JPS6368533A - Production of substituted catechol - Google Patents

Abstract

PURPOSE:To obtain a substituted catechol in high yield, by heating a 2- substituted-2,5-dialkoxy-tetrahydrofuran in an organic solvent in the presence of specific amounts of an acidic catalyst and water. CONSTITUTION:A compound shown by formula I (R is 3-17C alkyl or aliphatic hydrocarbon group containing unsaturated double bond; R' and R'' are 1-3C alkyl) is heated in an organic solvent such as dioxane, tetrahydrofuran, alcohol, acetone, dimethylformamide, dimethyl sulfoxide, etc., in the presence of >=0.025 equivalent based on 1g compound shown by formula I of an acidic derivative (e.g. hydrochloric acid, sulfuric acid, perchloric acid, hydrobromic acid, etc.) and a small amount, preferably >=130ml, especially about 100-120ml based on 1g compound shown by formula I of water preferably at >=50 deg.C, especially 80 deg.C- reflux temperature for about 8-15hr to give the aimed compound shown by formula II in high yield.

Description

[Detailed description of the invention] (Industrial application field) The present invention relates to a method for producing substituted catechols.

(Prior art) Alkylcatechols have traditionally been synthesized using a veratrol derivative with the hydroxyl group of catechol protected as a starting material and obtained through a demethylation process (Osaka Institute of Technology Quarterly Report 1).
Volume 6, No. 52, page 1647.

(1965) and a method using a furan compound as a starting material are known.

Journal of the American Chemical Industry
icanChemical 5ociety) Vol. 82, p. 498 (I960), 2-heptadecanoyl-
2,5-dimethoxy-tetrahydrofuran was added at 0.65% in an aqueous solution of thidiochitin. When refluxed with IN hydrochloric acid for 2 hours, 3,4-diketoheneicosanaldehyde was obtained in a yield of 75%, and when this hydrolysis reaction was carried out for 24 hours, a yield of 3.4-diketoheneicosanaldehyde was obtained.
We report that pentadecylcatechol is obtained at 7%.

In addition, the Bulletin of the Chemical Society of Japan (Bulletin of the Chemical Society of Japan)
chemical 5ociety of Japan)
Volume 35, page 263 (I963) describes ethyl-α-(2
,5-shedkin-tetrahydro)fur70yl-α-
Heptadecyl acetate 0. It is described that the reaction product 9 was treated with lead acetate after addition to a mixed solution of IN hydrochloric acid and dioxane and heated at reflux temperature for 10 hours to obtain heptadecylcatechol in a yield of 34.7%.

(Problems to be Solved by the Invention) As described above, in the conventional methods, substituted catechols such as alkylcatechols can only be obtained in low yields, and the methods are not industrially applicable.

The present invention solves these problems.

(Means for Solving the Problems) The present invention is based on the general formula fi+ (wherein R is an alkyl group having 3 to 17 carbon atoms, and ,R
' and ' each independently represent an alkyl group having 1 to 3 carbon atoms) 2-substituted-45-dialkoxy-2
, 5-hydrofuran in an organic solvent, the 2-substituted-45
-0.02 per gram of dialkoxytetrahydrofuran
By heating in the presence of 5 or more equivalents of acidic catalyst and a small amount of water.

The present invention relates to a method for producing substituted tyrol, which is characterized by obtaining a substituted catechol represented by the general formula (It) (where 几 is the same as above).

Examples of the organic solvent include dioxane, tetrahydrofuran, alcohol, acetone, dimethylformamide, dimethyl sulfoxide, and the like.

Examples of the acidic catalyst include hydrochloric acid, R acid, and perchloric acid.

Hydrobromic acid and the like are used, and the acidic catalyst is used in an amount of 0.025 equivalent or more per 1 g of the 2-substituted-25-dialkoxy-tetrahydro7rane represented by the general formula (I). If there is too little acidic catalyst, the yield will decrease.

If the amount is too large, side reactions tend to occur, so the amount is preferably 0.25 equivalent or less.

It is easy to use the acidic catalyst as a 0.5-5N aqueous solution.

Also, a small amount of water is present in the reaction system. The presence of large amounts of water reduces the yield. The amount of water is preferably 130 ml or less per gram of 2-Jt-converted-2,5-dialkoxy-tetrahydrofuran represented by the general formula (I1). Operationally, it is easy to adjust the amount to about 100 to 120 ml. .

In the above reaction, the heating temperature is preferably 50°C or higher.

Particularly preferred is a temperature of 80°C to reflux temperature. If the reaction temperature is too low, the reaction progresses too slowly.

The reaction time is appropriately determined, but approximately 8 to 15 hours is appropriate. Care must be taken because if the reaction time is not long, the yield will decrease due to the formation of by-products such as polymers.

The 2-substituted-2,5-dialkoxy-tetrahydrofuran represented by the general formula (I1) can be obtained in the following manner.

Furfural is reacted with a Guineal reagent represented by the general formula RMgBr (where R is the same as in the above-mentioned bifurcated formula (I)) in an organic solvent such as dry diethyl ether,
Synthesize carbinol represented by general formula (5) (in formula 9, R is the same as above), and oxidize it with an oxidizing agent such as manganese oxide to obtain general formula (B) (in formula 9, R is the same as above). is the same as above), and further, this ketone is synthesized in an alcohol represented by the general formula R′′OH (where R′′′ represents a methyl group, an ethyl group, or a propyl group). .

A compound represented by the general formula (C) (where R, R' and 几" are the same as above) is synthesized by electrolytic oxidation, and then this compound is hydrogenated to form a compound represented by the general formula (I). -substituted-45-dialkoxy-tetrahydrofuran can be obtained.

The above steps can be performed by conventionally known methods.

In addition, in electrolytic oxidation, NHaBrNH4NO3
A supporting salt such as 1MeONa may be used, and a platinum electrode may be used as the electrode. Also.

A catalyst such as palladium activated carbon or Raney nickel can be used for the hydrogenation.

The substituted catechol obtained by the present invention is subjected to silica gel column chromatography (benzene, etc. can be used as a solvent), and recrystallization (as a solvent, petroleum ether, ether, acetone-alcohol mixed solvent, etc. can be used).
rtwl can be performed by, for example,

The degree of purification can be confirmed by carrying out a blending test with a standard sample of the substituted catechol obtained according to the present invention and showing no depression in the melting point.

(Example) Next, two examples of the present invention will be shown, but first, a synthesis example of a raw material of the present invention will be shown.

Hereinafter, NM⇠ indicates the δ value of the nuclear magnetic resonance spectrum,
t is a triplet, m is a multiplet.

bs indicates a broad singlet, and s indicates a singlet. ■几 indicates the infrared absorption spectrum.

Its absorption position (am-') is shown. MS shows the mass spectrum and shows its parent peak position.

Synthesis Example 1 (Synthesis of I-(2-furyl)-heptadecanol) Furfural [Procedure] Mg 169. Dry ether (50 ml) and It;
A small amount was added and stirred in a warm bath (40°C).

When Mg was activated, 61.4 g of n-hexadecylpropylene (N-hexadecylpropylene) dissolved in K in dry ether (50 ml) and dry ether (200 mj) were added dropwise in small portions, and after one drop, the mixture was stirred for 1 hour. Dry ether (50
ml ) dissolved furfural 9.6 g (0,1
After adding 9 drops of 9 drops, the mixture was stirred for 2 hours.

〔process〕

The reaction solution was transferred to a 1000 m/beaker, and ice was added little by little while stirring until no scuttling occurred. The precipitate was removed by filtration, and the filtrate was salted out and dried. After removing the solvent in vacuo, column chromatography (silica gel, ELU
Purified with ENT: benzene: ethyl acetate = 95:5),
1-(2-furyl)-caheptadecanol was obtained. Yield 20.59 Yield 64 chi (
m, p53.5 55.0°C) [Analysis] NMR δ value: 0.9 (t, 3H), Ll-1,4
(ms 28 H) t L 6 (bsy IH)
, 1.8 (rrb2H), 4.6 (t, IH),
6.1 (m, IHJ=0.9, 3.6 Hz
), 6.2 (m, I H, J=1.8°3.6
Hz), 7.3 (m, I H, J = 0.
9.1.8Hz) Absorption at IR3350cm-' MS 322 (Mw: 322) Synthesis Example 2 [Synthesis of 2-heptadecanoyl 7 run] 1-
(2-Furyl)-heptadecanol [Procedure] 300 ml triangular class = + to 1-(2-7Ryl)-heptadecanol 6.09 (I,6X 10-” mol
) and dissolved in benzene (200 ml). Activated Mn0m 309 was added to this solution and allowed to rise at room temperature for 50 hours.

〔process〕

Activated Mn0z was removed by filtration, and the filtrate was salted out and dried. The solvent was removed in vacuo to obtain product (2).

Yield i3.99. Yield 65% (m-psa, o-s5.
o℃).

Purification was performed by column chromatography (silica gel).

ELUENT: benzene).

〔analysis〕

NMR δ value: 0.9 (t, 3H), 1.1-1
．． 5 (m, 26H), 1.5-1.7 (m, 2H).

2. 8 (t, 2H), 6.4 (m, I
HJ=1.8°3.3Hz>, 7.1 (m, I
HJ = 0.9.3.3Hz), 7.4 (mt I
HJ=0.9.1.8Hz) IR1680ao-' has absorption MS 320 (Mw: 320) Synthesis Example 3 [Synthesis of 2-heptadecanoyl-45-dimethoxy-2,5-dihydrofuran] [Operation] 100 m/ 10.19 (&
I x 10-'moI and LiCl0a: 0.
Added 19. While stirring the solution, constant current electrolysis (3F
/mo! ) was carried out.

〔process〕

After neutralizing the reaction solution with sat, NaHCOs aqueous solution.

The solvent was distilled off. Ethyl acetate (50 ml) was added to the residue, followed by salting out and drying. Remove the solvent in vacuo.

Column chromatography (silica gel, ELUENT
Obtained. Yield fiQ, 89 yield 67chi (b, p161-16
5℃/1 mmHg) [Analysis] NMR δ value: 0.8 (t, 3H), 1.2-1
．． 6 (m.

28H), Z6 (t, 2H) 41-3.5 (84 pieces,
6H; cis&trans) 5.4-al
(rib3H) IR2830, 1730, 1140-1020cm-'
MS 350 (Δ(w: 382)) Synthesis Example 4 [Synthesis of 2-heptadecanoyl-2,5-dimethoxy-tetrahydrofuran] [Procedure] In a 100 m round bottom flask, 2-hepta was dissolved in 80 ml of ethyl acetate. Decanoyl 5-dimethoxy-λ
5-dihydro7rane (3) 1.0 g (Z6 Xl
0-3 mol) and Pd activated carbon: 0.29 were added.

After the inside of this eggplant flask was degassed under reduced pressure, H2 gas was passed through the flask for about 24 hours without stirring.

〔process〕

Pd activated carbon was removed by filtration, and the filtrate was salted out and dried.

After distilling off the solvent, vacuum distillation was performed to obtain product (4). Yield 0
．． 9g yield 90% (b, p159-164”C/1
mmHg) [Analysis] NMR δ value: 0.9 (t, 3H), 1.1-1
．． 6<m, 28H), 1.8-2.2 (m, 4H).

Z6 (tt 2H), 3.1-a4 (SX4゜6
H: cis&trans), 4.9-al
(m, IH) IR2830, 1725, 1100-1
020cm-' absorption MS 384 (Mw: 384) Example 1 [Synthesis of hydrourushiol] s o ml e dioxane 2
00mI! (contains 5% water by weight) and 2-heptadecanoyl 5-dimethoxy-tetrahydrofuran (410
.

, [Treatment] Water (200mj') was added to the reaction solution, and ethyl acetate (I0
0mI! X3) and repeated washing with a sat and NaCl aqueous solution until the washing water became neutral. After drying, the solvent was distilled off, and column chromatography (silica gel, ELUE
NT: benzene) to obtain product (I). Yield o, ag
Yield 72% (m-p 57.0-57.5°C) [Analysis] NMR δ value: 0.9 (t, 3H), 1.1-1.
6 (m, 26H), 15 (t, 2H), 4.7-4.
9 (bsX2, 2H), 6.5 (m, 3H) I 几
3400, 1580, 720C! M8 with absorption in O-1
320 (Mw: 320) Comparative Example 1 In Example 1, lN-HCl! Instead of an aqueous solution, 9 to 0. lN-HCl! An aqueous solution was used, and dioxane containing 1JH 35% by weight of water was used.

The procedure of Example IK was followed except that the mixture was refluxed for 24 hours. As a result, a compound represented by Formula 1 (% Formula %) was obtained as the main product (yield: 48%). Approximately 240 ml of water was present for compound 19 (4).

Examples 2 to 5 The procedure of Example 1 was repeated except that a compound represented by Formula 9 was used instead of 2-heptadecanoyl-2,5-dimethoxy-tetrahydrofuran. The results are shown in Table 1.

Table 1 (Effects of the Invention) According to the present invention, substituted catechols represented by general formula (II) can be obtained in high yield.

What...

Claims (1)

[Claims] 1. General formula (I) ▲ Numerical formula, chemical formula, table, etc. ▼ (I) (However, in the formula, R is an alkyl group having 3 to 17 carbon atoms or a fat having an unsaturated double bond. group hydrocarbon group, R'
and R'' each independently represent an alkyl group having 1 to 3 carbon atoms) in an organic solvent, the 2-substituted-2,5-
0.025 per gram of dialkoxy-tetrahydrofuran
By heating in the presence of an equivalent amount or more of an acidic catalyst and a small amount of water, it is possible to form a compound represented by the general formula (II) ▲Mathematical formula, chemical formula, table, etc.▼(II) (wherein R is the same as above) A method for producing a substituted catechol, characterized by obtaining a substituted catechol.