JPS5828257B2 - Method for producing dehydrohomoadamantanol and alkoxydehydrohomoadamantane - Google Patents

Description

[Detailed description of the invention] The present invention relates to a method for producing homoadamanthenes.

More specifically, the present invention is characterized by reacting e-2-bromohomoadamantene 4 represented by the formula with a lower alcohol or water (wherein R represents a hydrogen atom or a lower alkyl group). ) relates to a method for producing homoadamanthenes represented by

The present inventors previously reported that e-2-fromhomoadamanthene-4
High stereospecificity, efficient and simple synthesis,
Furthermore, extensive research into its use revealed that the 2-position bromine atom of this substance is extremely chemically active.
It has been found that it reacts with water, alcohols, amines, and various other nucleophiles to give eftreal-substituted homoadamanthene-4 derivatives in a stereospecific manner in high yield.

As an example of a nucleophilic substitution reaction, when heated under reflux in a lower alcohol such as methanol, e-2 is produced in a high yield of over 90%.
- gives alkoxy homoadamantene 4.

Further, when hydrolysis is carried out by heating under reflux in a mixed solvent of a polar solvent such as dioxane and water, e-2-hydroxyhomoadamantene-4 is quantitatively produced.

The above solvolysis and hydrolysis are represented by the general formula shown below.

(In the formula, R represents hydrogen and an alkyl group.) Comparison of NMR spectra proved that the structure of the above reaction product was maintained in its steric configuration.

As mentioned above, when hydrolysis is carried out in aqueous dioxane without catalyst, only the 2-substituted product is selectively obtained, but Na
When hydrolysis is carried out in the same solvent in the presence of an alkali metal or alkaline earth metal hydroxide or carbonate such as 2CO3, KOH, AgClO4 and a catalyst such as silver perchlorate, the above e2-hydroxyhomoadamantene-
At the same time as 4, e-5-hydroxy 2 is thought to be produced via a homoallylic cation intermediate as shown in the reaction formula below.
- 4-dehydrohomoadamantane is obtained.

Mixing ratio of both (2-hydroxyform and 15-hydroxyform)
is 1:6 to 7 (analyzed by gas chromatography), and can be separated by conventional separation methods, such as silica gel columnography.

Regarding the structure of the 5-hydroxy-2,4-dehydrohomoadamantane, there is no characteristic absorption due to olefins in the NMR spectrum, and the proton at the 5th position couples with the adjacent bridgehead proton.
By showing a triple line in ppm, and further by chromic anhydride-pyridine oxidation, 2.4 dehydrohomoadamancune-5-
It was proven that the known 2,4-dehydrohomoadamantane was produced by subjecting it to Wolff Kitschiner reduction.

As described above, dehydrohomoadamantanols are stereospecifically retained in good yields by the method of the present invention, and these are all novel compounds that are useful as synthetic intermediates for pharmaceuticals, fragrances, and the like.

This will be explained below with reference to examples.

Example 1 e-2-7” romhomoadamantene-4 (45■, 0
．． A solution of 2mM) dissolved in methanol (1m) was added to
The reaction mixture is heated under reflux for a period of time, and the solvent is distilled off under reduced pressure. The resulting residue is purified by silica gel chromatography to obtain the target product e-2-methoxyhomoadamantene-4.

Yield: 32■ (90%), boiling point: 101-104℃/22℃Hg MS (m/e): 178 (M+)IR (Cr
rL-li:29501166011450.1380
．． 119011090.945.885.735.71
5 NMR δ (CCI4): 1.10-2.57 (broad complex multiplet, 12H) 3.20 (broad singlet, LH
), 3.26 (single line, 3H), r.

6.00 (multiplet, 2 H) ppm Elemental analysis: H as Cl2H180 Theoretical value (%) 80.85 10.18 Actual value (%)
80.72 10.39 Example 2 e-2-from homoadamanthene-4 (449■, 1.
98 mM) in 20 ml of 25% aqueous dioxane solution and heated under reflux for 2 hours.

A NaHCO3 aqueous solution was added to the reaction solution, extracted with CH2Cl2, the extract was washed with saturated brine, dried over anhydrous Na2SO4, the solvent was distilled off under reduced pressure, and the resulting solid was recrystallized from n-hexane to give e- 2-Hydroxyhomoadamantene-4 (322 μm, 99%) is obtained.

Melting point: 226-229°C MS (m/e): 164 (M+96%), 9
1 (97%), 79 (100%) IR (Nujol, CrrL-1): 3300129
50.1650 1460 1380.1025, 1O NMRδ (CDc13): 1.10-2.70 (broad complex multiplet, 12H), 2.01 (single line, IH
, OH), 3.93 (broad single line, IH), 6.05
(Multiplet, 2H) ppm elemental analysis: H as C11H160 Theoretical value (%) 80,44 9.83 Actual value (%) 80,34 9.96 Example 3 e-2-bromohomoadamantene-4 (322 ■、1.
4mM) and Na2C03 (278■) are dissolved in a 25% dioxane aqueous solution 101111 and heated under reflux for 3 hours to react.

After cooling, the reaction solution was added to water, extracted with CH2Cl2, the extract was washed with saturated brine, dried over anhydrous Na2SO4, and the solvent was distilled off to obtain a mixture containing dehydrohomoadamantanol (220ml, 9.99%). It will be done.

The mixing ratio of 2-hydroxy compound and 15-hydroxy compound is 1:62.
It is.

(by gas chromatography analysis).

This was subjected to silica gel chromatography and eluted with a mixture of n-hexane and ether (95:5) to obtain pure e-5-hydroxy-2,4-dehydrohomoadamantane (97■), followed by the above 5-hydroxy body and e-2
-Mixture of hydroxyhomoadamantene-4 (121■
) are separated.

Melting point: 264-265°C MS (m/e): 164 (M+26%), 1
46 (100%) IR (Nujol, CrfL'): 3300,295
0.146011380.1035 M δ (CDCl5): 0.67-2.33 (broad complex multiplet, 14H), 1.67 (single line, IH
. The same reaction product is obtained if KOH is used instead of .

Claims (1)

[Claims] 1 Formula % Formula % A method for producing homoadamantenes represented by the general formula (in the formula, R represents a hydrogen atom or a lower alkyl group), which is characterized by reacting with a lower alcohol or water. .