JPH11209358A - Production of aminomercapto-1,3,4-thiadiazole compound - Google Patents
Production of aminomercapto-1,3,4-thiadiazole compoundInfo
- Publication number
- JPH11209358A JPH11209358A JP10009959A JP995998A JPH11209358A JP H11209358 A JPH11209358 A JP H11209358A JP 10009959 A JP10009959 A JP 10009959A JP 995998 A JP995998 A JP 995998A JP H11209358 A JPH11209358 A JP H11209358A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- aminomercapto
- acetonitrile
- thiadiazole
- 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
Links
- -1 aminomercapto-1,3,4-thiadiazole compound Chemical class 0.000 title claims abstract description 44
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002243 precursor Substances 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 abstract description 45
- 150000001875 compounds Chemical class 0.000 abstract description 12
- 238000006243 chemical reaction Methods 0.000 abstract description 10
- MCEZDOFEOWFIIH-UHFFFAOYSA-N s-(1,3,4-thiadiazol-2-yl)thiohydroxylamine Chemical compound NSC1=NN=CS1 MCEZDOFEOWFIIH-UHFFFAOYSA-N 0.000 abstract description 10
- 239000006227 byproduct Substances 0.000 abstract description 6
- 229920000137 polyphosphoric acid Polymers 0.000 abstract description 6
- 230000002378 acidificating effect Effects 0.000 abstract description 4
- 125000003277 amino group Chemical group 0.000 abstract description 4
- 239000002904 solvent Substances 0.000 abstract description 4
- 238000002156 mixing Methods 0.000 abstract description 3
- 125000002883 imidazolyl group Chemical group 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 229910052709 silver Inorganic materials 0.000 abstract description 2
- 239000004332 silver Substances 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 13
- 239000000203 mixture Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- KCOYHFNCTWXETP-UHFFFAOYSA-N (carbamothioylamino)thiourea Chemical compound NC(=S)NNC(N)=S KCOYHFNCTWXETP-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- XCRNRYWRXNGRHQ-UHFFFAOYSA-N 1-(carbamothioylamino)-1-phenylthiourea Chemical compound NC(=S)NN(C(N)=S)C1=CC=CC=C1 XCRNRYWRXNGRHQ-UHFFFAOYSA-N 0.000 description 1
- SKYYTGUCWARUCL-UHFFFAOYSA-N 1-amino-3-ethylthiourea Chemical compound CCNC(=S)NN SKYYTGUCWARUCL-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- KKIGUVBJOHCXSP-UHFFFAOYSA-N 4-phenylthiosemicarbazide Chemical compound NNC(=S)NC1=CC=CC=C1 KKIGUVBJOHCXSP-UHFFFAOYSA-N 0.000 description 1
- GDGIVSREGUOIJZ-UHFFFAOYSA-N 5-amino-3h-1,3,4-thiadiazole-2-thione Chemical compound NC1=NN=C(S)S1 GDGIVSREGUOIJZ-UHFFFAOYSA-N 0.000 description 1
- BOJLJKMUGYYKCZ-UHFFFAOYSA-N 5-anilino-3h-1,3,4-thiadiazole-2-thione Chemical compound S1C(=S)NN=C1NC1=CC=CC=C1 BOJLJKMUGYYKCZ-UHFFFAOYSA-N 0.000 description 1
- ZTLMHGOWADYAHM-UHFFFAOYSA-N 5-phenyl-3h-1,3,4-thiadiazole-2-thione Chemical compound S1C(S)=NN=C1C1=CC=CC=C1 ZTLMHGOWADYAHM-UHFFFAOYSA-N 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical class NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明はアミノメルカプト−
１，３，４−チアジアゾール化合物の製造方法に関する
ものである。アミノメルカプト−１，３，４−チアジア
ゾール化合物は、特にハロゲン化銀写真感光材料分野に
おいて、カブリ防止剤、現像促進剤などとして非常に有
用な化合物である。TECHNICAL FIELD The present invention relates to an aminomercapto-
The present invention relates to a method for producing a 1,3,4-thiadiazole compound. The aminomercapto-1,3,4-thiadiazole compound is a compound very useful as an antifoggant, a development accelerator and the like, particularly in the field of silver halide photographic materials.
【０００２】[0002]
【従来の技術】アミノメルカプト−１，３，４−チアジ
アゾール化合物の合成方法としては、ヒドラジノジチオ
カルバミド化合物の酸性条件下による閉環反応により合
成する方法が一般的に知られている。また、ヒドラジノ
ジチオカルバミドと二硫化炭素の共存下による合成（Bo
ll. Chim. Farm. （１９７９），３９１−６．、J. Ind
ian Chem. Soc.（１９６７），１４５−７．）、ヒドラ
ジウム塩とチオホスゲンを水中で反応させて合成する方
法（Den. Act. Chem. Scand., B(１９７６）７１−８
２．）、などが報告されている。しかし、これらの合成
法は、例えば、アミノ基に置換基を有する化合物の合成
では、非対称のヒドラジノジチオカルバミド化合物を用
いる必要があり、この場合環化形態の異なる副生物生成
の回避が困難であったり、また、収率的にも十分でない
などの問題点があった。2. Description of the Related Art As a method of synthesizing an aminomercapto-1,3,4-thiadiazole compound, a method of synthesizing a hydrazinodithiocarbamide compound by a ring closing reaction under acidic conditions is generally known. In addition, the synthesis by coexistence of hydrazinodithiocarbamide and carbon disulfide (Bo
ll. Chim. Farm. (1979), 391-6. , J. Ind
ian Chem. Soc. (1967), 145-7. ), A method of reacting hydrazinium salt with thiophosgene in water to synthesize (Den. Act. Chem. Scand., B (1976) 71-8).
2. ), Etc. are reported. However, in these synthetic methods, for example, in the synthesis of a compound having a substituent on an amino group, it is necessary to use an asymmetric hydrazinodithiocarbamide compound, and in this case, it is difficult to avoid the generation of by-products having different cyclized forms. And the yield is not sufficient.
【０００３】[0003]
【発明が解決しようとする課題】対称型のアミノメルカ
プト−１，３，４−チアジアゾール化合物の他に、一方
のアミノ基に置換基を有する非対称型アミノメルカプト
−１，３，４−チアジアゾールの製造においても、副生
物の生成がなく、高収率で得ることができる製造方法を
提供することにある。Production of asymmetric aminomercapto-1,3,4-thiadiazole having a substituent at one amino group in addition to symmetric aminomercapto-1,3,4-thiadiazole compound It is another object of the present invention to provide a production method capable of obtaining a high yield without producing by-products.
【０００４】[0004]
【課題を解決するための手段】上記の課題を解決すべく
鋭意検討を行い、ヒドラジノジチオカルバミド化合物の
一方のアミノ基に脱離性に優れたイミダゾール基を導入
することにより、環化形態の異なる副生物がなく、収率
的にも優れた合成法を見出し、本発明に至った。すなわ
ち、チオセミカルバジド化合物とチオカルボニルジイミ
ダゾールとの反応により得られた下記式イミダゾリノチ
オカルボニルチオセミカルバジド化合物（１）を前駆体
とすることを特徴とする、アミノメルカプト−１，３，
４−チアジアゾール化合物（２）の製造方法である。The present invention has been studied diligently to solve the above-mentioned problems, and by introducing an imidazole group having excellent elimination property to one amino group of a hydrazinodithiocarbamide compound, the cyclized form can be obtained. The present inventors have found a synthesis method having no different by-products and excellent in yield, and have led to the present invention. That is, aminomercapto-1,3, characterized by using, as a precursor, the following imidazolinothiocarbonylthiosemicarbazide compound (1) obtained by reacting a thiosemicarbazide compound with thiocarbonyldiimidazole.
This is a method for producing a 4-thiadiazole compound (2).
【０００５】[0005]
【化２】 Embedded image
【０００６】（式中、Ｒはアルキル基、アリール基、ア
ラルキル基を表す。）(In the formula, R represents an alkyl group, an aryl group, or an aralkyl group.)
【０００７】[0007]
【発明の実施の形態】本発明の化合物の製造方法につい
て詳細に説明する。本発明で用いられる前駆体ヒドラジ
ノジチオカルバミド化合物の置換基Ｒにおけるアルキル
基としては例えば、メチル基、エチル基、イソプロピル
基、ｎ−ヘキシル基，ｎ−オクチル基を表し、アリール
基としては、フェニル基、ナフチル基を表し、アラルキ
ル基としてはベンジル基、フェネチル基を表す。また、
Ｒはさらにアルキル基、アリール基、アラルキル基、カ
ルバモイル基、スルファモイル基、ウレイド基、ハロゲ
ン原子等で置換されていてもよい。BEST MODE FOR CARRYING OUT THE INVENTION The method for producing the compound of the present invention will be described in detail. The alkyl group in the substituent R of the precursor hydrazinodithiocarbamide compound used in the present invention represents, for example, a methyl group, an ethyl group, an isopropyl group, an n-hexyl group, an n-octyl group, and the aryl group is a phenyl group. And aralkyl groups, and a benzyl group and a phenethyl group. Also,
R may be further substituted with an alkyl group, an aryl group, an aralkyl group, a carbamoyl group, a sulfamoyl group, a ureido group, a halogen atom, or the like.
【０００８】次にイミダゾリノチオカルボニルチオセミ
カルバジド化合物（１）及びアミノメルカプト−１，
３，４−チアジアゾール化合物（２）の製造法について
詳細に説明する。本発明のイミダゾリノチオカルボニル
チオセミカルバジド化合物（１）はスキーム１のように
チオセミカルバジド化合物とチオカルボニルジイミダゾ
ールとの反応によって容易に得ることができる。 スキーム１Next, imidazolinothiocarbonylthiosemicarbazide compound (1) and aminomercapto-1,
The method for producing the 3,4-thiadiazole compound (2) will be described in detail. The imidazolinothiocarbonylthiosemicarbazide compound (1) of the present invention can be easily obtained by reacting a thiosemicarbazide compound with thiocarbonyldiimidazole as shown in Scheme 1. Scheme 1
【０００９】[0009]
【化３】 Embedded image
【００１０】（スキーム中、Ｒは式（Ｉ）と同義であ
り、アルキル基、アリール基、アラルキル基を表す。）(In the scheme, R has the same meaning as in formula (I) and represents an alkyl group, an aryl group, or an aralkyl group.)
【００１１】スキーム１の反応において、チオカルボニ
ルジイミダゾールはチオセミカルバジド化合物に対して
当モル〜１．５倍モル用いるのがよく、好ましくは１．
１〜１．３倍モル用いるのがよい。スキーム１の反応に
おいて用いられる溶媒としては、反応に関与しない限り
は特に制限はないが、アセトニトリル、ＤＭＡｃ等を用
いると有利に進行する。反応物の取り出しの観点からア
セトニトリルを用いるのがより好ましい。In the reaction of Scheme 1, thiocarbonyldiimidazole is preferably used in an equimolar amount to 1.5 times the molar amount of the thiosemicarbazide compound.
It is preferable to use 1 to 1.3 times mol. The solvent used in the reaction of Scheme 1 is not particularly limited as long as it does not participate in the reaction, but the use of acetonitrile, DMAc, or the like proceeds advantageously. It is more preferable to use acetonitrile from the viewpoint of taking out a reactant.
【００１２】この反応において、チオセミカルバジド化
合物とチオカルボニルジイミダゾールの混合時は低温で
行い、その後加温させることにより円滑に反応を進行さ
せることができる。高収率化のためには、混合時は−４
〜−６℃、混合後は室温で反応させるのが好ましい。In this reaction, when the thiosemicarbazide compound and thiocarbonyldiimidazole are mixed at a low temperature and then heated, the reaction can proceed smoothly. For high yield, -4
The reaction is preferably performed at room temperature after mixing at -6 ° C.
【００１３】次にアミノメルカプト−１，３，４−チア
ジアゾール（２）の製造法について説明する。スキーム
１で得られたイミダゾリノチオカルボニルチオセミカル
バジド化合物（１）を前駆体として、スキーム２のよう
に酸性条件下で環化させることによりアミノメルカプト
−１，３，４−チアジアゾール化合物（２）を得ること
ができる。 スキーム２Next, a method for producing aminomercapto-1,3,4-thiadiazole (2) will be described. The aminomercapto-1,3,4-thiadiazole compound (2) is cyclized under acidic conditions as shown in Scheme 2 using the imidazolinothiocarbonylthiosemicarbazide compound (1) obtained in Scheme 1 as a precursor. Obtainable. Scheme 2
【００１４】[0014]
【化４】 Embedded image
【００１５】（スキーム中、Ｒは式（Ｉ）と同義であ
り、アルキル基、アリール基、アラルキル基を表す。）(In the scheme, R has the same meaning as in formula (I) and represents an alkyl group, an aryl group, or an aralkyl group.)
【００１６】スキーム２で表されるイミダゾリノチオカ
ルボニルチオセミカルバジド（１）の化合物の環化によ
るアミノメルカプト−１，３，４−チアジアゾール化合
物（２）の合成のためには酸を用いるのがよく、用いる
酸としてはポリリン酸、塩酸、ｐ−トルエンスルホン酸
などが挙げられ、ポリリン酸が特に好ましい。使用量は
イミダゾリノチオカルボニルチオセミカルバジド１モル
に対して５００〜１２００ｇが好ましく、さらに好まし
くは８００〜１０００ｇである。For the synthesis of the aminomercapto-1,3,4-thiadiazole compound (2) by cyclization of the imidazolinothiocarbonylthiosemicarbazide (1) compound shown in Scheme 2, an acid is often used. Examples of the acid used include polyphosphoric acid, hydrochloric acid, p-toluenesulfonic acid and the like, and polyphosphoric acid is particularly preferred. The amount used is preferably 500 to 1200 g, more preferably 800 to 1000 g, per mol of imidazolinothiocarbonylthiosemicarbazide.
【００１７】使用する溶媒としては、アセトニトリル、
ＤＭＡｃ等を用いることができるが無溶媒で行うのが好
ましい。また反応温度としては４０℃〜８０℃で行うの
がよく、好ましくは５０℃〜６０℃である。As the solvent to be used, acetonitrile,
Although DMAc or the like can be used, it is preferable to carry out without solvent. The reaction is carried out at a temperature of preferably from 40 ° C to 80 ° C, more preferably from 50 ° C to 60 ° C.
【００１８】反応後の取り出しは、反応混合物に水を加
えることによって容易に濾取により単離することができ
る。以下に、上記製造法で合成されたイミダゾリノチオ
カルボニルチオセミカルバジド化合物（１）及びアミノ
メルカプト−１，３，４−チアジアゾール化合物（２）
の具体例を示すが、本発明の化合物はこれに限定される
ものではない。The product after the reaction can be easily isolated by filtration by adding water to the reaction mixture. Hereinafter, the imidazolinothiocarbonylthiosemicarbazide compound (1) and the aminomercapto-1,3,4-thiadiazole compound (2) synthesized by the above production method are described below.
Are shown below, but the compound of the present invention is not limited thereto.
【００１９】[0019]
【表１】 [Table 1]
【００２０】[0020]
【実施例】次に、実施例により本発明をさらに詳細に説
明するが、本発明はこれら実施例に限定されるものでは
ない。Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.
【００２１】合成例１（化合物１−１の合成） 三口フラスコにチオカルボニルジイミダゾール５．２ｇ
（２９ミリモル）とアセトニトリル１００ｍｌを加え、
よく攪拌しながら氷−メタノールで冷却した。内温を−
４〜−６℃に保ちながら４−フェニル−３−チオセミカ
ルバジド４．０ｇ（２４ミリモル）のアセトニトリル溶
液（１００ｍｌ）を滴下した。滴下後、室温で２時間反
応させ、アセトニトリルを減圧留去することによりオイ
ル状の生成物を得た。酢酸エチル５０ｍｌを加えて晶析
させ１時間攪拌後減圧濾取し４−フェニルイミダゾリノ
チオカルボニルチオセミカルバジド５．２ｇを得た（収
率７９％）。Synthesis Example 1 (Synthesis of Compound 1-1) 5.2 g of thiocarbonyldiimidazole was placed in a three-necked flask.
(29 mmol) and 100 ml of acetonitrile,
The mixture was cooled with ice-methanol while stirring well. Internal temperature
A solution of 4.0 g (24 mmol) of 4-phenyl-3-thiosemicarbazide in acetonitrile (100 ml) was added dropwise while maintaining the temperature at 4 to -6 ° C. After the dropwise addition, the mixture was reacted at room temperature for 2 hours, and acetonitrile was distilled off under reduced pressure to obtain an oily product. After adding 50 ml of ethyl acetate for crystallization, stirring for 1 hour and filtering under reduced pressure, 5.2 g of 4-phenylimidazolinothiocarbonylthiosemicarbazide was obtained (yield 79%).
【００２２】合成例２（化合物１−３の合成） 三口フラスコにチオカルボニルジイミダゾール５．２ｇ
（２９ミリモル）とアセトニトリル１００ｍｌを加え、
よく攪拌しながら氷ーメタノールで冷却した。内温を−
４〜−６℃に保ちながら４−エチル−３−チオセミカル
バジド２．９ｇ（２４ミリモル）のアセトニトリル溶液
（１００ｍｌ）を滴下した。滴下後、室温で２時間反応
させ、アセトニトリルを減圧留去することによりオイル
状の生成物を得た。酢酸エチル５０ｍｌを加えて晶析さ
せ、１時間攪拌後減圧濾取し４−エチルイミダゾリノチ
オカルボニルチオセミカルバジド４．５ｇを得た（収率
８２％）。Synthesis Example 2 (Synthesis of Compound 1-3) 5.2 g of thiocarbonyldiimidazole was placed in a three-necked flask.
(29 mmol) and 100 ml of acetonitrile,
The mixture was cooled with ice-methanol while stirring well. Internal temperature
A solution of 2.9 g (24 mmol) of 4-ethyl-3-thiosemicarbazide in acetonitrile (100 ml) was added dropwise while maintaining the temperature at 4 to -6 ° C. After the dropwise addition, the mixture was reacted at room temperature for 2 hours, and acetonitrile was distilled off under reduced pressure to obtain an oily product. Crystallization was performed by adding 50 ml of ethyl acetate, and the mixture was stirred for 1 hour and filtered under reduced pressure to obtain 4.5 g of 4-ethylimidazolinothiocarbonylthiosemicarbazide (yield: 82%).
【００２３】合成例３（化合物２−１の合成） 三口フラスコに４−フェニルイミダゾリノチオカルボニ
ルチオセミカルバジド２．０ｇ（７．２ミリモル）とポ
リリン酸６ｇを加え、窒素気流下、６０℃で３０分間攪
拌させた。水１００ｍｌを添加して室温で３０分間攪拌
させ、析出した結晶を濾取し、水、続いてアセトニトリ
ルでかけ洗いした。得られた粗結晶１．４ｇ（粗収率９
３％）をエタノール５ｍｌから再結晶し、２−メルカプ
ト−５−フェニル−１，３，４−チアジアゾール１．３
ｇ（収率８５％）を得た。融点２１０〜２１１℃。Synthesis Example 3 (Synthesis of Compound 2-1) In a three-necked flask, 2.0 g (7.2 mmol) of 4-phenylimidazolinothiocarbonylthiosemicarbazide and 6 g of polyphosphoric acid were added, and the mixture was heated at 60 ° C. under a nitrogen stream at 30 ° C. Stirred for minutes. 100 ml of water was added, and the mixture was stirred at room temperature for 30 minutes. The precipitated crystals were collected by filtration, and washed with water and then with acetonitrile. 1.4 g of crude crystals obtained (crude yield 9
(3%) was recrystallized from 5 ml of ethanol to give 2-mercapto-5-phenyl-1,3,4-thiadiazole 1.3.
g (85% yield). Melting point 210-211C.
【００２４】合成例４（化合物２−１２の合成） 三口フラスコに７−〔３−（４−イミダゾリノチオカル
ボニルチオセミカルバジド）ベンズアミド〕−１０−プ
ロパルギル−１，２，３，４−テトラヒドロアクリジニ
ウム トリフロロメタンスルホネート５．０ｇ（７２ミ
リモル）とポリリン酸７ｇを加え、窒素気流下、拌させ
た。水１００ｍｌを添加して室温で３０分間攪拌させ、
析出した結晶を濾取し、水、続いてアセトニトリルでか
け洗いした。得られた結晶にアセトニトリル２５ｍｌと
０．２ｍｌのトリフロロメタンメタンスルホン酸を加え
て１０分間攪拌させた。不溶物を濾去して３０℃以下で
濾液を減圧留去し、２０ｍｌのエーテルを加えて析出し
た結晶を濾取、エーテルでかけ洗いし、７−〔３−（２
−メルカプト−１，３，４−チアジアゾール−５−イル
アミノ）ベンズアミド〕−１０−プロパルギル−１，
２，３，４−テトラヒドロアクリジニウム トリフロロ
メタンスルホネート０．２ｇ（収率６３％）を得た。融
点２３５〜２３７℃Synthesis Example 4 (Synthesis of Compound 2-12) 7- [3- (4-Imidazolinothiocarbonylthiosemicarbazide) benzamide] -10-propargyl-1,2,3,4-tetrahydroacridi 5.0 g (72 mmol) of trifluoromethanesulfonate and 7 g of polyphosphoric acid were added, and the mixture was stirred under a nitrogen stream. Add 100 ml of water and stir at room temperature for 30 minutes,
The precipitated crystals were collected by filtration, washed with water and then with acetonitrile. 25 ml of acetonitrile and 0.2 ml of trifluoromethanemethanesulfonic acid were added to the obtained crystals, and the mixture was stirred for 10 minutes. The insoluble material was removed by filtration, the filtrate was distilled off under reduced pressure at 30 ° C. or lower, 20 ml of ether was added, and the precipitated crystals were collected by filtration, washed with ether and washed with 7- [3- (2
-Mercapto-1,3,4-thiadiazol-5-ylamino) benzamide] -10-propargyl-1,
0.2 g (yield 63%) of 2,3,4-tetrahydroacridinium trifluoromethanesulfonate was obtained. 235-237 ° C
【００２５】比較合成例（化合物２−１の比較例） 三口フラスコにモノフェニルヒドラジノジチオカルバミ
ド２．３ｇ（１０ミリモル）とポリリン酸８ｇを加え、
窒素気流下、７０℃で３時間攪拌させた。水１００ｍｌ
を添加して室温で３０分間攪拌させ、析出した結晶を濾
取し、水、続いてアセトニトリルでかけ洗いした。薄層
クロマトグラフィーにより、目的物２−メルカプト−５
−フェニルアミノ−１，３，４−チアジアゾールと副生
物５−アミノ−２−メルカプト−１，３，４−チアジア
ゾールがほぼ１：１の比率で生成していることがわかっ
た。得られた粗結晶０．５ｇ（粗収率２４％）をエタノ
ール２ｍｌから再結晶し、２−メルカプト−５−フェニ
ルアミノ−１，３，４−チアジアゾール０．４ｇ（収率
１９％）を得た。２１０〜２１１℃。この比較合成例の
スキームを以下に示す。 スキーム３Comparative Synthesis Example (Comparative Example of Compound 2-1) In a three-necked flask, 2.3 g (10 mmol) of monophenylhydrazinodithiocarbamide and 8 g of polyphosphoric acid were added.
The mixture was stirred at 70 ° C. for 3 hours under a nitrogen stream. 100 ml of water
Was added and the mixture was stirred at room temperature for 30 minutes, and the precipitated crystals were collected by filtration, washed with water and then with acetonitrile. The target substance, 2-mercapto-5, was obtained by thin-layer chromatography.
It was found that -phenylamino-1,3,4-thiadiazole and by-product 5-amino-2-mercapto-1,3,4-thiadiazole were produced at a ratio of about 1: 1. 0.5 g of the obtained crude crystals (crude yield 24%) were recrystallized from 2 ml of ethanol to obtain 0.4 g of 2-mercapto-5-phenylamino-1,3,4-thiadiazole (19% yield). Was. 210-211 ° C. The scheme of this comparative synthesis example is shown below. Scheme 3
【００２６】[0026]
【化５】 Embedded image
【００２７】[0027]
【発明の効果】イミダゾリノチオカルボニルチオセミカ
ルバジドを用いて、酸性条件下閉環反応によりアミノメ
ルカプト−１，３，４−チアジアゾールを合成する方法
において、非対称のヒドラジノジチオカルバミドを用い
た場合に起こる環化形態の異なる副生物の生成がなく、
高収率で目的物を得ることができる。Industrial Applicability In a method of synthesizing aminomercapto-1,3,4-thiadiazole by using an imidazolinothiocarbonylthiosemicarbazide by a ring closure reaction under acidic conditions, a ring generated when an asymmetric hydrazinodithiocarbamide is used. Without the formation of by-products with different
The desired product can be obtained in high yield.
Claims (1)
ニルジイミダゾールとの反応により得られた下記式イミ
ダゾリノチオカルボニルチオセミカルバジド化合物
（１）を前駆体とすることを特徴とする、アミノメルカ
プト−１，３，４−チアジアゾール化合物（２）の製造
方法。 【化１】 （式中、Ｒはアルキル基、アリール基、アラルキル基を
表す。）1. An aminomercapto-1,3,3 characterized by using, as a precursor, the following imidazolinothiocarbonylthiosemicarbazide compound (1) obtained by reacting a thiosemicarbazide compound with thiocarbonyldiimidazole. Production method of 4-thiadiazole compound (2). Embedded image (In the formula, R represents an alkyl group, an aryl group, or an aralkyl group.)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10009959A JPH11209358A (en) | 1998-01-21 | 1998-01-21 | Production of aminomercapto-1,3,4-thiadiazole compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10009959A JPH11209358A (en) | 1998-01-21 | 1998-01-21 | Production of aminomercapto-1,3,4-thiadiazole compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH11209358A true JPH11209358A (en) | 1999-08-03 |
Family
ID=11734490
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10009959A Pending JPH11209358A (en) | 1998-01-21 | 1998-01-21 | Production of aminomercapto-1,3,4-thiadiazole compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH11209358A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2003011276A1 (en) * | 2001-07-26 | 2004-11-18 | 株式会社エムズサイエンス | NFκB inhibitor |
-
1998
- 1998-01-21 JP JP10009959A patent/JPH11209358A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2003011276A1 (en) * | 2001-07-26 | 2004-11-18 | 株式会社エムズサイエンス | NFκB inhibitor |
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