JPH0272156A - Production of 4-substituted thiobutyric acid-based compound - Google Patents
Production of 4-substituted thiobutyric acid-based compoundInfo
- Publication number
- JPH0272156A JPH0272156A JP22407988A JP22407988A JPH0272156A JP H0272156 A JPH0272156 A JP H0272156A JP 22407988 A JP22407988 A JP 22407988A JP 22407988 A JP22407988 A JP 22407988A JP H0272156 A JPH0272156 A JP H0272156A
- Authority
- JP
- Japan
- Prior art keywords
- group
- general formula
- formula
- boiling point
- compound
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 43
- -1 4-substituted thiobutyric acid Chemical class 0.000 title claims description 27
- 238000004519 manufacturing process Methods 0.000 title claims description 14
- 238000009835 boiling Methods 0.000 claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 19
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 18
- 125000003118 aryl group Chemical group 0.000 claims abstract description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 11
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
- 230000001476 alcoholic effect Effects 0.000 claims abstract description 7
- 239000000126 substance Substances 0.000 claims abstract 6
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical class SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 abstract description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 abstract description 4
- 239000000654 additive Substances 0.000 abstract description 3
- 239000000010 aprotic solvent Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 16
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 14
- 239000013078 crystal Substances 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 2
- 125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- WNAHIZMDSQCWRP-UHFFFAOYSA-N dodecane-1-thiol Chemical compound CCCCCCCCCCCCS WNAHIZMDSQCWRP-UHFFFAOYSA-N 0.000 description 2
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 125000006038 hexenyl group Chemical group 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910000103 lithium hydride Inorganic materials 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 125000005064 octadecenyl group Chemical group C(=CCCCCCCCCCCCCCCCC)* 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- FCAJYRVEBULFKS-UHFFFAOYSA-N 2-(oxolan-2-yl)ethanol Chemical compound OCCC1CCCO1 FCAJYRVEBULFKS-UHFFFAOYSA-N 0.000 description 1
- DCHXKQJDUGHDPB-UHFFFAOYSA-N 2-butoxy-5-(2,4,4-trimethylpentan-2-yl)benzenethiol Chemical compound CCCCOC1=CC=C(C(C)(C)CC(C)(C)C)C=C1S DCHXKQJDUGHDPB-UHFFFAOYSA-N 0.000 description 1
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 1
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- SAHIZENKTPRYSN-UHFFFAOYSA-N [2-[3-(phenoxymethyl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound O(C1=CC=CC=C1)CC=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 SAHIZENKTPRYSN-UHFFFAOYSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- DGAODIKUWGRDBO-UHFFFAOYSA-N butanethioic s-acid Chemical class CCCC(O)=S DGAODIKUWGRDBO-UHFFFAOYSA-N 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 125000004966 cyanoalkyl group Chemical group 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- ONDXXAPHPJPFKQ-UHFFFAOYSA-N n-[bis(dimethylamino)phosphoryl]-n-methylmethanamine;oxolane Chemical compound C1CCOC1.CN(C)P(=O)(N(C)C)N(C)C ONDXXAPHPJPFKQ-UHFFFAOYSA-N 0.000 description 1
- QJAOYSPHSNGHNC-UHFFFAOYSA-N octadecane-1-thiol Chemical compound CCCCCCCCCCCCCCCCCCS QJAOYSPHSNGHNC-UHFFFAOYSA-N 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- G—PHYSICS
- G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
- G03C—PHOTOSENSITIVE MATERIALS FOR PHOTOGRAPHIC PURPOSES; PHOTOGRAPHIC PROCESSES, e.g. CINE, X-RAY, COLOUR, STEREO-PHOTOGRAPHIC PROCESSES; AUXILIARY PROCESSES IN PHOTOGRAPHY
- G03C1/00—Photosensitive materials
- G03C1/005—Silver halide emulsions; Preparation thereof; Physical treatment thereof; Incorporation of additives therein
- G03C1/06—Silver halide emulsions; Preparation thereof; Physical treatment thereof; Incorporation of additives therein with non-macromolecular additives
Landscapes
- Physics & Mathematics (AREA)
- Chemical & Material Sciences (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- General Physics & Mathematics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Silver Salt Photography Or Processing Solution Therefor (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野〕
本発明は、４−置換チオ酪酸系化合物の製造方法に関し
、更に詳しくは、写真用添加剤や各種化合物の中間体と
して有用な４−置換チオ酪酸系化合物の製造方法に関す
るものである。Detailed Description of the Invention [Industrial Application Field] The present invention relates to a method for producing 4-substituted thiobutyric acid compounds, and more specifically, 4-substituted thiobutyric acid compounds useful as photographic additives and intermediates for various compounds. The present invention relates to a method for producing thiobutyric acid compounds.
［従来の技術］
４−：α換チＡ酪酸系化合物は、例えば写真用カプラー
等の写真用添加剤、並びに界面活性化作用を有する化合
物や抗菌、除草等の作用を有する化合物の中間体として
有用である。[Prior Art] 4-:α-methylated thiA-butyric acid compounds are used, for example, as photographic additives such as photographic couplers, and as intermediates for compounds having surface-activating effects and compounds having antibacterial and herbicidal effects. Useful.
従来、４−置換チオ酪酸系化合物は、γ−ブチロラク［
〜ンとメルカプタンとをアブロティツク溶媒（水素結合
に必要な水素を有さない溶ＩＲ）中で合成して得ていた
。例えば、リチャード・ヒューチンソン等（Ｃ，Ｒ１ｃ
ｈａｒｄ １−（ｕｔｃｈｉｎｓｏｎ ｅｔ ａｔ、
）のジャーナル・オブ・ザ・オルガニック・ケミストリ
ーＬＪ 、 Ｏｒｇ、 Ｃｈｅｍ ） ４９巻 ２８３
７頁（１９８４年〉では、Ｔ−ブチロラクトンとメルカ
プタンのリチウム塩とをジメチルホルムアミド溶液中、
還流条件下で反応させて目的物を得ている。Conventionally, 4-substituted thiobutyric acid compounds are γ-butyrolac [
- and mercaptan were synthesized in an abrotic solvent (a soluble IR solution that does not contain hydrogen necessary for hydrogen bonding). For example, Richard Huchinson et al. (C, R1c
hard 1-(utchinson et at,
) Journal of the Organic Chemistry LJ, Org, Chem) Volume 49, 283
7 (1984), T-butyrolactone and lithium salt of mercaptan are dissolved in dimethylformamide solution.
The target product is obtained by reacting under reflux conditions.
また、ベーリー・エム・トロスト等（３ａｒｒｙ Ｍ
。In addition, Bailey M. Trost et al.
.
Ｔｒｏｓｔ ｅｔ ａｔ、 ）のジャーナル・オブ・ザ
・オルガニック・ケミストリー（Ｊ、 Ｏｒ（＋、 Ｃ
ｈｅｍ ）４７巻７４８頁（１９８２年〉では、γ−ブ
チロラクトンとメルカプタンとを、水素化リチウムを塩
基として用い、テトラヒドロフラン−ヘキサメチルホス
ホリックトリアミドの混合溶媒中、空温で反応させて目
的物を得ている。さらにピー・フェラボスキー等（Ｐ、
Ｆｅｒｒａｂｏｓｃｈｉ ｅｔ ａｌ、）のシンセシ
ス”ツー１：ユニケーシＥ ン（Ｓｙｎｔｈ、 Ｃｏｍ
ｍｕｎ ）１４巻 １１９９頁（１９８４年）では、Ｔ
−ブチロラクトンとメルカプタンとを水素化ナトリウム
を塩基として用い、テトラヒドロフラン−エタノールの
混合溶媒中、還流条件下で反応させて目的物を得ている
。Trost et at,) Journal of the Organic Chemistry (J, Or(+, C
hem) Vol. 47, p. 748 (1982), γ-butyrolactone and mercaptan were reacted at air temperature in a mixed solvent of tetrahydrofuran-hexamethylphosphoric triamide using lithium hydride as a base to obtain the desired product. In addition, P. Ferabowski et al.
Ferraboschi et al.
mun), vol. 14, p. 1199 (1984), T.
-Butyrolactone and mercaptan are reacted under reflux conditions in a mixed solvent of tetrahydrofuran-ethanol using sodium hydride as a base to obtain the desired product.
［発明が解決しようとする課題］
しかしながら、これら従来の方法はいずれも、ある程度
高い収率（５０〜９０％）を得るために、ジメチルホル
ムアミド、テトラヒドロフラン、ヘキサメチルホスホリ
ックトリアミド等の極性の高いアブロティツク溶媒を使
わなければならず、そしてこのような溶媒の使用によっ
てもまだまだ収率の点で充分に満足とは言えず、さらに
は高価な溶媒の使用のため製造コストが高いという欠点
があった。[Problems to be Solved by the Invention] However, in all of these conventional methods, in order to obtain a somewhat high yield (50 to 90%), highly polar compounds such as dimethylformamide, tetrahydrofuran, hexamethylphosphoric triamide, etc. Abrotic solvents had to be used, and even with the use of such solvents, the yield was still unsatisfactory, and furthermore, the production costs were high due to the use of expensive solvents. .
従って、本発明の目的は上記従来のこれらの欠点に鑑み
てなされたちのであり、その目的とするところは、高価
なアブロティツク溶媒を使わずに安価にしかも従来のア
ブロティツク溶媒の使用のときよりも、さらに高い収率
で４−置換チオ酪酸系化合物を得る製造方法を提供する
ことにある。Therefore, the object of the present invention has been made in view of the above-mentioned drawbacks of the conventional art, and the object thereof is to reduce the cost by eliminating the use of expensive abrotic solvents, and which is more effective than when using conventional abrotic solvents. It is an object of the present invention to provide a manufacturing method for obtaining 4-substituted thiobutyric acid compounds in higher yields.
［課題を解決するための手段〕
即ち、本発明の上記目的は、
（式中、Ｒ＋ 、Ｒ２、Ｒ３，Ｒ４、Ｒ５およびＲ６は
、各々、水素原子、アルキル基、アルケール基、シクロ
アルキル基、アリール基または複素環基を示ず）で表わ
される化合物と、
一般式［ＩＩ］
ＳＨ
（式中、Ｒはアルキル基、アルケニル基、シクロアルキ
ル基、アリール基または複索環基を示す）で表わされる
化合物とを、沸点８０℃以上のアルコール系溶媒中で、
反応させることを特徴とするＲ、Ｒ，Ｒ。[Means for Solving the Problems] That is, the above object of the present invention is as follows: aryl group or heterocyclic group) and a compound represented by the general formula [II] in an alcoholic solvent with a boiling point of 80°C or higher,
R, R, R characterized by reacting.
（式中、Ｒ＋ 、Ｒ２、Ｒ３，Ｒ４、Ｒｓ及びＲ６は前
記一般式［Ｉ］と同義であり、Ｒは前記一般式［１１］
と同義である）で表わされる４−置換チオ酪酸系化合物
の製造方法によって達成される。(In the formula, R+, R2, R3, R4, Rs and R6 have the same meanings as in the above general formula [I], and R is in the above general formula [11]
This is achieved by a method for producing a 4-substituted thiobutyric acid compound represented by (synonymous with).
−ＩＱ式［Ｉ ］ ｌ、：おいＴ、Ｒ＋ 、Ｒ２、Ｒ３
。-IQ formula [I] l,: Hey T, R+, R2, R3
.
Ｒ４、ＲｓおよびＲ６は、それぞれ、水素原子、アルキ
ル基、アルケニル基、シクロアルキル基、アリール基又
は複素環基を示すが、このうち、アルキル基としては、
直鎖又は分岐のアルキル基、例えば、メチル、エチル、
イソプロピル、ブチル、［−ブチル、オクチル、ペンタ
デシル、エイコシル等が挙げられ、また、アルケニル基
としては、例えばビニル、プロペニル、ブテニル、ヘキ
セニル、ペンタデセニル、オクタデセニル等の多基が挙
げられる。さらにシクロアルキル基としては、例えば、
シクロペンチル、シクロヘキシル、シクロヘキセニル等
の多基、アリール基としては、例えば、フェニル、ナフ
チル等の多基が、ざらに複素１ｉ ｌとしては、例えば
、ピリジル、フリル等の多基がそれぞれ挙げられる。こ
れらアルキル基、アルケニル基、シクロアルキル基、ア
リール基および複素環基は、いずれも置換基を有するも
のを含み、そして置換基の例としては、ハロゲン原子、
ヒドロキシル基、ニトロ塁、シアへＬアルキル塁、アル
コキシ基、アリールオキシ阜、アルキルスルホニル基、
アリールスルホニル基、アシルオキシ基、アシルアミノ
基、カルバモイル基、スルホンアミド基、スルファモイ
ル基等を挙げることができる。更に置換基中のアルキル
鎖は直鎖または分校のものを用いることができる。一般
式り丁］におけるＲ＋、Ｒ２，Ｒ３，ＩＩ楊、Ｒ５およ
びＲ６の基の好ましいものとしては、水素原子またはア
ルキル基である。またＲ＋（Ｒ２ＮおよびＲ３（Ｒ４）
が共にアルキル基の場合は、これらが互に結合して５〜
７員の炭化水素環基を形成してもよく、さらにまた、Ｒ
３（Ｒ＋）およびＲ５（Ｒ６）が共にアルキル基の場合
は、これらが互に結合して５〜７員の炭化水素環基を形
成してもよい。R4, Rs and R6 each represent a hydrogen atom, an alkyl group, an alkenyl group, a cycloalkyl group, an aryl group or a heterocyclic group, and among these, the alkyl group is
Straight-chain or branched alkyl groups, such as methyl, ethyl,
Examples include isopropyl, butyl, [-butyl, octyl, pentadecyl, eicosyl, etc., and examples of alkenyl groups include polygroups such as vinyl, propenyl, butenyl, hexenyl, pentadecenyl, and octadecenyl. Furthermore, as the cycloalkyl group, for example,
Examples of polygroups such as cyclopentyl, cyclohexyl, and cyclohexenyl; examples of the aryl group include polygroups such as phenyl and naphthyl; and examples of the complex complex include polygroups such as pyridyl and furyl. These alkyl groups, alkenyl groups, cycloalkyl groups, aryl groups, and heterocyclic groups all include those having substituents, and examples of substituents include halogen atoms,
Hydroxyl group, nitro group, cyanoalkyl group, alkoxy group, aryloxy group, alkylsulfonyl group,
Examples include an arylsulfonyl group, an acyloxy group, an acylamino group, a carbamoyl group, a sulfonamide group, and a sulfamoyl group. Furthermore, the alkyl chain in the substituent may be a straight chain or a branched chain. Preferred groups for R+, R2, R3, II, R5 and R6 in the general formula R2 are a hydrogen atom or an alkyl group. Also R+(R2N and R3(R4)
are both alkyl groups, these are bonded to each other to form 5 to
A 7-membered hydrocarbon ring group may be formed, and furthermore, R
When 3 (R+) and R5 (R6) are both alkyl groups, they may be bonded to each other to form a 5- to 7-membered hydrocarbon ring group.
次に本発明で用いられる一般式［Ｉ］で示される化合物
の代表的な具体例を以下に示すが、本発明はこれらに限
定されない。Next, typical specific examples of the compound represented by the general formula [I] used in the present invention are shown below, but the present invention is not limited thereto.
例示化合物
＋−２
＋−１，１
以下余白
■
一般式［１１］において、Ｒはアルキル基、アルケニル
基、シクロアルキル基、アリール基、または複索環基を
示すが、具体的には、アルキル基としては、直鎖又は分
校のアルキル基、例えばメチル、エチル、イソプロピル
、ブチル、ｔ−ブチル、オクチル、ドデシル、ペンタデ
シル、エイコシル等の多基、アルケニル基としては、例
えばビニル、プロペニル、ブテニル、ヘキセニル、ペン
タデセニル、オクタデセニル等の多基、シクロアルキル
基としては、例えば、シクロペンチル、シクロヘキシル
等の多基、アリール基としては、例えば、フェニル、ナ
フチルの多基、および複素環基としては、例えば、ピリ
ジル、フリル、チエニル等の多基をそれぞれ挙げること
ができる。これらアルキル基、アルケニル基、アリール
基および複素環基はいずれも置換基を有するものを含み
、そして置換基としては、例えば、ハロゲン原子、ヒド
ロキシル基、ニトロ基、シアン基、アルキル基、アルコ
キシ基、アリールオキシ基、アルキルスルホニル基、ア
リールスルホニル基、アシルオキシ基、アシルアミノ基
、カルバモイル
ド基、スルファモイル基等を挙げることができる。Exemplary Compound +-2 +-1,1 Space below■ In the general formula [11], R represents an alkyl group, an alkenyl group, a cycloalkyl group, an aryl group, or a polycyclic group. Examples of groups include linear or branched alkyl groups, such as methyl, ethyl, isopropyl, butyl, t-butyl, octyl, dodecyl, pentadecyl, eicosyl, etc., and alkenyl groups, such as vinyl, propenyl, butenyl, hexenyl. , pentadecenyl, octadecenyl, etc.; cycloalkyl groups include, for example, cyclopentyl and cyclohexyl; aryl groups include, for example, phenyl and naphthyl; and heterocyclic groups include, for example, pyridyl, Examples include multiple groups such as furyl and thienyl. These alkyl groups, alkenyl groups, aryl groups, and heterocyclic groups all include those having substituents, and examples of the substituents include halogen atoms, hydroxyl groups, nitro groups, cyan groups, alkyl groups, alkoxy groups, Examples include an aryloxy group, an alkylsulfonyl group, an arylsulfonyl group, an acyloxy group, an acylamino group, a carbamoyl group, and a sulfamoyl group.
更に置換基中のアルキル鎖は直鎖または分枝のらのを用
いる。Furthermore, the alkyl chain in the substituent may be straight or branched.
一般式［ＩＩ］におけるＲとしては、アルキル基または
アリール基が特に好ましい。As R in general formula [II], an alkyl group or an aryl group is particularly preferable.
次に本発明で用いられる一般式［■］で示される化合物
の代表的具体例を以下に示すが、本発明はこれらに限定
されない。Next, typical examples of the compound represented by the general formula [■] used in the present invention are shown below, but the present invention is not limited thereto.
以下余白 一般式（ＩＩ） ＳＨの例示化合物 （ｎ）Ｃ＝Ｈ，ｔ ＳＨ ロー３ （ｎ）Ｃ＋１）ｌｚｓ Ｓ）Ｉ ■ （ｎ）Ｃ．、）（、、−Ｓ Ｈ ローフ ＣＨ，−ＳＨ ■−９ ＩＩ−１０ （ｔ）Ｃ．Ｈ． −Ｓ Ｈ １１−１．１ ■−１２ （ｎ）Ｃ，、Ｈ２１−ＳＨ （ｎ）Ｃ，、Ｈ２．−ＳＨ （ｎ）Ｃ，、Ｈ，、−ＳＨ （ｉ）ＣｓＨ， Ｓ）ｌ （ ｔ ） Ｃ ｓ Ｈ ＳＨ ■−１９ ＩＩ−２０ 以下余白 ＣＨ．＝ＣＨＣＨ。Margin below General formula (II) Exemplary compounds of SH (n)C=H,t S.H. low 3 (n)C+1)lzs S)I ■ (n)C. ,)(,,-S H loaf CH, -SH ■-9 II-10 (t)C. H. -S H 11-1.1 ■-12 (n)C,,H21-SH (n)C,,H2. -SH (n)C,,H,,-SH (i)CsH, S)l ( t ) Cs H S.H. ■-19 II-20 Margin below CH. =CHCH.
ＳＨ
ＣｔＨ，ＯＣＨ．ＣＨ２
Ｈ
本発明の一般式［Ｉ］および［ＩＩ］に表わされる化合
物は、いずれも市販されており容易に入手できる。SH CtH,OCH. CH2H The compounds represented by the general formulas [I] and [II] of the present invention are all commercially available and can be easily obtained.
本発明の一般式［１１１］で表される４−置換チオ酪酸
系化合物は、一般式［Ｉ］で表わされる化合物と一般式
［ＩＩ］で表わされる化合物とを、塩基の存在下、沸点
８０℃以上のアルコール系溶媒中で反応させることによ
り合成される。この反応で用いられる塩基としては、溶
媒として用いられるアルコールと実質的に反応しない塩
基が用いられる。ここで「実質的に反応」とは、例えば
、メタノール中のナトリウムメトキシドは厳密な意味で
は溶媒であるメタノールと水素の交換反応をしているが
、このような３８合を含まず、金属ナトリウムとアルコ
ールとの反応で水素を発生したり、あるいは水素化ナト
リウムとアルコールとの反応で水素を発生する反応をい
う。本発明において好ましく用いられるｍｌとしては、
水酸化物イオン、アルコキシアニオン、アリールオキシ
アニオン、アミノ基を有する化合物等を挙げることがで
きる。The 4-substituted thiobutyric acid compound represented by the general formula [111] of the present invention is prepared by combining the compound represented by the general formula [I] and the compound represented by the general formula [II] in the presence of a base, with a boiling point of 80 It is synthesized by reaction in an alcoholic solvent at a temperature of ℃ or above. The base used in this reaction is a base that does not substantially react with the alcohol used as a solvent. Here, "substantially reacts" means, for example, that sodium methoxide in methanol undergoes a hydrogen exchange reaction with methanol, which is a solvent, but does not include such a reaction, and does not contain metallic sodium methoxide. A reaction in which hydrogen is generated by the reaction between sodium hydride and alcohol, or hydrogen is generated by the reaction between sodium hydride and alcohol. The ml preferably used in the present invention is:
Examples include hydroxide ions, alkoxy anions, aryloxy anions, and compounds having amino groups.
アルコキシアニオンとしてはメトキシアニオン、エトキ
シアニオン等があり、アリールオキシアニオンとしては
フェノキシアニオン、クロロフェノキシアニオン等があ
り、さらに７ミノ基を有する化合物としてはトリエチル
アミン、Ｎ、Ｎ−ジメチルアニリン等が具体的に挙げら
れる。これら塩基のうち、アルコキシアニオンが特に好
ましい。Examples of alkoxy anions include methoxy anions and ethoxy anions; examples of aryloxy anions include phenoxy anions and chlorophenoxy anions; and specific examples of compounds having a 7-mino group include triethylamine, N,N-dimethylaniline, etc. Can be mentioned. Among these bases, alkoxy anions are particularly preferred.
該アルコキシアニオンは、反応直前に、アルカリ金属（
リチウム、ナトリウム、カリウム等）、アルカリ金属の
水素化物（水素化リチウム、水素化ナトリウム等）、ア
ルカリ土類金属の水素化物（水素化カルシウム等）とア
ルコールとの反応で調整してもよいし、市販のものを用
いてもよい、。The alkoxy anion is treated with an alkali metal (
lithium, sodium, potassium, etc.), alkali metal hydrides (lithium hydride, sodium hydride, etc.), alkaline earth metal hydrides (calcium hydride, etc.), and alcohol. Commercially available ones may also be used.
この反応において用いられる塩基の吊は、一般式［ＩＩ
］で示される化合物１モルに対して０．８〜１０．０モ
ル、好ましくは１．０モル〜３．０モルの範囲である。The base used in this reaction can be expressed by the general formula [II
] It is in the range of 0.8 to 10.0 mol, preferably 1.0 mol to 3.0 mol, per 1 mol of the compound represented by.
また、この反応で用いられる沸点８０℃以上のアルコー
ル系溶媒としては、ｎ−プロパツール（沸点９７℃）、
ｉ−プロパツール（沸点８２℃）、ローブタノール（沸
点１１８℃）、ｉ−ブタノール（沸点１０８℃）、２−
ブタノール（沸点９８℃）、ｔ−ブタノール（沸点８３
℃）、１−ペンタノール（沸点１３６〜１３８℃）、ｔ
−アミルアルコール（沸点１０２℃）、エチレングリコ
ール（沸点１９６〜１９８℃）等を挙げることができる
。In addition, the alcoholic solvents with a boiling point of 80°C or higher used in this reaction include n-propanol (boiling point 97°C),
i-propertool (boiling point 82°C), lobetanol (boiling point 118°C), i-butanol (boiling point 108°C), 2-
Butanol (boiling point 98℃), t-butanol (boiling point 83℃)
°C), 1-pentanol (boiling point 136-138 °C), t
-Amyl alcohol (boiling point: 102°C), ethylene glycol (boiling point: 196-198°C), and the like.
用いられるアルコール系溶媒の沸点が８０℃以下のとき
は、この反応がほとんど進行せず、また、沸点が２００
℃を超えると、好ましからざる副反応が進行するので、
上記アルコール系溶媒は沸点８０℃以上で２００℃を超
えないものを用いるのが好ましい。これら溶媒は、一般
式［ＩＩ］の化合物１徂量部当り１〜５０重１部、好ま
しくは２〜１０重吊部の割合で用いられる。When the boiling point of the alcoholic solvent used is 80°C or lower, this reaction hardly proceeds;
If the temperature exceeds ℃, undesirable side reactions will proceed.
It is preferable to use an alcohol solvent having a boiling point of 80°C or higher and not exceeding 200°C. These solvents are used in a ratio of 1 to 50 parts by weight, preferably 2 to 10 parts by weight, per 1 part by weight of the compound of general formula [II].
反応温度は８０〜２００℃が好ましく、特に９０〜１２
０℃が好ましい。反応に要する時間は、特に限定されな
いが、好ましくは５分〜２０時間、より好ましくは１時
間〜１０時間である。上記記載の如き本発明の方法によ
れば、一般式［Ｉ［［］で示される４−買換チオ酪酸系
化合物が高収率で得られる。The reaction temperature is preferably 80 to 200°C, particularly 90 to 12°C.
0°C is preferred. The time required for the reaction is not particularly limited, but is preferably 5 minutes to 20 hours, more preferably 1 hour to 10 hours. According to the method of the present invention as described above, a 4-purchased thiobutyric acid compound represented by the general formula [I[[] can be obtained in high yield.
次に本発明の一般式［１］で示される化合物の代表的具
体例を以下に示すが、本発明はこれらに限定されない。Next, typical examples of the compound represented by the general formula [1] of the present invention are shown below, but the present invention is not limited thereto.
以下余白
（ｎ）−Ｃ，Ｈ
，５（ＣＨ２）３Ｃｏ２Ｈ
（ｎ ） Ｃ、−Ｈ−Ｓ （ＣＨ２） −ＣＯ２Ｈ１
ｌ−３
（ｎ）−Ｃ
、Ｈ，，５（ＣＨ２）、ＣＯ，Ｈ
１ｌ−４
（ｎ）−Ｃ
、Ｈ，，５（ＣＨ２）、Ｃ０２Ｈ
１ｌ−５
（ｎ） Ｃ５Ｈ１−
（ｎ）−Ｃ，Ｈ，、ＣＨＣ）Ｉ、５（ＣＨ２）、ＣＯ２
Ｈ■−１３
■−１５
ＣＦ７
■−１６
■−１７
ＮＨＣＯＣＲ。Below margin (n) -C,H ,5(CH2)3Co2H (n) C, -H-S (CH2) -CO2H1
l-3 (n)-C , H,,5(CH2), CO,H 1l-4 (n)-C , H,,5(CH2), C02H 1l-5 (n) C5H1- (n)- C,H,,CHC)I,5(CH2),CO2
H■-13 ■-15 CF7 ■-16 ■-17 NHCOCR.
■−７
Ｃ２Ｈ６ＯＣＨ２ＣＨ，５（ＣＨ２）、ＣＯ，Ｈ（ｎ）
Ｃ
ＯＨ２
５ＣＨ２ＣＨ２ＣＨＣＯ，Ｈ
ＣＨ。■-7 C2H6OCH2CH,5(CH2),CO,H(n)
C OH2 5CH2CH2CHCO,H CH.
■−１０ ＣＨ。■-10 CH.
（ｎ）−Ｃ ２Ｈ２５ＳＣＨ，ＣＨ２ＣＣ０２Ｈ ＣＨ。(n)-C 2H25SCH, CH2CC02H CH.
■−１１ Ｃ，Ｈ ５（ｎ） （ロ）−Ｃ 、Ｈ，ｔＳＣＨＣＨ２ＣＨ，ＣＯ２１（■−１２ ＣＨ） ＣＨ，＝ＣＨＣＨ２５ＣＣＨ，ＣＨ２Ｃ０２）１ＣＨ。■-11 C,H 5(n) (b)-C , H, tSCHCH2CH, CO21 (■-12 CH) CH,=CHCH25CCH,CH2C02)1CH.
−ｉｓ ■−１９ Ｉ［１−２０ ＣＨ。-is ■-19 I[1-20 CH.
（ｉ）−Ｃ，Ｈ，５ＣＨ２ＣＨ，ＣＣ０２ＨＣＨ。(i) -C,H,5CH2CH,CC02HCH.
（ｎ）−Ｃ，Ｈ 、ＣＣＨ２ＣＨ２Ｃ０２Ｈ ＣＨ。(n)-C,H ,CCH2CH2C02H CH.
■−２２
（ｎ ） Ｃ１２Ｈ２ｓ ＣＨＣＨ２ＣＨ２ＣＯ２）
（ＣＦ。■-22 (n) C12H2s CHCH2CH2CO2)
(CF.
■−２３
■−２４
以下余白
［実施例］
以下に本発明の具体的実施例を記載するが、本発明はこ
れらによって限定されるものではない。■-23 ■-24 Below margins [Examples] Specific examples of the present invention will be described below, but the present invention is not limited thereto.
実施例１
５−チオヘプタデカン酸（例示化合物■−２）（その１
）の製造
ドデシルメルカプタン
ブタノール１ｙに溶解し、２８重量％ナトリウムメトキ
シドのメタノール溶液を加え、撹拌しながら９６℃に加
熱し、生成したメタノールを留去したくメタノールの沸
点６６℃）。その後、γーブチロラクトン（ Ｉ −
１ ＞ ９４．４０を含む２−ブタノール溶液（沸点９
８℃）４００戟を４５分か【ノで還流条件下滴下した。Example 1 5-thioheptadecanoic acid (Exemplary compound ■-2) (Part 1
28% by weight of sodium methoxide in methanol was added, and the mixture was heated to 96°C with stirring to distill off the methanol produced (the boiling point of methanol is 66°C). Then, γ-butyrolactone (I-
2-butanol solution containing 1 > 94.40 (boiling point 9
400 m (8°C) was added dropwise under reflux conditions over 45 minutes.
滴下終了後、さらに４時間撹拌しながら還流を続１プだ
。After the dropwise addition was completed, reflux was continued for another 4 hours while stirring.
反応終了後、塩酸を加えて中和し、有機層を抽出し、ざ
らに熱飽和食塩水で洗浄し、有機層を蒸留乾固させ、例
示化合物ｍ−２の粗結晶２９８ｇを得た。After the reaction was completed, hydrochloric acid was added to neutralize the reaction mixture, and the organic layer was extracted and washed with hot saturated brine, and the organic layer was distilled to dryness to obtain 298 g of crude crystals of Exemplary Compound m-2.
この粗結晶を１．８２のｎ−ヘキサンで再結晶させて、
無色、うろこ状結晶の例示化合物ｆｉｒ−２を得た。こ
の化合物の収量は２７８Ｑ （収率９５％）、また融
点は５７〜５８℃で、ＦＤ−マススペクトルは２８８を
示し、ＩＲ，ＮＭＲも上記構造を支持した。This crude crystal was recrystallized with 1.82 n-hexane,
Exemplary compound fir-2 was obtained as colorless, scaly crystals. The yield of this compound was 278Q (yield 95%), the melting point was 57-58°C, the FD-mass spectrum showed 288, and IR and NMR also supported the above structure.
元素分析値（ Ｃ＋６Ｈ３２ ０２ Ｓ ）計算値（％
） Ｃ ： ６６、６１ Ｈ ： １１．１Ｂ０
： １１．０９ Ｓ ： １１．１１実測値（％）
Ｃ ： ６６、８８ ８ ： １１．１００ ：
１０．９９ Ｓ ： １１．０３実施例２
５−チオヘプタデカン？ｌＩ（例示化合物■−２）（そ
の２）の製造
ドデシルメルカプタン（ Ｉｔ − ３ ） ２０３
ｇをブタノール１ｙに溶解し、２８重措％ナトリウムメ
トキシドのメタノール溶液を加え、撹拌しながら１０５
℃に加熱し、生成したメタノールを留去した（メタノー
ルの沸点６６℃）。その後、γーブチロラクトン（Ｉ−
１）９４．４ＣＩを含むｉ−ブタノール溶液４ ０ ０
ｎｆ！を４５分かけて還流条件下滴下した。滴下終了
後、さらに４時間撹拌還流を続けた。Elemental analysis value (C+6H32 02 S) Calculated value (%
) C: 66, 61 H: 11.1B0
: 11.09 S : 11.11 Actual value (%)
C: 66, 88 8: 11.100:
10.99 S: 11.03 Example 2 5-thioheptadecane? Production of lI (Example Compound ■-2) (Part 2) Dodecyl mercaptan (It-3) 203
Dissolve g in butanol, add a methanol solution of 28% sodium methoxide, and add 105 g with stirring.
The methanol produced was distilled off (boiling point of methanol: 66°C). Then, γ-butyrolactone (I-
1) i-butanol solution containing 94.4 CI 400
nf! was added dropwise over 45 minutes under reflux conditions. After the dropwise addition was completed, stirring and refluxing was continued for an additional 4 hours.
反応終了後、塩酸を加えて中和し、有機層を油出、さら
に熱飽和食塩水で洗浄し、有は層を蒸留乾固させ、例示
化合物Ｉ１１−２の粗結晶２９６ｇを得た。After the reaction was completed, hydrochloric acid was added to neutralize, and the organic layer was washed with oil and then hot saturated brine, and the organic layer was distilled to dryness to obtain 296 g of crude crystals of Exemplified Compound I11-2.
この粗結晶を１．８ｉの０−ヘキサンで再結晶させて、
無色、うろこ状結晶の例示化合物ｍ−２を得た。収量２
６３（＋ （収率９０％）、融点５６〜５７℃。ＩＲ
およびＮＭＲは実施例１で得た例示化合物１１１−２と
完全に一致した。This crude crystal was recrystallized with 1.8i 0-hexane,
Exemplary compound m-2 was obtained as colorless, scaly crystals. Yield 2
63(+ (90% yield), melting point 56-57°C. IR
and NMR were completely consistent with Exemplified Compound 111-2 obtained in Example 1.
実施例３
５−チオトリコサンＭ（例示化合物■−４）の製造
オクタデシルメルカプタン
］１ーブタノール１！に溶解し、２８重准％ナトリウム
メトキシドのメタノール溶液を加え、撹拌しながら１１
８℃に加熱し、生成したメタノールを留去した（メタノ
ールの沸点６６℃）。その後、Ｔープチロラクトン（
Ｉ − １ ） ９４．４（ｌを含む１−ブタノール溶
液４ ０ ０ １Ｊ２を４５分かけて還流条件下滴下し
た。滴下終了後、さらに４時間撹拌還流を続けた。Example 3 Production of 5-thiotricosane M (exemplified compound 1-4) Octadecyl mercaptan] 1-butanol 1! Add a 28% sodium methoxide solution in methanol, and add 11% sodium methoxide while stirring.
The mixture was heated to 8°C and the generated methanol was distilled off (the boiling point of methanol is 66°C). Then, T-butyrolactone (
A 1-butanol solution containing 94.4 (l) of 400 1J2 was added dropwise over 45 minutes under refluxing conditions. After the dropwise addition was completed, stirring and refluxing was continued for an additional 4 hours.
反応終了後、塩酸を加えて中和し、有機層を抽出、ざら
に熱飽和食塩水で洗浄し、有機層を蒸留乾固させ、例示
化合物１１１−４の粗結晶３７５ｇを得た。After the reaction was completed, hydrochloric acid was added to neutralize, and the organic layer was extracted and washed with hot saturated brine, and the organic layer was distilled to dryness to obtain 375 g of crude crystals of Exemplary Compound 111-4.
この粗結晶を２．４ｙのｎ−ヘキサンで再結晶させて、
無色、うろこ状結晶の例示化合物１ｔ−４を得た。収は
３４３（１（収率９２％）、融点７６〜７７℃、ＦＤ−
マススペクトルが３７２を示し、ｌＲ，ＮＭＲも上記構
造を支持した。This crude crystal was recrystallized with 2.4y n-hexane,
Exemplary compound 1t-4 was obtained as colorless, scaly crystals. Yield: 343 (1 (yield 92%), melting point: 76-77°C, FD-
The mass spectrum showed 372, and 1R and NMR also supported the above structure.
元素分析値（Ｃ２２Ｈ４４ＳＯ２）
計惇（山〈％） Ｃ： ７０．９１ ）（： １１
．９００： ８．５９ Ｓ： ８．６０実測値（
％） Ｃ： ７１．０９ Ｈ： １１．７２０：
８．４２ ３： ８．７７
実施例４
４−（２’ −ブトキシ−５’ −ｔｅｒｔ−オクチル
フェニルチオ）酪Ｍ（例示化合物■−６）の製造２−ブ
トキシ−５−ｔｅｒｔ−オクチルチオフェノール（ＩＩ
−１５） ２９５ｇを２−ブタノール１ｙに溶解し
、２８重量％ナトリウムメトキシドのメタノール溶液を
加え、撹拌しながら９６℃に加熱し、生成したメタノー
ルを留去した（メタノールの沸点６６℃）。その後、γ
−ブチロラクトン（Ｉ−１） ９４．４０を含む２−ブ
タノール溶液４００１１２を４５分かけて還流条件下滴
下した。滴下終了後、さらに４時間撹拌還流を続けた。Elemental analysis value (C22H44SO2) Measurement (mountain %) C: 70.91 ) (: 11
．． 900: 8.59 S: 8.60 Actual value (
%) C: 71.09 H: 11.720:
8.42 3: 8.77 Example 4 Production of 4-(2'-butoxy-5'-tert-octylphenylthio)butyric M (exemplary compound ■-6) 2-butoxy-5-tert-octylthiophenol (II
-15) 295g was dissolved in 2-butanol 1y, a methanol solution of 28% by weight sodium methoxide was added, and the mixture was heated to 96°C with stirring, and the generated methanol was distilled off (boiling point of methanol: 66°C). After that, γ
-Butyrolactone (I-1) A 2-butanol solution 400112 containing 94.40% was added dropwise under reflux over 45 minutes. After the dropwise addition was completed, stirring and refluxing was continued for an additional 4 hours.
反応終了後、塩酸を加えて中和し、有機層を抽出、さら
に熱飽和食塩水で洗浄し、２−ブタノールを留去して、
３８４ｇのオイルを得た。After the reaction was completed, hydrochloric acid was added to neutralize, the organic layer was extracted, washed with hot saturated brine, and 2-butanol was distilled off.
384 g of oil was obtained.
このオイルをカラムクロマトグラフィー［溶離液：酢酸
エチル−ヘキサン＝１−１ （Ｖ／Ｖ）（但し■は容積
を示す。）］で精製して、無色オイル状の例示化合物Ｉ
［１−６を得た。収ｆｉ ３６２Ｑ（収率９５％）、Ｆ
Ｄ−マススペクトルが３８０を示し、ＩＲ，ＮＭＲも上
記構造を支持した。This oil was purified by column chromatography [eluent: ethyl acetate-hexane = 1-1 (V/V) (where ■ indicates volume)] to obtain Exemplified Compound I as a colorless oil.
[1-6 was obtained. Yifi 362Q (yield 95%), F
The D-mass spectrum showed 380, and IR and NMR also supported the above structure.
元素分析値（Ｃ２２Ｈ３６０３Ｓ）
計算値（％） Ｃ：６９．４３ １（： ９．５３
０ ： １２．６１ Ｓ ： ８．４２実、１！１
値（％） Ｃ：６９．８３ Ｈ： ９．２４０
： １２．８３ Ｓ ： ８．１０比較例
−１（従来法）
５−チオヘプタデカン酸（例示化合物■−２）の製造
ドデシルメルカプタン
チルホルムアミド１２に溶解し、２８重量％ナトリウム
メトキシドのメタノール溶液を加え、撹拌しながら１１
５℃に加熱し、生成したメタノールを留去したくメタノ
ールの沸点６６℃）。その後、Ｔ−ブチロラクトン（
Ｉ − １ ＞ ９４．４ｇを含むジメチルホルムアミ
ド溶液４００ｄを４５分かけて内温１１０℃で滴下した
。滴下終了後、さらに４時間内温１１０℃で撹拌を続け
た。Elemental analysis value (C22H3603S) Calculated value (%) C:69.43 1(: 9.53
0: 12.61 S: 8.42 actual, 1!1
Value (%) C: 69.83 H: 9.240
: 12.83 S : 8.10 Comparative Example-1 (Conventional Method) Production of 5-thioheptadecanoic acid (Exemplary Compound ■-2) Dissolved in dodecyl mercaptanyl formamide 12 and added a 28% by weight methanol solution of sodium methoxide. , while stirring 11
The boiling point of methanol is 66°C) to distill off the methanol produced. Then, T-butyrolactone (
400 d of a dimethylformamide solution containing 94.4 g of I-1 was added dropwise over 45 minutes at an internal temperature of 110°C. After the dropwise addition was completed, stirring was continued for an additional 4 hours at an internal temperature of 110°C.
反応終了後、塩酸を加えて中和し、さらに酢酸エチルを
加え有機層を抽出、ざらに熱飽和食塩水で洗浄し、有機
層を蒸留乾固させ、例示化合物１１１−２の粗結晶２８
３ｇを得た。After the reaction was completed, hydrochloric acid was added to neutralize, ethyl acetate was added to extract the organic layer, and the organic layer was washed with hot saturated brine, and the organic layer was distilled to dryness to obtain crude crystals of Exemplified Compound 111-2.
3g was obtained.
この粗結晶を１．８２のｎ−ヘキサンで再結晶して、無
色、うろこ状結晶の例示化合物ｎｌ−２を得た。収量１
９９（１ （収率６８％）、融点５６〜５７℃。ＩＲ
およびＮＭＲは実施例１で得た例示化合物ｍ−２と完全
に一致した。The crude crystals were recrystallized with 1.82% n-hexane to obtain exemplified compound nl-2 as colorless, scaly crystals. Yield 1
99(1 (yield 68%), melting point 56-57°C. IR
and NMR were completely consistent with exemplified compound m-2 obtained in Example 1.
［発明の効果］
実施例からも分かるように、本発明の４−置換チオ酪酸
系化合物の製造方法は、置換基の適応範囲が広く、高収
率で目的物が得られる優れた方法であり、しかも高価な
アブロティツク溶媒を使用せずに低コストで製造するこ
とかできるから、従来の上記化合物の製造方法に比べて
きわめてすぐれた製造方法と言える。[Effects of the Invention] As can be seen from the examples, the method for producing 4-substituted thiobutyric acid compounds of the present invention is an excellent method that can be applied to a wide range of substituents and provides the desired product in high yield. Moreover, since it can be produced at low cost without using expensive abrotic solvents, it can be said to be an extremely superior production method compared to conventional production methods for the above-mentioned compounds.
Claims (2)
びＲ＿６は、各々、水素原子、アルキル基、アルケニル
基、シクロアルキル基、アリール基または複素環基を示
す）で表わされる化合物と、 一般式［II］ ＲＳＨ （式中、Ｒはアルキル基、アルケニル基、シクロアルキ
ル基、アリール基または複素環基を示す）で表わされる
化合物とを、沸点８０℃以上のアルコール系溶媒中で、
反応させることを特徴とする一般式［III］ ▲数式、化学式、表等があります▼ （式中、Ｒ＿１、Ｒ＿２、Ｒ＿３、Ｒ＿４、Ｒ＿５及び
Ｒ＿６は前記一般式［ I ］と同義であり、Ｒは前記一
般式［II］と同義である）で表わされる４−置換チオ酪
酸系化合物の製造方法。(1) General formula [I] ▲ Numerical formulas, chemical formulas, tables, etc. (represents an aryl group or a heterocyclic group); and a compound represented by the general formula [II] RSH (wherein R represents an alkyl group, an alkenyl group, a cycloalkyl group, an aryl group, or a heterocyclic group). and in an alcoholic solvent with a boiling point of 80°C or higher,
General formula [III] characterized by reaction ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1, R_2, R_3, R_4, R_5 and R_6 are synonymous with the above general formula [I], and R is the same as the general formula [II]).
びＲ＿６は、各々、水素原子、アルキル基、アルケニル
基、シクロアルキル基、アリール基または複素環基を示
す）で表わされる化合物と、 一般式［II］ ＲＳＨ （式中、Ｒはアルキル基、アルケニル基、シクロアルキ
ル基、アリール基または複素環基を示す）で表わされる
化合物とを、沸点８０℃以上のアルコール系溶媒中、塩
基の存在下で、反応させることを特徴とする一般式［I
II］ ▲数式、化学式、表等があります▼ （式中、Ｒ＿１、Ｒ＿２、Ｒ＿３、Ｒ＿４、Ｒ＿５及び
Ｒ＿６は前記一般式［ I ］と同義であり、Ｒは前記一
般式［II］と同義である）で表わされる４−置換チオ酪
酸系化合物の製造方法。(2) General formula [I] ▲ Numerical formulas, chemical formulas, tables, etc. (represents an aryl group or a heterocyclic group); and a compound represented by the general formula [II] RSH (wherein R represents an alkyl group, an alkenyl group, a cycloalkyl group, an aryl group, or a heterocyclic group). of the general formula [I
II] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1, R_2, R_3, R_4, R_5 and R_6 have the same meaning as the above general formula [I], and R has the same meaning as the above general formula [II]. A method for producing a 4-substituted thiobutyric acid compound represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP22407988A JPH0272156A (en) | 1988-09-07 | 1988-09-07 | Production of 4-substituted thiobutyric acid-based compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP22407988A JPH0272156A (en) | 1988-09-07 | 1988-09-07 | Production of 4-substituted thiobutyric acid-based compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0272156A true JPH0272156A (en) | 1990-03-12 |
Family
ID=16808230
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP22407988A Pending JPH0272156A (en) | 1988-09-07 | 1988-09-07 | Production of 4-substituted thiobutyric acid-based compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0272156A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013522213A (en) * | 2010-03-09 | 2013-06-13 | ノーバス・インターナショナル・インコーポレイテッド | Production of methionine or selenomethionine from homoserine via lactone intermediate |
-
1988
- 1988-09-07 JP JP22407988A patent/JPH0272156A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013522213A (en) * | 2010-03-09 | 2013-06-13 | ノーバス・インターナショナル・インコーポレイテッド | Production of methionine or selenomethionine from homoserine via lactone intermediate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2137523C (en) | One-pot process for the preparation of 3-quinolonecarboxylic acid derivatives | |
| CA1215978A (en) | Process for preparing 2-carbamoyloxyalkyl-1,4- dihydropyridine derivatives and intermediates useful for the process | |
| JP3071019B2 (en) | Method for producing 1- (alkoxymethyl) pyrrole compound of insecticide | |
| KR20040084915A (en) | Novel boronate esters | |
| JPH0272156A (en) | Production of 4-substituted thiobutyric acid-based compound | |
| US4267348A (en) | Fluorine-containing benzimidazoles | |
| US5723665A (en) | Ethenyl amide compound production process | |
| US4925944A (en) | Process for the preparation of o-carboxypyridyl- and o-carboxyquinolylimidazolinones | |
| JP2002105058A (en) | Method for manufacturing 1,3-dialkylimidazolium iodide salt | |
| EP0490326B2 (en) | Astaxanthin intermediates | |
| KR20190002519A (en) | Method for preparing pedestrial pyridinium imidazolon compounds | |
| JPH05117263A (en) | Production of 3-amino-2-thiophenecarboxylic acid derivative | |
| JP3066594B2 (en) | Aniline derivative and method for producing the same | |
| JPS6399063A (en) | Production of 4-amino-1,2,4-triazoline-5-thione compound | |
| JP2915068B2 (en) | Method for producing dihydrofuranone derivative | |
| JPH0528708B2 (en) | ||
| JP4194856B2 (en) | 2-Phenyl-4- (1-naphthyl) imidazole | |
| JP3632283B2 (en) | Bisquaryl compounds | |
| US5166441A (en) | Astaxanthin intermediates | |
| JPH0665213A (en) | Dicyanopyrazine derivative and its production | |
| JP3689158B2 (en) | 4-Acylaminophenylacetylene alcohol compound and method for producing 4-acylaminophenylacetylene compound using the same | |
| JP3044383B2 (en) | Method for producing nitrogen-containing 6-membered ring compound | |
| Li et al. | Asymmetric synthesis and absolute stereochemistry of 4, 4-bis-(trifluoromethyl) imidazoline based ACAT inhibitors | |
| JPS61126066A (en) | Novel method of polysulfide production | |
| CN101402632A (en) | Aryl hydrazide compounds with antineoplastic activity |