JPS5919951B2 - Production method of γ-butyrolactones - Google Patents
Production method of γ-butyrolactonesInfo
- Publication number
- JPS5919951B2 JPS5919951B2 JP49107158A JP10715874A JPS5919951B2 JP S5919951 B2 JPS5919951 B2 JP S5919951B2 JP 49107158 A JP49107158 A JP 49107158A JP 10715874 A JP10715874 A JP 10715874A JP S5919951 B2 JPS5919951 B2 JP S5919951B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- chloro
- decane
- oxaspiro
- oxo
- 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
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical class O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 title claims description 7
- 239000002253 acid Substances 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 238000006114 decarboxylation reaction Methods 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 3
- 229930040373 Paraformaldehyde Natural products 0.000 claims 1
- 229920002866 paraformaldehyde Polymers 0.000 claims 1
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 1
- -1 chloro-2-oxo-1-oxaspiro[4,5]decane compound Chemical class 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 230000001754 anti-pyretic effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- WQKHERPPDYPMNX-UHFFFAOYSA-N 6-chloro-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=CC(Cl)=CC=C21 WQKHERPPDYPMNX-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- DUMMLBFJPQGNSA-BTJKTKAUSA-N (z)-but-2-enedioic acid;decane Chemical compound OC(=O)\C=C/C(O)=O.CCCCCCCCCC DUMMLBFJPQGNSA-BTJKTKAUSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- JEGMWWXJUXDNJN-UHFFFAOYSA-N 3-methylpiperidine Chemical compound CC1CCCNC1 JEGMWWXJUXDNJN-UHFFFAOYSA-N 0.000 description 1
- UZOFELREXGAFOI-UHFFFAOYSA-N 4-methylpiperidine Chemical compound CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000000911 decarboxylating effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- PCACNTVTAHRXMP-UHFFFAOYSA-N ethyl 6-chloro-2-oxo-1-oxaspiro[4.5]decane-3-carboxylate Chemical compound O1C(=O)C(C(=O)OCC)CC11C(Cl)CCCC1 PCACNTVTAHRXMP-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- DYUWTXWIYMHBQS-UHFFFAOYSA-N n-prop-2-enylprop-2-en-1-amine Chemical compound C=CCNCC=C DYUWTXWIYMHBQS-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
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- Furan Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は、γ−ブチロラクトン類およびその酸付加塩の
製法に関し、更に詳しくは、一般式
（式中、Ｒ１およびＲ２は同じか或いは異なる低級アル
キル基もしくは低級アルケニル基を示すか、または隣接
する窒素原子とともに置換もしくは非置換複素環を形成
していることを示す。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing γ-butyrolactones and acid addition salts thereof, and more specifically, the present invention relates to a method for producing γ-butyrolactones and acid addition salts thereof, and more specifically, the present invention relates to a method for producing γ-butyrolactones and acid addition salts thereof, and more particularly, the present invention relates to a method for producing γ-butyrolactones and acid addition salts thereof, and more particularly, the present invention relates to a method for producing γ-butyrolactones and acid addition salts thereof. or to form a substituted or unsubstituted heterocycle with the adjacent nitrogen atom.
）にて表わされる３−（Ｎ一置換）アミノメチル−６−
クロロ−２−オキソ一１−オキサスピロ〔４・５〕デカ
ン化合物およびその酸付加塩の製造法に関する。上記一
般式において、Ｒ１またはＲ２で示される低級アルキル
基は、メチル、エチル、プロピル、ブチル基などであり
、また、低級アルケニル基は、プロペニル、ブテニル、
ペンテニル基などである。) 3-(N-monosubstituted)aminomethyl-6-
The present invention relates to a method for producing a chloro-2-oxo-1-oxaspiro[4,5]decane compound and its acid addition salt. In the above general formula, the lower alkyl group represented by R1 or R2 is methyl, ethyl, propyl, butyl group, etc., and the lower alkenyl group is propenyl, butenyl,
Such as pentenyl group.
Ｒ１およびＲ２が隣接する窒素原子とともに形成する複
素環基は、その複素環内に他のヘテロ原子、例えば窒素
原子、酸素原子或いは硫黄原子などを有していてもよく
、それ等の例としてはピロリジノ、オキサゾリジノ、ピ
ペリジノ、モルホリノ、チアモルホリノ、ピペラジノ基
などである。更に、その複素環基の任意の位置に１個ま
たはそれ以上の置換基を有していてもよく、またその複
素環基が縮合環の一部を形成していてもよい。それ等の
例としては、１・２・３・４−テトラヒドロキノリ一１
−イル：１・２・３・４−テトラヒドロイソキノリ一２
−イル基などがある。本発明を詳細に説明すると、まず
、
一般式
（式中、Ｒは低級アルキル基を示す。The heterocyclic group formed by R1 and R2 together with the adjacent nitrogen atom may have other heteroatoms such as nitrogen atom, oxygen atom or sulfur atom within the heterocycle, examples of which include: These include pyrrolidino, oxazolidino, piperidino, morpholino, thiamorpholino, and piperazino groups. Furthermore, the heterocyclic group may have one or more substituents at any position, and the heterocyclic group may form part of a condensed ring. Examples of these include 1,2,3,4-tetrahydroquinol-1
-yl: 1,2,3,4-tetrahydroisoquinol-2
-yl group, etc. To explain the present invention in detail, first, the general formula (wherein R represents a lower alkyl group).
）にて表わされる３−アルコキシカルボニル−６−クロ
ロ−２−オキソ一１−オキサスピロ〔４・５〕デカン（
式中、Ｒ１およびＲ２は前記と同じ。）にて表わされる
二級アミンとをいわゆるマンニツヒ反応によつて反応せ
しめ、一般式
（式中、Ｒ．Ｒｌお・よびＲ２は前記と同じ）にて表わ
されるマンニツヒ塩基型化合物とする。) 3-alkoxycarbonyl-6-chloro-2-oxo-1-oxaspiro[4.5]decane (
In the formula, R1 and R2 are the same as above. ) is reacted with a secondary amine represented by the formula (R.
上記反応において用いられる二級アミンは、無機酸塩或
いは有機酸塩であつてもよく、また反応の溶媒としては
、マンニツヒ反応において通常用いられる溶媒、例えば
水、アルコール、ジオキサンまたはＮ−Ｎ−ジメチルホ
ルムアミドその他を用いる。次に、このマンニツヒ塩基
型化合物を加水分解、脱炭酸させれば、３−（Ｎ一置換
）アミノメチル６−クロロ−２−オキソ一１−オキサス
ピロ〔４・５〕デカン化合物をきわめて容易に得ること
ができる。The secondary amine used in the above reaction may be an inorganic acid salt or an organic acid salt, and the reaction solvent may be a solvent commonly used in the Mannitz reaction, such as water, alcohol, dioxane or N-N-dimethyl. Formamide and others are used. Next, by hydrolyzing and decarboxylating this Mannitz base type compound, a 3-(N-monosubstituted)aminomethyl 6-chloro-2-oxo-1-oxaspiro[4.5]decane compound can be obtained very easily. be able to.
この際、酸で加水分解すると、加水分解と同時に脱炭酸
も行なうことができる。At this time, when hydrolyzed with an acid, decarboxylation can be performed simultaneously with the hydrolysis.
酸は特に反応の容易さの点で濃塩酸が最も好ましい。こ
こに得られる３−（Ｎ一置換）アミノメチル一６−クロ
ロ−２−オキソ一１−オキサスピロ〔４・５〕デカン化
合物は常法によりその酸付加塩に導くことができ、特に
油状物の場合には精製も容易となる。The acid is most preferably concentrated hydrochloric acid, especially from the viewpoint of ease of reaction. The 3-(N-monosubstituted)aminomethyl-6-chloro-2-oxo-1-oxaspiro[4.5]decane compound obtained here can be converted into its acid addition salt by a conventional method. In some cases, purification becomes easier.
その酸付加塩に用いられる酸としては、塩化水素酸、臭
化水素酸、硫酸、硝酸、燐酸などの無機酸およびシユウ
酸、マレイン酸、フマール酸、コハク酸、クエン酸、リ
ンゴ酸、サリチル酸などの有機酸がある。本発明の方法
によつて得られる３−（Ｎ一置換）アミノメチル−６−
クロロ−２−オキソ一１−オキサスピロ〔４・５〕デカ
ンおよびその酸付加塩は、動物実験においてカラゲニン
による後肢水腫に対して顕著な抑制作用を示し、鎮痛解
熱作用を併有するものを含めて抗炎症作用を有し、解熱
、鎮痛、消炎剤として有用なものである。Acids used in the acid addition salts include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid, and oxalic acid, maleic acid, fumaric acid, succinic acid, citric acid, malic acid, and salicylic acid. There are organic acids. 3-(N-monosubstituted)aminomethyl-6- obtained by the method of the invention
Chloro-2-oxo-1-oxaspiro[4,5]decane and its acid addition salts have shown remarkable inhibitory effects on carrageenan-induced hindlimb edema in animal experiments, and have antipyretic effects, including those that also have analgesic and antipyretic effects. It has inflammatory effects and is useful as an antipyretic, analgesic, and antiinflammatory agent.
次に実施例を挙げて本発明を説明する。Next, the present invention will be explained with reference to Examples.
実施例
６−クロロ−３−エトキシカルボニル−２−オキソ一１
−オキサスピロ〔４・５〕デカン２．６ｔ（１０ミリモ
ル）、ピペリジン１．０２７（１２ミリモル）、氷酢酸
０．７２ｙ（１２ミリモル）および３７％ホルムアルデ
ヒド０．９８７（１２ミリモル）をエタノール３０ｍ１
に溶解し、１８時間加熱還流後溶媒を減圧溜去する。Example 6-Chloro-3-ethoxycarbonyl-2-oxo-1
- Oxaspiro[4,5]decane 2.6t (10 mmol), piperidine 1.027 (12 mmol), glacial acetic acid 0.72y (12 mmol) and 37% formaldehyde 0.987 (12 mmol) in ethanol 30ml
After heating under reflux for 18 hours, the solvent was distilled off under reduced pressure.
得られた残渣を酢酸エチルに溶解し、希塩酸と振盪して
塩酸層を分取し、酸酸エチルで１回洗滌後炭酸ナトリウ
ム末でアルカリ性とし、分離してくる油性成分を酢酸エ
チルで抽出する。この抽出液を水洗後無水硫酸マグネシ
ウムで乾燥し、溶媒を溜去して粗製塩基１．６７を得る
。この塩基を濃塩酸１５ｍ１に溶解し、１２０℃で７時
間加熱還流して加水分解、脱炭酸させる。冷後、適量の
水を加えて希釈し、炭酸ナトリウムでアルカリ性として
酢酸エチルで抽出し、飽和食塩水で洗滌後無水硫酸マグ
ネシウムで乾燥し、溶媒を溜去して粘性塩基６−クロロ
−２−オキソ一３−ピペリジツメチル−１−オキサスピ
ロ〔４・５〕デカン１．１７を得る。これを常法に従つ
てマレイン酸塩となし、エタノールで再結晶してモノマ
レイン酸塩１．４２ｔを得る。収率３５．４％ Ｍ．ｐ
．ｌ４２〜１４３℃ピペリジンの代りにジメチルアミン
、メチルエチルアミン、ジアリルアミン、３−メチルピ
ペリジン、４−メチルピペリジン、モルホリン、チアモ
ルホリンまたは１・２・３・４−テトラヒドロイソキノ
リンを用い、それぞれ６−クロロ−３−ジメチルアミノ
メチル−２−オキソ一１−オキサスピロ〔４・５〕デカ
ン モノマレイイ１叛Ｍ．ｐ．ｌ２ｌ〜１２２℃；６−
クロロ−３−メチルエチルアミノメチル−２−オキソ一
１−オキサスピロ〔４・５〕デカン モノマレイン酸塩
、Ｍ．ｐ．ｌ６４〜１６５℃；６−クロロ−３−ジアリ
ルアミノメチル−２−オキソ一１−オキサスピロ〔４・
５〕デカン モノマレイン酸塩、Ｍ．ｐ．ｌ９５〜１９
６℃；６−クロロ−３−（３−メチルピベリジノ）メチ
ル−２−オキソ一１−オキサスピロ〔４・５〕デカン
モノマレイン酸塩、Ｍ．ｐ．ｌ２ｌ〜１２２℃：６−ク
ロロ−３−（４−メチルピペリジノ）メチル−２−オキ
ソ一１−オキサスピロ〔４・５〕デカン モノマレイン
酸塩、Ｍ．ｐ．ｌ５５〜１５６．５℃；６−クロロ−３
−モルホリノメチル−２−オキソ一１−オキサスピロ〔
４・５〕デカン モノマレイン酸塩、Ｍ．ｐ．ｌ３４〜
１３５℃；６−クロロ−２−オキソ一３チアモルホリノ
メチル一１−オキサスピロ〔４・５〕デカン モノマレ
イン酸塩、Ｍ．ｐ．ｌ５ｌ〜１５２℃；６−クロロ−３
−（１・２・３・４テトラヒドロイソキノリ一２−イル
）メチル−２オキソ一１−オキサスビロ〔４・５〕デカ
ン一塩酸塩、Ｍ．ｐ．ｌ３３〜１３５℃（分解）を得る
。The resulting residue is dissolved in ethyl acetate, shaken with dilute hydrochloric acid, the hydrochloric acid layer is separated, washed once with ethyl acetate, made alkaline with sodium carbonate powder, and the separated oily component is extracted with ethyl acetate. . This extract is washed with water, dried over anhydrous magnesium sulfate, and the solvent is distilled off to obtain crude base 1.67. This base is dissolved in 15 ml of concentrated hydrochloric acid and heated under reflux at 120° C. for 7 hours for hydrolysis and decarboxylation. After cooling, it was diluted with an appropriate amount of water, made alkaline with sodium carbonate, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off to give the viscous base 6-chloro-2- 1.17 of oxo-3-piperiditumethyl-1-oxaspiro[4.5]decane is obtained. This was converted into maleate according to a conventional method, and recrystallized from ethanol to obtain 1.42 t of monomaleate. Yield 35.4% M. p
．． l42-143℃ Dimethylamine, methylethylamine, diallylamine, 3-methylpiperidine, 4-methylpiperidine, morpholine, thiamorpholine or 1,2,3,4-tetrahydroisoquinoline is used in place of piperidine, and 6-chloro-3 is used, respectively. -dimethylaminomethyl-2-oxo-1-oxaspiro[4.5]decane Monomaleii 1 M. p. l2l~122℃; 6-
Chloro-3-methylethylaminomethyl-2-oxo-1-oxaspiro[4.5]decane monomaleate, M. p. l64-165°C; 6-chloro-3-diallylaminomethyl-2-oxo-1-oxaspiro[4.
5] Decane monomaleate, M. p. l95-19
6°C; 6-chloro-3-(3-methylpiberidino)methyl-2-oxo-1-oxaspiro[4.5]decane
Monomaleate, M. p. l2l~122°C: 6-chloro-3-(4-methylpiperidino)methyl-2-oxo-1-oxaspiro[4.5]decane monomaleate, M.I. p. 155-156.5℃; 6-chloro-3
-morpholinomethyl-2-oxo-1-oxaspiro [
4.5] Decane monomaleate, M. p. l34~
135°C; 6-chloro-2-oxo-3-thiamorpholinomethyl-1-oxaspiro[4.5]decane monomaleate, M.I. p. l5l~152°C; 6-chloro-3
-(1,2,3,4tetrahydroisoquinol-2-yl)methyl-2oxo-1-oxasbiro[4,5]decane monohydrochloride, M. p. Obtain l33-135°C (decomposition).
Claims (1)
ロ−２−オキソ−１−オキサスピロ〔４・５〕デカンと
一般式 ▲数式、化学式、表等があります▼ （式中、Ｒ＾１およびＲ＾２は同じか或いは異なる低級
アルキル基もしくはアルケニル基を示すか、または隣接
する窒素原子とともに置換もしくは非置換複素環基を形
成していることを示す。 ）にて表わされる二級アミンとホルムアルデヒドまたは
パラホルムアルデヒドとを反応せしめた後、加水分解、
脱炭酸させることを特徴とする。一般式 ▲数式、化学式、表等があります▼ （式中、Ｒ＾１およびＲ＾２は前記と同じ）にて表わさ
れるγ−ブチロラクトン類およびその酸付加塩の製法。[Claims] 1 3-alkoxycarbonyl-6-chloro-2-oxo-1 represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R represents a lower alkyl group.) -Oxaspiro[4.5]decane and general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1 and R^2 are the same or different lower alkyl or alkenyl groups, or adjacent Indicates that a substituted or unsubstituted heterocyclic group is formed with the nitrogen atom.) After reacting the secondary amine represented by () with formaldehyde or paraformaldehyde, hydrolysis,
It is characterized by decarboxylation. A method for producing γ-butyrolactones and their acid addition salts represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1 and R^2 are the same as above).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP49107158A JPS5919951B2 (en) | 1974-09-19 | 1974-09-19 | Production method of γ-butyrolactones |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP49107158A JPS5919951B2 (en) | 1974-09-19 | 1974-09-19 | Production method of γ-butyrolactones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS51125068A JPS51125068A (en) | 1976-11-01 |
| JPS5919951B2 true JPS5919951B2 (en) | 1984-05-09 |
Family
ID=14451957
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP49107158A Expired JPS5919951B2 (en) | 1974-09-19 | 1974-09-19 | Production method of γ-butyrolactones |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5919951B2 (en) |
-
1974
- 1974-09-19 JP JP49107158A patent/JPS5919951B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS51125068A (en) | 1976-11-01 |
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