JP2535999B2 - Method for the benzylideneation of the α-position of acetonyl phosphonates - Google Patents
Method for the benzylideneation of the α-position of acetonyl phosphonatesInfo
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- JP2535999B2 JP2535999B2 JP63000583A JP58388A JP2535999B2 JP 2535999 B2 JP2535999 B2 JP 2535999B2 JP 63000583 A JP63000583 A JP 63000583A JP 58388 A JP58388 A JP 58388A JP 2535999 B2 JP2535999 B2 JP 2535999B2
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- chloroform
- general formula
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- 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
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【発明の詳細な説明】 （産業上の利用分野） 本発明はα−ベンジリデン−アセトニトリルホスホネ
ート類の製法に関する。TECHNICAL FIELD The present invention relates to a method for producing α-benzylidene-acetonitrile phosphonates.
本発明で提供されるα−ベンジリデン−アセトニルホ
スホネート誘導体は多置換ホスホネート誘導体の中間体
（F.BARBOT,E.PARAISO and Ph.MIGNIAC,Tetrahedron Le
tt.,25（39）,4369−4370（1984）を参照）、共役ジエ
ンの合成中間体（J.M.McIntosh and R.A.Sieler,Can.J.
Chem.,56,226−231（1977）を参照）あるいは医薬品の
中間体（特開昭59−161392,60−69089,60−248693,60−
258194,61−030591,61−63688,61−63689を参照）とし
て有用な化合物である。The α-benzylidene-acetonylphosphonate derivative provided by the present invention is an intermediate of a polysubstituted phosphonate derivative (F.BARBOT, E.PARAISO and Ph.MIGNIAC, Tetrahedron Le.
tt., 25 (39), 4369-4370 (1984)), a synthetic intermediate of conjugated dienes (JMMcIntosh and RASieler, Can.J.
Chem., 56 , 226-231 (1977)) or intermediates for pharmaceuticals (JP-A-59-161392, 60-69089, 60-248693, 60-
258194, 61-030591, 61-63688, 61-63689)).
（従来技術） アセトニルホスホネートと芳香族アルデヒドとの反応
はPudovikらによって初めて報告された（A.N.Pudovik,
G.E.Yastrebova and V.I.Nikitina,Zh,Obsh.Khim.,37
（２）,510−511（1967）を参照）。彼らはベンズアル
デヒドとジエチルアセトニルホスホネートの反応をピペ
リジン触媒で縮合させて、64.7％の収率でα−ベンジリ
デン−アセトニルホスホネートを得ている。（式１） しかし、芳香環に電子吸引基が置換している場合は、
Horner−Emmons反応と呼ばれる脱リン酸反応が優先し目
的とするホスホネート誘導体は得られないことが報告さ
れている（S.Patai and A.Schwartz,J.Org.Chem.,25,12
32−1234（1960）を参照）。本発明者らも（１）式と同
様な条件で反応を試みたところHorner−Emmons反応が優
先的に進行することを確認した（式２、比較例２を参
照）。(Prior Art) Reaction of Acetonyl Phosphonate with Aromatic Aldehyde
Was first reported by Pudovik et al. (A.N.Pudovik,
G.E.Yastrebova and V.I.Nikitina, Zh, Obsh.Khim.,37
(2), 510-511 (1967)). They are benz al
Pipette the reaction of diethyl acetonyl phosphonate with
Condensation with a lysine catalyst gave α-benzylidene in a yield of 64.7%.
The den-acetonyl phosphonate is obtained. (Equation 1) However, when the electron-withdrawing group is substituted on the aromatic ring,
The dephosphorylation reaction called the Horner-Emmons reaction is the priority.
It was reported that the target phosphonate derivative could not be obtained.
(S.Patai and A.Schwartz, J.Org.Chem.,twenty five, 12
32-1234 (1960)). The present inventors also have the same equation (1) as
When the reaction was tried under such conditions, the Horner-Emmons reaction was excellent.
It was confirmed that the process proceeded in advance (see Formula 2 and Comparative Example 2).
See).
Pataiらは、芳香族アルデヒドとホスホン酸α−メチ
レンとの縮合にピペリジン−酢酸を触媒として用いると
良好な結果が得られることを発見し（S.Patai and A.Sc
hwartz,J.Org.Chem.,25,1232−1234（1960）を参照）、
以後この方法が幅広く利用されて今日に至っている（式
３を参照）。 Patai et al. Found that good results were obtained using piperidine-acetic acid as a catalyst for the condensation of aromatic aldehydes with α-methylene phosphonates (S. Patai and A. Sc.
hwartz, J.Org.Chem., 25, referring to the 1232-1234 (1960)),
Since then, this method has been widely used (see Equation 3).
本方法を利用して多くのα−ベンジリデン−アセトニ
ルホスホネート誘導体が合成されているが（特開昭59−
161392,60−248693を参照）、特にNO2基などの強い電子
吸引基が置換している芳香族アルデヒドの場合は極めて
低収率である。これは、本発明者らの研究結果によれば
Horner−Emmons反応によって一般式（ａ） Ara−CH＝CHCOCH3 （ａ） （式中、Araは、電子吸引基によって置換されたフェニ
ル基を意味する。） で表わされるメチルスチリルケトン誘導体を副生するば
かりではなく、一般式（ｂ） （式中、Araは前述と同じ意味であり、Ra,Rbは同一もし
くは相異ってアルキル基を意味するか、またはRa,Rbと
一緒になってアルキレン基を意味する。） で表わされる化合物や一般式（ｃ） （式中、Araは前述と同じ意味である。） で表わされる化合物が副生することが原因である。 Many α-benzylidene-acetonylphosphonate derivatives have been synthesized using this method (JP-A-59-59).
161392, 60-248693), especially in the case of an aromatic aldehyde substituted by a strong electron-withdrawing group such as NO 2 group, the yield is extremely low. According to the results of research conducted by the present inventors,
A methyl styryl ketone derivative represented by the general formula (a) Ar a —CH═CHCOCH 3 (a) (wherein Ar a represents a phenyl group substituted by an electron-withdrawing group) by a Horner-Emmons reaction. Not only by-products, but general formula (b) (In the formula, Ar a has the same meaning as described above, R a and R b are the same or different and each represents an alkyl group, or R a and R b together represent an alkylene group. ) Or a compound represented by the general formula (c) (In the formula, Ar a has the same meaning as described above.) The cause is that the compound represented by
このように、従来方法に従って、一般式（ｄ） （式中、Ra,Rbは前述と同じ意味である。）により表わ
されるアセトニルホスホネートに、一般式（ｅ） AraCHO （ｅ） （式中、Araは上述と同じ意味である。）により表わさ
れる置換ベンズアルデヒドを反応させただけでは、得ら
れる一般式（ｆ） （式中、Ara,Ra,Rbは前述と同じ意味である。）により
表わされるα−ベンジリデン−アセトニルホスホネート
誘導体の収率は低い。Thus, according to the conventional method, the general formula (d) (In the formula, R a and R b have the same meanings as described above.) The acetonylphosphonate represented by the general formula (e) Ar a CHO (e) (wherein, Ar a has the same meaning as described above). The reaction of the substituted benzaldehyde represented by (In the formula, Ar a , R a and R b have the same meanings as described above.) The yield of the α-benzylidene-acetonylphosphonate derivative is low.
（発明が解決しようとする問題点） 一般式（ｅ）によって表わされる置換ベンズアルデヒ
ドと一般式（ｄ）によって表わされるアセトニルホスホ
ネートとの反応により、一般式（ｆ）によって表わされ
るα−ベンジリデン−アセトニルホスホネート誘導体を
合成する際の低い収率を高くしようとした。(Problems to be Solved by the Invention) The reaction of a substituted benzaldehyde represented by the general formula (e) with an acetonylphosphonate represented by the general formula (d) results in an α-benzylidene-acetate represented by the general formula (f). Attempts were made to increase the low yield in synthesizing the nylphosphonate derivative.
（問題点を解決するための手段） 本発明者は、 一般式（Ｉ） ArCHO 〔Ｉ〕 〔式中、Arは、ニトロ基、クロロメチル基、ジクロロメ
チル基、トリクロロメチル基、トリフルオロメチル基、
−CONR7R8（R7、R8は、お互いに同一又は相異なり、炭
素数１乃至５のアルキル基を意味する。）、−Ｃ（Ｏ）
R7,−OC（Ｏ）R7,−OSO3R7,−OCF3,−Ｓ（＝Ｏ）2R7,−
CNまたは−SO3R7から選ばれた１個または２個以上の置
換基によって置換されたフェニル基を意味する。〕によ
り表わされるアルデヒドと一般式〔II〕 〔式中、R1、R2は、お互いに同一若しくは相異なり、炭
素数１乃至12の飽和若しくは不飽和の脂肪族基を意味す
るか；又はR1とR2が一緒になって炭素数１乃至３のアル
キル基の１乃至４コで置換された若しくは無置換の1,2
−エチレン基、1,3−プロピレン基若しくは1,4−ブチレ
ン基を意味する。〕により表されるアセトニルホスホネ
ートを反応させる際に、塩基性化合物存在下、四塩化チ
タンを脱水剤として用いると、高収率、高選択的に、目
的とする一般式〔III〕 〔式中、Ar、R1及びR2は、上述と同じ意味である。〕に
より表わされるα−ベンジリデン−アセトニルホスホネ
ート誘導体が得られることを見出し、本発明を完成し
た。(Means for Solving Problems) The present inventor has found that ArCHO [I] [wherein Ar represents a nitro group, a chloromethyl group, a dichloromethyl group, a trichloromethyl group, or a trifluoromethyl group. ,
-CONR 7 R 8 (R 7 and R 8 are the same or different from each other and mean an alkyl group having 1 to 5 carbon atoms), -C (O)
R 7, -OC (O) R 7, -OSO 3 R 7, -OCF 3, -S (= O) 2 R 7, -
It means a phenyl group substituted by one or more substituents selected from CN or —SO 3 R 7 . ] And an aldehyde represented by the general formula [II] [Wherein R 1 and R 2 are the same or different from each other and represent a saturated or unsaturated aliphatic group having 1 to 12 carbon atoms; or, when R 1 and R 2 are combined, the number of carbon atoms is 1,2 substituted or unsubstituted with 1 to 4 alkyl groups of 1 to 3
-Ethylene group, 1,3-propylene group or 1,4-butylene group. ] In the reaction of the acetonyl phosphonate represented by the following, in the presence of a basic compound, using titanium tetrachloride as a dehydrating agent, high yield, high selectivity, the general formula [III] [In the formula, Ar, R 1 and R 2 have the same meanings as described above. ] And found that an α-benzylidene-acetonylphosphonate derivative represented by
触媒として用いられる塩基性化合物の例として、ジエ
チルアミン、ピペリジン、モルホリン、ピペラジン等を
代表例とする２級アミン類が好ましく、中でもピロリジ
ン、ピペリジン、ピペラジン、ジエチルアミン等が更に
好ましい。As an example of the basic compound used as a catalyst, secondary amines represented by diethylamine, piperidine, morpholine, piperazine and the like are preferable, and among them, pyrrolidine, piperidine, piperazine and diethylamine are more preferable.
この反応条件において、四塩化チタンが存在しない場
合は、Horner−Emmons反応（式４を参照） 〔式中、Ar、R1、R2は上述と同意味である。〕 これに反して、この反応系に、脱水剤として四塩化チ
タンを共存させておくと、このHorner−Emmons反応はほ
ぼ完全に抑制され、目的とするα−ベンジリデン−アセ
トニルホスホネート誘導体が高収率で得られる。Under these reaction conditions, if titanium tetrachloride is not present, Horner-Emmons reaction (see equation 4) [In the formula, Ar, R 1 and R 2 have the same meanings as described above. On the other hand, when titanium tetrachloride is allowed to coexist in this reaction system as a dehydrating agent, this Horner-Emmons reaction is almost completely suppressed, and the target α-benzylidene-acetonylphosphonate derivative has a high yield. You get at a rate.
本発明の反応に用いられる四塩化チタン、塩基、一般
式〔Ｉ〕により表されるアルデヒド、一般式〔II〕によ
り表される化合物のモル比は、四塩化チタン：塩基：
〔Ｉ〕：〔II〕＝（0.8〜2.0）：（0.8〜4.0）：（0.4
〜2.0）：（0.4〜2.0）、好ましくは四塩化チタン：塩
基：〔Ｉ〕：〔II〕＝（0.95〜1.05）：（1.90〜2.1
0）：（0.95〜1.05）：（0.95〜1.05）である。The molar ratio of titanium tetrachloride, a base, an aldehyde represented by the general formula [I], and a compound represented by the general formula [II] used in the reaction of the present invention is as follows: titanium tetrachloride: base:
[I]: [II] = (0.8 to 2.0): (0.8 to 4.0): (0.4
To 2.0): (0.4 to 2.0), preferably titanium tetrachloride: base: [I]: [II] = (0.95 to 1.05): (1.90 to 2.1)
0): (0.95 to 1.05): (0.95 to 1.05).
反応温度は、氷冷下から使用した溶媒の還流温度の間
であり、好ましくは０〜50℃の範囲である。反応溶媒に
はTHFなどのようなエーテル系溶媒、DMF,DMA（ジメチル
アセタミド）Ｎ−メチルピロリドンなどのアミド系溶
媒、ジクロロメタン、クロロホルムなどのハロゲノアル
カン系溶媒、DMSOなどのスルホキシド系溶媒、アセトニ
トリルなどのニトリル系溶媒、トルエン、ベンゼンなど
の芳香族炭化水素系溶媒、酢酸エチルなどのエステル系
溶媒などが利用できる。The reaction temperature ranges from under ice cooling to the reflux temperature of the solvent used, preferably in the range of 0 to 50 ° C. The reaction solvent is an ether solvent such as THF, an amide solvent such as DMF and DMA (dimethylacetamide) N-methylpyrrolidone, a halogenoalkane solvent such as dichloromethane and chloroform, a sulfoxide solvent such as DMSO, and acetonitrile. A nitrile solvent such as, an aromatic hydrocarbon solvent such as toluene and benzene, and an ester solvent such as ethyl acetate can be used.
以下に、本発明を実施例により更に具体的に説明す
る。なお、本発明はこれらの実施例によって限定される
ものではない。Hereinafter, the present invention will be described more specifically by way of examples. The present invention is not limited to these examples.
実施例１ クロロホルム100mlに四塩化チタン19gを溶解し、氷冷
した。これに、ピペリジン17gを溶解したクロロホルム
溶液50mlを20分かけて滴下した。氷冷下、アセトニルホ
スホン酸2,2−ジメチルプロピレンエステル20.6g、ｍ−
ニトロベンズアルデヒド15.1gを溶解したクロロホルム
溶液50mlを加え、約20℃で10時間攪拌した。10％塩酸10
0mlを加えて充分しんとうし、クロロホルム層を分液し
た。氷層をクロロホルム50mlで抽出し、有機層を合わせ
て無水硫酸ナトリウムで脱水した。クロロホルムを減圧
下留去し、残渣にトルエン200mlを加えて、５℃で10時
間放置すると目的とするα−（ｍ−ニトロベンジリデ
ン）−アセトニルホスホン酸2,2−ジメチルプロピレン
エステルの結晶が析出した。収量22.5g、融点142〜143
℃。本取得物は、Ｅ体とＺ体の混合物である。Example 1 19 g of titanium tetrachloride was dissolved in 100 ml of chloroform and cooled with ice. To this, 50 ml of a chloroform solution in which 17 g of piperidine was dissolved was added dropwise over 20 minutes. Under ice cooling, acetonylphosphonic acid 2,2-dimethylpropylene ester 20.6 g, m-
50 ml of a chloroform solution in which 15.1 g of nitrobenzaldehyde was dissolved was added, and the mixture was stirred at about 20 ° C for 10 hours. 10% hydrochloric acid 10
0 ml was added and the mixture was mashed well and the chloroform layer was separated. The ice layer was extracted with 50 ml of chloroform, and the organic layers were combined and dried over anhydrous sodium sulfate. Chloroform was distilled off under reduced pressure, 200 ml of toluene was added to the residue, and the mixture was allowed to stand at 5 ° C. for 10 hours to precipitate crystals of the target α- (m-nitrobenzylidene) -acetonylphosphonic acid 2,2-dimethylpropylene ester. did. Yield 22.5g, melting point 142-143
° C. The acquired product is a mixture of E form and Z form.
実施例２ クロロホルム5mlに四塩化チタン1.14gを溶解し氷冷し
た。これに、ピペリジン1.02gを溶解したクロロホルム
溶液5mlを３分かけて滴下した。室温下アセトニルホス
ホン酸2,2−ジメチルプロピレンエステル1.03g、ｐ−ニ
トロベンズアルデヒド0.76gを溶解したクロロホルム溶
液10mlを20分かけて滴下し約20℃で４時間攪拌した。10
％塩酸7mlに加えて充分しんとうしクロロホルム層を分
液した。水層をクロロホルム10mlで抽出し、有機層を合
わせて無水流酸ナトリウムで脱水した。クロロホルムを
減圧下留去し残渣をシリカゲルクロマトグラフィー（溶
離液、酢酸エチル;Rf値0.6）に処し目的とする2,2−ジ
メチルプロピレンα−（ｐ−ニトロベンジリデン）−ア
セトニルホスホネート1.35g（収率73.7％）を得た。本
取得物はＥ体とＺ体の混合物である。Example 2 1.14 g of titanium tetrachloride was dissolved in 5 ml of chloroform and cooled with ice. To this, 5 ml of a chloroform solution in which 1.02 g of piperidine was dissolved was added dropwise over 3 minutes. At room temperature, 10 ml of a chloroform solution in which 1.03 g of acetonylphosphonic acid 2,2-dimethylpropylene ester and 0.76 g of p-nitrobenzaldehyde were dissolved was added dropwise over 20 minutes, and the mixture was stirred at about 20 ° C. for 4 hours. Ten
% Hydrochloric acid (7 ml) was added and the mixture was sufficiently mashed and the chloroform layer was separated. The aqueous layer was extracted with 10 ml of chloroform, and the organic layers were combined and dehydrated with anhydrous sodium sulfate. Chloroform was distilled off under reduced pressure and the residue was subjected to silica gel chromatography (eluent, ethyl acetate; Rf value 0.6) to obtain the desired 2,2-dimethylpropylene α- (p-nitrobenzylidene) -acetonylphosphonate (1.35 g, yield). Rate 73.7%). The obtained product is a mixture of E form and Z form.
実施例３ クロロホルム5mlに四塩化チタン1.14gを溶解し氷冷し
た。これに、ピペリジン1.02gを溶解したクロロホルム
溶液5mlを３分かけて滴下した。室温下アセトニルホス
ホン酸2,2−ジメチルプロピレンエステル1.03g、ｏ−ニ
トロベンズアルデヒド0.76gを溶解したクロロホルム溶
液10mlを10分かけて滴下し約20℃で３時間攪拌した。10
％塩酸7mlを加えて充分しんとうしクロロホルム層を分
液した。水層をクロロホルム10mlで抽出し、有機層を合
わせて無水硫酸ナトリウムで脱水した。クロロホルムを
減圧下留去し残渣をシリカゲルクロマトグラフィー（溶
離液：酢酸エチル;Rf値0.6）に処し目的とする2,2−ジ
メチルプロピレンα−（ｏ−ニトロベンジリデン）−ア
セトニルホスホネート0.83g（収率43％）を得た。本取
得物はＥ体とＺ体の混合物である。Example 3 1.14 g of titanium tetrachloride was dissolved in 5 ml of chloroform and cooled with ice. To this, 5 ml of a chloroform solution in which 1.02 g of piperidine was dissolved was added dropwise over 3 minutes. At room temperature, 10 ml of a chloroform solution containing 1.03 g of 2,2-dimethylpropylene ester of acetonylphosphonic acid and 0.76 g of o-nitrobenzaldehyde was added dropwise over 10 minutes, and the mixture was stirred at about 20 ° C. for 3 hours. Ten
% Hydrochloric acid (7 ml) was added, and the mixture was sufficiently mashed and the chloroform layer was separated. The aqueous layer was extracted with 10 ml of chloroform, and the organic layers were combined and dried over anhydrous sodium sulfate. Chloroform was distilled off under reduced pressure, and the residue was subjected to silica gel chromatography (eluent: ethyl acetate; Rf value 0.6) to obtain the desired 2,2-dimethylpropylene α- (o-nitrobenzylidene) -acetonylphosphonate 0.83 g (yield: Rate 43%). The obtained product is a mixture of E form and Z form.
参考例１ クロロホルム5mlに四塩化チタン1.14gを溶解し氷冷し
た。これに、ピペリジン1.02gを溶解したクロロホルム
溶液5mlを３分かけて滴下した。室温下アセトニルホス
ホン酸2,2−ジメチルプロピレンエステル1.03g、ｐ−ク
ロロベンズアルデヒド0.70gを溶解したクロロホルム溶
液10mlを10分かけて滴下し約20℃で３時間攪拌した。10
％塩酸7mlを加えて充分しんとうしクロロホルム層を分
液した。水層をクロロホルム10mlで抽出し、有機層を合
わせて無水硫酸ナトリウムで脱水した。クロロホルムを
減圧下留去し残渣をシリカゲルクロマトグラフィー（溶
離液：酢酸エチル;Rf値0.6）に処し目的とする2,2−ジ
メチルプロピレンα−（ｐ−クロロベンジリデン）−ア
セトニトリルホスホネート0.75g（収率43.2％）を得
た。本取得物はＥ体とＺ体の混合物である。Reference Example 1 1.14 g of titanium tetrachloride was dissolved in 5 ml of chloroform and ice-cooled. To this, 5 ml of a chloroform solution in which 1.02 g of piperidine was dissolved was added dropwise over 3 minutes. At room temperature, 10 ml of a chloroform solution containing 1.03 g of acetonylphosphonic acid 2,2-dimethylpropylene ester and 0.70 g of p-chlorobenzaldehyde was added dropwise over 10 minutes, and the mixture was stirred at about 20 ° C. for 3 hours. Ten
% Hydrochloric acid (7 ml) was added, and the mixture was sufficiently mashed and the chloroform layer was separated. The aqueous layer was extracted with 10 ml of chloroform, and the organic layers were combined and dried over anhydrous sodium sulfate. Chloroform was distilled off under reduced pressure and the residue was subjected to silica gel chromatography (eluent: ethyl acetate; Rf value 0.6) to obtain the desired 2,2-dimethylpropylene α- (p-chlorobenzylidene) -acetonitrilephosphonate 0.75 g (yield 43.2%). The obtained product is a mixture of E form and Z form.
参考例２ クロロホルム5mlに四塩化チタン1.14gを溶解し氷冷し
た。これに、ピペリジン1.02gを溶解したクロロホルム
溶液5mlを３分かけて滴下した。室温下アセトニルホス
ホン酸2,2−ジメチルプロピレンエステル1.03g、ｐ−メ
トキシベンズアルデヒド0.68gを溶解したクロロホルム
溶液10mlを加え約20℃で１時間約40℃で３時間攪拌しさ
らに２時間還流した。10％塩酸7mlを加えて充分振とう
しクロロホルム層を分液した。水層をクロロホルム10ml
で抽出し有機層を合わせて無水硫酸ナトリウムで脱水し
た。クロロホルムを減圧下留去し残渣をシリカゲルクロ
マトグラフィー（溶離液：酢酸エチル,Rf値0.5）に処し
目的とする2,2−ジメチルプロピレンα−（ｐ−メトキ
シベンジリデン）−アセトニルホスホネート0.48g（収
率28.4％）を得た。本取得物はＥ体とＺ体の混合物であ
る。Reference Example 2 1.14 g of titanium tetrachloride was dissolved in 5 ml of chloroform and ice-cooled. To this, 5 ml of a chloroform solution in which 1.02 g of piperidine was dissolved was added dropwise over 3 minutes. At room temperature, 10 ml of a chloroform solution containing 1.03 g of acetonylphosphonic acid 2,2-dimethylpropylene ester and 0.68 g of p-methoxybenzaldehyde was added, and the mixture was stirred at about 20 ° C. for 1 hour and at 40 ° C. for 3 hours, and further refluxed for 2 hours. 7 ml of 10% hydrochloric acid was added, and the mixture was shaken well and the chloroform layer was separated. Aqueous layer is chloroform 10 ml
The organic layers were combined and dried over anhydrous sodium sulfate. Chloroform was distilled off under reduced pressure, and the residue was subjected to silica gel chromatography (eluent: ethyl acetate, Rf value 0.5) to obtain the desired 2,2-dimethylpropylene α- (p-methoxybenzylidene) -acetonylphosphonate 0.48 g (yield). Rate 28.4%). The obtained product is a mixture of E form and Z form.
参考例３ クロロホルム5mlに四塩化チタン1.14gを溶解し氷冷し
た。これに、ピペリジン1.02gを溶解したクロロホルム
溶液5mlを３分かけて滴下した。室温下アセトニルホス
ホン酸2,2−ジメチルプロピレンエステル1.03g、ベンズ
アルデヒド0.53gを溶解したクロロホルム溶液10mlを10
分かけて滴下し、約20℃で２時間攪拌した。10％塩酸7m
lを加えて充分しんとうし、クロロホルム層を分液し
た。水層をクロロホルム10mlで抽出し、有機層を合わせ
て無水硫酸ナトリウムで脱水した。クロロホルムを減圧
下留去し、残渣をシリカゲルクロマトグラフィー（溶離
液：酢酸エチル,Rf値0.6）に処し目的とする2,2−ジメ
チルプロピレンα−ベンジリデン−アセトニルホスホネ
ート1.02g（69％）を得た。本取得物はＥ体とＺ体の混
合物である。Reference Example 3 1.14 g of titanium tetrachloride was dissolved in 5 ml of chloroform and ice-cooled. To this, 5 ml of a chloroform solution in which 1.02 g of piperidine was dissolved was added dropwise over 3 minutes. At room temperature, 10 ml of 10 ml of a chloroform solution containing 1.03 g of acetonylphosphonic acid 2,2-dimethylpropylene ester and 0.53 g of benzaldehyde was dissolved.
The mixture was added dropwise over minutes and stirred at about 20 ° C for 2 hours. 10% hydrochloric acid 7m
l was added and the mixture was mixed well and the chloroform layer was separated. The aqueous layer was extracted with 10 ml of chloroform, and the organic layers were combined and dried over anhydrous sodium sulfate. Chloroform was evaporated under reduced pressure, and the residue was subjected to silica gel chromatography (eluent: ethyl acetate, Rf value 0.6) to obtain the desired 2,2-dimethylpropylene α-benzylidene-acetonylphosphonate 1.02 g (69%). It was The obtained product is a mixture of E form and Z form.
比較例１（従来法の例；ピペリジンと酢酸の共存下） 2,2−ジメチルプロピレン アセトニルホスホネート
1.9gとｍ−ニトロベンズアルデヒド1.5gをベンゼン2ml
に溶解しピペリジン0.5ml、酢酸２滴を加えて３時間共
沸脱水させた。冷後反応液をシリカゲルクロマトグラフ
ィー（溶離液、酢酸エチル：メタノール＝9:1（v/v）;R
f値0.7）に処し、目的とする2,2−ジメチルプロピレン
α−（ｍ−ニトロベンジリデン）−アセトニルホスホネ
ート0.99g（収率31％）を得た。Comparative Example 1 (example of conventional method; in the presence of piperidine and acetic acid) 2,2-dimethylpropylene acetonylphosphonate
1.9 g and m-nitrobenzaldehyde 1.5 g, benzene 2 ml
0.5 ml of piperidine and 2 drops of acetic acid were added, and the mixture was azeotropically dehydrated for 3 hours. After cooling, the reaction mixture was subjected to silica gel chromatography (eluent, ethyl acetate: methanol = 9: 1 (v / v); R
The f value was 0.7) to obtain 0.99 g (yield 31%) of the target 2,2-dimethylpropylene α- (m-nitrobenzylidene) -acetonylphosphonate.
比較例２（ピペリジンの存在下） 2,2−ジメチルプロピレン アセトニルホスホネート
1.9gとｍ−ニトロベンズアルデヒド1.5gをベンゼン2ml
に溶解しピペリジン0.5mlを加えて1.5時間共沸脱水させ
た。冷後反応液をシリカゲルクロマトグラフィー（溶離
後、酢酸エチル：メタノール＝9:1（v/v）;Rf値0.7）に
処し、目的とする2,2−ジメチルプロピレンα−（ｍ−
ニトロベンジリデン）−アセトニルホスホネート1.15g
（収率36％）を得た。Comparative Example 2 (in the presence of piperidine) 2,2-dimethylpropylene acetonylphosphonate
1.9 g and m-nitrobenzaldehyde 1.5 g, benzene 2 ml
And 0.5 ml of piperidine were added thereto, followed by azeotropic dehydration for 1.5 hours. After cooling, the reaction solution was subjected to silica gel chromatography (after elution, ethyl acetate: methanol = 9: 1 (v / v); Rf value 0.7) to obtain the target 2,2-dimethylpropylene α- (m-
Nitrobenzylidene) -acetonylphosphonate 1.15 g
(Yield 36%) was obtained.
比較例３（ピペリジンの存在下） 2,2−ジメチルプロピレン アセトニルホスホネート1
gにｍ−ニトロベンズアルデヒド0.75gをベンゼン10mlに
溶解しピペリジン1gを加えて室温で24時間攪拌した。本
反応液を高速液体クロマトグラフィー（ODS逆相カラ
ム：溶離液、MeOH:H2O＝3:2（v/v）,UV（254nm）検出）
で分析したところ、Horner−Emmons反応の生成物である
メチル（ｍ−ニトロスチリル）ケトンのみが生成してい
ることが観測された。Comparative Example 3 (in the presence of piperidine) 2,2-dimethylpropylene acetonylphosphonate 1
0.75 g of m-nitrobenzaldehyde was dissolved in 10 ml of benzene, 1 g of piperidine was added, and the mixture was stirred at room temperature for 24 hours. High performance liquid chromatography (ODS reverse phase column: eluent, MeOH: H 2 O = 3: 2 (v / v), UV (254nm) detection)
As a result, it was observed that only the product of the Horner-Emmons reaction, methyl (m-nitrostyryl) ketone, was produced.
Claims (1)
チル基、トリクロロメチル基、トリフルオロメチル基、
−CONR7R8（R7、R8は、お互いに同一又は相異なり、炭
素数１乃至５のアルキル基を意味する。）、−OSO3R7、
−OCF3、−Ｓ（＝Ｏ）2R7、−CN又は−SO3R7から選ばれ
た１個又は２個以上の置換基によって置換されたフェニ
ル基を意味する。〕により表されるアルデヒドと一般式
〔II〕 〔式中、R1、R2は、お互いに同一若しくは相異なり、炭
素数１乃至12の飽和若しくは不飽和の脂肪族基を意味す
るか；又はR1とR2が一緒になって、炭素数１乃至３のア
ルキル基の１乃至４個によって置換された若しくは置換
されていない1,2−エチレン基、1,3−プロピレン基若し
くは1,4−ブチレン基を意味する。〕により表されるア
セトニルホスホネートを、四塩化チタン・塩基の存在下
で反応させることを特徴とする一般式〔III〕 〔式中、Ar、R1及びR2は、上述と同じ意味である。〕で
表されるα−ベンジリデン−アセトニルホスホネート類
の製法。1. A general formula (I) ArCHO [I] [wherein Ar represents a nitro group, a chloromethyl group, a dichloromethyl group, a trichloromethyl group, a trifluoromethyl group,
-CONR 7 R 8 (R 7 and R 8 are the same or different from each other and mean an alkyl group having 1 to 5 carbon atoms), -OSO 3 R 7 ,
-OCF 3, -S (= O) 2 R 7, means a phenyl group substituted by one or more substituents selected from -CN or -SO 3 R 7. ] And an aldehyde represented by the general formula [II] [Wherein R 1 and R 2 are the same or different from each other and represent a saturated or unsaturated aliphatic group having 1 to 12 carbon atoms; or R 1 and R 2 together form a carbon atom; It means a 1,2-ethylene group, a 1,3-propylene group or a 1,4-butylene group which is substituted or unsubstituted by 1 to 4 of the alkyl groups of the numbers 1 to 3. ] The acetonylphosphonate represented by the general formula [III] characterized by reacting in the presence of titanium tetrachloride / base [In the formula, Ar, R 1 and R 2 have the same meanings as described above. ] The manufacturing method of (alpha)-benzylidene acetonyl phosphonate represented by these.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63000583A JP2535999B2 (en) | 1987-01-22 | 1988-01-05 | Method for the benzylideneation of the α-position of acetonyl phosphonates |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62-12936 | 1987-01-22 | ||
| JP1293687 | 1987-01-22 | ||
| JP63000583A JP2535999B2 (en) | 1987-01-22 | 1988-01-05 | Method for the benzylideneation of the α-position of acetonyl phosphonates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6485986A JPS6485986A (en) | 1989-03-30 |
| JP2535999B2 true JP2535999B2 (en) | 1996-09-18 |
Family
ID=26333598
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63000583A Expired - Lifetime JP2535999B2 (en) | 1987-01-22 | 1988-01-05 | Method for the benzylideneation of the α-position of acetonyl phosphonates |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2535999B2 (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1572406A (en) * | 1976-12-24 | 1980-07-30 | Ciba Geigy Ag | Aliphatic phosphonic/carboxylic acid compounds |
-
1988
- 1988-01-05 JP JP63000583A patent/JP2535999B2/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| ・"Ｊ．Ｏｒｇ．Ｃｈｅｍ．"第２５巻，第１２３２〜１２３４頁、１９６０年 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6485986A (en) | 1989-03-30 |
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