JPS6064975A - Preparation of 8alpha,12-epoxy-13,14,15,16-tetranorlabdane - Google Patents

Abstract

PURPOSE:To obtain the titled substance useful as perfume having amber aroma, by treating methyl levopimarate, etc. with an oxidizing agent, subjecting the reaction product to witting reaction, treating the prepared compound with an oxidizing agent, reducing agent, dehydrating agent, and further a reducing agent, etc. CONSTITUTION:A compound shown by the fomula I (R1 is CO2H, or CO2CH3), for example, is oxidized by combination of ozone oxidation and Jones oxidation to give a compound shown by the formula II (R2 is CHO, or CO2H, or CO2 CH3), which is subjected to Wittig reaction, to give a compound shown by the formula III. It is treated with an oxidizing agent (e.g., perbenzoic acid), a reducing agent, and a dehydrating agent to give a compound shown by the formula IV(R3 is CO2H, CO2CH3, CH2OH, CH2OSO2CH3, CH2OSO2C6H4 CH3), which is further treated with a reducing agent and an oxidizing agent, to give a compound shown by thr formula V.

Description

Detailed Description of the Invention The present invention processes a compound represented by the following general formula (I) to convert it into 8α,12-epoxy-13,14,15,16-7 represented by 1. -) It relates to a method for producing Ranorgun. Chemical formula 61) is dodecahydro-3a, 6, 6 according to the nomenclature of Gummy Abstracts magazine.
, 9a-tetramethylna7)[2,1-b]7 run, and is also commonly called ambrox.

Compound G1 is a substance useful as a perfume with an excellent amber aroma. Compound (g) or Ambrox is
It is manufactured using manur and scleraol as raw materials, but these are both compounds extracted from coniferous trees produced in New Sealant, and their production is low and expensive.

The purpose of unexploded IJJ is to provide a method for producing compounds with an amber aroma from inexpensive raw tar with a large amount of m9 produced, but to be more precise, the following compounds (
I) Provides a method for producing compound (A) from (including compounds (Ia) and (Ib)), and is not limited to raw powder tar.

Raw tar resin contains various compounds, the main components of which are levobima and ruic acid (compound (Ia) below). Its content ranges from about 15% to 50%, for example in Organic Synthesis.
.

Col Active Volume V, 69
The method described in page 9) can easily purify the compound.

When compound (Ia) is diluted with diazomethane,
Methyl levopimarate (compound (It) below) is 1! When compound (Ib) is oxidized, compound (1,1a
) can be found. As the oxidation method, for example, ozone oxidation and Jones oxidation are used in combination.
Ocinide is generated with ozone-containing gas at °C, and ocinide is decomposed with potassium iodine or dimethyl sulfide. The above compound (Ila) is contained in the product of this ozone oxidation, but by further Jones oxidizing the product, that is, dissolving the product in acetone and using Jones reagent (chromic acid-sulfuric acid aqueous solution). )
By adding and reacting at -10 to 20°C, the yield of compound (Ila) can be increased. Compound (IIa) is extracted as a saponified product from the Jones oxidized product, and then reacted with diazomethane to obtain compound (1).
, To) By changing K, purification by silica gel column chromatography becomes easier.

When compound (nb) is subjected to Wittig reaction, compound (Irll)) is formed. Phosphonium salts used in the Wittig reaction include methyltriphenylphosphonium bromide, methyltriphenylphosphonicum iocide, methyltriphenylphosphonicum chloride, and bases include:
Calicum tert-gutoxide, calicum tert-amyloxide, etc. are preferred, and as a solvent, isopropyl ether, toluene, benzene, etc. are preferred. Appropriate reaction temperatures and reaction times are approximately 1, room temperature to 110°C, and 1 to 6 hours.

The compound (ITo) is dissolved in a solvent such as taloloform, methylene chloride, and a peracid, preferably m-talol perbenzoic acid, perbenzoic acid, peracetic acid, perphthalic acid, etc., for about 1 hour.
When the reaction is carried out at 5 to 80°C for about 3 to 48 hours, epoxidation of the double bond occurs and compound QV) is obtained.

Compound (IV) is treated using a reducing agent such as lyticum aluminum hydride and a solvent such as tetrahydrofuran,
In ethyl ether etc. about θ~6 (1°C1 about 0.
5-12 o'clock I? 3J ly, -response-tz ruto compound e
y (V) is f! ) Rareru.

Compound ff) is dissolved in a salt-free solvent such as pyridine/I
'/L, when reacted with methanesulfonyl chloride, the compound Qla) is formed, and the reaction temperature of the il is 0 to 50.
℃, and the reaction time is preferably 6 to 48 hours.

Further, when compound (V) is reacted with (■)-toluenesulfonyl chloride under the same conditions as above, compound (■l)) is obtained.

Alternatively, compound (Vlc) can be obtained by dissolving compound (V) in a solvent such as toluene or benzene, adding dimethyl sulfoxide and tarolotrimethylsilane, and reacting at 15 to 110°C for 10 minutes to 24 hours.

Compound (Wc) is dissolved in a basic solvent such as pyridine,
When reacted with methanesulfonyl chloride, the compound (Wa
) is obtained, and when compound (Wc) is similarly reacted with P-)toluenesulfonic acid, compound (VTb) is obtained. Conversely, when compound (Vla) or (SIb) is hydrolyzed under acidic or basic conditions, compound (■C) is obtained.

Also, from compound (dish)) to compound (■) or the same (1Tc
), there is another method as follows. That is, the compound (Peng) is dissolved in alkaline methyl alcohol and heated to 0°C for 2 cef.
treatment for 1 to 24 hours results in partial hydrolysis and release of compound (lla).

Compound (■) is obtained by dissolving compound (lla) in a solvent such as acetic acid, tetrahydrofuran, methyl alcohol, etc., and reacting it with acid expansion such as sulfuric acid, hydrochloric acid, etc.
Ru.

Compound (■) is heated at about 0 to 60°C in a solvent such as tetrahydro7ran, ethyl ether, etc. using a base agent such as hydrogenated lydicium aluminum.
Compound (V) is obtained by reacting for ~12 hours.

Further, when the compound (J) is dissolved in a solvent such as tetrahydrofuran using a reducing agent such as diporan, compound (Vld) is obtained. compound (\ld) as i
Compound (Iic) is obtained by converting the compound (Iic) into a σ11 element using a l', 1 element, such as water-rice-formed sudicum aluminum.

Compound (lla) or compound (■b) is mixed with 17 base agents.1.
Therefore, compound C1 [phase] or f! ) can be done. super base agent and t
For example, sodium iodine
In this 161 mixture, N1N-dimethylborumamide, 1]phosphoric acid-Keysomesaltriamide, and 80 to 140"C11 to 17J hours were added."'Z
It is appropriate to make it clear.

When ('f+c) is replaced with an acid (L), the compound (We) is fR.As an anesthetic for this removal, for example, pyridinicum chlorochromate, or chromic acid-pyridine. Using a complex number, 0 to 30°C, 0.5 to 1 hour [convex 1 reaction.

When compound (We) is subjected to Wolff-Kissiner reduction, compound 4 is obtained. That is, when the aldehyde group of compound (Vle) is converted into hydrazone or Kamidamakar/kushin and heated in the presence of a strong base such as alkali-terminated alkoxy 1, 6 g of compound is obtained.

In addition, the compound (We) can be converted to ethane scissors using an acid catalyst.
ζ01f during the synthesis by reacting with ol to form thiogtal.
In addition to 17, compound 1 can also be obtained by further desulfurization using an 8-element agent, such as Raney Nila gel.

Here, Compound (I), Compound (Ia), Compound (Ib); Compound 00, Compound (Ila), Compound (nb), -, Compound (11
0, same (lla), same (old)) 1 compound ■; compound (
V); Compound (Vl), times (1'la), same (er),
Same (Wc), times 0'ld), same (Wp), same (■f)
; Compound (ν■; Compound 11'/, q G's [hi chemical formula is shown all at once. Dada j,, R1 ke CO211t or CO
2CH3 group, R2 is C)(O, C02H).

1f7) Coalescence compound (Ia)) where R1 is C02H
Jλ′J(〒; Compound 01))R] of CO2CH3 or CO2CI 3.1 2 is 'M Qj' of co2n;
f′X′＞21(lla)R1 is (X)2 (11
3. R2 is CO2CH3, 11. ,I rH,,I
'(1 compound (Il+)) old is Co 2 CH3, R2 is C
In the case of 02H; compound (Ilb) R1 is Co 2 CH
3. When R2 is CO2CH3; Compound (Illb) Compound (VD When R3 is CH20SO2CH3: Compound (Via)
When R3 is C)I20SO2C6H4CH3: Compound (Vlb) When R3 is CH20H: Compound (Vic)
When R3 is CO2CH3: Compound (eggplant) R3 is CHO
FT? J: Compound (■e) Compound No. 6 Next, an example of the present invention will be described. 2.5 g of methyl levopimarate (compound (Tb)) prepared by Kibo was dissolved in 20 rnl of methylene chloride, and methyl alcohol 10
m1 was added. While cooling this solution to -70°C with dry ice-acetone cryogen, ozone-oxygen mixed gas was added at 1°C.
I took the time. Next, after removing excess ozone by blowing in nitrogen gas, 2.5 ml of dimethyl sulfide was added to JRl.
I brought it back to room temperature.

Anti-1. After reducing the pressure of the 8 liquid to J3 (W), add 50 m of acetone
Dissolve K and add Jones reagent (chromic acid 1) under water cooling.
(3.3 g dissolved in 12 ml of sulfuric acid - 25 ml of water)
Drop 5 ml, then cool with water for 1 hour 1i)j'IsΣ
Stir, improvise, add 2 ml of alcohol and add excess 1"i'2 (Hino 1J 'x molecule'j'?,
After that, water 200 + n 1 and ethyl ether 2 (10
ml was removed and extracted with ether. 200 ml of 2N water f'i + 2-hydrogen hydroxide solution was added to the neechit layer, and the nitrate was extracted into the aqueous layer. To 11 liters of this water were added salt, ethyl needle, and ethyl needle, and the phosphorus compound was extracted into an ether layer.The ether layer was washed with a saturated trisium water bath and dehydrated with anhydrous sodium sulfate. After that, an ethyl ether solution of diazomethane was added to obtain the carboxylic acid as methyl ester.The reaction solution was concentrated under reduced pressure, and the resulting mixture was subjected to silica gel column chromatography (hexane:ethyl acetate 5:l). 1.2 g of compound (nb) was obtained.

Compound (nb): pale yellow oil Ctyttz60s
(Molecular fi) 310) Yield 48.9% (Paulownia compound Qb)) I R: 1730o+' (CO2Me)13C-N
R4R: 209, 6ppm (C-a,;c=O
) 178, 4 pptn (C-18, -CO2-) 173.4 pIin! Summer 1 (C=12, -(02-)
52, 111T plate n(-0CH3) 51.7ppm
(-0CH3) (2) Preparation of compound 6 (llllb) from compound (III)) 7.8 g of 7methyl l-liphenylphosphonium iodide
Then, 2.1 g of caricum tert-butoxide was poured into 70 ml of isopropyl ether with nitrogen, and dispersed by flowing down.
Stirred at 60°C for 30 minutes. There the compound (Ilb)
2.8 g of isopropyl ether was turbulent for an hour.

After cooling, 50 ml of water was added and stirred for 30 minutes.

The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. Further, the filtrate concentrated under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate 8:1) to yield the compound (rlTo) 1 , 65 g/fl.

Chemical compound (1!To) White crystal Melting point 65-68℃ C
18H28Q4 (molecule Rt308) Yield>4'-59,31@ (counter compound (ITo)) I
R: 1730 tym' (-CO2Me)13C
-('VIMR: 179.Oppm(C18, -CO
2-) 174.2ppm(C-12,-(02-) 51.9ppm(-()CH3) 51.6ppm(-
0CH3) 107.0ppm (C-17,=ClI2
) 148.4 ppm (C-8, gloss) (3) Production of compound (Via) from compound (Illb) 1.45 g of compound (IllTo) was dissolved in 100 g of chloroform
m-chloroperbenzoic acid. Og
was added, dissolved and left at room temperature for 18 hours. The reaction solution was converted into sodium iodine aqueous solution, sodium thiosulfate aqueous solution, sodium bicarbonate aqueous solution, and saturated chloride).
Wash with an aqueous solution of IJ cum, dehydrate with anhydrous sulfuric acid, dehydrate with IJ cum, reduce pressure to 9M, and obtain 1.5 of the crude compound (to).
4 g was obtained.

g of tetrahydrofuran 5 (1 ml K-dispersed, compound α) crude product 1.54 g of tetrahydrofuran 2 ('
1m I i″δ liquid is dropped, and the amount is 211VJ
゛l internal return γ・:t. h', and) t\-encompassion rf9
trichum varicella fluid, white '/A: M54 was removed. Oki, rshi to 51・1, LE ti=i to rri I-ko°, conversion ir C:3 (V) remanufacturing quick 1,2 g i:rifl >+poji.

%3 (V)3i 1; False 1.2 g
; nl ('lo+ol K i'r:;f'i'
! Add 2.0 ml of nocun sulfonyl chloride to 'A'-111r, then add 2.0ml of nocun sulfonyl chloride to
' j73. l quiet jr5j l,ta. 1 sentence, 200 + n I and 2 ml of water (add river ml,
I held Kojiworu Lottery I1. Ether layer constant supply salt 1 he, r!
+f Water + i・Water washed with sodium chloride aqueous solution
It is 11"trichum;, i, water, 3N radish rA 1.4:4, 111, 111, 111, 1, 2, 1, 1, 1, 1, 1, 1, 1, 1, 4, 111, 111, 111.
0.55 g of the IL compound (■a) was added to a solution (3:1) of the IL compound (■a) by tIJ.

(>4.”J (Via> fj color crystal melting point 109
-110'c c17j (30Q, (S (molecular grade 330
) Yield 35.4 qt) (Counter compound (1111>) ) 1 1 R: 1340d' 1180 cfn (-0SO
2C1i3) 13cmN! +iR: 79, 4ppm
((-8, -C-0-) 77.6 ppm (to C-1 -CO2-()-5OS 64.8 ppm (C-(Z, -(I2-()-) 3
7, 1 ppm (-0SOzCj13) (4) Synthesis of Compound (Via) 3.2 g of Compound 1 (Via) was dissolved in 50 ml of N,N-dimethylphono I/Mur3d, and zinc powder (activated by acid washing) was added. To the mixture were added 3.2 g of sodium chloride and 5.0 g of sodium iodide, heated to 115°C, and stirred for 6 hours.

After cooling, 100 ml of ethyl acetate was added and stirred.

After the p liquid was concentrated with a sodium thiosulfate aqueous solution and a saturated sodium chloride aqueous solution, it was dehydrated with anhydrous sulfur filtrate and further reduced in IUE. Silica gel strength gym chromatography (Heki! rn: Vinegar C)
2 Ezal 20:1) to form the compound 6 or 8α
, 1.2 g of 12-epoxy-13,14,15,16-tetranollagdan and 1.0 of compound (Vla)
g k t ``jta...

Compound O White crystal Melting point 73-74℃ C16112
80 (Molecular weight 1236) Yield 52.4% (ZJ compound (■a)) IR1010L
J-' 13 C-NMR79, 7p pan (C-8, AI
-@ -) 64, 8 p p buy 1+ (C-12,
-C112-(-)-)

Claims (1)

[Claims] A compound represented by the following general formula I is treated with an oxidizing agent to obtain a compound represented by the following general formula
tig Reaction A compound represented by the general formula 2 below is treated with an oxidizing agent, a reducing agent, and a dehydrating agent, or a mineral acid, a reducing agent, and a dehydrating agent are used to form a compound represented by the general formula 2 below. 8α,12-epoxy compound represented by the following general formula 11, which is further treated with a reducing agent or a reducing agent and an oxidizing agent.
13,14,15°I R1 is C02H or CO2CH3 I R1 is C02H or C02CH3 R2 is Cll01. C02H or CO2C) 1 to I3 R1 is C02H or Co2 CH3 R2 is C) 10, C02H or Co2Cl 3R3 is C02H, CO2CH3, CH20HCl1zO5Oz
CH3 or CH20SO2C6H4CH3 (VTtD