JPS6248655B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 1,3-diones. More specifically, the present invention converts 1,3-diones useful as intermediates in medicines, agricultural chemicals, and fragrances into 2,3-diones.
The present invention relates to a method advantageously produced by an isomerization reaction of epoxy-1-ones. A typical example of 1,3-diones is 1,3-
Cyclopentadione is known as an example of a useful intermediate [Rel _y le et al., Journal of Organic Chemistry (J.Org. Chem),
40 , 50 (1975) and references thereof]. A conventionally known method for producing this product is the Dieckmann condensation reaction of β-ketoadipate ethyl ester [R.Richter, Helv.Chim.Acta, 32 , 1123 (1949) and J.H.
Brothe et al., Journal of American Chemical Society (J.Amer, Chem, Soc)
75 , 1732 (1953)] or the cyclization reaction of levulinic acid ethyl ester (J. Sraga et al.
Synthesis 282 (1977) and Z.
Chem, 15 , 189 (1975)). However, these methods are not necessarily satisfactory for industrial production in terms of yield and operational complexity. Furthermore, as a method for synthesizing 1,3-diones, a method using Friedel-Crafts reaction of vinyl acetate and acid chloride is known (A.Sieylitz
et al., Chem. Ber, 84 , 607 (1951)), but this method also has a low yield and is not a satisfactory method.
Although further improvements were made to this method, it is still difficult to consider it to be a valid method considering the yield (F.Merenyi et al., Acta.Chem.Scand, 17 , 1801
(1963): 18 , 441 (1964): and 17 1801
(1963)). On the other hand, a method for producing 1,3-cyclopentadione using cyclopentadiene via 4-cyclopentenediol is known (LNOnen et al., J. Chem. Soc, 4035 (1952): G .
M. Korach et al. Org. Syntn, 42 , 50 (1962): G.
H. Rasmussen et al., Org・Synth, Coll. Val. V, 234
(1973): JM. Mcintoch et al., J.Org.Chem,
37 , 2905 (1972) and references cited therein).
However, these methods also have drawbacks in terms of yield and process complexity. In addition, the advantageous production of 1,3-cyclopentadione using norbornene has recently been proposed (C.
(See Lick et al., Chem. Ber, 111 , 2461 (1978)).
This method has significantly improved productivity compared to conventional manufacturing methods. However, the process involves several steps and is not always satisfactory in terms of operation. The present inventors focused on this point, overcame the drawbacks of the above methods, specifically isomerized 1,2-epoxy-1-ones, and made 1,3-diones industrially advantageous. As a method for obtaining 1,3-diones, we have previously proposed a method for producing 1,3-diones using metallic palladium, palladium chloride, or a palladium complex as an isomerization catalyst (Japanese Patent Application No. 142821/1982). Based on this knowledge, the present inventors conducted further intensive research and found that if a specific phosphorus compound is used in combination with the above-mentioned isomerization catalyst such as palladium metal, palladium chloride, or a complex of palladium, the yield will be even higher than that of the above method. industrially advantageous at a rate of 1.3
-The present invention was achieved by discovering that diones can be produced. That is, the present invention is based on the following formula [] [In the formula, R ₁ and R ₂ are the same or different and represent an organic group having 1 to 10 carbon atoms. In this case, R ₁ and R ₂ may be bonded to each other. R ₃ represents a hydrogen atom or a lower alkyl group. ] 2,3-epoxy-1-ones represented by
The following formula is characterized by isomerization in the presence of a palladium complex and a specific diphenylphosphine derivative [] [In the formula, the definitions of R ₁ , R ₂ , and _{R 3} are the same as above. ] This is a method for producing 1,3-diones represented by 2,3- which is a raw material represented by the above formula [] used as a raw material compound in the method of the present invention
Epoxy-1-ones can be easily obtained by epoxidizing α,β-unsaturated ketones by a commonly known method. In [] above, R ₁ ,
R ₂ is the same or different and is an organic group having 1 to 10 carbon atoms, and R ₁ and R ₂ may be bonded to each other to form a ring. Examples of such organic groups having 1 to 10 carbon atoms include alkyl groups such as methyl, ethyl, propyl, hexyl, and decyl, aryl groups such as phenyl, O, m, p-tolyl, and pyridyl, benzyloxyheptyl, and tetrahydropyranyl. Preferably used are alkoxyalkyl groups such as oxyhexyl, aralkyl groups such as benzyl and 3-phenylpropyl, and alkoxycarbonylalkyl groups such as 6-methoxycarbonylhexyl and 6-ethoxycarbonylheptyl. Further, as the ring-forming group, for example, alkylene groups such as ethylene, trimethylene, tetramethylene, pentamethylene, and nonamethylene groups are preferably used. Moreover, these alkylene groups may be substituted. In the above formula [], R ₃ is a hydrogen atom or a lower alkyl group, and such lower alkyl groups include, for example, a methyl group, an ethyl group, a propyl group, an n
-butyl group, etc. In the method of the present invention, 2,3-epoxy-1-ones represented by the above formula [] are isomerized using a palladium complex and a specific diphenylphosphine derivative. The palladium complex has the following formula [] PdXm(PR ₃ )l ... [] where X is a halogen atom, R is a monovalent organic group,
m is 1 or 2, l is 1 or 4. ] A palladium complex represented by these is preferably used. Among these, palladium tetrakistriphenylphosphine complexes are particularly preferred among the palladium complexes represented by the above formula []. Furthermore, palladium acetonide complexes,
That is, for example, palladium tribenzylidene acetylacetone (formula below), Alternatively, palladium acetylacetonide and the like are also suitable as the isomeric catalyst of the present invention. Further, such a palladium complex can also be used as a complex bound to an organic polymer, and in this case there is an advantage that post-treatment of the reaction becomes simpler. The amount of the isomerization catalyst used may be a catalytic amount, but specifically, it is used in an amount of 10.0 to 0.0001% by weight, preferably 0.5 to 0.001% by weight, and more preferably 0.1 to 0.005% by weight based on the raw material compound. Further, in the present invention, a diphenylphosphine derivative is used together with such a palladium complex. Diphenylphosphine derivatives include 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane, 2,3-
0-isopropylidene-2,3-dihydroxy-
1,4-bis(diphenylphosphino)butane,
Preferred examples include bis(2-diphenylphosphinoethyl)phenylphosphinoethyl. The amount of the diphenylphosphine derivative used is almost the same as the amount of the isomerization catalyst as described above, and specifically, it is 10.0 to 0.0001% by weight, preferably 0.5 to 0.001% by weight based on the raw material compound. % by weight, more preferably from 0.1 to 0.005% by weight. The reaction proceeds smoothly at 0-200°C, preferably at 10-150°C. Therefore, the reaction may normally be carried out at room temperature. A solvent may be used to make the reaction proceed more smoothly. These include ethers such as ether, tetrahydrofuran, and isopropyl ether; hydrocarbons such as pentane and hexane; aromatic hydrocarbons such as benzene-toluene; and aprotons such as halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform. Examples include sterile solvents. These solvents can be used alone or as a mixed solvent of two or more. Furthermore, if the product is soluble in water, the product can be easily isolated by reacting in a two-layer system of these solvents and water. The progress and end point of the reaction can be determined by thin layer chromatography or the like, based on the disappearance of spots of raw materials. After completion of the reaction, the reaction product can be obtained by separating the palladium compound by filtration or centrifugation, and purifying it by conventional treatment methods, concentration, distillation, chromatography, etc. Thus, according to the method of the present invention, the above formula []
1,3-diones represented by can be obtained. Specific examples of such compounds include, for example, 5
-Methyl-2,4-hexanedione, 1,3-cyclopentanedione, 1,3-cyclohexanedione, 1,3-cycloheptanedione, 1,3-
Cyclooctanedione, 1,3 cyclodotecanedione, 3,4-epoxy-3-methylheptane-
2-one, 2-methyl-5-isopropyl-1,
3-cyclohexanedione is particularly preferred. These 1,3-diones, such as 1,3-cyclopentanedione, are important starting materials for various pharmaceuticals, fragrances, agricultural chemicals, and the like.
(e.g. Aldrichimica Acta 10 , 19 (1977)
). Moreover, this product can also be used as an intermediate for synthesizing prostides, which have been attracting attention in recent years. The method of the present invention is also useful as a unit reaction for organic reactions. Briefly speaking, the feature of the method of the present invention is that the above-mentioned useful compounds can be
By using a catalytic amount of a palladium compound rather than -epoxy-1-ones, it can be easily obtained in a high yield under very mild conditions. Hereinafter, the method of the present invention will be explained in more detail with reference to Examples. Example 1 247 mg of 5,6-epoxytridecane-4-one, 71 mg of Pd (PPh ₃ ) ₄ , 25 mg of 1,2-bis(diphenylphosphino)ethane, and 2 ml of toluene in a sealed tube.
After replacing with argon, the reactor was sealed and reacted at 140°C for 90 hours. A column (10 g of SiO ₂ , eluted with benzene:hexane = 1:1) was fractionated to obtain 221 mg (yield: 89.3%) of 4,6-tridecanedione. Additionally, 15 mg (5.9%) of raw material was recovered. The yield based on the consumed raw material was 94.8%. The physical properties of the obtained β-diketone were as follows. Rf; 0.39 (silica gel; hexane: benzene =
1:1) IR; 3600~2400cm ^-1 , 1700cm ^-1 , 1640~1560
(broad) NMR (CCl ₄ ) δ; 0.87 (3H, t, J=7Hz, -C
H ₃ ), 0.94 (3H, t, J=7Hz, -C H ₃ ),
1,10~1.80(12H,br, _-CH2 -),2.20
(4H, J=7.5Hz, [formula]), 3.37 (0.1H, S, [formula]), 5.33 (1H, S, [formula]), 15.35~15, 75 (0.5H, br, [formula] ) Mass (m/e); 212 (M ⁺ ) Analysis value; C, 73.34, H, 11.37, Calculated value: C,
73.53; H, 11.39 Example 2 64.8 mg of 8,9-epoxy-9-phenylnonan-7-one, Pd (PPh ³ ) ₄ 16.0 mg, 1,2 in a sealed tube
-Bis(diphenylphosphino)ethane 5.9mg,
After adding 2 ml of toluene and purging with argon, it was sealed and reacted at 140°C for 17 hours. Column (SiO ₂ 5
g, hexane:ethyl acetate = 15:1) and β-diketone (9-phenylnonane-7,
9-dione) was obtained (53.2 mg (yield 82.1%)). The physical properties of this material are as follows. Rf = 0.58 (silica gel; hexane: ethyl acetate =
5:1) IR; 3600~2400cm ^-1 , 1700~1600cm ^-1
(broad) NMR (CCl ₄ ) δ; 0.92 (3H, t, J=6Hz, -
C H ₃ ), 1.20-2.00 (8H, br, -C H ₂ ) ₄
−), 2.37 (2H, t, J=7Hz,
[Formula]), 3.95 (0.2H, S, [Formula]), 6.06 (0.7H, S, [Formula]), 7.20~7.60 (3H, aromatic), 7.7g~7.88 (2H, aromatic), Mass ( m/e; 232 (M ⁺ ) High resolution mass spectrometry Observed value; 232.14343, Calculated value; 232.14632 Example 3 In a sealed tube, 58 mg of cinnamaldehyde oxide
(3.9×10 ^-4 mol), Pd(PPh ₃ ) ₄ 42mg (3.7×
10 ^-5 mol), 14 mg (3.6 x 10 ^-5 mol) of 1,2-bis(diphenylphosphino)ethane, and 1.5 ml of degassed toluene were purged with argon, sealed, and heated at 55°C.
Reacted for 19 hours. Column (1 g of SiO ₂ , eluted with benzene:ethyl acetate = 2:1) was fractionated and 12.1 mg (20.8 mg of 3-phenylpropane-1,3-dione)
%)Obtained. The physical property values are as follows. NMR (CCl ₄ ) δ: 3.60 (singlet,
[Formula]), 5.25 (singlet, [Formula]), 7.10-7.75 (broad, aromatic), IR (CHCl ₃ ); 3600-3100cm ^-1 , 1640-1595cm
^-1 (broad) Example 4 3,4-epoxy-3-methylheptan-2-one (224 mg, 1.58×10 ^-3 mol), Pd in a sealed tube
(PPh ₃ ) ₄ (94 mg, 8.17×10 ^-5 mol), 1,2-bis(diphenylphosphino)ethane (32 mg, 8.07×
10 ^-5 mol) and degassed toluene (0.5 ml) were added, and after replacing the alkone, the tube was sealed and reacted at 140°C for 47 hours. The reaction mixture was separated using a column (SiO ₂ , 10 g, hexane-ethyl acetate (20:1)), and 72.7 mg (32.5%) of a mixture containing 3-methylheptane-2,4-dione was collected.
I got it. Example 5 2,3-epoxycyclohexanone (109 mg, 9.71×10 ^-4 mol), Pd (PPh ₃ ) ₄ (36 mg,
3.07×10 ⁻⁵ mol), 1,2-bis(diphenylphosphino)ethane (12 mg, 3.12×10 ⁻⁵ mol), 1 ml of toluene, and 1 ml of H ₂ O, and after purging with argon, the mixture was reacted for 24 hours. After filtering the reaction mixture, add water (2 ml x
5) and concentrated the aqueous layer to give 67.7 mg (yield;
62.3%) of 1,3-cyclohexanedione was obtained. Example 6 2,3-epoxycyclooctanone in a sealed tube
73.1 mg, Pd (PPh ₃ ) ₄ 58.9 mg, 1,2-bis(diphenylphosphino)ethane 20.3 mg, toluene 2
ml, and after purging with argon, it was sealed and reacted at 140°C for 40 hours. Column (5 g of SiO ₂ , eluted with benzene:ethyl acetate = 10:1) was fractionated, and the raw material and β-diketone (1,3-cyclooctanedione) were separated.
65.8 mg of a mixture of 2:1 was obtained.
The yield based on the consumed raw material was 75.0%.
The physical property values are as follows. Rf = 0.24 (silica gel; hexane: ethyl acetate =
5:1) NMR (CCl ₄ ) δ; 1.50-2.00 (6H, -CH ₂ ) ₃
−), 2.30~2.50 (4H,
[Formula] 3.40 (2H, S, [Formula]) Example 7 2,3-epoxycycloheptanone in a sealed tube
282 mg, 2.24×10 ^-3 mol), Pd(PPh ₃ ) ₄ (107 mg,
9.29×10 ^-5 mol), 1,2-bis(diphenylphosphino)ethane (3.54 mg, 8.89×10 ^-5 mol), and degassed toluene (2 ml) were added, and after purging with argon, the mixture was sealed and heated at 100°C. The reaction was allowed to proceed for 20 hours. Column {SiO ₂ , 10
g, eluted with hexane-ethyl acetate (5:1)).
169.4 mg (60% yield) of 1,3-cycloheptanedione was obtained. NMR (CCl ₄ ) 8; 1.89-2.20 (4H, m, CH ₂
− CH ₂ −), 2.35 to 2.98 (4H,
[Formula]), 3.45 (2H, S, [Formula]), IR (meat); 1730, 1700cm ^-1 Mass (me); 126 (M ⁺ ) Example 8 2,3-Epoxy-5- in a sealed tube Isopropyl-2-methylcyclohexanone 127.1mg, Pd
88.6 mg of (PPh ₃ ) ₄ , 30.6 mg of 1,2-bis(diphenylphosphino)ethane, and 2 ml of toluene were added, and the mixture was replaced with argon, sealed, and reacted at 140°C for 66 hours. Column (SiO ₂ 20g, benzene:ethyl acetate = 20:
eluted at a ratio of 1 to 5:1), and β-diketone (5-
Isopropyl-2-methylcyclohexane-1,
23.1 mg (18.2%) of 3-dione) was obtained. Rf=0.46 (silica gel; benzene: ethyl acetate=
1:1) IR (CHCl ₂ ); 3600-3100cm ^-1 , 1735, 1700,
1620cm ^-1 NMR (CD ₃ OD) δ; 0.96 (6H, d, J = 7Hz
-CH( _CH3 ) ₂ )1.65(3H,S,
[Formula] 1.30-2.60 (6H) Analysis value: C, 71.45; H, 9.29 Calculated value: C,
71.39; H, 9.59 Example 9 2,3-epoxycyclododecane (239 mg, 1.22×10 ^-3 mol), Pd(PPh ₃ ) ₄ (136.mg,
Add ² ml of toluene ( ^1.17
Allowed time to react. The reaction mixture was subjected to TLL fractionation (hexane-ethyl acetate = 20:1, developed 3 times),
129.8 mg (54.4% yield) of 1,3-cyclododecanedione was obtained. Examples 10 to 12 Using 2,3-epoxycyclododecane, reactions were carried out under various conditions as shown in Table 1.
1,3-cyclododecanedione was obtained. The yield under each reaction condition is shown in Table 1. [Table] Example 13 3,4-epoxypentan-2-one in a sealed tube
196mg (1.96×10 ^-3 mole), Pd (PPh ₃ ) ₄ 69mg
(5.98×10 ^-5 mole), 23.7 mg (5.95×10 ^-5 mole) of 1,2-bis(diphenylphosphino)ethane, then 0.5 ml of degassed toluene, replaced with argon, sealed, and heated to 140°C. The reaction was carried out for 11 hours. GLC yield was determined using n-methyl caprate as an internal standard. As a result, 2,4-pentadione (81
%), 3-pentan-2-one (8.2%) was obtained. The conditions for GLC are as follows. column; 3mm×2m 5%DEGS on
NeopaklA column Temperature; 75℃ Dctector; 250℃ Injector; 250℃ Carrier; 0.6Kg/cm ² Examples 14 to 19 Using 3,4-epoxypentan-2-one, under the conditions shown in Table 2. Almost the same experiment as in Example 13 was conducted. The results are shown in Table 2. 【table】

Claims (1)

[Claims] 1. The following formula [] [In the formula, R ₁ and R ₂ are the same or different and represent a hydrocarbon group having 1 to 10 carbon atoms that may contain an oxygen atom or a nitrogen atom, and R ₁ and R ₂ are bonded to each other. It's okay. R ₃ represents a hydrogen atom or a lower alkyl group. ] 2,3-epoxy-1-ones represented by
Palladium complex and 1,2-bis(diphenylphosphino)ethane, 1,3-bis-(diphenylphosphino)propane, 2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis (diphenylphosphino)butane and bis(2-diphenylphosphinoethyl)phenylphosphine, which is isomerized in the presence of a diphenylphosphine derivative selected from the group consisting of [] [In the formula, the definitions of R ₁ , R ₂ and R ₃ are the same as above. ] A method for producing 1,3-diones represented by