JPS5943451B2 - 2,4-bishomobrendan-2-one - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides 2,4-bishomoprene dan-2-one (
Tricyclo [6.2.1.04, 9] Undecane-2
-on, formula I).

Compound I is 4-homoisotwistane (tricyclo[5.
3.1.03,8]Undecane) is a useful substance as a synthetic intermediate.

That is, when 1 is reduced, the corresponding hydrocarbon is obtained, which is isomerized to 4-homoisotwistane with high selectivity by the action of an acid catalyst. The present inventors (J, Med, Chem. 19, 536 (1976
)).

Compound (I) of the present invention is a 4-homobrendan-2-one (tricyclo[5.2.1.0
3,8] Decan-2-one, formula (■) is led to amino alcohol QV) via cyanohydrin trimethylsilyl ether (I), and synthesized by demyanofuteipheno (DemjanowTi to tene-an) rearrangement with nitrous acid in (■) I can do that.

α.

-0, Etta- (■) (11) NaNO2, HCI CH2NH2 (I) Cl COOH QV) Aminoalcono (to) Demiyano Futei Fuenoichi (
In the DemjanOw-Tiffeneau) rearrangement, two types of bishomobrendanones may be generated.

That is, there are two types of compounds of the present invention: 2-one (1) and its 3-keto isomer (3-one). However, when the reaction was actually carried out at 0 V), it was found that only one type of isomer was produced (according to Golay column GO-MS analysis). It is considered clear from the following facts that this actually produced compound has a 2-one (1) structure. That is, two structural isomers of 2-hydroxy-2-aminomethylnorbornane (exo-hydroxyendo-aminomethyl (7) and exo-aminomethyl-nindo-hydroxy isomer (7)) were prepared using Demiyanofuteiphenol, respectively. (DemjanOw-Tiffeneau)
If rearranged, 91% of the endo-aminomethyl form,
From the exo-aminomethyl form, bicyclo[3.2.1]octan-2-one () is predominantly produced with a selectivity of 62% (M.A. McKi-Nney et al., J. Or.
g. Chem. 38, 4O59 (1973)).
A amino alcohol (IV) is 2-hydroxy-
Since it can be regarded as a trimethylene derivative of 2-aminomethylnorbornane, it is thought that steric and electronic factors similar to those in norbornane compounds are at work in the Demiyano-Futei phenol rearrangement of 2-aminomethylnorbornane. No problem,
Therefore, it must be 2-one (1) that is predominantly obtained from QV).

On the other hand, the selectivity for producing (1) from 0 V) was extremely high, which means that the selectivity for bicyclo[3.2.1]octan-2-one from the endo-aminomethyl form of the norbornane compound was 90%. Considering the above, it is considered that this suggests that the coordination of the aminomethyl group in (IV) is endo. The starting material of the present invention, 4-homoprenetan-2-one (), has already been prepared by Shpoorrock et al. (J. Amer. Chem. SOc., 95, 8339).
(1973)), but the exo-2-acetoxy-4- It can be obtained from homoprentane by reduction with lithium aluminum hydride and dionez oxidation of the corresponding exo-2-ol.

Examples of the present invention are shown below.

Example 2 - Trimethylsilyloxy-2-cyano-4-homoprenetane (button).

4-homoprenetan-2-one ()3.0y (0.02
After mixing and dissolving 3.09 (0.03 mol) of trimethylsilyl cyanide and 20 ml of dry benzene,
Add small pieces of zinc iodide crystals and stir at room temperature for 4 hours.

When benzene is distilled off under mild reduced pressure, () is obtained as a residue in an approximately quantitative yield.

2-Aminomethyl-2-hydroxy-4-homoprenetane (5) and its hydrochloride.

The crude solution obtained above was dissolved in 30 ml of ether, and this was added dropwise to a suspension of 3.79'It (0.1 mol) of lithium aluminum hydride in 30 ml of ether while stirring well. do.

Then, the mixture is heated under reflux for 3 hours. The reaction mixture is treated as usual with sodium hydroxide and water and extracted with ether. The ether solution is dried over anhydrous sodium sulfate, and the ether is distilled off to obtain crude 0V). The above obtained ether 5
0 ml and pass in dry hydrogen chloride gas for 2 hours at room temperature.

Take the precipitate, wash it with ether, and dry under reduced pressure to obtain a crude (I
V) hydrochloride salt 3.797 (87% overall yield from ) is obtained. A portion of this is taken and recrystallized from methanol-acetone to obtain pure hydrochloride. 2,4-bishomoprenetane-
2-one (1), (IV) hydrochloride 3.357 (0.01
5 mol) and anhydrous sodium acetate 1.3y (0.016
mol) is dissolved in a solution consisting of 3TfL1 acetic acid and 20 ml water.

2.While keeping the temperature below C and stirring, add sodium nitrite 1
．． A solution of 287 (0.019 mol) in 10 ml of water is added dropwise.

It is then stirred at room temperature for 2.5 hours. The reaction solution was extracted three times with 50 ml of ether each time, and the extract was washed successively with a sodium bicarbonate solution and a saturated saline solution, and then dried over anhydrous sodium sulfate. If ether is distilled off, crude (1) 1.47
(Yield 580!)) is obtained. Reference example 1 2,4-bishomoprenetan-2-one (1) 1.46
g (0.09 mono(c), potassium hydroxide 3g, 100
A mixture consisting of 2 g of hydrazine hydrate (0.04 mono(c)) and 20 ml of diethylene glycol was stirred for 2 hours while being maintained at 140°C.

Next, the reaction temperature is gradually raised while distilling off the water produced, and when it reaches 210°C, it is maintained at this temperature and heated under reflux for 4 hours. The reaction mixture was allowed to cool and extracted three times with 30 ml portions of n-hexane. The hexane solution was washed twice with 20 ml portions of water, and then dried over anhydrous sodium sulfate.

If hexane is distilled off, 0.0% crude 2,4-bishomoprenetane.
87 g (yield 65(f)) are obtained. A pure product was obtained by purification using preparative gas chromatography. Reference Example 2 A mixture consisting of 0.1 g of 2,4-bishomoprenetane, 0.1 g of trifluoromethanesulfonic acid, and 5 ml of dry methylene chloride is heated under reflux for 5 hours under a nitrogen stream.

The reaction mixture was poured into 10 ml of ice water, and the aqueous layer was extracted with 5 ml of preparative methylene chloride.

The methylene chloride solution is combined, washed with a saturated aqueous sodium bicarbonate solution and water, and then dried over anhydrous calcium chloride. Methylene chloride was distilled off, and the residue was vacuumed (10071 LmHg).
), 4-homoisotwistane 0.0
83 g (83% yield) are obtained. The melting point, RlH and 13C NMR, and mass spectrum of () obtained here are all those of the standard product (Reference Example 34-Homoisotwistane 25 g (0.17 mol) in acetonitrile 5
00ml solution, add 130ml of concentrated sulfuric acid at a temperature of 10 to 20°C.
C. and then bromine 136 (0.55 mol) is added dropwise.

This mixture is stirred at room temperature for 24 hours. After the reaction is completed, the reaction solution is added to an aqueous sodium thiosulfate solution to remove excess bromine, and extracted with ether. The ester layer is washed with sodium bicarbonate solution and then with water and dried. Extracting the ether yields a viscous liquid residue. If this is washed with n-hexane, 30.2 g of 3-acetylamino-4-homisotistane (yield 86%) is obtained as a yellow crystal of the crude product (melting point 110-120°C).
is obtained. If it is recrystallized from n-hexane-acetone, it becomes a pure white crystal product with a melting point of 125-126°C. Reference example
4 8.4 g of caustic soda in 60 ml of diethylene glycol (
0.21 mono(c) is dissolved by heating and stirring, and 3-acetylamino-4-homoisotwistane 5.2 is added to this solution.
Add 2 g (0.025 mol) and stir under reflux for 5 hours.

The reaction mixture was cooled, poured into 200 ml of water, and then extracted three times with 50 ml of ether. After drying the ether layer over anhydrous potassium carbonate, the ether is distilled off to obtain 2.63 g of crude 3-amino-4-homisotwistane (yield 64%).
is obtained. This material deliquesces immediately due to its hygroscopic nature.
This product is dissolved in 50 ml of ethyl ether, dried over anhydrous potassium carbonate, blown with dry hydrogen chloride gas, and then the ether is distilled off to obtain colorless crystals of 3-amino-4-homisotwistane hydrochloride. Yield 3.1g0~-1'Bi1-▼-? 1V1,' No parent peak is observed, but a peak for 3-amino-4-homoisotwistade is observed.

Claims (1)

[Claims] 1. 2,4-bishomobrendan represented by formula I
2-one (tricyclo[6.2.1.0^4,^9]undecane-2-one) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I)