JPS6220188B2 - - Google Patents
Info
- Publication number
- JPS6220188B2 JPS6220188B2 JP84500166A JP50016684A JPS6220188B2 JP S6220188 B2 JPS6220188 B2 JP S6220188B2 JP 84500166 A JP84500166 A JP 84500166A JP 50016684 A JP50016684 A JP 50016684A JP S6220188 B2 JPS6220188 B2 JP S6220188B2
- Authority
- JP
- Japan
- Prior art keywords
- dihydro
- carboxy
- pyran
- reaction
- dihalogenobutane
- 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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000000034 method Methods 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- OXUPSEKWDOSMIN-UHFFFAOYSA-N 3,4-dihydro-2h-pyran-6-carboxylic acid Chemical class OC(=O)C1=CCCCO1 OXUPSEKWDOSMIN-UHFFFAOYSA-N 0.000 description 8
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 8
- 229910002091 carbon monoxide Inorganic materials 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 229910017052 cobalt Inorganic materials 0.000 description 7
- 239000010941 cobalt Substances 0.000 description 7
- -1 cobalt carbonyl compound Chemical class 0.000 description 7
- 239000000376 reactant Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000005810 carbonylation reaction Methods 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- MQIKJSYMMJWAMP-UHFFFAOYSA-N dicobalt octacarbonyl Chemical group [Co+2].[Co+2].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-] MQIKJSYMMJWAMP-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 2
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 235000011941 Tilia x europaea Nutrition 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000006315 carbonylation Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000004571 lime Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- CPRMKOQKXYSDML-UHFFFAOYSA-M rubidium hydroxide Chemical compound [OH-].[Rb+] CPRMKOQKXYSDML-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- NIDSRGCVYOEDFW-UHFFFAOYSA-N 1-bromo-4-chlorobutane Chemical compound ClCCCCBr NIDSRGCVYOEDFW-UHFFFAOYSA-N 0.000 description 1
- PHMXXMFOSQBXNV-UHFFFAOYSA-N 2,3-dichlorooxane Chemical compound ClC1CCCOC1Cl PHMXXMFOSQBXNV-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
- ZQXSFZAMFNRZOQ-UHFFFAOYSA-N 2-methylpropan-2-ol;hydrate Chemical compound O.CC(C)(C)O ZQXSFZAMFNRZOQ-UHFFFAOYSA-N 0.000 description 1
- GJYYUTBMUNNEOF-UHFFFAOYSA-N 3-chlorooxane-2-carbonitrile Chemical compound ClC1CCCOC1C#N GJYYUTBMUNNEOF-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910019440 Mg(OH) Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrane Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
請求の範囲
１ ６−カルボキシ−３・４−ジハイドロ−2H
−ピランの製造方法において、１・４−ジハロゲ
ノブタンと一酸化炭素とを、液体溶剤媒質中にお
いて触媒量のコバルトカルボニル化合物およびア
ルカリ無機塩基の存在下、高められた温度および
圧力で反応させることを特徴とする前記の製造方
法。Claim 1 6-carboxy-3,4-dihydro-2H
- A process for the production of pyran, characterized in that 1,4-dihalogenobutane and carbon monoxide are reacted at elevated temperature and pressure in the presence of a catalytic amount of a cobalt carbonyl compound and an alkali inorganic base in a liquid solvent medium. The above manufacturing method.
２ 前記の１・４−ジハロゲノブタンのハロゲン
が、臭素、塩素または沃素である特許請求の範囲
第１項に記載の方法。2. The method according to claim 1, wherein the halogen of the 1,4-dihalogenobutane is bromine, chlorine or iodine.
３ 前記の一酸化炭素圧力が、300〜3000psigで
ある特許請求の範囲第１項に記載の方法。3. The method of claim 1, wherein the carbon monoxide pressure is between 300 and 3000 psig.
４ 前記の反応を、30℃〜150℃の温度で行う特
許請求の範囲第１項に記載の方法。4. The method according to claim 1, wherein the reaction is carried out at a temperature of 30°C to 150°C.
５ 前記のコバルトカルボニル化合物が、ジコバ
ルト−オクタカルボニルである特許請求の範囲第
１項に記載の方法。5. The method according to claim 1, wherein the cobalt carbonyl compound is dicobalt-octacarbonyl.
６ 前記の液体溶剤媒質が、水およびアルコール
の混合物である特許請求の範囲第１項に記載の方
法。6. The method of claim 1, wherein said liquid solvent medium is a mixture of water and alcohol.
７ 前記のアルコールが、６個までの炭素原子を
含有する飽和、線状または分枝、脂肪族、一価、
または多価化合物である特許請求の範囲第６項に
記載の方法。7. The alcohol is saturated, linear or branched, aliphatic, monovalent, containing up to 6 carbon atoms,
or the method according to claim 6, which is a polyvalent compound.
８ 前記のアルコールが、ｔ−ブタノールである
特許請求の範囲第７項に記載の方法。8. The method according to claim 7, wherein the alcohol is t-butanol.
９ 前記のアルコールが、イソプロパノールであ
る特許請求の範囲第７項に記載の方法。9. The method according to claim 7, wherein the alcohol is isopropanol.
明細書
本発明は、６−カルボキシ−３・４−ジハイド
ロ−2H−ピランおよびそれらの新規の環置換誘
導体に関する。さらに、本発明は、それらの製造
方法に関する。Description The present invention relates to 6-carboxy-3,4-dihydro-2H-pyrans and novel ring-substituted derivatives thereof. Furthermore, the invention relates to a method for their production.
かような酸の実用的価値は、これらが医薬品、
特殊薬品の合成およびポリマー製造用として使用
できることである。 The practical value of such acids is that they are used as pharmaceuticals,
It can be used in the synthesis of special chemicals and in the production of polymers.
６−カルボキシ−３・４−ジハイドロ−2H−
ピランおよび６−カルボキシ−３・４−ジハイド
ロ−2H−ピランの誘導体の製造は多数の研究の
主題となつている。 6-carboxy-3,4-dihydro-2H-
The preparation of pyran and derivatives of 6-carboxy-3,4-dihydro-2H-pyran has been the subject of numerous studies.
例えば、２・３−ジクロロテトラハイドロピラ
ンを溶剤の不存在下でCu2（CN）2で処理して２−
シアノ−３−クロロテトラハイドロピランにし、
続いてこれをトリエチルアミンで処理することに
よつて６−シアノ−2H−ジハイドロピランに転
化できることが、リオベ（Riobe）等によつてシ
ー．アール．（C.R.）Acad.Sc.パリーシリースＣ
272 1045〜1048頁、1971年に報告されてい
る。６−シアノ−2H−ジハイドロピラン生成物
は、次に塩基による加水分解によつて６−カルボ
キシ−３・４−ジハイドロ−2H−ピランに転化
される。また、ラボー（Labouc）らは、シンセ
シス（Synthesis）610〜613頁、1979年に、６−
リシオ−３・４−ジハイドロ−2H−ピランを二
酸化炭素で処理して少量の６−カルボキシ−３・
４−ジハイドロ−2H−ピランが形成できること
を報告している。 For example, 2,3-dichlorotetrahydropyran can be treated with Cu 2 (CN) 2 in the absence of solvent to give 2-
into cyano-3-chlorotetrahydropyran,
Riobe et al. reported that this can be converted to 6-cyano-2H-dihydropyran by subsequent treatment with triethylamine. R. (CR)Acad.Sc.Parry Series C
272 pp. 1045-1048, reported in 1971. The 6-cyano-2H-dihydropyran product is then converted to 6-carboxy-3,4-dihydro-2H-pyran by base hydrolysis. In addition, Labouc et al., Synthesis, pp. 610-613, 1979, 6-
Lisio-3,4-dihydro-2H-pyran was treated with carbon dioxide to produce a small amount of 6-carboxy-3.
It has been reported that 4-dihydro-2H-pyran can be formed.
６−カルボキシ−３・４−ジハイドロ−2H−
ピランが、式、
［式中、R1、R2、R3、R4およびR5は、上記に定義
したのと同じであり、ＸおよびＹは同じか異な
り、液体溶剤媒質中において反応条件下のソルボ
リシスに対して不活性な離脱基（leaving
group）である］に相当する１および４位置に離
脱基を有する１・４−ジハロゲノブタンを、触媒
量のコバルトカルボニル化合物およびアルカリ金
属無機塩基もしくはアルカリ土類金属無機塩基の
存在下、300〜3000psigの圧力で一酸化炭素でカ
ルボニル化することによつて製造できることが見
出された。 6-carboxy-3,4-dihydro-2H-
Piran, formula, [wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined above, and leaving an inert leaving group
1,4-dihalogenobutane having leaving groups in the 1 and 4 positions corresponding to 1 and 4 groups) was reacted at 300 to 3000 psig in the presence of a catalytic amount of a cobalt carbonyl compound and an alkali metal or alkaline earth metal inorganic base. It has been found that it can be prepared by carbonylation with carbon monoxide at pressure.
本発明の方法で使用するのに好適な１・４−ジ
ハロゲノブタン反応体は、それらの製造方法と共
に当業界において公知である。 1,4-dihalogenobutane reactants suitable for use in the process of the invention are known in the art, as are methods for their manufacture.
この型の少数の例には、 １・４−ジブロモブタン、 が含まれる。 A few examples of this type include 1,4-dibromobutane, is included.
特に有用な反応体は、１・４−ジブロモブタン
である。 A particularly useful reactant is 1,4-dibromobutane.
反応は、反応媒質として水およびアルコールの
混合物の存在下で行なわれる。 The reaction is carried out in the presence of a mixture of water and alcohol as reaction medium.
反応に使用するアルコールは、好ましくは直
鎖、分枝もしくは環状であり、６個までの炭素原
子を有するものが好ましい。メタノール、エタノ
ール、プロパノール、イソプロパノール、ｎ−ブ
タノール、イソブタノール、ｔ−ブタノールおよ
びｔ−アミルアルコールが例に挙げられる。テト
ラハイドロフランのような環状エーテルも使用で
きる。特に好ましい溶剤アルコールは、ｔ−ブタ
ノールである。約10〜90重量％の水と約90〜10重
量％のアルコールとを含有する混合物が一般に使
用される。好ましい混合物は、30〜80重量％の水
と70〜20重量％のアルコールとを含有する。 The alcohols used in the reaction are preferably linear, branched or cyclic and preferably have up to 6 carbon atoms. Examples include methanol, ethanol, propanol, isopropanol, n -butanol, isobutanol, t-butanol and t -amyl alcohol. Cyclic ethers such as tetrahydrofuran can also be used. A particularly preferred solvent alcohol is t -butanol. Mixtures containing about 10-90% water and about 90-10% alcohol by weight are generally used. A preferred mixture contains 30-80% water and 70-20% alcohol.
反応は、コバルトカルボニル化合物を使用し
て、好適にはアルカリ金属水酸化物またはアルカ
リ土類金属水酸化物の存在下で行う。反応の間、
１・４−ジハロゲノブタン反応体は、一酸化炭素
および塩基性物質と反応して６−カルボキシ−
３・４−ジハイドロ−2H−ピランが形成され
る。 The reaction is carried out using a cobalt carbonyl compound, preferably in the presence of an alkali metal hydroxide or an alkaline earth metal hydroxide. During the reaction,
The 1,4-dihalogenobutane reactant reacts with carbon monoxide and a basic substance to form 6-carboxy-
3,4-dihydro-2H-pyran is formed.
本方法の実施に当つて使用することができる好
適な塩基性薬剤の特定の例には：LiOH、
NaOH、KOH、RbOH、Ca（CH）2、Ba（OH）2、
およびMg（OH）2が含まれる。LiOHおよびCa
（OH）2が特に好ましい。 Specific examples of suitable basic agents that can be used in practicing the method include: LiOH,
NaOH, KOH, RbOH, Ca(CH) 2 , Ba(OH) 2 ,
and Mg(OH) 2 . LiOH and Ca
(OH) 2 is particularly preferred.
使用される塩基性薬剤の量は、広い範囲内で変
化できる。アルカリ金属塩基またはアルカリ土類
金属塩基：１・４−ジハロゲノブタン反応体のモ
ル比は、一般に、好ましくは10：１〜１：１であ
る。 The amount of basic agent used can vary within wide limits. The molar ratio of alkali metal base or alkaline earth metal base:1,4-dihalogenobutane reactant is generally preferably from 10:1 to 1:1.
本明細書に記載の方法においては、カルボニル
化触媒としてコバルトカルボニル化合物を使用す
るのが好ましい。これらの触媒には、ジコバルト
−オクタカルボニルまたは、例えばそれらのカル
シウム、カリウムもしくはナトリウム塩のような
それらの塩が含まれる。ジコバルト−オクタカル
ボニルが特に好適である。これらの触媒は、固体
状態で媒質中に添加するか、またはカルボニル化
反応に使用される溶剤中の溶液の形態で添加でき
る。コバルトカルボニル化合物：１・４−ジハロ
ゲノブタン反応体のモル比率は、好ましくは0.1
〜25％である。 In the methods described herein, it is preferred to use cobalt carbonyl compounds as carbonylation catalysts. These catalysts include dicobalt-octacarbonyl or their salts, such as their calcium, potassium or sodium salts. Particularly preferred is dicobalt-octacarbonyl. These catalysts can be added in the solid state into the medium or in the form of a solution in the solvent used for the carbonylation reaction. The molar ratio of cobalt carbonyl compound:1,4-dihalogenobutane reactant is preferably 0.1
~25%.
反応溶剤中で使用される１・４−ジハロゲノブ
タンの濃度は、重要ではなく、広い範囲内で変化
できる。例えば溶剤の重量に基づいて１〜30重量
％の間でよいが、この限界の外でも不利になるこ
となく行うことができる。 The concentration of 1,4-dihalogenobutane used in the reaction solvent is not critical and can vary within a wide range. For example, it may be between 1 and 30% by weight, based on the weight of the solvent, although it is possible to work outside this limit without disadvantage.
本方法は、かく拌機を備えた好適な耐圧反応器
中窒素下で、水およびアルコール混合物中に懸濁
された１・４−ジハロゲノブタン反応体、コバル
トカルボニル触媒およびアルカリ金属塩基、また
はアルカリ土類金属塩基から成る混合物と、反応
を液相と気相との間にもたらすのに好適な方法に
よつて、所望の圧力および温度で導入された大過
剰の一酸化炭素（出発物質の１・４−ジハロゲノ
ブタン反応体１モル当り一酸化炭素２モルより多
い量）とを接触させることによつて有利に行うこ
とができる。 The process comprises a 1,4-dihalogenobutane reactant, a cobalt carbonyl catalyst and an alkali metal base, or an alkaline earth base, suspended in a water and alcohol mixture in a suitable pressure-resistant reactor equipped with a stirrer under nitrogen. A mixture consisting of a metal base and a large excess of carbon monoxide (1.4 - more than 2 moles of carbon monoxide per mole of dihalogenobutane reactant).
カルボニル化反応は、30℃〜150℃、好ましく
は50℃〜100℃の範囲内の温度で３〜60時間、典
型的には３〜20時間に亘つて行なわれる。 The carbonylation reaction is carried out at a temperature in the range of 30°C to 150°C, preferably 50°C to 100°C, for a period of 3 to 60 hours, typically 3 to 20 hours.
一般にこの反応は、300psig〜3000psigの範囲
である高められた一酸化炭素圧力で行なわれる。
この反応を500psig〜1000psigの範囲内の圧力で
行うのが好ましい。一酸化炭素は、窒素のような
不活性気体を含有するかまたはこれと混合されて
いてもよい。 Generally, this reaction is conducted at elevated carbon monoxide pressures ranging from 300 psig to 3000 psig.
Preferably, this reaction is carried out at a pressure within the range of 500 psig to 1000 psig. Carbon monoxide may contain or be mixed with an inert gas such as nitrogen.
反応が完結して生成物混合物を濾過すると、ア
ルカリ金属塩基性薬剤またはアルカリ土類金属塩
基性薬剤が主要固体成分として液体反応成分から
分離される。所望の６−カルボキシ−３・４−ジ
ハイドロ−2H−ピラン生成物は、蒸留、抽出、
結晶化などのような方法によつて、得られた反応
混合物から容易に分離される。 Once the reaction is complete and the product mixture is filtered, the alkali metal or alkaline earth metal basic agent is separated as the predominant solid component from the liquid reaction components. The desired 6-carboxy-3,4-dihydro-2H-pyran product can be obtained by distillation, extraction,
It is easily separated from the resulting reaction mixture by methods such as crystallization.
次の実施例で本発明を説明する。 The following examples illustrate the invention.
実施例 １
300mlのオートクレーブに9.02ｇ（52.0ミリモ
ル）の１−クロロ−４−ブロモブタンおよび70ml
のｔ−BuOHを装填した。次に、CO下で0.9ｇ
（2.76ミリモル）のCo2（CO）8を添加し、次いで
15.4ｇ（約200ミリモル）の石灰と30mlのH2Oと
の混合物を添加した。オートクレーブに850psiの
COを装填後、反応混合物を約１時間で90℃まで
加熱し、同温度を15時間保持した。約７時間後に
COの吸収は停止した。遠心分離後、固体を20ml
部の50：50t−ブタノール／水溶液で１回すす
ぎ、次いで約450ミリモルのHClを含有する150ml
のHCl溶液で酸性にした。ジエチルエーテル（２
×120ml）で水性溶液から遊離酸を抽出し、内部
標準を有するプロトンNMRデータに基づいて
1.12ｇ（収率19％）の６−カルボキシ−３・４−
ジハイドロ−2H−ピランを得た。濾液を50mlの
ジエチルエーテルで抽出し、抽出物を捨てた。残
留水性溶液を10％HClで酸性にし、ジエチルエー
テルで抽出した（３×50ml）。MgSO4上で乾燥
し、溶剤を蒸発後、６−カルボキシ−３・４−ジ
ハイドロ−2H−ピランの第２の収量を得て
（3.16ｇ、収率54％）、６−カルボキシ−３・４−
ジハイドロ−2H−ピランの合計収量4.28ｇ（収
率73％）を得た。Example 1 9.02 g (52.0 mmol) 1-chloro-4-bromobutane and 70 ml in a 300 ml autoclave
of t-BuOH was loaded. Then 0.9g under CO
(2.76 mmol) of Co 2 (CO) 8 was added and then
A mixture of 15.4 g (approximately 200 mmol) lime and 30 ml H 2 O was added. 850psi to autoclave
After charging with CO, the reaction mixture was heated to 90° C. in about 1 hour and held at the same temperature for 15 hours. After about 7 hours
CO absorption has ceased. After centrifugation, 20ml of solid
Rinse once with 50:50 t-butanol/water solution, then 150 ml containing approximately 450 mmol HCl
acidified with HCl solution. diethyl ether (2
Extract free acid from aqueous solution with
1.12g (yield 19%) of 6-carboxy-3,4-
Dihydro-2H-pyran was obtained. The filtrate was extracted with 50 ml of diethyl ether and the extract was discarded. The remaining aqueous solution was acidified with 10% HCl and extracted with diethyl ether (3 x 50ml). After drying over MgSO4 and evaporating the solvent, a second crop of 6-carboxy-3,4-dihydro-2H-pyran was obtained (3.16 g, 54% yield) and 6-carboxy-3,4 −
A total yield of 4.28 g (73% yield) of dihydro-2H-pyran was obtained.
実施例 ２
300mlのオートクレーブに8.83ｇ（40.93ミリモ
ル）の１・４−ジブロモブタンと70mlのｔ−
BuOHとを装填した。次に、CO下で0.7ｇ（2.05
ミリモル）のCo2（CO）8を添加し、次いで、
12.11ｇ（163.7ミリモル）の石灰と30mlのH2Oと
の混合物を添加した。オートクレーブに850psiの
COを装填後、反応混合物を約１時間で90℃に加
熱し、同温度を15時間保持した。約11時間後に
COの吸収は停止した。遠心分離後、固体を20ml
部の50：50t−ブタノール−水溶液で１回すす
ぎ、次いで約350ミリモルのHClを含有する150ml
のHCl溶液で酸性にした。ジエチルエーテル（２
×120ml）で水性溶液から遊離酸を抽出し、内部
標準を有するプロトンNMRデータに基づいて
0.21ｇ（収率41％）の６−カルボキシ−３・４−
ジハイドロ−2H−ピランを得た。濾液を50mlの
ジエチルエーテルで抽出し、抽出物を捨てた。残
留水性溶液を10％HClで酸性にし、ジエチルエー
テルで抽出した（３×50ml）。MgSO4上で乾燥
し、溶剤を蒸発後、６−カルボキシ−３・４−ジ
ハイドロ−2H−ピランの第２の収量（3.45ｇ、
収率67.6％）を得て、６−カルボキシ−３・４−
ジハイドロ−2H−ピランの合計収量3.66ｇまた
は71.1％を得た。Example 2 In a 300 ml autoclave, 8.83 g (40.93 mmol) of 1,4-dibromobutane and 70 ml of t-
Loaded with BuOH. Then 0.7 g (2.05
mmol) of Co 2 (CO) 8 and then
A mixture of 12.11 g (163.7 mmol) lime and 30 ml H2O was added. 850psi to autoclave
After charging with CO, the reaction mixture was heated to 90° C. for about 1 hour and held at the same temperature for 15 hours. After about 11 hours
CO absorption has ceased. After centrifugation, 20ml of solid
Rinse once with 50:50 t-butanol-water solution, then 150 ml containing about 350 mmol HCl
acidified with HCl solution. diethyl ether (2
Extract free acid from aqueous solution with
0.21 g (41% yield) of 6-carboxy-3,4-
Dihydro-2H-pyran was obtained. The filtrate was extracted with 50 ml of diethyl ether and the extract was discarded. The remaining aqueous solution was acidified with 10% HCl and extracted with diethyl ether (3 x 50ml). After drying over MgSO4 and evaporating the solvent, a second yield of 6-carboxy-3,4-dihydro-2H-pyran (3.45 g,
6-carboxy-3,4-
A total yield of 3.66 g or 71.1% of dihydro-2H-pyran was obtained.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US54439983A | 1983-10-21 | 1983-10-21 | |
| US544399 | 1983-10-21 | ||
| PCT/US1983/001799 WO1985001731A1 (en) | 1983-10-21 | 1983-11-15 | Preparation of 6-carboxy-3,4-dihydro-2h-pyran |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60501757A JPS60501757A (en) | 1985-10-17 |
| JPS6220188B2 true JPS6220188B2 (en) | 1987-05-06 |
Family
ID=24172012
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP84500166A Granted JPS60501757A (en) | 1983-10-21 | 1983-11-15 | Production of 6-carboxy-3,4-dihydro-2H-pyran |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0159993A4 (en) |
| JP (1) | JPS60501757A (en) |
| CA (1) | CA1243327A (en) |
| WO (1) | WO1985001731A1 (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4120874A (en) * | 1977-01-05 | 1978-10-17 | Monsanto Company | Diesters of 6-cyano-2,2-tetrahydropyrandicarboxylates |
-
1983
- 1983-11-15 JP JP84500166A patent/JPS60501757A/en active Granted
- 1983-11-15 WO PCT/US1983/001799 patent/WO1985001731A1/en not_active Ceased
- 1983-11-15 EP EP19840900419 patent/EP0159993A4/en not_active Withdrawn
- 1983-12-01 CA CA000442362A patent/CA1243327A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| WO1985001731A1 (en) | 1985-04-25 |
| EP0159993A1 (en) | 1985-11-06 |
| JPS60501757A (en) | 1985-10-17 |
| CA1243327A (en) | 1988-10-18 |
| EP0159993A4 (en) | 1987-01-20 |
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