっており、主要な医薬品のうち２０％を超える医薬品にフッ素原子が導入されている。生理活性を有する化合物へのフッ素原子の導入は、構造、ｐＫａ、効能、膜透過性、代謝経路、薬物動態性に大きな影響を与える。このため、フッ素原子を効率よく導入するための方法が種々検討されている。中でも優れた物理化学特性を有するペンタフルオロスルファニル基（以下ＳＦ5基）が医薬品等の分子の物理化学的特性を改善するために検討されている。 The fluorine atom is a very important factor in drug design and development, and fluorine atoms are introduced into more than 20% of the main drugs. The introduction of a fluorine atom to a compound having physiological activity has a great influence on the structure, pKa, efficacy, membrane permeability, metabolic pathway, and pharmacokinetics. For this reason, various methods for efficiently introducing a fluorine atom have been studied. Among them, a pentafluorosulfanyl group (hereinafter referred to as SF 5 group) having excellent physicochemical properties has been studied in order to improve the physicochemical properties of molecules such as pharmaceuticals.
非特許文献１はアリールジスルフィドを酸化的に塩素フッ素化し、次いでＡｒ－ＳＦ4Ｃｌを、ＺｎＦ2、ＨＦ、Ｓｂ（ＩＩＩ／Ｖ）フッ化物等のフッ素化剤と反応させてＣｌ－Ｆ交換反応によってＡｒ－ＳＦ5を得る方法を開示する。またＳＦ5基を有するピリジン（Ｐｙ）について、非特許文献２および３は、ピリジンジスルフィドを酸化的に塩素フッ素化し、次いでＡｇＦと反応させてＣｌ－Ｆ交換反応によりＰｙ－ＳＦ5を得る方法を開示する。 Non-Patent Document 1 oxidatively chlorine-fluorinates an aryl disulfide, and then reacts Ar-SF 4 Cl with a fluorinating agent such as ZnF 2 , HF, Sb (III / V) fluoride, etc. to perform Cl—F exchange reaction Discloses a method of obtaining Ar-SF 5 according to In addition, for pyridine (Py) having an SF 5 group, Non-patent Documents 2 and 3 disclose a method for oxidatively fluorinating pyridine disulfide and then reacting with AgF to obtain Py-SF 5 by Cl-F exchange reaction. Disclose.
ＡｒＳＦ4Ｃｌ体をＡｒＳＦ5体に変換する反応においてはＡｇＦやＺｎＦ2、ＩＦ5、ＨＦなどのフッ素化剤が必要であり、そのＡｒの性質に応じてこれらフッ素化剤を注意深く選定する必要がある。そのため、様々なＡｒに対応できる優れたＡｒＳＦ4Ｃｌ体をＡｒＳＦ5体に変換する方法が求められている。かかる事情を鑑み、本発明はＳＦ5基を有する芳香族化合物（ペンタフルオロスルファニル芳香族化合物）を効率よく製造する方法を提供することを課題とする。 In the reaction for converting ArSF 4 Cl into ArSF 5 , fluorinating agents such as AgF, ZnF 2 , IF 5 and HF are required, and these fluorinating agents need to be carefully selected according to the nature of Ar. is there. Therefore, there is a need for a method of converting an excellent ArSF 4 Cl form that can cope with various Ars into an ArSF 5 form. In view of the circumstances, it is an object of the present invention to provide a method for efficiently producing an aromatic compound (pentafluorosulfanyl aromatic compound) having a SF 5 group.
発明者らは特定の銀塩を存在させることによって、フッ素化剤として本来不可欠であったＡｇＦ、ＺｎＦ2、ＩＦ5、ＨＦ、Ｓｂ（ＩＩＩ／Ｖ）等のフッ化物を一切用いることなく、前記反応を円滑に進行させることを見出した。すなわち前記課題は以下の本発明によって解決される。
［１］一般式（１）： Ａｒ－（ＳＦ4Ｈａｌ）k
（式中、Ａｒは置換または非置換のアリール基またはヘテロアリール基であり、
ＨａｌはＣｌ基、Ｂｒ基、またはＩ基であり、
ｋは１～３の整数であり）
で表されるハロテトラフルオロスルファニル芳香族化合物と、
フッ素イオンを含まない銀塩を反応させることを含む、
一般式（２）： Ａｒ－（ＳＦ5）k
（式中、Ａｒ、ｋは前述のとおり定義される）
で表されるペンタフルオロスルファニル芳香族化合物の製造方法。
［２］前記銀塩が、Ａｇ2ＣＯ3、ＡｇＯ、Ａｇ2Ｏ、およびＡｇＯＴｆ、からなる群から選択される、［１］に記載の製造方法。
［３］前記銀塩がＡｇ2ＣＯ3である、［２］に記載の製造方法。
［４］前記反応を有機溶媒中で実施する、［１］～［３］のいずれかに記載の製造方法。
［５］前記ハロテトラフルオロスルファニル芳香族化合物およびペンタフルオロスルファニル芳香族化合物が、それぞれ後述する一般式（１’）および（２’）で表される、［１］～［４］のいずれかに記載の製造方法。
The inventors have made it possible to use a specific silver salt without using any fluoride such as AgF, ZnF 2 , IF 5 , HF, Sb (III / V), etc. which were originally essential as a fluorinating agent. It was found that the reaction proceeded smoothly. That is, the problems are solved by the present invention described below.
[1] General Formula (1): Ar- (SF 4 Hal) k
(Wherein, Ar is a substituted or unsubstituted aryl group or heteroaryl group,
Hal is a Cl group, a Br group or an I group,
k is an integer of 1 to 3)
A halotetrafluorosulfanyl aromatic compound represented by
Including reacting a silver salt not containing fluoride ion,
General formula (2): Ar- (SF 5 ) k
(Wherein, Ar, k are defined as described above)
The manufacturing method of the pentafluoro sulfanyl aromatic compound represented by these.
[2] The production method according to [1], wherein the silver salt is selected from the group consisting of Ag 2 CO 3 , AgO, Ag 2 O, and AgOTf.
[3] The production method according to [2], wherein the silver salt is Ag 2 CO 3 .
[4] The process according to any one of [1] to [3], wherein the reaction is carried out in an organic solvent.
[5] In any one of [1] to [4], wherein the halotetrafluorosulfanyl aromatic compound and the pentafluorosulfanyl aromatic compound are represented by the general formulas (1 ′) and (2 ′) described later, respectively. Manufacturing method described.
本発明により、ペンタフルオロスルファニル芳香族化合物を製造できる。 According to the present invention, pentafluorosulfanyl aromatic compounds can be produced.
本発明において「Ｘ～Ｙ」はその端値であるＸおよびＹを含む。また、「ＸまたはＹ」はＸ、Ｙのいずれかあるいはその両方を含む。以下、本発明を詳細に説明する。 In the present invention, “X to Y” includes X and Y which are the end values. Also, "X or Y" includes either X or Y or both. Hereinafter, the present invention will be described in detail.
１．本発明の製造方法
本発明は以下の反応工程を含む。
Ａｒ－（ＳＦ4Ｈａｌ）k＋特定の銀塩 → Ａｒ－（ＳＦ5）k
1. Production Method of the Present Invention The present invention comprises the following reaction steps.
Ar- (SF 4 Hal) k + specific silver salt → Ar- (SF 5 ) k
（１）ハロテトラフルオロスルファニル芳香族化合物
ハロテトラフルオロスルファニル芳香族化合物は一般式（１）：Ａｒ－（ＳＦ4Ｈａｌ）kで表される。Ａｒは置換または非置換のアリール基あるいは置換または非置換のヘテロアリール基である。アリール基とは芳香族炭化水素基であり、例えばフェニル基、ナフチル基などが挙げられる。ヘテロアリール基とは複素芳香族炭化水素基であり、例えばピリジル基、ピリミジル基、インドリル基、ベンゾチアゾリル基等が挙げられる。
(1) Halotetrafluorosulfanyl Aromatic Compound The halotetrafluorosulfanyl aromatic compound is represented by the general formula (1): Ar- (SF 4 Hal) k . Ar is a substituted or unsubstituted aryl group or a substituted or unsubstituted heteroaryl group. The aryl group is an aromatic hydrocarbon group, and examples thereof include a phenyl group and a naphthyl group. The heteroaryl group is a heteroaromatic hydrocarbon group, and examples thereof include pyridyl group, pyrimidyl group, indolyl group, benzothiazolyl group and the like.
アリール基およびヘテロアリール基（以下まとめて「Ａｒ基」ともいう）における置換基としては、（i）ハロゲン基、（ii）ハロゲン基を除く電子吸引基、および（iii）ハロゲン基を除く電子供与基が挙げられる。ハロゲン基としてはＦ基、Ｃｌ基、Ｂｒ基、Ｉ基が挙げられるが、入手容易性の観点からＦ基、Ｃｌ基、Ｂｒ基が好ましい。 As substituents for the aryl group and the heteroaryl group (hereinafter collectively referred to as “Ar group”), (i) a halogen group, (ii) an electron-withdrawing group excluding a halogen group, and (iii) an electron donating excluding a halogen group Groups are mentioned. Examples of the halogen group include F group, Cl group, Br group and I group. From the viewpoint of easy availability, F group, Cl group and Br group are preferable.
電子吸引基とは水素に比べて電子をひきつけやすい性質を有する基であり、本発明においては、好ましくはＨａｍｍｅｔｔ則にしたがって決定される置換基定数σが正の値となる基をいう。電子吸引基としては、ＣＦ3基、ＣＣｌ3基、ＣＢｒ3基、ＣＩ3基、ニトロ基（ＮＯ2基）、シアノ基（ＣＮ基）、ＣＯＯＨ基、ＣＯＯＲ1基（Ｒ1は炭素数１～３のアルキル基）、ＳＯ3Ｈ基、ＳＯ3Ｒ2基（Ｒ2は炭素数１～３のアルキル基、または炭素数１～３のパーフルオロアルキル基）が挙げられる。これらの中でもフッ素含有基が好ましい。フッ素含有基としては、ＣＦ3基、ＳＯ3ＣＦ3基が挙げられる。これらの中でも、ニトロ基、ＣＦ3基、またはシアノ基が好ましい。一般にハロゲン基も電子吸引基に分類されるが、ハロゲン基はメソメリー効果等によって電子供与基的にふるまう場合があるので、本発明おいて電子吸引基はハロゲン基を含まない。以下、ハロゲン基を除く電子吸引基を単に「電子吸引基」ともいう。なお、ＳＦ5基も電子吸引性であるが、本発明においてはここでいう置換基としての電子吸引基からは除外される。 The electron withdrawing group is a group having a property of attracting electrons more easily than hydrogen, and in the present invention, a group having a positive value of the substituent constant σ preferably determined according to the Hammett rule. As the electron withdrawing group, CF 3 group, CCl 3 group, CBr 3 group, CI 3 group, nitro group (NO 2 group), cyano group (CN group), COOH group, COOR 1 group (R 1 has 1 carbon number) And alkyl groups of -3), SO 3 H groups and SO 3 R 2 groups (where R 2 is an alkyl group of 1 to 3 carbon atoms or a perfluoroalkyl group of 1 to 3 carbon atoms). Among these, fluorine-containing groups are preferred. As a fluorine-containing group, a CF 3 group and an SO 3 CF 3 group can be mentioned. Among these, a nitro group, a CF 3 group or a cyano group is preferable. In general, a halogen group is also classified as an electron withdrawing group, but since a halogen group may behave like an electron donating group due to a mesomerization effect or the like, the electron withdrawing group in the present invention does not contain a halogen group. Hereinafter, the electron withdrawing group other than the halogen group is also simply referred to as "electron withdrawing group". Although the SF 5 group is also electron-withdrawing, it is excluded from the electron-withdrawing group as a substituent referred to in the present invention.
電子供与基とは水素に比べて電子を与えやすい性質を有する基であり、本発明においては、好ましくはＨａｍｍｅｔｔ則にしたがって決定される置換基定数σが負の値となる基をいう。電子供与基としてはアルキル基、アルコキシル基、水酸基、アミノ基等が挙げられる。アルキル基は直鎖状、分岐状、または環状の炭素数１～１８であるアルキル基が好ましく、炭素数１～５のアルキル基が好ましい。アルコシキル基におけるアルキル基についても同様である。前記理由と同様に、本発明おいて電子供与基はハロゲン基を除く。以下、ハロゲン基を除く電子供与基を単に「電子供与基」ともいう。 The electron donating group is a group having a property of giving electrons more easily than hydrogen, and in the present invention, a group having a negative value of the substituent constant σ preferably determined according to the Hammett rule. Examples of the electron donating group include an alkyl group, an alkoxyl group, a hydroxyl group and an amino group. The alkyl group is preferably a linear, branched or cyclic alkyl group having 1 to 18 carbon atoms, and more preferably an alkyl group having 1 to 5 carbon atoms. The same applies to the alkyl group in the alkoxy group. As in the above reasons, in the present invention, the electron donating group excludes a halogen group. Hereinafter, the electron donating group excluding the halogen group is also simply referred to as "electron donating group".
置換基（i）、（ii）、（iii）は化合物内に併存していてもよい。しかしながら後述するとおり、置換基の特性によって好ましい反応条件は異なるので、一態様において化合物内にこれらの置換基は併存しない。ただし、置換基（i）と（iii）は類似の特性を有するので他の態様において、化合物内に置換基は（i）と（iii）は併存する。 The substituents (i), (ii) and (iii) may co-exist in the compound. However, as described later, since preferable reaction conditions differ depending on the properties of the substituents, in one aspect, these substituents do not coexist in the compound. However, since substituents (i) and (iii) have similar properties, in another embodiment, the substituents (i) and (iii) coexist in the compound.
ＨａｌはＣｌ基、Ｂｒ基、またはＩ基であり、入手容易性の観点からはＣｌ基が好ましい。 Hal is a Cl group, a Br group or an I group, and a Cl group is preferable from the viewpoint of easy availability.
ｋはＳＦ4Ｈａｌ基の個数を表し、１～３の整数であり、好ましくは１または２、より好ましくは１である。 k represents the number of SF 4 Hal groups, and is an integer of 1 to 3, preferably 1 or 2, and more preferably 1.
ハロテトラフルオロスルファニル芳香族化合物は好ましくは、一般式（１’）で表される。 The halo tetrafluorosulfanyl aromatic compound is preferably represented by the general formula (1 ').
ＸはＣまたはＮであり、ＹはＣまたはＮである。環上のＮの個数をｎとする。ｎは０～２の整数である。ｋは前述のとおり定義される。 X is C or N and Y is C or N. Let n be the number of N on the ring. n is an integer of 0 to 2. k is defined as described above.
Ｒは環上の置換基であり、ｍはその個数を表す。Ｒは、前述の置換基（i）、（ii）、または（iii）であることが好ましい。ｍが０でない場合、複数のＲは同じであってもよいし異なっていてもよい。ｍは０～（６－ｋ－ｎ）で表される。すなわちｍは０～５の値をとりうる。 R is a substituent on the ring, and m represents the number thereof. R is preferably the above-mentioned substituent (i), (ii) or (iii). When m is not 0, a plurality of R may be the same or different. m is represented by 0 to (6-k-n). That is, m can take a value of 0-5.
式（１’）においてＮは１つ存在することが好ましい。またＮが存在する場合、Ｎを基準として３位に電子吸引基が存在すると本発明の効果がより顕著となる。 In the formula (1 '), one N is preferably present. When N is present, the effect of the present invention becomes more pronounced when the electron withdrawing group is present at the 3-position relative to N.
（２）銀塩
本発明で使用される銀塩はフッ素イオンを含まない。当該銀塩はＡｇ2ＣＯ3、ＡｇＯ、Ａｇ2Ｏ、およびＡｇＯＴｆからなる群から選択されることが好ましく、Ａｇ2ＣＯ3がより好ましい。これらの２種以上を組合せて使用してもよいがコスト等の観点からは単独で使用することが好ましい。銀塩の使用量は、目的化合物が得られる量であれば限定されないが、ＳＦ4Ｈａｌ基に対して好ましくは０．２当量以上、より好ましくは０．４当量以上である。使用量の上限は、コスト等の観点から２．０当量以下であることが好ましく、１．５当量以下であることがより好ましく、１．０当量以下であることがさらに好ましい。
(2) Silver salt The silver salt used in the present invention does not contain fluorine ion. The silver salt is preferably selected from the group consisting of Ag 2 CO 3 , AgO, Ag 2 O, and AgOTf, more preferably Ag 2 CO 3 . Two or more of these may be used in combination, but it is preferable to use them alone from the viewpoint of cost and the like. The amount of the silver salt used is not limited as long as the target compound can be obtained, but it is preferably 0.2 equivalents or more, more preferably 0.4 equivalents or more, to the SF 4 Hal group. The upper limit of the amount used is preferably 2.0 equivalents or less, more preferably 1.5 equivalents or less, and still more preferably 1.0 equivalents or less from the viewpoint of cost and the like.
（３）ペンタフルオロスルファニル芳香族化合物
本発明の製造方法で得られるペンタフルオロスルファニル芳香族化合物は一般式（２）：Ａｒ－（ＳＦ5）kで表される。Ａｒは一般式（１）におけるＡｒと同じである。ｋはＳＦ5基の個数を示し、１～３の整数であり、好ましくは１または２、より好ましくは１である。ペンタフルオロスルファニル芳香族化合物は好ましくは一般式（２’）で表される。
(3) Pentafluorosulfanyl Aromatic Compound The pentafluorosulfanyl aromatic compound obtained by the production method of the present invention is represented by the general formula (2): Ar- (SF 5 ) k . Ar is the same as Ar in General Formula (1). k represents the number of SF 5 groups, and is an integer of 1 to 3, preferably 1 or 2, and more preferably 1. The pentafluorosulfanyl aromatic compound is preferably represented by the general formula (2 ′).
ペンタフルオロスルファニル芳香族化合物の具体例を以下に示す。パーセンテージは一態様における精製後の単離した収率であり、かっこ内の値はフルオロベンゼンを内部標準として19Ｆ－ＮＭＲで求めた収率である。 Specific examples of pentafluorosulfanyl aromatic compounds are shown below. The percentage is the isolated yield after purification in one embodiment and the value in parentheses is the yield determined by 19 F-NMR with fluorobenzene as an internal standard.
反応条件は所望の収率を達成するために適宜調整できる。反応温度は特に限定されず、１５℃以上とすることが好ましい。温度の上限も限定されないが、１００℃以下とすることが好ましく、５０℃以下とすることがより好ましい。また溶媒中で反応を実施することが好ましい。ただし、Ａｒ基が電子吸引基を置換基として有するアリール基である場合やヘテロアリール基である場合等の反応の進行が遅い場合は、反応温度を８０℃以上とすることが好ましく、１００℃以上とすることがより好ましい。上限は１２０℃以下であることが好ましい。また、溶媒を用いて反応を実施してもよいが、Ａｒ基が電子吸引基を置換基として有するアリール基である場合やヘテロアリール基である場合など反応の進行が遅い場合は、無溶媒で行うことが好ましい。 The reaction conditions can be adjusted appropriately to achieve the desired yield. The reaction temperature is not particularly limited, and is preferably 15 ° C. or more. The upper limit of the temperature is also not limited, but is preferably 100 ° C. or less, and more preferably 50 ° C. or less. It is also preferred to carry out the reaction in a solvent. However, when the progress of the reaction is slow, such as when the Ar group is an aryl group having an electron withdrawing group as a substituent or a heteroaryl group, the reaction temperature is preferably 80 ° C. or higher, preferably 100 ° C. or higher. It is more preferable to The upper limit is preferably 120 ° C. or less. The reaction may be carried out using a solvent, but if the progress of the reaction is slow, such as when the Ar group is an aryl group having an electron withdrawing group as a substituent or a heteroaryl group, no solvent is used. It is preferred to do.
前述のとおり、反応は溶媒中で実施してもよいし、無溶媒で実施してもよい。溶媒としては、塩素系有機溶媒またはフッ素系有機溶媒等のハロゲン含有有機溶媒や、ヘキサン等の脂肪族炭化水素溶媒が挙げられる。中でも、ハロゲン含有有機溶媒が好ましく、塩素系有機溶媒がより好ましい。 As mentioned above, the reaction may be carried out in a solvent or without solvent. Examples of the solvent include halogen-containing organic solvents such as chlorine-based organic solvents or fluorine-based organic solvents, and aliphatic hydrocarbon solvents such as hexane. Among them, halogen-containing organic solvents are preferable, and chlorine organic solvents are more preferable.
［実施例１］
以下の反応を実施した。
Example 1
The following reactions were performed.
［実施例１－１］
グローブボックス内で、化合物１ａ～１ｅ（１．０ｍｍｏｌ）およびＡｇ2ＣＯ3（１３８ｍｇ、０．５ｍｍｏｌ（０．５当量））を、マグネチックスターラーを含むＦＥＰ製容器に量り取った。化合物１ａ～１ｅは化合物２ａ～２ｅに対応するＳＦ4Ｃｌ体である。例えば、１ａは、ｐ－ＣｌＰｈ－ＳＦ4Ｃｌである。当該容器内に乾燥ジクロロメタン（ＤＣＭ）（５ｍＬ）を加えた。２３℃で１２～２４時間撹拌して反応を行った。反応生成物を珪藻土ろ過し、ジクロロメタンで洗浄した。ろ液と洗浄した液を合わせ、氷浴中、減圧下にて濃縮した。ペンタン／ジクロロメタンを溶出溶媒として用いたシリカクロマトグラフィーによって粗生成物を精製し、目的化合物２ａ～２ｅを製造した。結果を以下に示す。パーセンテージは精製後の単離した収率であり、かっこ内のパーセンテージはフルオロベンゼンを内部標準として19Ｆ－ＮＭＲで求めた収率である。本反応に用いたハロテトラフルオロスルファニル芳香族化合物１は非特許文献１、２、３の方法によって合成した。
Example 1-1
In a glove box, compounds 1a-1e (1.0 mmol) and Ag 2 CO 3 (138 mg, 0.5 mmol (0.5 equivalents)) were weighed into a container made of FEP containing a magnetic stirrer. Compounds 1a to 1e are SF 4 Cl forms corresponding to compounds 2a to 2e. For example, 1a is p-ClPh-SF 4 Cl. Dry dichloromethane (DCM) (5 mL) was added into the vessel. The reaction was allowed to stir at 23 ° C. for 12-24 hours. The reaction product was filtered through diatomaceous earth and washed with dichloromethane. The filtrate and the washed solution were combined and concentrated in an ice bath under reduced pressure. The crude product was purified by silica chromatography using pentane / dichloromethane as the eluting solvent to produce the target compounds 2a-2e. The results are shown below. The percentage is the isolated yield after purification, and the percentage in parenthesis is the yield determined by 19 F-NMR with fluorobenzene as an internal standard. The halo tetrafluoro sulfanyl aromatic compound 1 used for this reaction was synthesize | combined by the method of a nonpatent literature 1, 2, 3.
［実施例１－２］
また、１．０当量のＡｇＯ、１．０当量のＡｇＯＴｆ、０．５当量のＡｇ2Ｏを用いて、実施例１－１と同様の反応を行い、化合物２ａを製造した。フルオロベンゼンを内部標準として19Ｆ－ＮＭＲで求めた収率は、それぞれ６８％、３２％、３０％であった。これらの値は、公知のフッ素化剤ＡｇＦを用いて同条件で製造した化合物２ａの収率（２９％）を上回っており、これらの銀塩も有用であることが明らかである。
Embodiment 1-2
Further, the same reaction as in Example 1-1 was performed using 1.0 equivalent of AgO, 1.0 equivalent of AgOTf, and 0.5 equivalent of Ag 2 O to produce a compound 2a. The yields determined by 19 F-NMR with fluorobenzene as an internal standard were 68%, 32% and 30%, respectively. These values exceed the yield (29%) of compound 2a produced under the same conditions using a known fluorinating agent AgF, and it is clear that these silver salts are also useful.
［実施例２］
反応温度を４０℃に変更した以外は、実施例１と同様にして以下の目的化合物を製造した。結果を以下に示す。
Example 2
The following target compounds were produced in the same manner as in Example 1 except that the reaction temperature was changed to 40 ° C. The results are shown below.
［実施例３］
反応温度を７０℃に変更し、溶媒を用いずに無用媒で反応を実施した以外は、実施例１と同様にして以下の目的化合物を製造した。結果を以下に示す。
[Example 3]
The following target compounds were produced in the same manner as in Example 1 except that the reaction temperature was changed to 70 ° C., and the reaction was carried out with no solvent without using a solvent. The results are shown below.
［実施例４］
反応温度を１００℃に変更し、溶媒を用いずに無用媒で反応を実施した以外は、実施例１と同様にして以下の目的化合物を製造した。結果を以下に示す。
Example 4
The following target compounds were produced in the same manner as in Example 1 except that the reaction temperature was changed to 100 ° C., and the reaction was carried out with no solvent without using a solvent. The results are shown below.
本発明によって、効率よくペンタフルオロスルファニル芳香族化合物を製造できることが明らかである。 It is apparent that pentafluorosulfanyl aromatic compounds can be produced efficiently by the present invention.
Claims (5)
（式中、Ａｒは置換または非置換のアリール基またはヘテロアリール基であり、
ＨａｌはＣｌ基、Ｂｒ基、またはＩ基であり、
ｋは１～３の整数であり）
で表されるハロテトラフルオロスルファニル芳香族化合物と、
フッ素イオンを含まない銀塩を反応させることを含む、
一般式（２）： Ａｒ－（ＳＦ5）k
（式中、Ａｒ、ｋは前述のとおり定義される）
で表されるペンタフルオロスルファニル芳香族化合物の製造方法。 General formula (1): Ar- (SF 4 Hal) k
(Wherein, Ar is a substituted or unsubstituted aryl group or heteroaryl group,
Hal is a Cl group, a Br group or an I group,
k is an integer of 1 to 3)
A halotetrafluorosulfanyl aromatic compound represented by
Including reacting a silver salt not containing fluoride ion,
General formula (2): Ar- (SF 5 ) k
(Wherein, Ar, k are defined as described above)
The manufacturing method of the pentafluoro sulfanyl aromatic compound represented by these.
ＸはＣまたはＮであり、
ＹはＣまたはＮであり、
Ｒは独立に、ハロゲン基、ハロゲン基を除く電子吸引基、またはハロゲン基を除く電子供与基であり、
ｋは１～３の整数であり、
ｍは０～（６－ｋ－ｎ）で表される整数であり、
ｎは前記Ｎの個数である）
請求項１～４のいずれかに記載の製造方法。 The halotetrafluorosulfanyl aromatic compound and the pentafluorosulfanyl aromatic compound are represented by the general formulas (1 ′) and (2 ′), respectively
X is C or N,
Y is C or N,
R independently represents a halogen group, an electron withdrawing group excluding a halogen group, or an electron donating group excluding a halogen group,
k is an integer of 1 to 3 and
m is an integer represented by 0 to (6-k-n),
n is the number of said N)
The method according to any one of claims 1 to 4.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010522213A (en) * | 2007-03-23 | 2010-07-01 | アイエム・アンド・ティー・リサーチ・インコーポレーテッド | Method for producing aryl sulfur pentafluoride |
| JP2014513037A (en) * | 2011-02-15 | 2014-05-29 | 宇部興産株式会社 | Industrial production method of arylsulfapentafluoride |
| WO2017090746A1 (en) * | 2015-11-25 | 2017-06-01 | 宇部興産株式会社 | Pentafluorosulfanylpyridine |
| WO2018159515A1 (en) * | 2017-02-28 | 2018-09-07 | 宇部興産株式会社 | Method for producing pentafluorosulfanyl aromatic compound |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010522213A (en) * | 2007-03-23 | 2010-07-01 | アイエム・アンド・ティー・リサーチ・インコーポレーテッド | Method for producing aryl sulfur pentafluoride |
| JP2014513037A (en) * | 2011-02-15 | 2014-05-29 | 宇部興産株式会社 | Industrial production method of arylsulfapentafluoride |
| WO2017090746A1 (en) * | 2015-11-25 | 2017-06-01 | 宇部興産株式会社 | Pentafluorosulfanylpyridine |
| WO2018159515A1 (en) * | 2017-02-28 | 2018-09-07 | 宇部興産株式会社 | Method for producing pentafluorosulfanyl aromatic compound |
Non-Patent Citations (1)
| Title |
|---|
| CUI, BENQIANG ET AL.: "Silver-induced self-immolative Cl-F exchange fluorination of arylsulfur chlorotetrafluorides: synthesis of arylsulfur pentafluorides", CHEMICAL COMMUNICATIONS, vol. 53, no. 95, 11 December 2017 (2017-12-11), pages 12738 - 12741, XP055679280, ISSN: 1359-7345 * |
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