JPS6165877A - Hydroxylactone - Google Patents

Abstract

NEW MATERIAL:A hydroxylactone shown by the formula I (R1 is methyl, or 4-methyl-3-pentenyl; R2 is 3-methyl-2-butenyl when R1 is methyl, and R2 is H when R1 is 4-methyl-3-pentenyl). USE:Useful as a raw material for synthesizing perylene or rosefuran. Capable of producing industrially perylene or rosefuran useful as perfume, etc. without producing position isomers. PREPARATION:For example, beta-methallyl alcohol is reacted with n-butyl lithium in the presence of excess N,N,N,N-tetramethylethylene-diamine to give a lithium derivative of beta-methallyl alcohol, this lithium derivative is reacted with 3,3- dimethylallyl chloride to give a compound shown by the formula II. Then, the compound shown by the formula II is oxidized, refluxed with sodium cyanide to give a reaction product shown by the formula III, which is dehydrated and subjected to ring closure to give a compound shown by the formula I.

Description

Detailed Description of the Invention [Industrial Application Field] This invention relates to a compound of the first formula (wherein R1 represents either a methyl group or a 4-methyl-3-bentenyl group, R2 is R
When 1 is a methyl group, it is a 3-methyl-2-butenyl group, and when R1 is a 4-methyl-3-pentenyl group, it is a hydrogen atom. ), and more specifically, the present invention relates to hydroxylactones represented by Formula 1, which are useful raw materials for the synthesis of perylene and rosefuran, for example.

[Prior Art] Furans having substituents at the 3-position or the 2- and 3-positions are widely distributed in nature. For example, furan or perylene having a substituent at the 3-position as shown in formula 2 is isolated from plants and animals.

Furthermore, furan having substituents at the 2- and 3-positions as shown in formula 3, ie rose furan, is isolated from Bulgarian rose.

Since the above-mentioned perylene and rosefuran are useful, for example, in fragrances, it is desired to establish a method for synthesizing them. As a method for synthesizing them, a method by reduction from furanobutenolide shown in formulas 4 and 5 has been reported. has been [D,
R., Gerlge et al., Tetrahe
Dron Lett, (1977), 4443
].

H3 [Problems to be solved by the invention] In the synthesis of rosefuran etc. according to the above-mentioned report, 4-methyl-(5H)-furan-2-one is used as a starting material and a dimethylallyl group in the side chain is introduced. However, positional isomers are produced as by-products, resulting in a low yield of the desired precursor, and furthermore, it is difficult to separate and purify the desired precursor.

[Means for Solving the Problems] Based on the above circumstances, the inventors aimed to synthesize the furanobutenolides represented by the fourth and fifth formulas in a high yield and as a single product without by-products. The present invention was achieved by discovering that it is possible to synthesize hydroxylactones that have the following properties.

The hydroxytictones represented by the first formula according to the present invention can be further represented by the following formulas 6 and 7, both of which are novel compounds.

(The following is a blank space) The hydroxylactones according to the present invention can all be synthesized using methallyl alcohol as a starting material in the following manner. That is, when synthesizing the hydroxylactone represented by the sixth formula, first, excess N, N, N,
β-methallyl alcohol and n-butyllithium are reacted in the presence of N-tetramethylethylenediamine to form β
- Obtaining a lithiated product of methallyl alcohol, and reacting this lithiated product with 3,3-dimethylallyl chloride to obtain an allyl alcohol derivative represented by Formula 8.

In addition, when synthesizing the hydroxylactone represented by formula 7, β-methallyl alcohol is treated with, for example, diphenyl disulfide (1,5 equivalents) and tri-n-butylphosphine (1,1 equivalents, pyridine solution, 0°C). to obtain a sulfide compound represented by formula 9, and then this sulfide compound was 3,3
-dimethylallyl chloride to obtain a compound of formula 10.

(However, in the 9th and 10th formulas, ph represents a phenyl group.) The compound represented by this 1st formula, for example, m-chloroperbenzoic acid (1.0 equivalent, methylene chloride solution, -20°C
) etc., a sulfoxide compound represented by formula 11 is produced, and when this sulfoxide compound is treated with, for example, triethyl phosphite or diethylamine, an allyl alcohol compound represented by formula 12 is obtained.

The allyl alcohol compound represented by the 12th formula and the allyl alcohol compound represented by the 8th formula have an isomer relationship.

H3 Allyl alcohol compounds represented by formulas 8 and 12 are converted to hydroxylactone by the same method.

That is, taking the allyl alcohol compound represented by the 8th formula as an example, first, the allyl alcohol compound represented by the 8th formula is, for example, vanadyl acetylacetonate (2
mol%, methylene chloride solution, 0 °C) with t-butyl hydroperoxide (2,0 eq.),
The epoxide compound represented by formula 13 is then 0,
When this epoxide compound was refluxed with sodium cyanide (5, C1 amount) in ethanol for 16 hours, a series of reactions accompanied by Payne rearrangement resulted in the dihydroxycarboxylic acid represented by Formula 14. When this dihydroxycarboxylic acid compound is azeotropically refluxed in toluene, it undergoes dehydration and ring closure, yielding a hydroxylactone represented by Formula 6.

Similarly, the allyl alcohol compound represented by the 12th formula is oxidized with a peroxide to form the epoxide compound represented by the 15th formula, and this epoxide compound is heated together with a cyanide compound in alcohol to undergo the Payne rearrangement. Through the introduction of a cyano group and hydrolysis, a dihydroxycarboxylic acid compound represented by the 16th formula is obtained, and by dehydrating and ring-closing this dihydroxycarboxylic acid compound, a hydroxylactone represented by the 7th formula is obtained. The hydroxylactones obtained can be easily converted into furanobutenolides represented by formulas 4 and 5 by a simple dehydration reaction without producing positional isomer by-products, and these furanobutenolides are As mentioned above, perylene and rosefuran can be easily derived almost quantitatively by reduction reaction. Therefore, the hydroxylactones according to the present invention are useful raw materials for the synthesis of perylene and rosefuran, and since the hydroxyfurans according to the present invention can be derived from β-methallyl alcohol, perylene and rosefuran are useful. Industrial production of francs can be made possible.

[Example] Next, the present invention will be explained in more detail by referring to Reference Examples and Examples.

(Reference example 1) Synthesis of allyl alcohol compound represented by Formula 12.

β-methallyl alcohol 7.2 g (0.1 l) and tri-n-butylphosphine 30.35 g (0.1 l)
5 mat ) and diphenyl disulfide 32.7 g (0
, 15 mol) at room temperature.
The mixture was stirred for 15 minutes. After stirring, pyridine was distilled off under reduced pressure, diethyl ether was added to the resulting residue, and the mixture was diluted with 10% hydrochloric acid, 10% aqueous sodium hydroxide solution, water and saturated brine.
Washing operations were performed in this order.

After washing, it was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. When the obtained residue is distilled, bp=125~1
At 31°C, the sulfide represented by formula 9 was obtained in a yield of 68%.

Next, the sulfide 500B (3.05 mmol
) in 5 ml of tetrahydrofuran solution at -78°C.
A 10% n-hexane solution of n-butyllithium was added dropwise while cooling to 0.05%, and the mixture was stirred for 5 minutes. Then, at the same temperature, 627 mg (627 mg
, 1 mmol) in tetrahydrofuran was added dropwise thereto, and after stirring for 25 minutes, the mixture was returned to room temperature and stirred for 35 minutes to obtain a product liquid. A saturated aqueous sodium hydrogen carbonate solution was added to this product solution, then diluted with diethyl ether,
The resulting organic layer was washed with saturated brine and then dried over magnesium sulfate. After drying, the solvent was distilled off under reduced pressure and the 10th
870 mg of the compound represented by the formula was obtained.

Compound 7.07g (30.47m
12.8 g (152.4 mmol) of sodium hydrogen carbonate was added to 100 ml of methylene chloride solution of 5.0 mol) of m-chloroperbenzoic acid while cooling with salt-ice.
Added 26g. A product liquid was obtained by stirring for 25 minutes while cooling to the same temperature. A 2% aqueous solution of sodium thiosulfate was added to the resulting solution, and the organic layer was separated. After washing the organic layer with water and saturated brine, the organic layer was dried over magnesium sulfate.

After drying, the solvent was distilled off from this organic layer, and the resulting residue was subjected to silica gel column chromatography, and the residue was purified from a diethyl ether/n-hexane (l:4, V/V) distillate using Equation 11. 3.63g of the sulfoxide compound shown
I got it.

This sulfoxide compound 1.00 g (4.03 mm
al) to 20ml of methanol solution, add 70ml of diethylamine.
．． 885 g (12.1 mmal) was added and heated under reflux for 10 hours. The solvent was distilled off from the resulting product solution under reduced pressure, and the residue was diluted with diethyl ether. This diethyl ether solution was washed with 2% hydrochloric acid, water, 15% aqueous sodium hydroxide solution, water, and saturated saline in this order. After washing, the a-layer was dried with magnesium sulfate, and then the solvent was distilled off to obtain a residue. This residue was subjected to silica gel column chromatography, and the title allyl alcohol compound 740B was obtained from a distillate of diethyl ether/n-hexane (1:6, V/V).

IR(y,c+a-1) 3600.3420.13
70.99O NMR (δ, ppm) 1.58 (IH%S)1
．． 60 (3H, S) 1.70 (6H, 5X2) 2.72 (2H, dd, J = 6 , m) 5.20-5.50 (LH, m) (Reference example?) Synthesis of an epoxide compound represented by Formula 15.

200 mg of allyl alcohol compound synthesized in Reference Example 1
(1,43 mmol) (7) Methylene chloride solution 1
0ml of vanadyl acetylacetonate 7.6 mg
of methylene chloride solution (concentration: 2 mo1%) was added, and then, under water cooling, 1.41 ml of a methylene chloride solution containing 2.86 mmol of t-butyl hydroperoxide was added.
was added, and then stirred at room temperature for 3.5 hours to obtain a product liquid.

After adding an 8% aqueous sodium sulfite solution to the resulting solution, the organic layer was separated, washed with saturated brine, and dried over magnesium sulfate. After distilling off the solvent, it was subjected to silica gel column chromatography to extract diethyl ether/n-hexane (l
: 2, V/V) from a distillate of 8
Obtained with a yield of 5%.

IR (y, cm-') 3400.1440.1370.
1010 35N (δ, ppm) 1.33 (3H,S)1
．． 66 (3H, S) 1.73 (3H, S) 1.92-2.53 (3H, m) 3.03 (IH, t, J=7Hz) 3.63 (2H, br, S) 4. 9.2-5.40 (IH, m) (Example 1) Synthesis of hydroxylactone represented by formula 7.

Epoxide compound 150B (0,962
mmal) and water-containing ethanol [ethanol/water = 2/
3, V/V], 236 mg of sodium cyanide was added to this solution, and the mixture was heated under reflux for 7 hours. Ethanol was distilled off under reduced pressure, and concentrated hydrochloric acid was added to the resulting residue to adjust the PL to 1 to 2, followed by extraction with methylene chloride.The extract was washed with saturated brine, and then extracted with sulfuric acid. It was dried over magnesium, and the solvent was distilled off under reduced pressure.The obtained residual liquid was dissolved in toluene 251, and this was heated under reflux for 6 hours.The obtained product liquid was diluted with diethyl ether, and saturated sodium hydrogen carbonate was added. After washing with an aqueous solution and a saturated saline solution in this order, it was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure.The obtained residue was subjected to silica gel column chromatography, and diethyl ether/n-hexane (1
:1, V/V), the title hydroxylactone was obtained as a colorless oil in 56% yield.

IR(y, cm-1) 3350.176ONMR(
δ, ppm) 1.36 (3H,S) 1.66
(3H,S) 1.73 (3H,S) 2.01~2.56 (2H,m) 2.59 (2H,S) 2.73 (IH,br,S) 4.34 (IH,dd , J=8X6 Hz) 5.00-5.43 (IH, m) (Example 2) Synthesis of furanobutenolide represented by formula 5.

100 mg of hydroxylactone synthesized in Example 1 above
(0.53 m+wol) was dissolved in 5.1 methylene chloride, and 0.0.
27 ml (1,96 mmol) and methanesulfonyl chloride 0.076 ml (0,978 mmol
) was added. Thereafter, the mixture was stirred at room temperature for 3.5 hours. The resulting product solution was diluted with methylene chloride, washed in this order with water, 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine, and then dried over magnesium sulfate. After drying, the solvent was distilled off under reduced pressure, the resulting residue was subjected to silica gel column chromatography, and quantitatively extracted from a diethyl ether/n-hexane (l:3, V/V) distillate. The compounds shown in the table were obtained.

IR (ν, cm-1) l 755.164o, 117
O NMR (δ, ppm) 1.63 (3H,S)1.
69 (3H,S) 2.07 (3H,S) 2.20~2.76 (2H,m) 4.66~5.26 (IH+LH,m) 5.66~5.92 (IH,m) As is clear from this example, furanobutenolide, which is a raw material for rosefuran and is represented by Formula 5, can be easily and quantitatively synthesized from hydroxylactone represented by Formula 7.

(Reference example 3) Synthesis of allyl alcohol compound represented by formula 8.

Under an argon stream, 12.8 m of n-hexane solution (concentration: 10%) containing 20 mmol of n-butyllithium
N-hexane was distilled off from 1 under reduced pressure, and 3.N,N,N,N-tetramethylethylenediamine was added to the resulting residue.
51, 12 ml of diethyl ether and 3 ml of tetrahydrofuran were added. β-methallyl alcohol-JL/720 mg (10 mmo
+) Total dropwise addition L. After the dropwise addition, the mixture was stirred at room temperature for 1.5 hours. Then, while cooling, 4.70 g (45 mmol) of 3,3-dimethylallyl chloride was added dropwise, and after the dropwise addition, the mixture was stirred for 40 minutes. The mixture was further stirred at room temperature for 30 minutes. The resulting product solution was diluted with diethyl ether, and then the diethyl ether layer was washed with Yuwa carbonated sodium hydrogen aqueous solution, wood, saturated copper sulfate aqueous solution, 5% hydrochloric acid, water, and saturated brine in this order. After washing, the obtained diethyl ether layer was dried with magnesium sulfate, and then the diethyl ether was distilled off under reduced pressure to obtain a residue. This residue was subjected to silica gel column chromatography to obtain the title allyl alcohol compound in a yield of 30% from a distillate of diethyl ether/n-hexane (l:4, V/V).

IR (y, cm-') 3340, 1650.90ONM
R(δ, pp厘) 1.62 (3H,S)
1.70 (3H,S) 2.05~2.30 (4H,m) 1.97 (IH,br) 4.06 (2H,S) 4.80~5.10 (2H,m) 5. 12 (LH, m) MS (m/e) 140 (M) (Reference Example 4) Synthesis of an epoxide compound represented by Formula 13.

Using the allyl alcohol compound synthesized in Reference Example 3 as a raw material, the title epoxide compound was obtained in a yield of 81% in the same manner as in Reference Example 2.

IR(ν, cm-1) 3440.89ONMR(
δ, ppm) 1.6゛1 (3H,S)1.68
(3H, S) 1.75-2.35 (3H, m) 2.68 (IH, d, J=4.5 Hz) 2.88 (IH, d, J=4.5 Hz) 3.58 ~3.83 (2H, m) 0.90 N1.40 (2H, m) MS (m/e) 156 (M+) (Example 3) Synthesis of hydroxylactone represented by formula 6.

Using the epoxide compound synthesized in Reference Example 4 as a raw material, the title hydroxylactone was obtained in a yield of 64% in the same manner as in Example 1.

I R(y, am-') 3410.178ONM
R(δ, PP!I) 0.90~1.30 (2H,
m) 162 (3H,S) 1.68 (3H,S) 1.80~2.23 (2H1m) 2.55 (2H,S) 4.18 (zH,s) 4.85 (L H,br ) 5.10 (IH, m) MS (m/e) 166 (M -18) Molecular weight (as C1oH1603) Calculated value: 184.1099 Actual value: 184.1100 (Example 4) Shown by the 4th formula Synthesis of furanobutenolide.

Using the hydroxylactone synthesized in Example 3 as a raw material, the title furanobutenolide was obtained in a yield of 92% in the same manner as in Example 2.

IR(y,c,m-') 1780.1745.163
5.885 NMR (δ, ppm) 1.63 (3H,S)1.
70 (3H, S) 2.20-2.60 (4H, m) 4.68 (2H, d, J = 1.5Hz) 4.90-5.31 (LH, m) 5.75-5. 92 (IH, m) MS (III/I!) 166 (M+-18
) As is clear from this example, furanobutenolide, which is a raw material for perylene synthesis, and which is represented by Formula 4, can be easily produced from hydroxylactone represented by Formula 6, and
It can be synthesized in high yield.

Claims (1)

[Claims] Formula 1 ▲ Numerical formulas, chemical formulas, tables, etc. ▼...(1) (However, in the first formula, R_1 is a methyl group and 4-
It represents any methyl-3-pentenyl group, and R_2 is a 3-methyl-2-butenyl group when R_1 is a methyl group, and a hydrogen atom when R_1 is a 4-methyl-3-pentenyl group. ) Hydroxylactones.