JPH05163259A - 1,2,5-thiadiazole derivative and its production - Google Patents

1,2,5-thiadiazole derivative and its production

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Publication number
JPH05163259A
JPH05163259A JP3353109A JP35310991A JPH05163259A JP H05163259 A JPH05163259 A JP H05163259A JP 3353109 A JP3353109 A JP 3353109A JP 35310991 A JP35310991 A JP 35310991A JP H05163259 A JPH05163259 A JP H05163259A
Authority
JP
Japan
Prior art keywords
group
carbon atoms
atom
thiadiazole
alkyl group
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
JP3353109A
Other languages
Japanese (ja)
Inventor
Yasuaki Hanazaki
保彰 花崎
Hiroyuki Watanabe
博幸 渡辺
Kenji Tsuzuki
建治 続木
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tosoh Corp
Original Assignee
Tosoh Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Tosoh Corp filed Critical Tosoh Corp
Priority to JP3353109A priority Critical patent/JPH05163259A/en
Publication of JPH05163259A publication Critical patent/JPH05163259A/en
Pending legal-status Critical Current

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Classifications

    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts

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  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

PURPOSE:To provide the subject new 1,2,5-thiadiazole derivatives useful as an organic intermediate or an intermediate for synthesis of a medical and agricultural drug and to provide a production method capable of synthesizing them from readily available raw materials in high yields and of readily and safely introducing an arbitrary substituent group. CONSTITUTION:3-R<2>-4-R<1>-1,2,5-thiadiazole derivatives [In the formula, R<1> is hydrogen atom, a 1-6C alkyl group (which may be substituted with fluorine atom or a 1-3C alkoxy group) or -C6H3XY (X and Y are same or mutually different and denote fluorine atom, chlorine atom, trifluoromethyl group, a 1-6C alkyl group or a 1-3C alkoxy group) and R<2> is a 1-6C alkyl group, provided that compounds in which R<1> and R<2> are respectively hydrogen atom or methyl group and methyl group are excluded].

Description

【発明の詳細な説明】Detailed Description of the Invention

【０００１】[0001]

【産業上の利用分野】本発明は新規な１，２，５−チア
ジアゾール誘導体及びその製造法に関する。本発明によ
って得られるチアジアゾール誘導体は、有機中間体及び
医・農薬の中間体として有用な化合物である。FIELD OF THE INVENTION The present invention relates to a novel 1,2,5-thiadiazole derivative and a method for producing the same. The thiadiazole derivative obtained by the present invention is a compound useful as an organic intermediate and an intermediate for medicines and agricultural chemicals.

【０００２】[0002]

【従来の技術】従来、特定の３−アルキル−１，２，５
−チアジアゾールの製造法として次のような製造法が公
知である。例えば、３，４−ジメチル−１，２，５−チ
アジアゾールの製造法としてジメチルグリオキシムと一
塩化硫黄との反応が、また３−メチル−１，２，５−チ
アジアゾールの製造法として１，２−ジアミノプロパン
と一塩化硫黄との反応（L.M.Weinstock et al.,J.Org.C
hem.,32,2823(1967)）が報告されている。さらに、３−
メチル−４−フェニル−１，２，５−チアジアゾールの
製造法としてメチルベンジルケトンと四硫化四窒素との
反応（S.Mataka et al.,Synthesis,524(1979) ）等が報
告されている。2. Description of the Related Art Conventionally, specific 3-alkyl-1,2,5
-The following production method is known as a production method of thiadiazole. For example, the reaction of dimethylglyoxime with sulfur monochloride is a method for producing 3,4-dimethyl-1,2,5-thiadiazole, and the method for producing 3-methyl-1,2,5-thiadiazole is 1,2. -Reaction of diaminopropane with sulfur monochloride (LM Weinstock et al., J.Org.C
hem., 32, 2823 (1967)) has been reported. Furthermore, 3-
As a method for producing methyl-4-phenyl-1,2,5-thiadiazole, a reaction between methylbenzyl ketone and tetranitrogen tetrasulfide (S. Mataka et al., Synthesis, 524 (1979)) and the like have been reported.

【０００３】[0003]

【発明が解決しようとする課題】前者の製造法では出発
原料の入手が困難かつ収率が低いという欠点を有してい
る。後者の製造法では四硫化四窒素が爆発性物質のため
取り扱いにくく、収率も低いという欠点を有している。The former production method has the drawbacks that starting materials are difficult to obtain and the yield is low. The latter manufacturing method has drawbacks that tetranitrogen tetrasulfide is an explosive substance and is difficult to handle, and the yield is low.

【０００４】[0004]

【課題を解決するための手段】本発明者らは、１，２，
５−チアジアゾール誘導体の製造法について鋭意研究を
重ねた結果、入手容易な出発原料から良好な収率で、し
かも任意の置換基を安全かつ簡便に導入する製造法を見
い出し、本発明を完成した。The inventors of the present invention have
As a result of intensive studies on a method for producing a 5-thiadiazole derivative, the present invention has been completed by finding a method for producing a starting material which is easily available with a good yield and in which a desired substituent is safely and conveniently introduced.

【０００５】すなわち、本発明は、３−Ｒ2 −４−Ｒ1
−１，２，５−チアジアゾール誘導体［式中、Ｒ1 は水
素原子、（フッ素原子、炭素数１〜３のアルコキシ基で
置換されてもよい）炭素数１〜６のアルキル基または−
Ｃ6 Ｈ3 ＸＹ（Ｘ、Ｙは同一または異なってフッ素原
子、塩素原子、トリフルオロメチル基、炭素数１〜６の
アルキル基、炭素数１〜３のアルコキシ基を示す）を示
し、Ｒ2 は炭素数１〜６のアルキル基を示す。ただし、
Ｒ1 が水素原子またはメチル基を示し、Ｒ2 がメチル基
である化合物を除く。］、および３−ブロモ−４−Ｒ3
−１，２，５−チアジアゾール［式中、Ｒ3は水素原
子、（フッ素原子、炭素数１〜３のアルコキシ基で置換
されてもよい）炭素数１〜６のアルキル基または（フッ
素原子、塩素原子、トリフルオロメチル基、炭素数１〜
６のアルキル基、炭素数１〜３のアルコキシ基で置換さ
れてもよい）フェニル基を示す。］を有機亜鉛反応剤Ｒ
2 Ｒ4 Ｚｎ［Ｒ2 は前記と同じ、Ｒ4 はＲ2 またはハロ
ゲン原子を示す。］とパラジウム化合物触媒の存在下、
反応させることによる３−Ｒ2 −４−Ｒ3 −１，２，５
−チアジアゾール誘導体［式中、Ｒ2 、Ｒ3 は前記と同
じ。］の製法を提供するものである。That is, the present invention relates to 3-R 2 -4-R 1
-1,2,5-thiadiazole derivative [in the formula, R 1 is a hydrogen atom, (optionally substituted with a fluorine atom, an alkoxy group having 1 to 3 carbon atoms), an alkyl group having 1 to 6 carbon atoms, or
C 6 H 3 XY (X and Y are the same or different and each represents a fluorine atom, a chlorine atom, a trifluoromethyl group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 3 carbon atoms), and R 2 Represents an alkyl group having 1 to 6 carbon atoms. However,
Excluding compounds in which R 1 represents a hydrogen atom or a methyl group and R 2 is a methyl group. ], And 3-bromo-4-R 3
-1,2,5-thiadiazole [in the formula, R 3 is a hydrogen atom, a fluorine atom, an alkyl group having 1 to 6 carbon atoms (which may be substituted with an alkoxy group having 1 to 3 carbon atoms) or (a fluorine atom, Chlorine atom, trifluoromethyl group, carbon number 1
6 alkyl group, may be substituted with an alkoxy group having 1 to 3 carbon atoms) phenyl group. ] Is an organozinc reactant R
2 R 4 Zn [R 2 is the same as above, R 4 is R 2 or a halogen atom. ] And the presence of a palladium compound catalyst,
3-R 2 -4-R 3 -1,2,5 by reacting
-Thiadiazole derivative [in the formula, R 2 and R 3 are the same as defined above. ] Is provided.

【０００６】[0006]

【作用】次に、本発明を具体的に説明する。Next, the present invention will be specifically described.

【０００７】本発明化合物である３−Ｒ2 −４−Ｒ1 −
１，２，５−チアジアゾール誘導体は、４位のＲ1 置換
基として水素原子、（フッ素原子、炭素数１〜３のアル
コキシ基で置換されてもよい）炭素数１〜６のアルキル
基または−Ｃ6 Ｈ3 ＸＹ（Ｘ、Ｙは同一または異なって
フッ素原子、塩素原子、トリフルオロメチル基、炭素数
１〜６のアルキル基、炭素数１〜３のアルコキシ基を示
す）を、３位のＲ2 置換基として炭素数１〜６のアルキ
ル基を有するものである。The compound of the present invention, 3-R 2 -4-R 1-
The 1,2,5-thiadiazole derivative is a hydrogen atom as the R 1 substituent at the 4-position, a fluorine atom, an alkyl group having 1 to 6 carbon atoms (which may be substituted with a fluorine atom or an alkoxy group having 1 to 3 carbon atoms), or-. C 6 H 3 XY (X and Y are the same or different and each represents a fluorine atom, a chlorine atom, a trifluoromethyl group, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 3 carbon atoms) It has an alkyl group having 1 to 6 carbon atoms as the R 2 substituent.

【０００８】本発明それぞれの１，２，５−チアジアゾ
ール誘導体における置換基である炭素数１〜６のアルキ
ル基としては、メチル基、エチル基、ｎ−プロピル基、
イソプロピル基、ｎ−ブチル基、イソブチル基、ｓｅｃ
−ブチル基、ｔｅｒｔ−ブチル基、ｎ−ペンチル基、シ
クロペンチル基、ｎ−ヘキシル基、シクロヘキシル基等
の炭素数１〜６の直鎖、分岐あるいは環状アルキル基を
挙げることができ、炭素数１〜３のアルコキシ基として
は、メトキシ基、エトキシ基、イソプロポキシ基等を挙
げることができる。ハロゲン原子としては、フッ素原
子、塩素原子、臭素原子、ヨウ素原子等を挙げることが
できる。As the alkyl group having 1 to 6 carbon atoms which is a substituent in each of the 1,2,5-thiadiazole derivatives of the present invention, a methyl group, an ethyl group, an n-propyl group,
Isopropyl group, n-butyl group, isobutyl group, sec
-Butyl group, tert-butyl group, n-pentyl group, cyclopentyl group, n-hexyl group, cyclohexyl group and the like can be mentioned straight-chain, branched or cyclic alkyl groups having 1 to 6 carbon atoms. Examples of the alkoxy group of 3 include a methoxy group, an ethoxy group, an isopropoxy group and the like. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

【０００９】本発明の原料となる３−ブロモ−４−Ｒ3
−１，２，５−チアジアゾールは、３−ヒドロキシ−４
−Ｒ3 −１，２，５−チアジアゾール（L.M.Weinstock
et al.,J.Org.Chem.,32,2823(1967)記載の方法によって
得られる。）を臭化ホスホリルと反応させることにより
製造することができる。3-bromo-4-R 3 which is a raw material of the present invention
-1,2,5-thiadiazole is 3-hydroxy-4
-R 3 -1,2,5- thiadiazole (LMWeinstock
It is obtained by the method described in et al., J. Org. Chem., 32, 2823 (1967). ) Is reacted with phosphoryl bromide.

【００１０】本発明の製造法において用いられるパラジ
ウム化合物触媒としては、ジクロロ［１，１’−ビス
（ジフェニルホスフィノ）フェロセン］パラジウム（Ｉ
Ｉ）、ジクロロ［１，３−ビス（ジフェニルホスフィ
ノ）プロパン］パラジウム（ＩＩ）、ジクロロ［１，４
−ビス（ジフェニルホスフィノ）ブタン］パラジウム
（ＩＩ）、ジクロロ［１，２−ビス（ジフェニルホスフ
ィノ）エタン］パラジウム（ＩＩ）、ジクロロビス（ト
リフェニルホスフィン）パラジウム（ＩＩ）、テトラキ
ス（トリフェニルホスフィン）パラジウム（０）等を挙
げることができる。また、酢酸パラジウム（ＩＩ）、塩
化パラジウム（ＩＩ）、ジクロロビス（アセトニトリ
ル）パラジウム（ＩＩ）、ジクロロビス（ベンゾニトリ
ル）パラジウム（ＩＩ）等のパラジウム化合物及び、ト
リエチルホスフィン、トリブチルホスフィン、トリフェ
ニルホスフィン、トリ−ｏ−トリルホスフィン、１，
１’−ビス（ジフェニルホスフィノ）フェロセン、１，
３−ビス（ジフェニルホスフィノ）プロパン、１，４−
ビス（ジフェニルホスフィノ）ブタン、１，２−ビス
（ジフェニルホスフィノ）エタン等の含リン化合物から
反応系内でパラジウム化合物触媒を調製することもでき
る。As the palladium compound catalyst used in the production method of the present invention, dichloro [1,1'-bis (diphenylphosphino) ferrocene] palladium (I
I), dichloro [1,3-bis (diphenylphosphino) propane] palladium (II), dichloro [1,4
-Bis (diphenylphosphino) butane] palladium (II), dichloro [1,2-bis (diphenylphosphino) ethane] palladium (II), dichlorobis (triphenylphosphine) palladium (II), tetrakis (triphenylphosphine) Palladium (0) etc. can be mentioned. In addition, palladium compounds such as palladium (II) acetate, palladium (II) chloride, dichlorobis (acetonitrile) palladium (II), dichlorobis (benzonitrile) palladium (II), and triethylphosphine, tributylphosphine, triphenylphosphine, tri- o-tolylphosphine, 1,
1'-bis (diphenylphosphino) ferrocene, 1,
3-bis (diphenylphosphino) propane, 1,4-
The palladium compound catalyst can also be prepared in the reaction system from a phosphorus-containing compound such as bis (diphenylphosphino) butane or 1,2-bis (diphenylphosphino) ethane.

【００１１】本発明の製造法は反応溶媒の存在下で行
う。溶媒としては、ヘキサン、ベンゼン、トルエン、キ
シレン等の芳香族炭化水素類、ジエチルエーテル、テト
ラヒドロフラン等のエーテル類、ヘキサメチルホスホリ
ックトリアミド、Ｎ，Ｎ−ジメチルホルムアミド、１，
３−ジメチル−２−イミダゾリジノン等の極性溶媒等の
反応に不活性な溶媒の単一または混合物を挙げることが
できる。The production method of the present invention is carried out in the presence of a reaction solvent. As the solvent, aromatic hydrocarbons such as hexane, benzene, toluene and xylene, ethers such as diethyl ether and tetrahydrofuran, hexamethylphosphoric triamide, N, N-dimethylformamide, 1,
Mention may be made of single or mixtures of solvents inert to the reaction, such as polar solvents such as 3-dimethyl-2-imidazolidinone.

【００１２】溶媒量は、出発原料が完全に溶解する量で
あれば特に制限はないが、経済的理由により３−ブロモ
−４−Ｒ3 −１，２，５−チアジアゾール１重量部に対
して１〜１００重量部、好ましくは１〜３０重量部であ
る。The amount of the solvent is not particularly limited as long as the starting material is completely dissolved, but for economic reasons, it is based on 1 part by weight of 3-bromo-4-R 3 -1,2,5-thiadiazole. It is 1 to 100 parts by weight, preferably 1 to 30 parts by weight.

【００１３】反応に供される反応剤の量は、３−ブロモ
−４−Ｒ3 −１，２，５−チアジアゾール１当量に対し
て、有機亜鉛反応剤０．５〜３当量、好ましくは０．７
〜２．４当量、パラジウム化合物触媒は３−ブロモ−４
−Ｒ3 −１，２，５−チアジアゾールに対して０．５〜
３０ｍｏｌ％、好ましく１〜１０ｍｏｌ％である。The amount of the reactant used for the reaction is 0.5 to 3 equivalents, preferably 0, of the organozinc reactant to 1 equivalent of 3 -bromo-4-R3-1,2,5-thiadiazole. .7
~ 2.4 equivalents, the palladium compound catalyst is 3-bromo-4
-R 0.5~ against 3-1,2,5-thiadiazole
It is 30 mol%, preferably 1 to 10 mol%.

【００１４】反応温度が低すぎると目的とする反応が進
行せず、一方高すぎると種々の反応が進行し目的物を選
択的に製造することができない。従って、反応温度は−
７８〜１００℃、好ましくは−２０〜６０℃である。If the reaction temperature is too low, the desired reaction does not proceed, while if it is too high, various reactions proceed and the desired product cannot be selectively produced. Therefore, the reaction temperature is −
It is 78 to 100 ° C, preferably -20 to 60 ° C.

【００１５】反応時間は０．１〜７２時間、好ましくは
１〜３６時間である。反応時間が短すぎると反応が完全
に進行しない。The reaction time is 0.1 to 72 hours, preferably 1 to 36 hours. If the reaction time is too short, the reaction will not proceed completely.

【００１６】[0016]

【実施例】次に、実施例によって本発明を具体的に説明
するが、本発明はこれらの実施例のみに限定されるもの
ではない。EXAMPLES Next, the present invention will be specifically described by way of examples, but the present invention is not limited to these examples.

【００１７】実施例１ ３−メチル−４−フェニル−１，２，５−チアジアゾー
ルの製造 無水塩化亜鉛１．０６ｇのテトラヒドロフラン溶液中
へ、窒素雰囲気下、室温で臭化メチルマグネシウム
（０．９６Ｍテトラヒドロフラン溶液）７．３ｍｌを加
えた。０．５時間撹拌することにより調製した塩化メチ
ル亜鉛を３−ブロモ−４−フェニル−１，２，５−チア
ジアゾール０．７３ｇ、ジクロロビス（トリフェニルホ
スフィン）パラジウム（ＩＩ）０．０６３ｇのテトラヒ
ドロフラン溶液中へ、窒素下−７８℃で加えた。その後
ゆっくり室温まで昇温し、次に５０℃で３時間撹拌し
た。室温まで放冷後、反応混合物を希塩酸中に注ぎ反応
を停止させ、エーテルで抽出した。エーテル層を水、飽
和食塩水の順に洗浄し、無水硫酸マグネシウムで乾燥
後、溶媒を留去した。残渣をシリカゲルカラムクロマト
グラフィーにて精製することにより、３−メチル−４−
フェニル−１，２，５−チアジアゾール０．４０ｇを得
た。Example 1 Preparation of 3-Methyl-4-phenyl-1,2,5-thiadiazole Methylmagnesium bromide (0.96M tetrahydrofuran) was introduced into a tetrahydrofuran solution containing 1.06 g of anhydrous zinc chloride at room temperature under a nitrogen atmosphere. Solution) 7.3 ml was added. Methylzinc chloride prepared by stirring for 0.5 hour was dissolved in a tetrahydrofuran solution of 0.73 g of 3-bromo-4-phenyl-1,2,5-thiadiazole and 0.063 g of dichlorobis (triphenylphosphine) palladium (II). To nitrogen at -78 ° C. Thereafter, the temperature was slowly raised to room temperature, and then the mixture was stirred at 50 ° C. for 3 hours. After allowing to cool to room temperature, the reaction mixture was poured into dilute hydrochloric acid to stop the reaction, and the mixture was extracted with ether. The ether layer was washed with water and saturated brine in that order, dried over anhydrous magnesium sulfate, and the solvent was evaporated. By purifying the residue by silica gel column chromatography, 3-methyl-4-
0.40 g of phenyl-1,2,5-thiadiazole was obtained.

【００１８】ｎD 25.0＝１．６１３６ 1 Ｈ−ＮＭＲ（溶媒：ＣＤＣｌ3 、単位：δppm ）：
２．７３（ｓ，３Ｈ），７．４〜７．５５（ｍ，３
Ｈ），７．６５〜７．８（ｍ，２Ｈ）13 Ｃ−ＮＭＲ（溶媒：ＣＤＣｌ3 、単位：δppm ）：１
７．７，１２８．７，１２９．０，１２９．６，１３
３．３，１５８．２，１６０．８ ＩＲ（ＮａＣｌ、ｃｍ-1）：１４５０，１４０５，１０
１５，８３５，７７５，７１０，７００ 元素分析（％） 実測値：Ｃ；６１．３２，Ｈ；４．５６，Ｎ；１６．０
０ 計算値：Ｃ；６１．３４，Ｈ；４．５８，Ｎ；１５．８
９N D 25.0 = 1.6136 1 H-NMR (solvent: CDCl 3 , unit: δppm):
2.73 (s, 3H), 7.4 to 7.55 (m, 3
H), 7.65 to 7.8 (m, 2H) 13 C-NMR (solvent: CDCl 3 , unit: δppm): 1
7.7, 128.7, 129.0, 129.6, 13
3.3, 158.2, 160.8 IR (NaCl, cm -1 ): 1450, 1405, 10
15,835,775,710,700 Elemental analysis (%) Actual value: C; 61.32, H; 4.56, N; 16.0
0 Calculated value: C; 61.34, H; 4.58, N; 15.8
9

【００１９】実施例２ ３−ブチル−４−フェニル−１，２，５−チアジアゾー
ルの製造 無水塩化亜鉛１．２０ｇのテトラヒドロフラン溶液中
へ、窒素雰囲気下、室温でブチルリチウム（１．６２Ｍ
ヘキサン溶液）４．９ｍｌを加えた。０．５時間撹拌す
ることにより調製した塩化ブチル亜鉛を３−ブロモ−４
−フェニル−１，２，５−チアジアゾール０．９７ｇ、
ジクロロビス［１，１’−ビス（ジフェニルホスフィ
ノ）フェロセン］パラジウム（ＩＩ）０．０８８ｇのテ
トラヒドロフラン溶液中へ、窒素下−７８℃で加えた。
その後ゆっくり室温まで昇温し、次に５０℃で３時間撹
拌した。室温まで放冷後、反応混合物を希塩酸中に注ぎ
反応を停止させ、エーテルで抽出した。エーテル層を
水、飽和食塩水の順に洗浄し、無水硫酸マグネシウムで
乾燥後、溶媒を留去した。残渣をシリカゲルカラムクロ
マトグラフィーにて精製することにより、３−ブチル−
４−フェニル−１，２，５−チアジアゾール０．８１ｇ
を得た。Example 2 Preparation of 3-butyl-4-phenyl-1,2,5-thiadiazole Butyllithium (1.62M) was added to a solution of 1.20 g of anhydrous zinc chloride in tetrahydrofuran at room temperature under a nitrogen atmosphere.
Hexane solution) (4.9 ml) was added. Butylzinc chloride prepared by stirring for 0.5 hours was treated with 3-bromo-4.
-Phenyl-1,2,5-thiadiazole 0.97 g,
Dichlorobis [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) 0.088 g was added to a tetrahydrofuran solution at −78 ° C. under nitrogen.
Thereafter, the temperature was slowly raised to room temperature, and then the mixture was stirred at 50 ° C. for 3 hours. After allowing to cool to room temperature, the reaction mixture was poured into dilute hydrochloric acid to stop the reaction, and the mixture was extracted with ether. The ether layer was washed with water and saturated brine in that order, dried over anhydrous magnesium sulfate, and the solvent was evaporated. By purifying the residue by silica gel column chromatography, 3-butyl-
4-phenyl-1,2,5-thiadiazole 0.81 g
Got

【００２０】ｎD 25.4＝１．５７０７ 1 Ｈ−ＮＭＲ（溶媒：ＣＤＣｌ3 、単位：δppm ）：
０．８５〜１．０（ｍ，３Ｈ），１．３〜１．５（ｍ，
２Ｈ），１．７５〜１．９（ｍ，２Ｈ），２．９５〜
３．１（ｍ，２Ｈ），７．４〜７．６（ｍ，３Ｈ），
７．６〜７．８（ｍ，２Ｈ）13 Ｃ−ＮＭＲ（溶媒：ＣＤＣｌ3 、単位：δppm ）：１
４．０，２２．６，３０．６，３０．８，１２８．８，
１２８．９，１２９．５，１３３．６，１６０．８，１
６２．６ ＩＲ（ＮａＣｌ、ｃｍ-1）：２９５０，２９３０，２８
７０，１４４５，１４００，７６５，７３０，６９５ 元素分析（％） 実測値：Ｃ；６５．９５，Ｈ；６．３４，Ｎ；１２．６
２ 計算値：Ｃ；６６．０２，Ｈ；６．４６，Ｎ；１２．８
３N D 25.4 = 1.5707 1 H-NMR (solvent: CDCl 3 , unit: δ ppm):
0.85-1.0 (m, 3H), 1.3-1.5 (m,
2H), 1.75 to 1.9 (m, 2H), 2.95 to
3.1 (m, 2H), 7.4 to 7.6 (m, 3H),
7.6-7.8 (m, 2H) 13 C-NMR (solvent: CDCl 3 , unit: δppm): 1
4.0, 22.6, 30.6, 30.8, 128.8,
128.9, 129.5, 133.6, 160.8, 1
62.6 IR (NaCl, cm -1 ): 2950, 2930, 28
70, 1445, 1400, 765, 730, 695 Elemental analysis (%) Actual value: C; 65.95, H; 6.34, N; 12.6
2 Calculated value: C; 66.02, H; 6.46, N; 12.8
Three

【００２１】実施例３ ３−メチル−４−（４−クロロフェニル）−１，２，５
−チアジアゾールの製造 無水塩化亜鉛３．００ｇのテトラヒドロフラン溶液中
へ、窒素雰囲気下、室温で臭化メチルマグネシウム
（０．９６Ｍテトラヒドロフラン溶液）２１．０ｍｌを
加えた。０．５時間撹拌することにより調製した塩化メ
チル亜鉛を３−ブロモ−４−（４−クロロフェニル）−
１，２，５−チアジアゾール２．７８ｇ、ジクロロビス
（トリフェニルホスフィン）パラジウム（ＩＩ）０．３
６６ｇのテトラヒドロフラン溶液中へ、窒素下−７８℃
で加えた。その後ゆっくり室温まで昇温し、次に５０℃
で３時間撹拌した。室温まで放冷後、反応混合物を希塩
酸中に注ぎ反応を停止させ、エーテルで抽出した。エー
テル層を水、飽和食塩水の順に洗浄し、無水硫酸マグネ
シウムで乾燥後、溶媒を留去した。残渣をシリカゲルカ
ラムクロマトグラフィーにて精製することにより、３−
メチル−４−（４−クロロフェニル）−１，２，５−チ
アジアゾール１．５１ｇを得た。Example 3 3-Methyl-4- (4-chlorophenyl) -1,2,5
-Production of thiadiazole To a tetrahydrofuran solution containing 3.00 g of anhydrous zinc chloride, 21.0 ml of methylmagnesium bromide (0.96M tetrahydrofuran solution) was added at room temperature under a nitrogen atmosphere. Methylzinc chloride prepared by stirring for 0.5 hours was treated with 3-bromo-4- (4-chlorophenyl)-
1.78 g of 1,2,5-thiadiazole, dichlorobis (triphenylphosphine) palladium (II) 0.3
Into a solution of 66 g of tetrahydrofuran under nitrogen at -78 ° C.
Added in. Then slowly warm up to room temperature, then 50 ℃
It was stirred for 3 hours. After allowing to cool to room temperature, the reaction mixture was poured into dilute hydrochloric acid to stop the reaction, and the mixture was extracted with ether. The ether layer was washed with water and saturated brine in this order, dried over anhydrous magnesium sulfate, and the solvent was evaporated. By purifying the residue by silica gel column chromatography, 3-
1.51 g of methyl-4- (4-chlorophenyl) -1,2,5-thiadiazole was obtained.

【００２２】融点：２９〜３１℃ 1 Ｈ−ＮＭＲ（溶媒：ＣＤＣｌ3 、単位：δppm ）：
２．７０（ｓ，３Ｈ），７．４〜７．５５（ｍ，２
Ｈ），７．６〜７．７５（ｍ，２Ｈ）13 Ｃ−ＮＭＲ（溶媒：ＣＤＣｌ3 、単位：δppm ）：１
７．７，１２９．２，１２９．９，１３１．７，１３
５．８，１５８．０，１５９．５ ＩＲ（ＮａＣｌ、ｃｍ-1）：１４０５，１３９５，１０
９０，１００５，８３５，８３０，８１５ 元素分析（％） 実測値：Ｃ；５１．１９，Ｈ；３．２３，Ｎ；１３．０
８ 計算値：Ｃ；５１．３１，Ｈ；３．３５，Ｎ；１３．３
０Melting point: 29-31 ° C. 1 H-NMR (solvent: CDCl 3 , unit: δ ppm):
2.70 (s, 3H), 7.4 to 7.55 (m, 2
H), 7.6 to 7.75 (m, 2H) 13 C-NMR (solvent: CDCl 3 , unit: δppm): 1
7.7, 129.2, 129.9, 131.7, 13
5.8, 158.0, 159.5 IR (NaCl, cm -1 ): 1405, 1395, 10
90,1005,835,830,815 Elemental analysis (%) Actual value: C; 51.19, H; 3.23, N; 13.0
8 Calculated value: C; 51.31, H; 3.35, N; 13.3
0

【００２３】比較例 パラジウム化合物触媒を用いなかった以外は実施例１と
同様にして反応を行ったが、目的の３−メチル−４−フ
ェニル−１，２，５−チアジアゾールは得られなかっ
た。Comparative Example The reaction was carried out in the same manner as in Example 1 except that the palladium compound catalyst was not used, but the desired 3-methyl-4-phenyl-1,2,5-thiadiazole was not obtained.

【００２４】[0024]

【発明の効果】以上説明したように、本発明は、有機中
間体及び医・農薬の中間体として有用な化合物である新
規な１，２，５−チアジアゾール誘導体であり、また入
手容易な出発原料から良好な収率で、しかも任意の置換
基を安全かつ簡便に導入する製造法である。INDUSTRIAL APPLICABILITY As described above, the present invention is a novel 1,2,5-thiadiazole derivative which is a compound useful as an organic intermediate and an intermediate for medicines and agricultural chemicals, and an easily available starting material. Is a production method in which an arbitrary substituent is safely and conveniently introduced in a good yield.

Claims (2)

【特許請求の範囲】[Claims] 【請求項１】３−Ｒ2 −４−Ｒ1 −１，２，５−チアジ
アゾール誘導体。［式中、Ｒ1 は水素原子、（フッ素原
子、炭素数１〜３のアルコキシ基で置換されてもよい）
炭素数１〜６のアルキル基または−Ｃ6 Ｈ3 ＸＹ（Ｘ、
Ｙは同一または異なってフッ素原子、塩素原子、トリフ
ルオロメチル基、炭素数１〜６のアルキル基、炭素数１
〜３のアルコキシ基を示す）を示し、Ｒ2 は炭素数１〜
６のアルキル基を示す。ただし、Ｒ1 が水素原子または
メチル基を示し、Ｒ2 がメチル基である化合物を除
く。］1. A 3-R 2 -4-R 1 -1,2,5-thiadiazole derivative. [In the formula, R 1 is a hydrogen atom (may be substituted with a fluorine atom or an alkoxy group having 1 to 3 carbon atoms).
Alkyl or -C 6 H 3 XY (X 1 to 6 carbon atoms,
Y is the same or different and is a fluorine atom, a chlorine atom, a trifluoromethyl group, an alkyl group having 1 to 6 carbon atoms, or 1 carbon atom.
~ 3 alkoxy groups are shown) and R 2 has 1 to 3 carbon atoms.
6 represents an alkyl group. However, a compound in which R 1 represents a hydrogen atom or a methyl group and R 2 is a methyl group is excluded. ] 【請求項２】３−ブロモ−４−Ｒ3 −１，２，５−チア
ジアゾール［式中、Ｒ3 は水素原子、（フッ素原子、炭
素数１〜３のアルコキシ基で置換されてもよい）炭素数
１〜６のアルキル基または（フッ素原子、塩素原子、ト
リフルオロメチル基、炭素数１〜６のアルキル基、炭素
数１〜３のアルコキシ基で置換されてもよい）フェニル
基を示す。］を有機亜鉛反応剤Ｒ2 Ｒ4 Ｚｎ［Ｒ2 は前
記と同じ、Ｒ4 はＲ2 またはハロゲン原子を示す。］と
パラジウム化合物触媒の存在下、反応させることを特徴
とする３−Ｒ2 −４−Ｒ3−１，２，５−チアジアゾー
ル誘導体［式中、Ｒ2 、Ｒ3 は前記と同じ。］の製法。2. 3-Bromo-4-R 3 -1,2,5-thiadiazole [in the formula, R 3 is a hydrogen atom (which may be substituted with a fluorine atom or an alkoxy group having 1 to 3 carbon atoms). It represents an alkyl group having 1 to 6 carbon atoms or a phenyl group (which may be substituted with a fluorine atom, a chlorine atom, a trifluoromethyl group, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 3 carbon atoms). ] The organic zinc reactant R 2 R 4 Zn [R 2 is the same as above, R 4 is R 2 or a halogen atom. ] And palladium compound the presence of a catalyst, 3-R 2 -4-R 3 -1,2,5- thiadiazole derivative wherein, wherein the reacting, R 2, R 3 are as defined above. ] Manufacturing method.
JP3353109A 1991-12-18 1991-12-18 1,2,5-thiadiazole derivative and its production Pending JPH05163259A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP3353109A JPH05163259A (en) 1991-12-18 1991-12-18 1,2,5-thiadiazole derivative and its production

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP3353109A JPH05163259A (en) 1991-12-18 1991-12-18 1,2,5-thiadiazole derivative and its production

Publications (1)

Publication Number Publication Date
JPH05163259A true JPH05163259A (en) 1993-06-29

Family

ID=18428630

Family Applications (1)

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Country Status (1)

Country Link
JP (1) JPH05163259A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998001433A1 (en) * 1996-07-10 1998-01-15 The Dow Chemical Company ((4-phenyl-1,2,5-thiadiazol-3-yl)oxy)methyl ester thiocyanic acid compounds, compositions containing them and their use as antimicrobial and marine antifouling agents

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998001433A1 (en) * 1996-07-10 1998-01-15 The Dow Chemical Company ((4-phenyl-1,2,5-thiadiazol-3-yl)oxy)methyl ester thiocyanic acid compounds, compositions containing them and their use as antimicrobial and marine antifouling agents

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