JP2002088026A - Allene-substituted carboxylic acid ester - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new allene derivative and its production method. SOLUTION: A pure allene derivative free from substituent on the terminal, having added malonic acid ester and expressed by formula (1) (R1 is a 1-8C straight-chain alkyl, a branched alkyl-carbon compound having secondary or tertiary carbon, allyl group, an aromatic hydrocarbon group, 1,2-butadienyl group or 2,3-butadienyl group) can be synthesized by using 2-chloro-1,3-butadiene which is a diene compound easily available as a starting raw material and reacting the diene compound with sodium compound of a malonic acid ester using a palladium/phosphine compound as a catalyst.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for synthesizing an allene derivative or a substituted carboxylic acid ester thereof, which is a precursor of a barbital useful as a hypnotic or an analgesic.

[0002]

2. Description of the Related Art Heretofore, only three types of allene compounds represented by the following general formula have been known to which an unsubstituted malonic ester at position 1 has been added.

[0003]

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[0004] When synthesizing an allene-substituted carboxylate as a precursor of barbitals from this known compound, the substituent at the 2-position of the carboxylate attached to carbon is hydrogen and an allene derivative. Therefore, when barbitals are synthesized from these compounds, the substituents of the resulting compound are hydrogen other than the thiourea skeleton and the allene derivative. In the structure of barbitals, two substituents other than thiourea play an important role in determining their efficacy. However, in known compounds, one of the substituents is hydrogen, so that the degree of freedom of the substituent selectivity is low.
The reason for this is the difficulty in synthesizing allenes. As a method for synthesizing allenes, a specific acetylene is obtained by reacting malonic esters in the presence of a base. However, the synthesis of raw acetylenes is difficult, and as long as this synthesis method is used, the structure of the generated allenes is necessarily one of the substituents, and the free substituents of the barbitals synthesized from these compounds are hydrogen. The degree is not great.

[0005]

SUMMARY OF THE INVENTION The present invention provides a novel allene derivative and a carboxylic acid ester compound having an optional substituent and a method for synthesizing the same, which react with urea to form a barbital compound. Therefore, it also provides a new substituent to the barbital compound.

[0006]

Means for Solving the Problems The present inventors have conducted intensive studies for the development of new barbitals having various combinations of substituents such as allene derivatives, and as a result, they have developed novel precursors of these precursors. As a result of reviewing the method of synthesizing the allene-substituted carboxylic acid ester, they have found that an allene-substituted carboxylic acid ester can be easily produced by using a diene as a raw material by using a palladium catalyst, and have accomplished the present invention. That is, the present invention provides an allene-substituted carboxylic acid ester represented by the following general formula.

[0007]

Embedded image (Wherein R 1 is a linear alkyl group having 1 to 8 carbon atoms, a branched alkyl carbon compound having a secondary or tertiary carbon, an allyl group, an aromatic hydrocarbon, a 1,2-butadienyl group or a 2,3- Butadienyl group)

The compound containing two 2,3-butadienyl groups is the following compound.

[0009]

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[0010]

BEST MODE FOR CARRYING OUT THE INVENTION R1 may be a straight-chain alkyl group having 1 to 8 carbon atoms or a branched secondary or tertiary carbon alkyl carbon compound. , Ethyl group, straight-chain propyl group,
There are isopropyl group, straight-chain butyl group, isobutyl group and tertiary butyl group. R1 may be an allyl group or a phenyl group. Alternatively, a 2,3-butadienyl group may be used.

The compounds of the present invention are novel compounds which have not been described in any literature. This compound has, for example, 2-chloro-1,3-butadiene as a diene and a compound represented by the general formula

[0012]

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(R3 is a methyl or ethyl group, M is an alkali metal such as lithium, sodium, potassium, etc .;
2 is a methyl group, an ethyl linear propyl group, a linear butyl group,
A malonic ester derivative represented by isobutyl group, tertiary butyl group, allyl group or phenyl group), for example, methyl or ethyl ester,

[0014]

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Using a palladium compound represented by the following formula as a catalyst,

[0016]

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The compound can be produced by adding a phosphorus compound represented by the formula (1), dissolving them in a solvent and reacting them. As the solvent, ether is preferable, and for example, diethyl ether, dibutyl ether, tetrahydrofuran, and dioxane can be used.

The reaction temperature can be in the range from room temperature to 70 ° C.

From the reaction mixture thus obtained,
In order to isolate the target compound, first, the solvent is once removed by atmospheric distillation, and the residue is obtained by distillation under reduced pressure. Since the target compound thus obtained is a liquid compound having a high boiling point, it can be easily purified to high purity.

The compound of the present invention is identified as an allene derivative from its NMR spectrum.

[0021]

Next, the present invention will be described in more detail by way of examples. Example 1 In a reactor, 38 mg (426 μmol) of 2-chloro-1,3-butadiene and [PdCl
(Η ³ -C ₃ H ₅ )] ₂ at 1.5 mg (8.2 μmol / P
d) 4.7 g of 2,2′-bis (diphenylphosphanyl) 1,1′-biphenyl as an additive (9.0 μm)
mol) was dissolved in 5 ml of tetrahydrofuran, and 89 mg of sodium salt of dimethyl methyl malonate (4 mg) was added.
26 μmol) were mixed. The reaction was performed for 12 hours at room temperature. The solvent was removed from the reaction mixture by atmospheric distillation, and the desired product of the following formula was obtained by vacuum distillation. The yield was 70%. The NMR spectrum of this is shown in FIG.

[0022]

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NMR of diallene and monoallene
Are as follows. Dimethyl2- (2,3
-butadienyl) -2-methylpropane-1,3-dioate. (monoallene) 1HNMR (CDCl3): delta1.44 (s, 3H), 2.58 (dt, J = 7.9and2.4H
z, 2H), 3.73 (s, 6H), 4.67 (dt, J = 6.7and2.4Hz, 2H), 5.00 (t
t, J = 7.9and6.7Hz, 1H) .13C [1H] NMR (CDCl3): delta19.78,35.27,52.52,53.97,74.
55,84.51,172.19,210.22.Anal.CalcdforC10H14O4: C, 60.59; H, 7.12.Found: C, ----;
H, ----.

(Example 2) In Example 1, the starting material, 2-
By adding 189 mg of chloro-1,3-butadiene in excess, a compound of the following formula having two 2,3-butadienyl groups was obtained. The NMR spectrum is shown in FIG.

[0025]

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The NMR shift data is as follows. Dimethyl2-bis (2,3-butadienyl) propane-1,3-dioate.
(Dialene) 1H NMR (CDCl3): delta2.65 (dt, J = 8.1 and 2.4Hz, 4H), 3.73
(s, 6H), 4.67 (dt, J = 6.6and2.4Hz, 4H), 4.94 (tt, J = 8.1and
6.6 Hz, 2H) .13C [1H] NMR (CDCl3): delta 31.96, 52.47, 57.91, 74.66, 84.
10,170.94,210.13.Anal.CalcdforC13H16O4: C, 66.09; H,
6.83.Found: C, ----; H, ----.

Example 3 Example 1 is the same as Example 1 except that a methyl malonic acid diester compound as a raw material was replaced with an ethyl group.

[0028]

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(Example 4) The following compound was obtained in the same manner as in Example 1 except that a malonic ester was used instead of the methyl malonate compound.

[0030]

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The NMR shift data is as follows. Dimethyl 2- (2,3-butadienyl) propane-1,3-dioate.1H NMR (CDCl3): δ 2.60 (ddt, J = 7.4, 6.7, and 3.1Hz, 2H), 3.
51 (t, J = 7.4Hz, 1H), 3.74 (s, 6H), 4.72 (dt, J = 6.7 and 3.1 Hz,
2H), 5.14 (quint, J = 6.7Hz, 1H) .13C [1H] NMR (CDCl3): δ 27.40, 51.27, 52.53, 76.23, 8
6.63, 169.24, 208.72.Anal.CalcdforC9H12O4: C, 58.69;
H, 6.57.Found: C, ----; H, ----.

Example 5 The following compound was obtained in the same manner as in Example 1 except that an allyl malonic ester was used instead of the methyl malonic ester compound.

[0033]

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The shift data of NMR are as follows. Dimethyl 2-allyl-2- (2,3-butadienyl) propane-1,3-dio
ate.1H NMR (CDCl3): δ 2.61 (dt, J = 7.9 and 2.4 Hz, 2H), 2.69 (d
t, J = 7.4 and 1.1 Hz, 2H), 3.72 (s, 6H), 4.66 (dt, J =
6.6 and 2.4 Hz, 2H), 4.95 (tt, J = 7.9 and 6.6 Hz, 1H),
5.09-5.14 (m, 2H), 5.65 (ddt, J = 16.7, 10.3, and 7.4
Hz, 1H) .13C [1H] NMR (CDCl3): δ 31.94, 36.90, 52.39, 5
7.93, 74.63, 84.17, 119.33, 132.27, 171.04,210.15.Anal.CalcdforC12H16O4: C, 64.27; H, 7.19.Found: C, ----;
H, ----.

[0035]

【The invention's effect】

The compound of the present invention relates to a novel allene-substituted carboxylic acid ester compound which is a compound useful as a hypnotic or an analgesic and is a raw material for synthesizing various barbitals.

[Brief description of the drawings]

FIG. 1 is an NMR spectrum of an allene derivative of Example 1.

FIG. 2 is an NMR spectrum (enlarged view) of an allene derivative of Example 1.

FIG. 3 is an NMR spectrum (enlarged view) of an allene derivative of Example 1.

FIG. 4 is a C13-NMR spectrum of the allene derivative of Example 1.

FIG. 5 is an NMR spectrum of the allene derivative of Example 2.

FIG. 6 is an NMR spectrum (enlarged view) of the allene derivative of Example 2.

FIG. 7 is an NMR spectrum (enlarged view) of the allene derivative of Example 2.

FIG. 8 is a C13-NMR spectrum of an allene derivative of Example 2.

FIG. 9 is an NMR spectrum of the allene derivative of Example 4.

FIG. 10 is an NMR spectrum (enlarged view) of the allene derivative of Example 4.

FIG. 11 is an NMR spectrum (enlarged view) of an allene derivative of Example 4.

FIG. 12 is a C13-NMR spectrum of an allene derivative of Example 4.

FIG. 13 is an NMR spectrum of the allene derivative of Example 5.

FIG. 14 is an NMR spectrum (enlarged view) of the allene derivative of Example 5.

FIG. 15 is an NMR spectrum (enlarged view) of the allene derivative of Example 5.

FIG. 16 shows a C13-NMR spectrum of an allene derivative of Example 5.

Claims (4)

[Claims] An allene derivative represented by the following general formula: Embedded image (R1 is a linear alkyl group having 1 to 8 carbon atoms, a branched secondary or tertiary carbon alkyl carbon compound, an allyl group,
Aromatic hydrocarbon, 1,2-butadienyl group, or 2,
3-butadienyl group) 2. A diene compound and a malonic acid ester derivative, using ether as a solvent, in the presence of a phosphorus compound of the following formula: With the catalyst of the following formula, The method for producing an allene derivative according to claim 1, wherein the reaction is carried out. 3. The method for producing an allene derivative according to claim 2, wherein the diene compound is 2-chloro-1,3-butadiene or 2-bromo-1,3-butadiene. 4. The method for producing an allene derivative according to claim 2, wherein the solvent is at least one of diethyl ether, dibutyl ether, tetrahydrofuran, and dioxane.