JPH0477748B2 - - Google Patents
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- Publication number
- JPH0477748B2 JPH0477748B2 JP15854383A JP15854383A JPH0477748B2 JP H0477748 B2 JPH0477748 B2 JP H0477748B2 JP 15854383 A JP15854383 A JP 15854383A JP 15854383 A JP15854383 A JP 15854383A JP H0477748 B2 JPH0477748 B2 JP H0477748B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- mol
- cyanoimino
- residue
- ether
- 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.)
- Expired
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- -1 2-(N-cyanoimino)-3-substituted thiazolidine Chemical class 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 229910010082 LiAlH Inorganic materials 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- HBYVPSCMALYOLZ-UHFFFAOYSA-N (3-ethyl-1,3-thiazolidin-2-ylidene)cyanamide Chemical compound CCN1CCSC1=NC#N HBYVPSCMALYOLZ-UHFFFAOYSA-N 0.000 description 3
- FOTLMCLIMIZKGL-UHFFFAOYSA-N (3-methyl-1,3-thiazolidin-2-ylidene)cyanamide Chemical compound CN1CCSC1=NC#N FOTLMCLIMIZKGL-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 238000000197 pyrolysis Methods 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- KJQRGYHUJOFFIM-UHFFFAOYSA-N 3-ethyl-1,3-thiazolidine Chemical compound CCN1CCSC1 KJQRGYHUJOFFIM-UHFFFAOYSA-N 0.000 description 2
- DGYVIUKQSWPZCL-UHFFFAOYSA-N 3-methyl-1,3-thiazolidine Chemical compound CN1CCSC1 DGYVIUKQSWPZCL-UHFFFAOYSA-N 0.000 description 2
- PXAWJFBUXHYSSW-UHFFFAOYSA-N 3-phenyl-1,3-thiazolidine Chemical compound C1SCCN1C1=CC=CC=C1 PXAWJFBUXHYSSW-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Thiazole And Isothizaole Compounds (AREA)
Description
【発明の詳細な説明】
本発明は、式〔〕で示される３−置換チアゾ
リジンの製造法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a 3-substituted thiazolidine represented by the formula [].
〔式中、Ｒはアルキル、またはアリールを表わ
す〕。 [In the formula, R represents alkyl or aryl].
従来、上記チアゾリジン化合物〔〕は、式：
RNHCH2CH2SH
で示されるＮ−置換アミノエタンチオールとホル
ムアルデヒド（HCHO）とを反応させることに
より製造されている。しかしながら、このＮ−置
換アミノエタンチオールは化学的に不安定である
だけでなく、その製造においては、まず−SHを
適当な保護基で保護し、アミノ基を置換したのち
保護基を取除かなければならない。更にやつかい
なことは、この化合物は二級アミンであつて反応
中に存在する一級アミン、三級アミンとの分離が
極めて難しいことである。 Conventionally, the above thiazolidine compound [] has been produced by reacting N-substituted aminoethanethiol represented by the formula: RNHCH 2 CH 2 SH with formaldehyde (HCHO). However, not only is this N-substituted aminoethanethiol chemically unstable, but its production requires first protecting -SH with an appropriate protecting group, substituting the amino group, and then removing the protecting group. There must be. What is more difficult is that this compound is a secondary amine and is extremely difficult to separate from the primary amine and tertiary amine present during the reaction.
本発明は上記問題を解決したものである。 The present invention solves the above problem.
本発明によれば、式〔〕
〔式中、Ｒはアルキル、またはアリールを表わ
す〕
で示される２−（Ｎ−シアノイミノ）−３−置換チ
アゾリジンを、溶媒中、水素化リチウムアルミニ
ウム（LiAlH4）で還元することにより目的化合
物〔〕が得られる。 According to the invention, the formula [] [In the formula, R represents alkyl or aryl] By reducing the 2-(N-cyanoimino)-3-substituted thiazolidine represented by the following with lithium aluminum hydride (LiAlH 4 ) in a solvent, the target compound [] is obtained.
溶媒は、エーテルやテトラヒドロフランなどの
エーテル系溶媒が好ましい。反応は、０℃〜室温
までの温度において容易に進行する。 The solvent is preferably an ether solvent such as ether or tetrahydrofuran. The reaction readily proceeds at temperatures from 0°C to room temperature.
化合物〔〕におけるＲの例として、アルキル
には、メチル、エチル、イソプロピルなど、アリ
ールでは、フエニル、置換フエニルなどが挙げら
れる。 Examples of R in compound [] include methyl, ethyl, isopropyl, etc. for alkyl, and phenyl, substituted phenyl, etc. for aryl.
なお、本発明に使用されるチアゾリジン化合物
〔〕は、式：
で示されるＮ−シアノイミノチアゾリジンと、
式：
Ｒ−Ｘ 〔〕
〔式中、Ｘはハロゲンを表わす。Ｒは前記と同
じ〕
で示される化合物とを、溶媒（例えば、ジメチル
ホルムアミド）中、塩基（例えば、水素化ナトリ
ウム、ナトリウムアルコキサイド）の存在下に反
応させることにより容易に得られる。 The thiazolidine compound [] used in the present invention has the formula: N-cyanoiminothiazolidine represented by
Formula: R-X [] [In the formula, X represents halogen. R is the same as above] It can be easily obtained by reacting a compound represented by the following formula in a solvent (for example, dimethylformamide) in the presence of a base (for example, sodium hydride, sodium alkoxide).
実施例 １
３−メチルチアゾリジンの製造：
テトラヒドロフラン（THF）500mlに２−（Ｎ
−シアノイミノ）−３−メチルチアゾリジン14.1
ｇ（0.1モル）を懸濁させる。０〜５℃に冷却し、
LiALH45ｇ（0.13モル）を徐々に加える。添加
後室温にもどし、一夜攪拌する。反応液に2N水
酸化ナトリウム水溶液を加え過剰のLiAlH4を分
解する。反応液を過しメタノールで洗う。液
を合せて留去し、残渣を水とエーテルで振とうす
る。エーテル相を乾燥留去する。常圧蒸留して、
３−メチルチアゾリジンを得る。収量8.2ｇ
（79.6％）。沸点151〜152℃。Example 1 Production of 3-methylthiazolidine: 2-(N
-cyanoimino)-3-methylthiazolidine 14.1
g (0.1 mol) are suspended. Cool to 0-5℃,
Gradually add 5g (0.13 mol) of LiALH4 . After addition, return to room temperature and stir overnight. A 2N aqueous sodium hydroxide solution is added to the reaction solution to decompose excess LiAlH 4 . Filter the reaction solution and wash with methanol. The combined liquids are evaporated and the residue is shaken with water and ether. The ether phase is dried and distilled off. Distilled at atmospheric pressure,
3-methylthiazolidine is obtained. Yield 8.2g
(79.6%). Boiling point 151-152℃.
元素分析値（C4H9NS＝103.187として） 計算値（％）：C46.56，H8.79，N13.57。 Elemental analysis value (as C 4 H 9 NS = 103.187) Calculated value (%): C46.56, H8.79, N13.57.
実測値（％）：C46.33，H8.72，N13.29。 Actual value (%): C46.33, H8.72, N13.29.
実施例 ２
３−エチルチアゾリジンの製造：
THF500mlに２−（Ｎ−シアノイミノ）−３−エ
チルチアゾリジン15.5ｇ（0.1モル）を懸濁させ、
０〜５℃に冷却する。これにLiAlH45ｇ（0.13モ
ル）を徐々に加え、添加後室温にもどして一夜攪
拌する。反応液に2N水酸化ナトリウムを加え過
剰のLiAlH4を分解する。反応液を過しメタノ
ールで洗う。液を合せて留去し、残渣と水とエ
ーテルで振とうする。エーテル相を乾燥留去し、
残渣を減圧蒸留して、３−エチルチアゾリジンを
得る。収量10.9ｇ（93％）。沸点45〜47℃（25mm
Hg）。Example 2 Production of 3-ethylthiazolidine: 15.5 g (0.1 mol) of 2-(N-cyanoimino)-3-ethylthiazolidine was suspended in 500 ml of THF.
Cool to 0-5°C. 5 g (0.13 mol) of LiAlH 4 was gradually added thereto, and after the addition, the mixture was allowed to return to room temperature and stirred overnight. Add 2N sodium hydroxide to the reaction solution to decompose excess LiAlH 4 . Filter the reaction solution and wash with methanol. The combined liquids were evaporated and the residue was shaken with water and ether. Dry distillation of the ether phase;
The residue is distilled under reduced pressure to obtain 3-ethylthiazolidine. Yield 10.9g (93%). Boiling point 45-47℃ (25mm
Hg).
元素分析値（C5H11NS＝117.214として） 計算値（％）：C51.24，H9.46，N11.95 実測値（％）：C51.18，H9.37，N11.84。 Elemental analysis value (as C 5 H 11 NS = 117.214) Calculated value (%): C51.24, H9.46, N11.95 Actual value (%): C51.18, H9.37, N11.84.
実施例 ３
３−フエニルチアゾリジンの製造：
THF500mlに２−（Ｎ−シアノイミノ）−３−フ
エニルチアゾリジン20.3ｇ（0.1モル）を懸濁さ
せ、０〜５℃に冷却してLiAlH45ｇ（0.13モル）
を徐々に加える。添加終了後、室温にもどし一夜
攪拌する。反応液に2N水酸化ナトリウム水溶液
を加えて過剰のLiAlH4を分解する。過しメタ
ノールで洗い、液を合せて留去し、残渣を水と
エタノールで振とうする。エーテル相を乾燥留去
し、残渣を減圧蒸留して３−フエニルチアゾリジ
ンを得る。収量13.1ｇ（79.4％）。沸点159〜161
℃（11mmHg）
元素分析値（C9H11NS＝165.259として）
計算値（％）：C65.41，H6.71，N8.48
実測値（％）：C65.62，H6.78，N8.45。Example 3 Production of 3-phenylthiazolidine: 20.3 g (0.1 mol) of 2-(N-cyanoimino)-3-phenylthiazolidine was suspended in 500 ml of THF, cooled to 0 to 5°C, and 5 g (0.13 mol) of LiAlH 4 was suspended in 500 ml of THF. mole)
Add gradually. After the addition is complete, the mixture is returned to room temperature and stirred overnight. A 2N aqueous sodium hydroxide solution is added to the reaction solution to decompose excess LiAlH 4 . Wash with filtered methanol, combine and evaporate, and shake the residue with water and ethanol. The ether phase is removed by dry distillation, and the residue is distilled under reduced pressure to obtain 3-phenylthiazolidine. Yield: 13.1g (79.4%). Boiling point 159-161
°C (11mmHg) Elemental analysis value (C 9 H 11 NS = 165.259) Calculated value (%): C65.41, H6.71, N8.48 Actual value (%): C65.62, H6.78, N8. 45.
参考例 １
２−（Ｎ−シアノイミノ）−３−メチルチアゾリ
ジンの製造：
ジメチルホルムアミド（DMF）30mlに50％水
素化ナトリウム（NaH）1.13ｇ（24ミリモル）
を懸濁させ、０〜５℃の冷却下にＮ−シアノイミ
ノチアゾリジン３ｇ（24ミリモル）を加える。水
素の発生が止んだら、ヨウ化メチル3.35ｇ（24ミ
リモル）を徐々に滴下する。滴下後、室温にもど
し一夜攪拌する。DMFを減圧留去し、残渣を2N
水酸化ナトリウム水溶液と酢酸エチルで抽出す
る。酢酸エチル相を乾燥留去して２−（Ｎ−シア
ノイミノ）−３−メチルチアゾリジンの結晶2.1ｇ
（63％）を得る。融点97〜98℃。Reference Example 1 Production of 2-(N-cyanoimino)-3-methylthiazolidine: 1.13 g (24 mmol) of 50% sodium hydride (NaH) in 30 ml of dimethylformamide (DMF)
is suspended, and 3 g (24 mmol) of N-cyanoiminothiazolidine is added while cooling at 0-5°C. When hydrogen evolution has stopped, 3.35 g (24 mmol) of methyl iodide is gradually added dropwise. After dropping, the mixture was brought to room temperature and stirred overnight. Distill DMF under reduced pressure and reduce the residue to 2N
Extract with aqueous sodium hydroxide and ethyl acetate. Dry distillation of the ethyl acetate phase yielded 2.1 g of crystals of 2-(N-cyanoimino)-3-methylthiazolidine.
(63%). Melting point 97-98℃.
IR.νmax（Nujol）（cm-1）：2186，2154，1590，
1430，1245，1070。IR.νmax (Nujol) (cm -1 ): 2186, 2154, 1590,
1430, 1245, 1070.
参考例 ２
２−（Ｎ−シアノイミノ）−３−エチルチアゾリ
ジンの製造：
DMF200mlに50％NAH4.8ｇ（0.1モル）を懸
濁し、０〜５℃に冷却してＮ−シアノイミノチア
ゾリジン12.7ｇ（0.1モル）を徐々に加える。水
素の発生が止んだら、エチルブロマイド10.9ｇ
（0.1モル）を滴下し、滴下終了後室温にもどして
一夜攪拌する。反応液を減圧留去し、残渣に水を
加えると粗結晶が生成する。粗結晶をクロロホル
ムに溶解し、分液後乾燥留去し、エーテルから結
晶化させて２−（Ｎ−シアノイミノ）−３−エチル
チアゾリジンを得る。11.0ｇ（71％）。融点82〜
84℃。Reference Example 2 Production of 2-(N-cyanoimino)-3-ethylthiazolidine: Suspend 4.8g (0.1 mol) of 50% NAH in 200ml of DMF, cool to 0 to 5°C, and prepare 12.7g (0.1 mol) of N-cyanoiminothiazolidine. mol) gradually. When hydrogen generation stops, 10.9g of ethyl bromide
(0.1 mol) was added dropwise, and after the addition was completed, the mixture was returned to room temperature and stirred overnight. The reaction solution was distilled off under reduced pressure, and water was added to the residue to form crude crystals. The crude crystals are dissolved in chloroform, separated, and then evaporated to dryness and crystallized from ether to obtain 2-(N-cyanoimino)-3-ethylthiazolidine. 11.0g (71%). Melting point 82~
84℃.
IR.νmax（Nujol）：2200，1450，1320，1240，
1060，785（cm-1）。IR.νmax (Nujol): 2200, 1450, 1320, 1240,
1060,785 (cm -1 ).
Claims (1)
アゾリジンを、溶媒中、水素化リチウムアルミニ
ウムで還元することを特徴とする 式 〔式中、Ｒはアルキル、またはアリールを表わ
す〕 で示される３−置換チアゾリジンの製造法。[Claims] 1 formula [In the formula, R is the same as below] A 2-(N-cyanoimino)-3-substituted thiazolidine represented by the following formula is reduced with lithium aluminum hydride in a solvent. [In the formula, R represents alkyl or aryl] A method for producing a 3-substituted thiazolidine represented by the following.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15854383A JPS6051182A (en) | 1983-08-30 | 1983-08-30 | Preparation of 3-substituted thiazolidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15854383A JPS6051182A (en) | 1983-08-30 | 1983-08-30 | Preparation of 3-substituted thiazolidine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6051182A JPS6051182A (en) | 1985-03-22 |
| JPH0477748B2 true JPH0477748B2 (en) | 1992-12-09 |
Family
ID=15674000
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15854383A Granted JPS6051182A (en) | 1983-08-30 | 1983-08-30 | Preparation of 3-substituted thiazolidine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6051182A (en) |
-
1983
- 1983-08-30 JP JP15854383A patent/JPS6051182A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6051182A (en) | 1985-03-22 |
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