JPH0692903A - 5-formyloxy-3-pentenoic acid or its ester and production thereof - Google Patents

Abstract

PURPOSE:To provide 5-formyloxy-3-pentenoic acid or its ester as a key intermediate compound for producing a macrocyclic lactone compound with industrial advantage. CONSTITUTION:A compound of formula I (R is H or a 1 to 12C straight or branched chain saturated or unsaturated alkyl which may have a substituent group). This compound can be obtained by a photoreaction from levoglucosenone of formula II synthesized through thermal decomposition of cellulose in the presence of water or alcohol in an atmosphere of an inert gas. If a photosensitizer such as benzaldehyde, acetophenone or benzophenone is used in the photoreaction, the compound of formula I can be more efficiently produced. If the photosensitizer is not used, the selectivity of a geometric isomer is very high. In addition, the photoreaction of levoglucosenone proceeds more efficiently by ultraviolet rays or near ultraviolet rays.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to 5-formyloxy-3-pentenoic acid or its ester useful as an intermediate in the synthesis of pharmaceuticals such as macrolide antibiotics, pesticides, and perfume synthesis, and a process for producing the same.

[0002]

2. Description of the Related Art It is well known that many macrocyclic lactone compounds exhibit a high antibacterial action called macrolide antibiotics. In addition, macrocyclic lactone compounds have been found to have a wide range of uses as agricultural chemicals and fragrances. Therefore, it is significant to develop a process capable of industrially producing a macrocyclic lactone compound. In the synthesis of macrocyclic lactones represented by macrolide antibiotics, it is important to develop compounds that are key intermediates and efficient production methods thereof, and various methods have been used so far. Is being attempted. As one of them, the following general formula [III]

[Chemical 4] (Wherein R'represents a general alkyl group or alkenyl group) as a starting material (J. Am.
Chem. Soc, 113 , 1044 (1991)).

[0003]

However, the compound [III] is expensive and has a problem when it is used as a raw material in an industrial production method. In addition, the compound [III] analog has a complicated process and is problematic in terms of versatility. In view of such circumstances, an object of the present invention is to provide a novel intermediate that is industrially suitable and suitable for the synthesis of macrocyclic lactone compounds.

[0004]

That is, the present invention provides the following general formula [I]:

[Chemical 5] (In the formula, R represents hydrogen or an alkyl group which may have a linear or branched, saturated or unsaturated substituent having 1 to 12 carbon atoms), and 5-formyloxy-3-.
The present invention relates to pentenoic acid or its ester (hereinafter referred to as compound I). Compound I in the present invention is
It is a novel compound that has not been published in the literature. Compound I can be produced, for example, by the following method.

In the synthesis of compound I, first, a formula [I obtained by thermal decomposition of inexpensive cellulose as a starting material is used.
I]

[Chemical 6] Levoglucosenone (Chem. Lett.,
307 (1990)). Compound I is synthesized as follows. Compound I can be synthesized by photoreaction of levoglucosenone in the presence of water or alcohol in an inert gas atmosphere.

As the alcohol, monohydric alcohols such as methanol, ethanol, propanol and t-butanol, ethylene glycol, propylene glycol, butanediol, hexanediol, octanediol, 1-penten-3-ol and 2-propyne- are used. 1-all etc. can be mentioned. Further, as a solvent that can be used as necessary, benzene, fluorobenzene,
Aromatic compounds such as chlorobenzene, bromobenzene, methyl benzoate, anisole, and phenetole can be mentioned. In particular, it is preferable to use a solvent together in an aqueous reaction in which no alcohol is present. In this case, it suffices that the amount of water necessary for the reaction is contained, and if the amount of water is too much, the solubility of the raw material is lowered, which is not preferable.

In the photoreaction of levoglucosenone, the use of a photosensitizer such as benzaldehyde, acetophenone and benzophenone is an advantageous method for producing the compound I more efficiently. However, when the sensitizer is not used, the feature is that the selectivity of geometric isomers is very high.

The photoreaction of levoglucosenone proceeds effectively with ultraviolet light and near-ultraviolet light. The reaction can be carried out within a temperature range from 0 ° C. to the boiling point of the reaction reagent used.

The isolation and purification of the compound I in the present invention can be carried out by a conventional means such as extraction, column chromatography,
It can be performed by operations such as distillation and recrystallization.

[0010]

The present invention will be described in more detail with reference to the following examples. Example 1 Synthesis of 5-formyloxy-3-pentenoic acid (R = H in formula (I)) Levoglucosenone 500 mg (4 m
Hydrous benzene (40 mol) containing 0.2 wt% of water
ml) and purging dissolved oxygen by nitrogen bubbling, and then in a Pyrex test tube under a nitrogen atmosphere at 500
Light irradiation was performed for 30 hours using a W high-pressure mercury lamp. The reaction solution was purified by silica gel preparative thin layer chromatography (developing solvent; ethyl acetate / hexane = 1/3) to obtain 429 mg of the target compound as a colorless oil (yield 75%). IR (neat, cm ^-1 ): 2853, 1721.6,
1174.5 ¹ HNMR (CD ₃ OD, δ): 3.23 (s, d, J =
5.86Hz, 2H), 3.71 (s, 3H) 4.77
(D, J = 6.84 Hz, 2H), 5.76 and 5.8
9 (each m, each 1H), 8.13 (s,
1H) ¹³ CNMR (CD ₃ OD, δ): 34.93, 61.1
2, 127.67, 129.43, 163.44, 172.
84 MS (relative intensity): 14
5 (3.6), 116 (2.7), 98 (100), 81
(8.0), 70 (78.6), 55 (52.4) high-resolution mass: C ₆ H ₉ O
₄ calcd for 145.0501, found
145.0473. The reaction product is a geometrical isomer composition consisting of 96% by weight of Z isomer and 4% by weight of E isomer, and the selectivity of Z isomer is excellent.

Example 2 Synthesis of 5-formyloxy-3-pentenoic acid (R = H in formula (I)) Levoglucosenone 500 mg (4 mmol), acetophenone 480 mg as a photosensitizer and hydrous benzene (4
0 ml), and after purging dissolved oxygen by nitrogen bubbling, 50% in a Pyrex test tube under a nitrogen atmosphere.
Light irradiation was performed for 30 hours with a 0 W high pressure mercury lamp. The reaction solution is purified by silica gel preparative thin layer chromatography (developing solvent; ethyl acetate / hexane = 1/3),
429 mg of the target compound was obtained as a colorless oil (yield 75
%). The target compound consisted of 41% by weight of Z isomer and 59% by weight of E isomer. ¹ HNMR (CD ₃ OD, δ): 3.14 (s, d, j =
5.86Hz, 2H), 4.77 (d, j = 5.86H)
z, 2H), 5.74 to 6.00 (m, 2H), 8.1
The presence of 4 (s, 1H) E form was confirmed by ¹ HNMR.

Example 3 Methyl 5-formyloxy-3-pentenoate (formula (I)
In the synthesis of R = Me, 500 mg (4 mmol) of levoglucosenone was dissolved in methanol (40 ml), dissolved oxygen was driven out by nitrogen bubbling, and then light irradiation was performed for 30 hours by a 500 W high pressure mercury lamp in a Pyrex test tube under a nitrogen atmosphere. went. The reaction solution was purified by silica gel preparative thin layer chromatography (developing solvent; ethyl acetate / hexane = 1/3) to obtain 307 mg of the target compound as a colorless oil (yield 5
8%). IR (neat, cm ^-1 ): 1731, 1725, 11
67 ¹ HNMR (CDCl ₃ , δ): 3.21 (d, J = 7.3)
2Hz, 2H), 3.71 (s, 3H), 4.72
(D, J = 6.83 Hz, 2H), 5.77 and 5.8
7 (each m, each 1H), 8.07 (s,
1H) ¹³ C NMR (CDCl ₃ , δ): 32.85, 52.0
5,59.36, 126.21, 126.75, 160.7
5,171.38 MS (relative intensity): 15
9 (9.0), 158 (0.2), 127 (15.1),
113 (100), 98 (42.4), 81 (31.
9), 71 (69.4) high -resolution mass: C 7 H 10
O ₄ calcd for 158.0586, foun
d 158.0593. The reaction product is a geometrical isomer composition consisting of 99% by weight of the Z isomer and 1% by weight of the E isomer, and has excellent selectivity for the Z isomer.

Example 4 Synthesis of methyl 5-formyloxy-3-pentenoate Levoglucosenone 500 mg, Acetophenone 480 m
g in methanol (40 m
Dissolve in l). After the dissolved oxygen was driven out by nitrogen gas in the reaction vessel, a photoreaction was carried out for 6 hours with a 500 W high pressure mercury lamp. The reaction solution was purified by silica gel preparative thin layer chromatography (developing solvent; ethyl acetate / hexane = 1/3) to give the target compound 320 as a colorless oil.
mg was obtained (yield 64%). This reaction product is Z-5
-Methyl formyloxy-3-pentenoate 78% by weight,
It was confirmed to be a mixture of 22% by weight of methyl E-5-formyloxy-3-pentenoate. ¹ HNMR (CDCl ₃ , δ): 3.13 (d, j = 6.
83 Hz, 2H), 3.70 (s, 3H), 4.66
(D, j = 6.86 Hz, 2H), 5.72 to 5.91.
The presence of (m, 2H), 8.07 (s, 1H) E-form was confirmed by ¹ HNMR.

Example 5 Synthesis of 5-formyloxy-3-pentenoic acid butyl ester (R = t-Bu in the formula (I)) Levoglucosenone (500 mg, 4 mmol) was dissolved in tertiary butanol (40 ml), and nitrogen bubbling was performed. After the dissolved oxygen was driven out by the method, light irradiation was performed in a Pyrex test tube under a nitrogen atmosphere with a 500 W high pressure mercury lamp for 30 hours. The reaction solution was subjected to silica gel preparative thin layer chromatography (developing solvent; ethyl acetate / hexane = 1).
352 mg of the target compound as a colorless oil.
Was obtained (yield 44%). IR (neat, cm ^-1 ): 2981, 1729, 17
31,1153 ¹ HNMR (400 MHz, CDCl ₃ , δ): 1.45
(S, 9H), 3.10 (d, J = 7.32Hz, 2
H), 4.72 (d, J = 6.84 Hz, 2H), 5.7
4 and 5.85 (each m, each 1H),
8.07 (s, 1H) ¹³ C NMR (400 MHz, CDCl ₃ , δ): 28.0
4, 34.36, 59.53, 81.05, 125.73,
127.43160.77, 170.17 MS (relative intensity): 20
1 (10.1), 145 (19.8), 99 (27.
3), 81 (13.7), 57 (100), 41 (3
8) high-resolution mass: C 10 H 17
O ₄ calcd for 201.1127 foun
d 201.11.114. The reaction product is a geometrical isomer composition consisting of 99% by weight of Z isomer and 1% by weight of E isomer, and has excellent selectivity for Z isomer.

Example 6 Synthesis of 5-formyloxy-3-pentenoic acid butyl ester (R = t-Bu in the formula (I)) Levoglucosenone (500 mg, 4 mmol) and acetophenone (480 mg) were added to tertiary butanol (40 m).
l), dissolved oxygen is removed by nitrogen bubbling, and then 500 W in a Pyrex test tube under a nitrogen atmosphere.
Light irradiation was performed for 30 hours using a high pressure mercury lamp. The reaction solution was purified by preparative thin layer chromatography on silica gel (developing solvent; ethyl acetate / hexane = 1/3) to obtain the target compound as a colorless oil (yield 45%). The target compound was 55% by weight of Z form and 45% by weight of E form. ¹ HNMR (400 MHz, CDCl ₃ , δ): 1.45
(S, 9H), 3.02 (d, j = 6.83Hz, 2
H), 4.65 (d, j = 6.35 Hz, 2H), 5.
The presence of the 65-5.90 (m, 2H), 8.06 (s, 1H) E-form was confirmed by ¹ H NMR.

[0016]

INDUSTRIAL APPLICABILITY Levoglucosenone is an important intermediate for pharmaceuticals, pesticides, fragrances, etc. by performing a photoreaction in the presence of water or alcohol in an inert gas atmosphere. Certain 5-formyloxy-3-pentenoic acid compounds can be obtained.
In this photoreaction, the reaction time can be remarkably shortened by adding a photosensitizer, and the reaction time becomes longer in the reaction without addition, but only the Z-5-formyloxy-3-pentenoic acid compound is used. Can be selectively synthesized.

Claims (3)

[Claims] 1. A compound represented by the following general formula [I]: (In the formula, R represents hydrogen or an alkyl group which may have a linear or branched, saturated or unsaturated substituent having 1 to 12 carbon atoms), and 5-formyloxy-3-.
Pentenoic acid or its ester. 2. A formula [II]: A general formula [I] wherein levoglucosenone represented by the formula (I) is photoreacted in the presence of water or alcohol in an inert gas atmosphere. (In the formula, R represents hydrogen or an alkyl group which may have a linear or branched, saturated or unsaturated substituent having 1 to 12 carbon atoms), and 5-formyloxy-3-.
Process for producing pentenoic acid or its ester. 3. The method for producing 5-formyloxy-3-pentenoic acid or an ester thereof according to claim 2, wherein the photoreaction is carried out in the presence of a photosensitizer.