JPH09241275A - Selenoalkenylphosphonic acid ester and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new selenoalkenylphosphonic acid ester useful for synthesis, etc., of fine chemicals as a Horner-Emmons type reaction reagent, etc., by reacting an acetylene compound with a selenophosphoric acid ester in the presence of a palladium complex catalyst. SOLUTION: This selenoalkynylphosphonic acid ester is represented by formula I [R<1> and R<2> are H, an alkyl, a cycloalkyl, an aryl, a heteroaryl, an aralkyl, an alkenyl, an alkoxy, an aryloxy or a silyl; R<3> and R<4> are an alkyl, a cycloalkyl, an aralkyl or an aryl] and useful for synthesis, etc., for fine chemicals as a Horner-Emmons type reaction reagent, etc. This compound is obtained by reacting an acetylene compound represented by formula II (e.g. 1-octyn) with a selenophosphoric acid ester represented by formula III (e.g. diphenyl phenylselenophosphate).

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a selenoalkenyl phosphonate compound and a method for producing the same.

[0002] Selenoalkenyl phosphonates are
The carbanion species easily generated by the Michael addition reaction with the nucleophile is added to the carbonyl compound, and the Horner
-It is a group of compounds useful in the synthesis of fine chemicals, since an Emmons-type reaction is achieved.

[0003]

2. Description of the Related Art There is no known general method for synthesizing selenoalkenyl phosphonates from hydrocarbons in a one-step reaction. Therefore, for the synthesis thereof, a method of reacting a selenoalkenyl halide compound with a secondary phosphite under basic conditions, an addition reaction of a secondary phosphite to selenoalkyne, and the like are considered. The synthesis itself of the reactant itself is a detour and is not considered to be an industrially advantageous method.

[0004]

DISCLOSURE OF THE INVENTION The present invention provides a process for producing a selenoalkenyl phosphonate by a carbon-phosphorus bond forming reaction using a selenophosphate which can be synthesized very easily as a starting material, and a novel selenoalkenyl phosphonate. It is an object of the present invention to provide an ester compound.

[0005]

Means for Solving the Problems In order to solve the above-mentioned problems, the present inventors have conducted intensive studies on the reactivity between selenophosphate and a transition metal complex. As a result, the selenophosphate reacted with a low-valent complex, The possibility of cleaving the phosphorus-selenium bond was found, and the complex thus formed was found to be reactive with acetylene. Based on these facts, the present invention was completed.

That is, according to the present invention, a compound represented by the general formula

Embedded image (Wherein R ¹ and R ² are monovalent selected from a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, an alkenyl group, an alkoxy group, an aryloxy group, and a silyl group) An acetylene compound represented by the general formula

Embedded image Wherein R ³ and R ⁴ represent an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group.
General formula

Embedded image (Wherein R ¹ , R ² , R ³ and R ⁴ have the same meaning as described above). Further, according to the present invention, in the presence of a palladium complex catalyst, the general formula

Embedded image (Wherein, R ⁵ and R ⁷ are monovalent selected from a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, an alkenyl group, an alkoxy group, an aryloxy group, and a silyl group. And R represents
⁶ is an alkylene group, a cycloalkylene group, an arylene group, a heteroarylene group, an aralkylene group, an alkenylene group, an alkylenedioxy group, an arylenedioxy group,
The diacetylene compound represented by a divalent group selected from an oxaalkylene group and an oxaalkylenearylene group is represented by the general formula

Embedded image Wherein R ³ and R ⁴ represent an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group.

Embedded image (Wherein, R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ have the same meanings as described above), and a process for producing a bis (selenoalkenyl phosphonate ester) compound represented by the formula: Furthermore, according to the present invention, the general formula

Embedded image (Wherein R ¹ and R ² are monovalent selected from a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, an alkenyl group, an alkoxy group, an aryloxy group, and a silyl group) And R ³ and R ^{4 each} represent an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group). Furthermore, according to the invention, the general formula

Embedded image (Wherein, R ³ and R ⁴ represent an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group, and R ⁵ and R ⁷ represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, Aralkyl group, alkenyl group, alkoxy group, aryloxy group, a monovalent group selected from silyl group, R ⁶ represents an alkylene group,
Cycloalkylene group, arylene group, heteroarylene group, aralkylene group, alkenylene group, alkylenedioxy group, arylenedioxy group, oxaalkylene group,
There is provided a bis (selenoalkenylphosphonate) compound represented by a divalent group selected from the group of oxaalkylenearylene groups.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The selenophosphate used in the present invention is represented by the above general formula (3). Specific examples of R ³ and R ^{4 in} the formula include a methyl group, an ethyl group,
Examples thereof include a hexyl group, a cyclohexyl group, a phenyl group, a benzyl group and the like.

The acetylene compound used in the present invention is represented by the above general formula (1) or (4).
R ¹ , R ² , R ⁵ and R ⁷ include, for example, a hydrogen atom,
Examples include a methyl group, a propyl group, a benzyl group, a phenyl group, a thienyl group, a 3-butenyl group, an ethoxy group, a phenoxy group, and a trimethylsilyl group. Examples of R ⁶ include a tetramethylene group, a phenylene group, a thienylene group, a ferrocenylene group, and a phenylenedioxy group. Further, R ¹ , R ² , R ⁵ , R ⁶ and R ⁷ may be further substituted with various substituents. As the acetylene compound suitable for the production method of the present invention, unsubstituted acetylene, butyne, octyne, phenylacetylene, trimethylsilylacetylene, ethynylthiophene, 1,8-nonadiyne,
Examples include, but are not limited to, diethynylbenzene, hexinonitrile, propargyl ethers, cyclohexenylacetylene, and the like.

In order for the reaction of the present invention to occur, the use of a palladium catalyst is indispensable, and in the absence of a catalyst, no selenoalkenyl phosphonate is formed. Although various structures can be used as the palladium catalyst, preferred are so-called low-valent palladium complexes, particularly, zero-valent complexes having tertiary phosphine or tertiary phosphite as a ligand. preferable. It is also a preferred embodiment to use an appropriate precursor complex which is easily converted to a zero-valent palladium complex in the reaction system. Furthermore, a tertiary phosphine or a complex containing no tertiary phosphite as a ligand and a tertiary phosphine or a tertiary phosphite are mixed in a reaction system, and a tertiary phosphine or tertiary phosphite is used as a ligand. A preferred embodiment is a method in which a valence palladium complex is generated and used as a catalyst as it is. As a ligand which exhibits advantageous performance by any of these methods, various tertiary phosphines and tertiary phosphites can be cited, and those having an extremely strong electron donating property in terms of reaction rate. Not always advantageous. Examples of suitable ligands include triphenylphosphine, diphenylmethylphosphine, phenyldimethylphosphine, diphenylcyclohexylphosphine, phenyldicyclohexylphosphine, 1,4-bis (diphenylphosphino) butane, trimethylphosphite, and trimethylphosphine. Phenyl phosphite and the like. Examples of the complex which does not contain tertiary phosphine or tertiary phosphite as a ligand used in combination therewith include bis (benzylideneacetone) palladium, palladium acetate and the like, but are not limited thereto. Further, phosphine or phosphite complexes preferably used include dimethylbis (triphenylphosphine) palladium, dimethylbis (diphenylmethylphosphine) palladium, and (ethylene) bis (triphenylphosphine).
Palladium, tetrakis (triphenylphosphine) palladium and the like can be mentioned.

The amount of these palladium complexes to be used may be a so-called catalytic amount, and is generally sufficient to be not more than 20 mol% based on acetylene. Generally, the molar ratio of acetylene to selenophosphate ester is preferably 1: 1. However, if the molar ratio is larger or smaller than this, the occurrence of the reaction is not hindered. The reaction does not need to use a solvent, but can be carried out in a solvent if necessary. As the solvent, a hydrocarbon type or ether type solvent is generally used. If the reaction temperature is too low, the reaction does not proceed at an advantageous rate, and if the reaction temperature is too high, the catalyst decomposes. To be done. The intermediate of this reaction is sensitive to oxygen, and it is preferable to carry out the reaction in an atmosphere of an inert gas such as nitrogen, argon or methane. Separation of the purified product from the reaction mixture is easily achieved by chromatography, distillation or recrystallization.

[0011]

EXAMPLES The present invention will be described more specifically with reference to the following examples, but the present invention is not limited to these examples.

Example 1 Tetrahydrofuran: 1 ml: 1-octyne:
1 mmol, PhSeP (= O) (OPh) ₂ : 1 mmol, Pd (PPh ₃ ) ₄ : 3 mol% as a catalyst, and added under a nitrogen atmosphere at 67 ° C.
And reacted for 15 hours. The reaction solution was concentrated and isolated and purified by liquid chromatography to obtain 95% of diphenyl (Z) -2-phenylseleno-1-octenylphosphonate.
% Yield. This compound is a novel substance not described in the literature, and its spectral data and elemental analysis values are as follows. _{^{1 H NMR (CDCl 3, TMS}} ): δ 7.17~7.59 (m, 20H), 6.08
(d, 1H, JH-P = 17.3Hz), 2.16 (t, 2H, J = 7.4H
z), 1.00~1.37 (m, 8H ), 0.80 (t, 3H, J = 7.0Hz). 13
C NMR (CDCl ₃ , TMS): δ 166.1 (JC-P = 3.4 Hz), 1
50.5 (JC-P = 7.5 Hz), 136.9, 13.0.1, 129.3, 129.
1, 127.3, 125.0, 120.7 (JC-P = 4.7 Hz), 111.0
(JC-P = 198.9 Hz), 40.0 (JC-P = 21.2 Hz), 3
1.3, 28.9, 28.2, 22.4, 14.0. IR (NaCl, liquid film): 3062,
2958, 2930, 2860, 1593, 1568,1491, 1270, 1214, 11
93, 1164, 1025, 930, 770, 690 cm-1. Elemental analysis: Calculated as C ₂₆ H ₂₉ O ₃ PSe C, 62.53; H,
5.85. Found C, 62.80; H, 5.87. HRMS (EI, 70 eV): Calculated 500.1018. Found 500.098.
Four.

Examples 2 to 8 The results obtained by carrying out the reaction using various acetylene compounds in the same manner as in Example 1 are shown in Table 1.

[0014]

[Table 1]

These compounds are novel substances not described in the literature, and their spectral data and / or elemental analysis values are as follows.

The product of Example 2 is as follows. _{^{1 H NMR (CDCl 3, TMS}} ): δ 6.82~7.47 (m, 16H), 3.56
(t, 2H, J = 2.3 Hz), 2.70 (s, 3H). ¹³ C NMR (CDCl ₃ , TMS): δ 158.9 (JC-P = 5.6 Hz),
151.3 (JC-P = 7.2 Hz), 137.2, 129.9, 129.3, 129.
2, 125.9, 125.0, 121.1 (JC-P = 5.8 Hz), 111.2
(JC-P = 199.9 Hz), 75.8 (JC-P = 19.8 Hz), 5
7.8. 31P (D ₂ O, H ₃ PO ₄ ): δ 9.8. IR (NaCl, liquid film): 2934, 1591, 1491, 1270, 1214, 119
. 1, 1116, 1025, 932 , 770, 746, 690 cm-1 Elemental analysis: C ₂₂ H ₂₁ O ₃ Calculated C as PSe, 57.53; H,
4.61. Found C, 57.41; H, 4.61. HRMS (EI, 70 eV): Calculated 460.0341. Found 460.035
8.

The product of Example 3 is as follows. _{^{1 H NMR (CDCl 3, TMS}} ): δ 6.87~7.47 (m, 15H), 6.03
(d, 1H, JH-P = 16.0Hz), 1.85 (t, 2H, J = 7.2H
. z), 1.15 (t, 2H, J = 7.0 Hz), 0.91~1.00 (m, 2H) 13 C NMR (CDCl 3, TMS): δ 162.8 (JC-P = 22.7 H
z), 151.2 (JC-P = 7.2Hz), 136.9, 130.1, 129.6,
129.1, 127.4, 125.2, 121.1 (JC-P = 4.8 Hz), 11
8.6, 114.2 (JC-P = 196.7 Hz), 38.5 (JC-P = 2
1.8 Hz), 24.3 (JC-P = 1.4 Hz), 15.2.31P (D ₂ O, H ₃ PO ₄ ): δ 8.09. IR (NaCl, liquid film): 3062, 2248, 1591, 1568, 1267, 121
. 4, 1191, 1025, 932 , 770, 746, 690 cm-1 HRMS (EI, 70 eV): calculated for C ₂₄ H ₂₂ NO ₃ PSe 483.0
501.Measured value 483.0556.

The product of Example 4 is as follows. _{^{1 H NMR (CDCl 3, TMS}} ): δ 6.85~7.52 (m, 30H), 6.05
(d, 2H, JH-P = 16.5Hz), 1.80 (t, 4H, J = 7.1H
z), 0.79 to 0.89 (m, 4H), 0.37 to 0.47 (m, 2H). ¹¹³ C NM
R (CDCl ₃ , TMS): δ 165.4 (JC-P = 4.0 Hz), 151.4
(JC-P = 7.2Hz), 137.1, 129.9, 129.6, 129.5, 12
7.9, 125.1, 121.1 (JC-P = 4.8 Hz), 112.5 (JC-
P = 198.1 Hz), 39.8 (JC-P = 21.2 Hz), 28.6, 2
7.5. 31P (D ₂ O, H ₃ PO ₄ ): δ 8.8. IR (NaCl, liquid film): 3062, 2938, 1593, 1568, 1491, 126
7, 1214, 1191, 1164, 928, 770, 690 cm-1. Elemental analysis: C ₄₅ H ₄₂ O ₆ P ₂ Se ₂ Calculated C, 60.14;
H, 4.71. Found C, 60.33; H, 4.90.

The product of Example 5 is as follows. ¹ H NMR (CDCl ₃ , TMS): δ 6.65 to 7.51 (m, 20H), 6.45
. (d, H, JH- P = 17.0Hz) 13 C NMR (CDCl 3, TMS): δ 162.4 (JC-P = 5.3 Hz),
151.3 (JC-P = 7.4Hz), 140.5 (JC-P = 22.8 H
z), 135.2, 129.9, 129.8, 129.1, 128.8, 128.7, 128.
0, 127.8, 125.1, 121.0 (JC-P = 4.8 Hz), 117.2
(JC-P = 197.0Hz). 31P (D ₂ O, H ₃ PO ₄ ): δ 7.6. IR (NaCl, liquid film): 2989, 1593, 1557, 1491, 1439, 119
1, 1164, 1025, 1007, 934, 758, 690 cm-1. Elemental analysis: Calculated as C ₂₆ H ₂₁ O ₃ PSe C, 63.55; H,
4.31. Found C, 63.20; H, 4.26. HRMS (EI, 70 eV): Calculated 492.0392. Found 492.032
2.

The product of Example 6 is as follows. _{^{1 H NMR (CDCl 3, TMS}} ): δ 6.56~7.53 (m, 19H), 6.51
. (d, 1H, JH- P = 17.2Hz), 1.79 (s, 3H) 13 C NMR (CDCl 3, TMS): δ 161.9 (JC-P = 5.3 Hz),
151.5 (JC-P = 7.5Hz), 139.2, 137.6 (JC-P =
22.7 Hz), 134.8, 129.9, 128.8, 128.7, 128.1, 127.
8, 127.5, 125.1, 121.2 (JC-P = 4.7 Hz), 117.2
(JC-P = 198.1Hz), 20.9. 31P (D ₂ O, H ₃ PO ₄ ): δ 7.76. IR (NaCl, liquid film): 3062, 1593, 1553, 1491, 1270, 121
. 2, 1191, 1164, 1025 , 930, 764, 690 cm-1 HRMS (EI, 70 eV): C 27 H 23 O 3 calculated for PSe 506.05
49.Measured value 506.0539.

The products of Example 7 are as follows. _{^{1 H NMR (CDCl 3, TMS}} ): δ 6.84~7.50 (m, 15H), 6.35
(d, 1H, JH-P = 18.17 Hz), 5.72 to 75.75 (m, 1H),
1.54 to 1.75 (m, 4H), 0.93 to 1.06 (m, 4H). ¹³ C NMR (CDCl ₃ , TMS): δ 164.4 (JC-P = 4.5 Hz),
151.5 (JC-P = 7.5Hz), 138.3 (JC-P = 22.0H
z), 135.3, 132.1, 130.6, 129.9, 128.8, 127.9, 125.
0, 120.6 (JC-P = 5.0 Hz), 114.2 (JC-P = 197.
0 Hz), 28.3, 25.5, 22.2, 21.6. 31P (D ₂ O, H ₃ PO ₄ ): δ 8.6. IR (NaCl, liquid film): 2934 1593, 1553, 1491, 1272, 121
4, 1191, 1164, 930, 766cm-1. HRMS (EI, 70 eV): Calculated as C ₂₆ H ₂₅ O ₃ PSe 496.07
05.Measured 496.0691.

Example 8 The reaction of Example 1 was replaced with PhSeP (= O) (OPh) ₂ instead of PhSeP (= O).
When the same procedure was performed except that (OEt) ₂ was used, diethyl 2-phenylseleno-1-octenylphosphonate was obtained in a 90% yield. This compound is a novel substance not listed in the literature,
The spectrum data and elemental analysis values were as follows. _{^{1 H NMR (CDCl 3, TMS}} ): δ 7.50~7.52 (m, 2H), 6.91~
6.96 (m, 3H), 6.06 (d, 1H, JHP-14.0 Hz), 4.08
~ 4.21 (m, 4H), 2.07 (t, 2H, J = 7.3 Hz), 0.75-1.
31 (m, 17H). 31P (D ₂ O, H ₃ PO ₄ ): δ 16.5. IR (NaCl, liquid film): 2930, 1562, 1491, 1191, 1164, 102
. 5, 938, 743 cm- 1 HRMS (EI, 70 eV): C 18 H 29 O 3 PSe
Calculated as 404.1018. Found 404.1028.

Example 9 The same reaction as in Example 1 was carried out except that cis-Me ₂ Pd (PMePh ₂ ) ₂ was used instead of Pd (PPh ₃ ) ₄ as a catalyst. Diphenyl seleno-1-octenylphosphonate was obtained in 93% yield.

Example 10 The same reaction as in Example 1 was carried out except that unsubstituted acetylene was used in place of 1-octyne, to obtain diphenyl 2-phenylseleno-1-ethenylphosphonate.
Obtained in 2% yield.

[0025]

Industrial Applicability According to the present invention, a novel selenoalkenyl phosphonate useful for the synthesis of fine chemicals such as pharmaceuticals and agricultural chemicals can be synthesized simply, safely and efficiently only by reacting acetylenes with selenophosphate. It is also easy to separate and purify. Therefore, the industrial significance of the present invention is great.

Claims (4)

[Claims] (1) In the presence of a palladium complex catalyst, a compound represented by the general formula: (Wherein R ¹ and R ² are monovalent selected from a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, an alkenyl group, an alkoxy group, an aryloxy group, and a silyl group) An acetylene compound represented by the general formula: Wherein R ³ and R ⁴ represent an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group.
General formula (Wherein, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above). 2. In the presence of a palladium complex catalyst, a compound of the general formula (Wherein, R ⁵ and R ⁷ are monovalent selected from a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, an alkenyl group, an alkoxy group, an aryloxy group, and a silyl group. And R represents
⁶ is an alkylene group, a cycloalkylene group, an arylene group, a heteroarylene group, an aralkylene group, an alkenylene group, an alkylenedioxy group, an arylenedioxy group,
A diacetylene compound represented by a divalent group selected from an oxaalkylene group and an oxaalkylenearylene group is represented by the general formula: Wherein R ³ and R ⁴ represent an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group, characterized by reacting a selenophosphate ester represented by the general formula: (Wherein, R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ have the same meanings as described above). 3. A general formula: (Wherein R ¹ and R ² are monovalent selected from a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, an alkenyl group, an alkoxy group, an aryloxy group, and a silyl group) And R ³ and R ⁴ represent an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group). 4. A compound of the general formula (Wherein, R ³ and R ⁴ represent an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group, and R ⁵ and R ⁷ represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, Aralkyl group, alkenyl group, alkoxy group, aryloxy group, a monovalent group selected from silyl group, R ⁶ represents an alkylene group,
Cycloalkylene group, arylene group, heteroarylene group, aralkylene group, alkenylene group, alkylenedioxy group, arylenedioxy group, oxaalkylene group,
A bis (selenoalkenylphosphonic acid ester) compound represented by a divalent group selected from the oxaalkylenearylene groups.