JP3254746B2 - Terminal acetylene compound and method for producing the same - Google Patents
Terminal acetylene compound and method for producing the sameInfo
- Publication number
- JP3254746B2 JP3254746B2 JP23008492A JP23008492A JP3254746B2 JP 3254746 B2 JP3254746 B2 JP 3254746B2 JP 23008492 A JP23008492 A JP 23008492A JP 23008492 A JP23008492 A JP 23008492A JP 3254746 B2 JP3254746 B2 JP 3254746B2
- Authority
- JP
- Japan
- Prior art keywords
- terminal acetylene
- compound
- reaction
- general formula
- producing
- 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 - Fee Related
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Description
【０００１】[0001]
【産業上の利用分野】本発明は、医薬、飼料添加物など
として使用されるビタミンＡあるいはそのエステル化物
の新規な中間体およびその製造法に関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel intermediate of vitamin A or an ester thereof, which is used as a pharmaceutical or feed additive, and a method for producing the same.
【０００２】[0002]
【従来の技術】従来のビタミンＡあるいはそのエステル
化物の工業的な製造法は、例えば、(1)Helvetica Chemi
ca Acta, 30, 1911(1947) あるいは(2)Chemie Ingeniuo
r Technik, 45, 646(1973)に示されている。2. Description of the Related Art A conventional industrial production method of vitamin A or an ester thereof is described in, for example, (1) Helvetica Chemi.
ca Acta, 30, 1911 (1947) or (2) Chemie Ingeniuo
r Technik, 45, 646 (1973).
【０００３】[0003]
【発明が解決しようとする課題】上記の方法は、いずれ
も炭素数１３のβ−イオノンを原料とし、２段階の増炭
反応で炭素数２０のビタミンＡ骨格を合成している。す
なわち、(1) の方法では、β−イオノンにクロロ酢酸メ
チルを反応させ、炭素数１４のアルデヒド化合物とした
後、炭素数６のアセチレン化合物を反応させて、炭素数
２０の骨格を構築している。また、(2) の方法では、β
−イオノンとアセチレンの反応で炭素数１５のアルコー
ル化合物を得、さらに２段階を経て炭素数１５のホスホ
ニウム塩とした後、炭素数５のアルデヒドを反応させ
て、炭素数２０の骨格を合成している。In each of the above methods, a β-ionone having 13 carbon atoms is used as a raw material, and a vitamin A skeleton having 20 carbon atoms is synthesized by a two-stage enrichment reaction. That is, in the method (1), β-ionone is reacted with methyl chloroacetate to form an aldehyde compound having 14 carbon atoms, and then reacted with an acetylene compound having 6 carbon atoms to construct a skeleton having 20 carbon atoms. I have. In the method (2), β
-An alcohol compound having 15 carbon atoms is obtained by the reaction of ionone and acetylene, and a phosphonium salt having 15 carbon atoms is further obtained through two steps, and then an aldehyde having 5 carbon atoms is reacted to synthesize a skeleton having 20 carbon atoms. I have.
【０００４】このように従来の技術においては、β−イ
オノンから２段階の増炭反応をおこなっているため、工
程数が多くなり、工業的に必ずしも充分なものとは言い
がたかった。[0004] As described above, in the prior art, since the two-stage carbonization reaction is carried out from β-ionone, the number of steps is increased, and it cannot be said that it is necessarily industrially sufficient.
【０００５】本発明の目的は、β−イオノンから１段階
の増炭反応で炭素数２０の骨格を構築し得る、すなわ
ち、炭素数７のビタミンＡの中間体およびその製造法を
提供することにある。An object of the present invention is to provide an intermediate of vitamin C having 7 carbon atoms, which is capable of constructing a skeleton having 20 carbon atoms from β-ionone in a one-step enrichment reaction, and a process for producing the same. is there.
【０００６】[0006]
【課題を解決するための手段】すなわち、本発明は、一
般式（Ｉ） （式中、Ｒは水素原子またはアセチル基を示す。）で示
される末端アセチレン化合物およびその製造法を提供す
るものである。That is, the present invention provides a compound represented by the general formula (I): (Wherein, R represents a hydrogen atom or an acetyl group) and a method for producing the same.
【０００７】一般式（Ｉ）で示される末端アセチレン化
合物のうち、Ｒがアセチル基である化合物は、３−メチ
ル−１−ヘキセン−５−イン−３−オールと無水酢酸を
酸触媒の存在下、反応させることにより得ることができ
る。Among the terminal acetylene compounds represented by the general formula (I), those in which R is an acetyl group can be prepared by reacting 3-methyl-1-hexen-5-yn-3-ol and acetic anhydride in the presence of an acid catalyst. Can be obtained by reacting.
【０００８】原料の３−メチル−１−ヘキセン−５−イ
ン−３−オールは、例えば、J. Am.Chem. Soc., 90,614
1(1968)に記載の方法に準じて容易に得ることができ
る。The starting material, 3-methyl-1-hexen-5-yn-3-ol, is described in, for example, J. Am. Chem. Soc., 90,614.
It can be easily obtained according to the method described in 1 (1968).
【０００９】無水酢酸の使用量は、原料の３−メチル−
１−ヘキセン−５−イン−３−オールに対して１当量以
上、好ましくは１．５〜１０当量の範囲である。The amount of acetic anhydride used depends on the starting material, 3-methyl-
The amount is 1 equivalent or more, preferably 1.5 to 10 equivalents, based on 1-hexen-5-yn-3-ol.
【００１０】酸触媒として具体的には、硫酸、ｐ−トル
エンスルホン酸、メタンスルホン酸等が例示される。こ
れらの酸触媒の使用量は、通常、原料の３−メチル−１
−ヘキセン−５−イン−３−オールに対して０．０１〜
１０当量、好ましくは、０．０５〜５当量の範囲であ
る。Specific examples of the acid catalyst include sulfuric acid, p-toluenesulfonic acid, methanesulfonic acid and the like. The amount of these acid catalysts to be used is usually the amount of 3-methyl-1
-0.01 to hexen-5-in-3-ol
It is in the range of 10 equivalents, preferably 0.05 to 5 equivalents.
【００１１】反応溶媒としては、無水酢酸の過剰量を用
いても差し支えないが、他の溶媒を使用する場合には反
応に影響を与えない有機溶媒、例えば、ベンゼン、トル
エン、キシレン等の芳香族炭化水素類、ジクロロメタ
ン、クロロベンゼン等のハロゲン化炭化水素類、酢酸等
の脂肪酸類等が挙げられる。これらの溶媒の使用量は、
特に限定されない。反応温度は、通常、０〜１５０℃、
好ましくは、２０〜１００℃の範囲である。As the reaction solvent, an excess amount of acetic anhydride may be used, but when another solvent is used, an organic solvent which does not affect the reaction, for example, an aromatic solvent such as benzene, toluene and xylene. Examples thereof include hydrocarbons, halogenated hydrocarbons such as dichloromethane and chlorobenzene, and fatty acids such as acetic acid. The amount of these solvents used is
There is no particular limitation. The reaction temperature is usually 0 to 150 ° C,
Preferably, it is in the range of 20 to 100 ° C.
【００１２】反応終了後、通常の後処理操作、例えば、
抽出、洗浄、濃縮等の操作により、目的とする一般式
（Ｉ）で示される末端アセチレン化合物のうち、Ｒがア
セチル基である化合物を得ることができる。このもの
は、必要に応じて、蒸留等の操作でさらに精製すること
もできる。After completion of the reaction, a usual post-treatment operation, for example,
By a procedure such as extraction, washing, and concentration, a desired compound of the terminal acetylene compound represented by the general formula (I) wherein R is an acetyl group can be obtained. This product can be further purified by an operation such as distillation, if necessary.
【００１３】一般式（Ｉ）で示される末端アセチレン化
合物のうち、Ｒが水素原子である化合物は、上記で得た
一般式（Ｉ）で示される末端アセチレン化合物のうち、
Ｒがアセチル基である化合物を加水分解することにより
容易に得ることができる。この加水分解反応は、水の存
在下、塩基の共存下に行われる。Among the terminal acetylene compounds represented by the general formula (I), the compound wherein R is a hydrogen atom is selected from the terminal acetylene compounds represented by the general formula (I) obtained above.
It can be easily obtained by hydrolyzing a compound in which R is an acetyl group. This hydrolysis reaction is performed in the presence of water and in the presence of a base.
【００１４】この反応で用いられる具体的な塩基として
は、水酸化ナトリウム、水酸化カリウム、炭酸ナトリウ
ム、炭酸カリウム等が例示される。これらの塩基の使用
量は、原料の一般式（Ｉ）で示される末端アセチレン化
合物のうち、Ｒがアセチル基である化合物に対して、１
当量以上、好ましくは１．５〜１０当量の範囲である。Specific examples of the base used in this reaction include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like. The amount of these bases to be used is 1 to the compound in which R is an acetyl group among the terminal acetylene compounds represented by the general formula (I) as a raw material.
It is not less than equivalent, preferably in the range of 1.5 to 10 equivalent.
【００１５】この反応において溶媒を使用する場合、そ
の溶媒としてはメタノール、エタノール、イソプロピル
アルコール等のアルコール類、テトラヒドロフラン、
１，４−ジオキサン等のエーテル類等があげられる。こ
れらの溶媒の使用量は、特に制限されない。When a solvent is used in this reaction, the solvent may be alcohols such as methanol, ethanol and isopropyl alcohol, tetrahydrofuran,
Ethers such as 1,4-dioxane; The amount of these solvents used is not particularly limited.
【００１６】反応温度は、通常、−３０〜１００℃の範
囲であり、好ましくは、０〜５０℃の範囲である。The reaction temperature is generally in the range of -30 to 100 ° C, preferably in the range of 0 to 50 ° C.
【００１７】反応終了後、通常の後処理操作、例えば、
抽出、洗浄、濃縮等の操作により、目的とする一般式
（Ｉ）で示される末端アセチレン化合物のうち、Ｒが水
素原子である化合物を得ることができる。このものは、
必要に応じて、蒸留等の操作でさらに精製することもで
きる。After completion of the reaction, usual post-treatment operations, for example,
By performing operations such as extraction, washing, and concentration, a target compound of which R is a hydrogen atom among the terminal acetylene compounds represented by the general formula (I) can be obtained. This one is
If necessary, it can be further purified by an operation such as distillation.
【００１８】本発明の末端アセチレン化合物は下式に示
す方法により、ビタミンＡあるいはそのエステル化物へ
誘導することができる。The terminal acetylene compound of the present invention can be derived into vitamin A or an ester thereof by the method shown below.
【００１９】 （式中、Ｒは水素原子またはアセチル基を示す。）[0019] (In the formula, R represents a hydrogen atom or an acetyl group.)
【００２０】上式に示したがごとく、本発明の末端アセ
チレン化合物とβ−イオノンとの反応で１段階でビタミ
ンＡの炭素数と同じ炭素数２０の骨格を合成することが
でき、この後、容易な反応でビタミンＡあるいはそのエ
ステル化物へ誘導することができる。As shown in the above formula, by reacting the terminal acetylene compound of the present invention with β-ionone, a skeleton having 20 carbon atoms equal to that of vitamin A can be synthesized in one step. Vitamin A or its esterified product can be derived by an easy reaction.
【００２１】[0021]
【発明の効果】本発明の末端アセチレン化合物は、従来
の方法に比べ短い工程でビタミンＡを製造することがで
きるビタミンＡの工業的製造において非常に有用な中間
体である。Industrial Applicability The terminal acetylene compound of the present invention is a very useful intermediate in industrial production of vitamin A, which can produce vitamin A in a shorter process than conventional methods.
【００２２】[0022]
【実施例】以下、実施例により本発明をさらに詳細に説
明するが、本発明はこれらにより限定されるものではな
い。EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto.
【００２３】実施例１ 撹拌装置、温度計、コンデンサーおよび滴下ロートを装
着した４つ口フラスコに３−メチル−１−ヘキセン−５
−イン−３−オール１１．０ｇ、無水酢酸２０．４ｇお
よび酢酸１００ｍｌを仕込み、その後、ｐ−トルエンス
ルホン酸一水和物１．９ｇを酢酸４０ｍｌに溶解した溶
液を室温で滴下した。滴下終了後、６０℃まで昇温し、
同温で５時間撹拌した。Example 1 3-Methyl-1-hexene-5 was placed in a four-necked flask equipped with a stirrer, a thermometer, a condenser and a dropping funnel.
11.0 g of -in-3-ol, 20.4 g of acetic anhydride and 100 ml of acetic acid were charged, and then a solution of 1.9 g of p-toluenesulfonic acid monohydrate dissolved in 40 ml of acetic acid was added dropwise at room temperature. After dropping, the temperature was raised to 60 ° C,
The mixture was stirred at the same temperature for 5 hours.
【００２４】反応終了後、反応混合物を室温まで冷却
し、これを氷冷した１０％水酸化ナトリウム水溶液９０
０ｍｌ中に注入し、エーテル２００ｍｌで抽出した。分
液後、エーテル層を水２００ｍｌで洗浄し、減圧濃縮し
た。得られた残さを減圧蒸留し、酢酸３−メチル−２−
ヘキセン−５−イル１２．０ｇ（収率７９％）を無色液
体として得た。 沸点：７１〜７３℃／１０ｍｍＨｇ 1 Ｈ−ＮＭＲ（CDCl3 ）：δ＝5.67(t,1H,J=3Hz), 4.61
(d,2H,J=3Hz), 2.94(s,2H), 2.15(s,1H), 2.06(s,3H),
1.78(s,3H) ＩＲ（neat）：2140, 1750cm-1 After the completion of the reaction, the reaction mixture was cooled to room temperature, and cooled with ice-cooled 10% aqueous sodium hydroxide solution 90%.
0 ml and extracted with 200 ml of ether. After liquid separation, the ether layer was washed with 200 ml of water and concentrated under reduced pressure. The obtained residue was distilled under reduced pressure to give 3-methyl-2-acetic acid.
Hexen-5-yl (12.0 g, yield 79%) was obtained as a colorless liquid. Boiling point: 71-73 ° C./10 mmHg 1 H-NMR (CDCl 3 ): δ = 5.67 (t, 1H, J = 3 Hz), 4.61
(d, 2H, J = 3Hz), 2.94 (s, 2H), 2.15 (s, 1H), 2.06 (s, 3H),
1.78 (s, 3H) IR (neat): 2140,1750cm -1
【００２５】実施例２ 撹拌装置、温度計、コンデンサーおよび滴下ロートを装
着した４つ口フラスコに酢酸３−メチル−２−ヘキセン
−５−イル７．６ｇをメタノール１００ｍｌに溶解した
後、０〜５℃に冷却した。同温で１０％水酸化ナトリウ
ム水溶液８０ｇを滴下した後、室温まで昇温し、同温で
４時間撹拌した。Example 2 7.6 g of 3-methyl-2-hexen-5-yl acetate was dissolved in 100 ml of methanol in a four-necked flask equipped with a stirrer, thermometer, condenser and dropping funnel. Cooled to ° C. After 80 g of a 10% aqueous sodium hydroxide solution was added dropwise at the same temperature, the temperature was raised to room temperature, and the mixture was stirred at the same temperature for 4 hours.
【００２６】反応終了後、反応混合物にエーテル２００
ｍｌを加え、抽出した。分液後、水層をエーテル１００
ｍｌで再度抽出し、先のエーテル層と合わせて、飽和食
塩水１００ｍｌで２回洗浄した。これを減圧濃縮して得
られた残さを減圧蒸留し、３−メチル−２−ヘキセン−
５−イン−１−オール４．７ｇ（収率８７％）を無色液
体として得た。 沸点：４９〜５１℃／１５ｍｍＨｇ 1 Ｈ−ＮＭＲ（CDCl3 ）：δ＝5.71(t,1H,J=3Hz), 4.19
(d,2H,J=3Hz), 2.90(s,2H), 2.14(s,1H), 1.83(s,1H),
1.75(s,3H) ＩＲ（neat）：3350, 2140cm-1 After completion of the reaction, 200 ml of ether was added to the reaction mixture.
ml was added and extracted. After liquid separation, the aqueous layer was washed with ether 100
The mixture was extracted again with 100 ml of water, combined with the above ether layer, and washed twice with 100 ml of saturated saline. This was concentrated under reduced pressure, and the residue obtained was distilled under reduced pressure to give 3-methyl-2-hexene-
4.7 g (yield 87%) of 5-yn-1-ol was obtained as a colorless liquid. Boiling point: 49-51 ° C./15 mmHg 1 H-NMR (CDCl 3 ): δ = 5.71 (t, 1H, J = 3 Hz), 4.19
(d, 2H, J = 3Hz), 2.90 (s, 2H), 2.14 (s, 1H), 1.83 (s, 1H),
1.75 (s, 3H) IR (neat): 3350, 2140 cm -1
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ // Ｃ０７Ｂ 61/00 ３００ Ｃ０７Ｂ 61/00 ３００ (58)調査した分野(Int.Cl.7，ＤＢ名) C07C 27/02 C07C 33/042 C07C 67/08 C07C 69/14 B01J 31/02 103 C07B 61/00 300 ＣＡ（ＳＴＮ) ＣＡＯＬＤ（ＳＴＮ) ＲＥＧＩＳＴＲＹ（ＳＴＮ)──────────────────────────────────────────────────続 き Continuation of the front page (51) Int.Cl. 7 identification symbol FI // C07B 61/00 300 C07B 61/00 300 (58) Field surveyed (Int. Cl. 7 , DB name) C07C 27/02 C07C 33/042 C07C 67/08 C07C 69/14 B01J 31/02 103 C07B 61/00 300 CA (STN) CAOLD (STN) REGISTRY (STN)
Claims (3)
される末端アセチレン化合物。1. The compound of the general formula (I) (In the formula, R represents a hydrogen atom or an acetyl group.)
−オールと無水酢酸とを酸触媒の存在下に反応させるこ
とを特徴とする前記一般式（Ｉ）で示される末端アセチ
レン化合物に於いて、Ｒがアセチル基である化合物の製
造法。(2) 3-methyl-1-hexene-5-yn-3
-A method for producing a compound wherein R is an acetyl group in the terminal acetylene compound represented by the general formula (I), wherein ol and acetic anhydride are reacted in the presence of an acid catalyst.
ン化合物に於いて、Ｒがアセチル基である化合物を加水
分解することを特徴とする前記一般式（Ｉ）で示される
末端アセチレン化合物に於いて、Ｒが水素原子である化
合物の製造法。3. The terminal acetylene compound represented by the general formula (I), wherein the compound wherein R is an acetyl group is hydrolyzed in the terminal acetylene compound represented by the general formula (I). In which R is a hydrogen atom.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23008492A JP3254746B2 (en) | 1992-08-28 | 1992-08-28 | Terminal acetylene compound and method for producing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23008492A JP3254746B2 (en) | 1992-08-28 | 1992-08-28 | Terminal acetylene compound and method for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0672927A JPH0672927A (en) | 1994-03-15 |
| JP3254746B2 true JP3254746B2 (en) | 2002-02-12 |
Family
ID=16902302
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP23008492A Expired - Fee Related JP3254746B2 (en) | 1992-08-28 | 1992-08-28 | Terminal acetylene compound and method for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3254746B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3077366B1 (en) * | 2013-12-06 | 2017-08-09 | GE Healthcare AS | Alternative acetylation process in the synthesis of non-ionic xray contrast agents |
-
1992
- 1992-08-28 JP JP23008492A patent/JP3254746B2/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| Ｃｈｅｍｉｃａｌ Ａｂｓｔｒａｃｔｓ，６３：６８４５ｅ（１９６５） |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0672927A (en) | 1994-03-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH05331128A (en) | @(3754/24)r)-@(3754/24)-)-4-cyano-3-hydroxylactic acid t-butyl ester and its production | |
| JP3053872B2 (en) | Process for producing (+)-(1R) -cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid | |
| JPS623141B2 (en) | ||
| JP2013227345A (en) | Synthesis of half ester | |
| JP3254746B2 (en) | Terminal acetylene compound and method for producing the same | |
| JPH0129783B2 (en) | ||
| EP0349217A2 (en) | Novel process for the preparation of bronopol | |
| JPS609490B2 (en) | Production method of cyclohexanedione-(1,3) | |
| US4395561A (en) | Synthesis of 3-hydroxyoxetane | |
| JP2001302658A (en) | Method for manufacturing of 3-isochromanones | |
| JPH05286902A (en) | Production of alpha-chloro-beta-ketoester derivative | |
| JP3396097B2 (en) | Method for producing 4-isopropylcyclohexanecarboxylic acid ester derivative | |
| US2698341A (en) | Acidolysis of methylal with carboxylic acid anhydroides | |
| JP4081619B2 (en) | Method for producing optically active 5-hydroxy-2-decenoic acid and method for producing optically active soya lactone | |
| JP3993427B2 (en) | Method for producing alicyclic hydroxycarboxylic acid | |
| EP0652213B1 (en) | Method for producing alkyl 3-phthalidylideneacetate | |
| JP2001181271A (en) | Method for producing alpha-monoglyceride ketal | |
| JP3254745B2 (en) | Diol compound and method for producing the same | |
| JPH07149692A (en) | Preparation of pimelic acid ester | |
| KR20230154213A (en) | Process for producing alkyl-4-oxotetrahydrofuran-2-carboxylate | |
| EP0281661B1 (en) | 2-alkoxycarbonyl-4-(4-pyridyl)cyclohexanones and process for preparing them | |
| JP2542843B2 (en) | Novel norbornane derivative and method for producing the same | |
| JP3371009B2 (en) | Method for producing carboxylic acid derivative | |
| JPS6364416B2 (en) | ||
| JPH0215044A (en) | Production of royal jelly acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |