JPH02142742A - Production of optically active alkynyl alcohol - Google Patents
Production of optically active alkynyl alcoholInfo
- Publication number
- JPH02142742A JPH02142742A JP29741988A JP29741988A JPH02142742A JP H02142742 A JPH02142742 A JP H02142742A JP 29741988 A JP29741988 A JP 29741988A JP 29741988 A JP29741988 A JP 29741988A JP H02142742 A JPH02142742 A JP H02142742A
- Authority
- JP
- Japan
- Prior art keywords
- group
- alkyl
- carbon atoms
- phenyl
- optically active
- 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
- -1 alkynyl alcohol Chemical compound 0.000 title claims abstract description 36
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 6
- GUFUWKKDHIABBW-UHFFFAOYSA-N pyrrolidin-1-ylmethanol Chemical class OCN1CCCC1 GUFUWKKDHIABBW-UHFFFAOYSA-N 0.000 claims abstract description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 150000001721 carbon Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims 3
- 239000003905 agrochemical Substances 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 239000012776 electronic material Substances 0.000 abstract description 3
- 239000004973 liquid crystal related substance Substances 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 2
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- OTPVFZSTXFLWNJ-UHFFFAOYSA-N 1-trimethylsilylpent-1-yn-3-ol Chemical compound CCC(O)C#C[Si](C)(C)C OTPVFZSTXFLWNJ-UHFFFAOYSA-N 0.000 abstract 1
- LJRWLSKYGWLYIM-UHFFFAOYSA-N 3-trimethylsilylprop-2-ynal Chemical compound C[Si](C)(C)C#CC=O LJRWLSKYGWLYIM-UHFFFAOYSA-N 0.000 abstract 1
- XIJAGFLYYNXCAB-KRWDZBQOSA-N [(2s)-1-methylpyrrolidin-2-yl]-diphenylmethanol Chemical compound CN1CCC[C@H]1C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 XIJAGFLYYNXCAB-KRWDZBQOSA-N 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 125000001424 substituent group Chemical class 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 229910003002 lithium salt Inorganic materials 0.000 description 3
- 159000000002 lithium salts Chemical class 0.000 description 3
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000004079 stearyl 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])[H] 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001302 tertiary amino group Chemical group 0.000 description 2
- JJYKJUXBWFATTE-VIFPVBQESA-N (2s)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoic acid Chemical compound CO[C@@](C(O)=O)(C(F)(F)F)C1=CC=CC=C1 JJYKJUXBWFATTE-VIFPVBQESA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 241001000171 Chira Species 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 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 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000003136 n-heptyl 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])* 0.000 description 1
- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000006608 n-octyloxy group Chemical group 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005447 octyloxy 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])O* 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 125000003808 silyl group Chemical class [H][Si]([H])([H])[*] 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、医薬、農薬の中間体として、あるいは液晶材
料等の電子材料の中間体として有用な光学活性アルキニ
ルアルコールの製造法に関するものである。[Detailed Description of the Invention] [Field of Industrial Application] The present invention relates to a method for producing optically active alkynyl alcohol, which is useful as an intermediate for pharmaceuticals and agricultural chemicals, or as an intermediate for electronic materials such as liquid crystal materials. .
の
光学活性アルキニルアルコール！製造法としては、これ
まで種々検討され以下の方法が検討されている。optically active alkynyl alcohol! Various manufacturing methods have been studied so far, and the following methods have been considered.
／ Ｒ，Ｓ、 ＢｒｉｎｋｍｅｙｅｒらのＪ、 Ａｍ
、 Ｃｈｅｍ、 Ｓｏｃ、 。/ R, S, Brinkmeyer et al. J, Am
, Chem, Soc.
９９ ｇ、３３９（／９’１７）をはじめとするＴｅ
ｔｒａｈｅｄｒｏｎ Ｌｅｔｔ、、 ２ ／、 ／ ７
３！ｒ （／ ９ ｇＯ）；Ｊ、Ｏｒｇ、Ｃｈｅｍ、、
ｑｓ、 ｓｇ、２（／ｑｇｏ） ；Ｔｅｔｒａｈｅｄ
ｒｏｎ、 １１０． ／３’／／ （／９１４１ ）
； Ｊ。Te including 99 g, 339 (/9'17)
trahedron Lett,, 2 /, / 7
3! r (/9 gO); J, Org, Chem,,
qs, sg, 2 (/qgo); Tetrahed
ron, 110. /3'// (/9141)
; J.
Ａｍ、Ｃｈｅｍ、Ｓｏｃ、、 １０６． ｂ７
ｔｑ （／ ｑｇｔｘ） ；Ｂｕｌｌ、 Ｋｏｒ
ｅａｎ Ｃｈｅｍ、 Ｓｏｃ、、 ｇ、 Ｊ５？ （／
９ｇ７）に記載されているアセチレニノクケトンの還元
による方法。Am, Chem, Soc,, 106. b7
tq (/qgtx); Bull, Kor
ean Chem, Soc,, g, J5? (/
9g7) by reduction of acetyleninoketone.
２ Ｔ、 ＭｕｋａｉｙａｍａらのＣｈｅｍ、 Ｌｅ
ｔｔ、、 １１ ＩＩ ７（／９７９）に記載されてい
るアルデヒドのアルキニレ−ジョンによる方法。2 T, Mukaiyama et al. Chem, Le
tt, 11 II 7 (/979).
３ Ｋ、ＭｏｒｉらのＴｅｔｒａｈｅｄｒｏｎ Ｌｅ
ｔｔ、、 ’Ｉ ／ 、２り（１９７ｇ）に記載されて
いるラセミ体のアルキニルアルコールの酢酸エステルの
光学分割的加水分解による方法。3 Tetrahedron Le of K, Mori et al.
tt,, 'I/, 2 (197 g) by optical resolving hydrolysis of the acetate ester of a racemic alkynyl alcohol.
上記／及びコの反応は、不斉源となる化合物を化学量論
量以上必要とするものであり、実用的であるとは言えな
い。また、上記３の反応は、原理的に目的物の収率は、
高々原料のモル数の触媒量で行おうとするものである。The above/and (2) reactions require a stoichiometric amount or more of a compound serving as an asymmetric source, and cannot be said to be practical. In addition, in the reaction 3 above, in principle, the yield of the target product is
It is intended that the amount of catalyst be at most the number of moles of the raw material.
すなわち本発明は、ジアルキル亜鉛をアルキニルアルデ
ヒドに付加させることにより下記−般式（Ｉ）
Ｒ”−Ｃ：Ｃ−Ｃ１−１−０１−１・・・・・・・・・
・・ （Ｉ）■−
（式中、Ｒ１は炭素数／〜／ｇのアルキル基；原子、水
酸基、炭素数７〜／ｇのアルキル基もしくは炭素数７〜
／ｇのアルコキシ基で置換されていてもよいフェニル基
を示し、Ｒ２は炭素数／〜乙のアルキル基を示し、■は
不斉炭素原子を示す。）で示される光学活性アルキニル
アルコールを製造する方法において下記一般式（ｎ）（
式中、Ｒ６は炭素数７〜ｇのアルキル基を示し、Ｒ７、
Ｒ８は水素原子；又は炭素数／〜ｇのアルキル基、炭素
数／〜ｇのアルコキシ基もしくはハロゲン原子で置換さ
れていてもよいフェニル基を示し、Ｒ７とＲ８は同一で
あっても異っても良く、Ｍは水素原子又はＬｉを示す。That is, in the present invention, by adding dialkylzinc to alkynyl aldehyde, the following formula (I) R''-C:C-C1-1-01-1...
... (I)■- (wherein, R1 is an alkyl group having a carbon number of /~/g; an atom, a hydroxyl group, an alkyl group having a carbon number of 7~/g, or an alkyl group having a carbon number of 7~/g)
/g represents a phenyl group which may be substituted with an alkoxy group, R2 represents an alkyl group having a carbon number of /g, and ■ represents an asymmetric carbon atom. ) In the method for producing an optically active alkynyl alcohol represented by the following general formula (n) (
In the formula, R6 represents an alkyl group having 7 to g carbon atoms, R7,
R8 represents a hydrogen atom; or an alkyl group having a carbon number of ~g, an alkoxy group having a carbon number of ~g, or a phenyl group that may be substituted with a halogen atom, and R7 and R8 may be the same or different; may also be used, and M represents a hydrogen atom or Li.
苦は不斉炭素原子を示す。）で表わされろピロリジニル
メタノール誘導体を触媒として使用することを特徴とす
る光学活性アルキニルアルコールの製造方法を要旨とす
るものである。Aku indicates an asymmetric carbon atom. The gist of the present invention is a method for producing an optically active alkynyl alcohol, which is characterized in that a pyrrolidinyl methanol derivative represented by the following formula is used as a catalyst.
以下、本発明の詳細な説明するに、本発明の一般式〔Ｉ
〕におけるＲ１としてはメチル基、エチル基、ｎ−ブチ
ル基、１ｓｏ−ブチル基、ｔ−ブチル基、ｎ−ヘキシル
基、ｎ−オクチル基、１１−デシル基、ｎ−ドデシル基
、ｎ−ペンタデシル基、ステアリル基等の直鎖又は分岐
鎖状の炭素数／〜／ｇのアルキル基；トリメチルシリル
、トリエチルシリル、トリイソプロピルシリル、トリー
ローブチルシリル、ジメチル−ｔ−ブチ置換シリル基；
置換基（置換基としては例えばエチル基、ｎ−ブチル基
、１ｓｏ−ブチル基、を−ブチル基、ｎ−ペンチル基、
ｎ−ヘプチル基、ｎ−オクチル基、ｎ−デシル基、ｎ−
ドデシル基、ｎ−ペンタデシル基、ステアリル基等の直
鎖状又は分岐鎖状の炭素数／〜／ｇのアルキル基、メト
キシ基、エトキシ基、ｎ−ブチルオキシ基、１ｓｏ−ブ
チルオキシ基、ｔ−ブチルオキシ基、ｎ−へキシルオキ
シ基、ｎ−オクチルオキシ基、ｎ−テシルオキシ基、ｎ
−ドデシルオキシ基、ｎ−）リゾシルオキシ基、ｎ−ペ
ンタデシルオキシ基、ｎ−ステアリルオキシ基等の炭素
数／〜／ｇのアルコキシ基、塩素原子、臭素原子等のハ
ロゲン原子又は水酸基が挙げられる。）を有していても
よいフェニル基が挙ケラれる。Hereinafter, to explain the present invention in detail, the general formula [I
] R1 is a methyl group, ethyl group, n-butyl group, 1so-butyl group, t-butyl group, n-hexyl group, n-octyl group, 11-decyl group, n-dodecyl group, n-pentadecyl group , straight chain or branched alkyl group having carbon number /~/g such as stearyl group; trimethylsilyl, triethylsilyl, triisopropylsilyl, trilobylsilyl, dimethyl-t-buty-substituted silyl group;
Substituents (for example, ethyl group, n-butyl group, 1so-butyl group, -butyl group, n-pentyl group,
n-heptyl group, n-octyl group, n-decyl group, n-
Straight-chain or branched alkyl groups with carbon number/~/g such as dodecyl group, n-pentadecyl group, stearyl group, methoxy group, ethoxy group, n-butyloxy group, 1so-butyloxy group, t-butyloxy group , n-hexyloxy group, n-octyloxy group, n-tesyloxy group, n
-dodecyloxy group, n-)lysosyloxy group, n-pentadecyloxy group, n-stearyloxy group, etc., alkoxy groups having a carbon number of /~/g, halogen atoms such as chlorine atom, bromine atom, or hydroxyl group. ) phenyl group which may have.
Ｒ２としてはメチル基、エチル基、ｎ−プロピル基、イ
ソプロピル基、ｎ−ブチル基、ｔ−ブチル基、ｎ−ペン
チル基、ｎ−ヘキシル基等の炭素数／〜乙のアルキル基
が挙げられる。Examples of R2 include alkyl groups having a carbon number of 1 to 2, such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, t-butyl group, n-pentyl group, and n-hexyl group.
本発明で触媒として用いる一般式［ＩＤで示されるピロ
リジニルメタノール誘導体はに、 ５ｏａｉらのＪ、
Ａｍ、 Ｃｈｅｍ、 Ｓｏｃ、、 ／θ９ ’７／
／／（１９ｇ７）に記載の方法により次のようにして合
成することが出来る。The pyrrolidinyl methanol derivative represented by the general formula [ID] used as a catalyst in the present invention is J of 5oai et al.
Am, Chem, Soc, /θ9 '7/
It can be synthesized as follows using the method described in //(19g7).
すなわち、アミン基を保護したプロリンエステルに、フ
ェニルグリニア−及び置換フェニルグリニア−を反応さ
せたのちに、還元することにより、第三アミノアルコー
ルを得ることができる。又得られた第三アミノアルコー
ルとブチルリチウムのようなアルキルリチウムと反応さ
せることによりリチウム塩を得ることができる。That is, a tertiary amino alcohol can be obtained by reacting a proline ester with a protected amine group with phenyl Grinia and substituted phenyl Grinia, and then reducing the reaction mixture. A lithium salt can also be obtained by reacting the obtained tertiary amino alcohol with an alkyllithium such as butyllithium.
一般式〔■〕における置換基Ｒ６としては、メチル基、
エチル基、ｎ−ブチル基、ｎ−ヘキシル基、ｎ−オクチ
ル基、ネオペンチル基等の炭素数／〜ｇのアルキル基が
誉げられ、Ｒ７、Ｒ８は水素原子を示すか、置換基を有
していてもよいフェニル基を示す。フェニル基の置換基
としては、メチル基、エチル基、ｎ−ブチル基、ｔ−ブ
チル基、ｎ−オクチル基等の炭素数／〜ｇのアルキル基
、メトキシ基、エトキシ基、ｎ−ブチルオキシ基、ｎ−
オクチルオキシ基等の炭素数／〜ｇのアルコキシ基、塩
素原子、臭素原子等のハロゲン原子が誉げられる。As the substituent R6 in the general formula [■], methyl group,
Alkyl groups with a carbon number of ~g/g such as ethyl group, n-butyl group, n-hexyl group, n-octyl group, and neopentyl group are praised, and R7 and R8 represent a hydrogen atom or have a substituent. Indicates an optional phenyl group. Examples of substituents for the phenyl group include alkyl groups having a carbon number of ~g/g such as methyl group, ethyl group, n-butyl group, t-butyl group, n-octyl group, methoxy group, ethoxy group, n-butyloxy group, n-
Alkoxy groups having a carbon number of ~g/g such as an octyloxy group, halogen atoms such as a chlorine atom, a bromine atom, etc. are preferred.
一般式（ＩＩ）の具体例としては、（Ｓ） −（＋）ジ
フェニル（ｌ−メチルピロリジンーコーイル）メタノー
ル及びそのリチウム塩、（／Ｒ，，２’Ｓ）−（−）−
フェニル（／−メチルピロリシンーーーイル）メタノー
ル及びそのリチウム塩等が挙げられる。Specific examples of general formula (II) include (S)-(+)diphenyl(l-methylpyrrolidine-coyl)methanol and its lithium salt, (/R,,2'S)-(-)-
Examples include phenyl(/-methylpyrrolicin-yl)methanol and its lithium salt.
ジアルキル亜鉛としては炭素数７〜乙の直鎖状又は分岐
鎖状のアルキル基を有するジアルキル亜鉛が用いられ、
ジアルキル亜鉛を付加して一般式〔ＩＤを与えるアルキ
ニルアルデヒドとしては、下記一般式（１１０
％式％
を示す。）が挙げられる。As the dialkyl zinc, dialkyl zinc having a linear or branched alkyl group having 7 to 7 carbon atoms is used,
Examples of the alkynyl aldehyde that gives the general formula [ID by adding dialkylzinc] are the following general formulas (representing 110% formula %).
本発明の製造方法は具体的には以下の様にして実施する
ことが出来る。Specifically, the manufacturing method of the present invention can be carried out as follows.
まず、一般式〔叩のアルキニルアルデヒド及び触媒とし
て用いる、一般式〔■〕のピロリジニルメタノール誘導
体をヘキサン、シクロヘキサン、ベンゼン、トルエン、
テトラヒドロフラン、エーテルまたはこれらの混合溶媒
などの溶媒にイレ、−７ｇ℃ないし室温でジアルキル亜
鉛溶液を滴下し、Ｏ，Ｓないし２１Ｉ時間かくはんする
ことにより、得ることができる。First, a pyrrolidinyl methanol derivative of the general formula [■] used as an alkynyl aldehyde and a catalyst is added to hexane, cyclohexane, benzene, toluene,
It can be obtained by adding a dialkylzinc solution dropwise to a solvent such as tetrahydrofuran, ether or a mixed solvent thereof at -7gC to room temperature, and stirring for 0, S to 21 hours.
この際、触媒量はアルデヒドに対し、ｏ、７〜５０モル
％加え、ジアルキル亜鉛は、アルデヒドに対しｌ〜３．
５当量使用する。At this time, the catalyst amount is 7 to 50 mol % based on the aldehyde, and the dialkyl zinc is 1 to 3 mol % based on the aldehyde.
Use 5 equivalents.
本発明の製造法により、医薬、農薬の中間体あるいは液
晶材料等の電子材料等の中間体として有用な光学活性ア
ルキニルアルコールを光学純度よく製造することが出来
る。By the production method of the present invention, it is possible to produce optically active alkynyl alcohol with high optical purity, which is useful as an intermediate for medicines, agricultural chemicals, or electronic materials such as liquid crystal materials.
本発明を実施例により更に詳細に説明するが、本発明は
その要旨を越えない限り以下の実施例に限定されるもの
では無い。The present invention will be explained in more detail with reference to examples, but the present invention is not limited to the following examples unless the gist of the invention is exceeded.
実施例１
３−トリメチルシリルーコープロビナール（０，／ ２
Ａ ９、／、００ ｍｍｏｌ ）と（Ｓ） −（＋）
−ジフェニル（／−メチルピロリシンーコーイル）メ
タノ−ｈ（０，０／３ｊｊ、 Ｏ，０ｊｎｎｎｏｌ ）
をトルエン２ ｍｌに加え室温で３０分間攪拌した後−
２０℃に冷却し、／Ｍ濃度のジエチル亜鉛の１〇−
トルエン溶液２ ｍｌを加え、−２０℃で７．２時間橿
拌する。Example 1 3-trimethylsilyl-coprobinal (0,/2
A 9,/, 00 mmol) and (S) −(+)
-diphenyl(/-methylpyrrolisine-choyl)methano-h(0,0/3jj, O,0jnnnol)
was added to 2 ml of toluene and stirred at room temperature for 30 minutes.
Cool to 20°C, add 2 ml of a 10-toluene solution of diethylzinc at a concentration of /M, and stir at -20°C for 7.2 hours.
７Ｍ濃度の塩酸溶液３ ｍｌを加えた後ジクロルメタン
／θｍｌで３回抽出し、ジクロルメタン抽出液を合わせ
、硫酸ナトリウムで乾燥後、濃縮する。プレパラティプ
ＴＬＣ（担体；シリカゲル、展開溶媒；クロロホルム／
ヘキサフタ／／、Ｖ／Ｖ ）で精製し、下記の式
％式％
で表わされる／−トリメチルシリル−１−ペンチン−３
−オール０．７０ダｇ（収率６７％）を得た。After adding 3 ml of a 7M hydrochloric acid solution, the mixture is extracted three times with dichloromethane/θ ml, and the dichloromethane extracts are combined, dried over sodium sulfate, and concentrated. Preparatip TLC (carrier: silica gel, developing solvent: chloroform/
/-trimethylsilyl-1-pentyne-3 expressed by the following formula % formula %
-ol 0.70 dag (yield 67%) was obtained.
物性値
ｎ、 ｍ、 ｒ、 （ＣＤＣ１３） （δ値、ｐｐｍ）
： Ｉｌ、’Ｉ！；−乞／ ３（／Ｈ）、 ２．３３
（／Ｈ）、 ／、ｔ ７− ／、ｌＩｋ （，２Ｈ）
。Physical property values n, m, r, (CDC13) (δ value, ppm)
: Il, 'I! ;-beggar/3(/H), 2.33
(/H), /, t 7- /, lIk (,2H)
.
／、／ ｇ−０，７ｇ（３１−１）、 ０．／ ｌ、（
９Ｈ）ＩＲ（ｃｍ−”） ； ３３！；０．２９６０．
２／ｇＯ，／２６０光学純度は得られた光学活性アルコ
ールを（−）−α−メトキシ−α−（トリフルオロメチ
ル）フェニル酢酸のエステルにして、高速液体クロマト
グラフィーにてキラルカラム（ダイセル社製Ｃｈｉｒａ
ｌｃｅｌ ＯＤ、 ２３０ ｍｍ ：検出波長、２５ダ
ｎｍ；溶離液、ｏ、Ｏ／％コープロノきノルのヘキサン
溶液）を用いて測定した所７ｇ％ｅｅであった。/, / g-0,7g (31-1), 0. / l, (
9H) IR (cm-”); 33!; 0.2960.
2/gO, /260 optical purity was determined by converting the obtained optically active alcohol into an ester of (-)-α-methoxy-α-(trifluoromethyl)phenylacetic acid and using a chiral column (Chira manufactured by Daicel) using high performance liquid chromatography.
lcel OD, 230 mm; detection wavelength, 25 dnm; eluent, O, O/% copronol in hexane solution). It was 7 g%ee.
実施例コ
実施例／と同様の方法で第１表に示す原料を用い光学活
性アルキニルアルコールを合成した例を第１表に示した
。Table 1 shows an example in which an optically active alkynyl alcohol was synthesized using the raw materials shown in Table 1 in the same manner as in Example.
くべ 圏師 ヨヒKube Kenshi Yohi
Claims (1)
せることにより下記一般式〔 I 〕 ▲数式、化学式、表等があります▼・・・・・・・・・
・・・・・・・・・〔 I 〕〔式中、Ｒ＾１は炭素数１
〜１８のアルキル基；▲数式、化学式、表等があります
▼（Ｒ＾３、Ｒ＾４、Ｒ＾５は炭素数１〜６のアルキル
基又はフェニル基を示す。）；又はハロゲン原子、水酸
基、炭素数１〜１８のアルキル基もしくは炭素数１〜１
８のアルコキシ基で置換されていてもよいフェニル基を
示し、Ｒ＾２は炭素数１〜６のアルキル基を示し、＊は
不斉炭素原子を示す。〕で示される光学活性アルキニル
アルコールを製造する方法において下記一般式〔II〕 ▲数式、化学式、表等があります▼・・・・・・・・・
・・・・・・・・・〔II〕（式中、Ｒ＾６は炭素数１〜
８のアルキル基を示し、Ｒ＾７、Ｒ＾８は水素原子；又
は炭素数１〜８のアルキル基、炭素数１〜８のアルコキ
シ基もしくはハロゲン原子で置換されていてもよいフェ
ニル基を示し、Ｒ＾７とＲ＾８は同一であっても異って
も良く、Ｍは水素原子又はＬｉを示し、＊は不斉炭素原
子を示す。）で表わされるピロリジニルメタノール誘導
体を触媒として使用することを特徴とする光学活性アル
キニルアルコールの製造方法。(1) By adding dialkylzinc to alkynyl aldehyde, the following general formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・・・・
・・・・・・・・・〔I〕〔In the formula, R^1 is the number of carbon atoms 1
~18 alkyl groups; ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (R^3, R^4, R^5 represent alkyl groups or phenyl groups having 1 to 6 carbon atoms); or halogen atoms, hydroxyl groups , an alkyl group having 1 to 18 carbon atoms or 1 to 1 carbon atoms
represents a phenyl group optionally substituted with 8 alkoxy groups, R^2 represents an alkyl group having 1 to 6 carbon atoms, and * represents an asymmetric carbon atom. ] In the method for producing optically active alkynyl alcohol, the following general formula [II] ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・・・・
・・・・・・・・・[II] (In the formula, R^6 is a carbon number of 1 to
8 represents an alkyl group, and R^7 and R^8 represent a hydrogen atom; or a phenyl group optionally substituted with an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, or a halogen atom; , R^7 and R^8 may be the same or different, M represents a hydrogen atom or Li, and * represents an asymmetric carbon atom. 1. A method for producing optically active alkynyl alcohol, which comprises using a pyrrolidinyl methanol derivative represented by ) as a catalyst.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29741988A JPH02142742A (en) | 1988-11-25 | 1988-11-25 | Production of optically active alkynyl alcohol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29741988A JPH02142742A (en) | 1988-11-25 | 1988-11-25 | Production of optically active alkynyl alcohol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02142742A true JPH02142742A (en) | 1990-05-31 |
Family
ID=17846265
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP29741988A Pending JPH02142742A (en) | 1988-11-25 | 1988-11-25 | Production of optically active alkynyl alcohol |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02142742A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023036995A1 (en) * | 2021-09-13 | 2023-03-16 | Centre National De La Recherche Scientifique | Alkynylcarbinols with high cytotoxicity |
-
1988
- 1988-11-25 JP JP29741988A patent/JPH02142742A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023036995A1 (en) * | 2021-09-13 | 2023-03-16 | Centre National De La Recherche Scientifique | Alkynylcarbinols with high cytotoxicity |
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