SU522596A1 - Method of obtaining alkyl-1-adamantylketones - Google Patents

Description

The invention concerns a process for the preparation of new substituted 1-adamantyl ketones, which are the starting compounds for the synthesis of antiviral preparations and surface active substances.

Known representatives of the lower alkyladamethyl ketones.

A known method for producing 1-adamantyl ketone by pyrolysis of a mixture of acetic acid and 1-adamantanecarboxylic acid over platinum oxide at. However, the target product is obtained with a yield of .15-20% 1.

In addition, 1-adamantyl methyl ketone was obtained by reacting 1-adamantylcarboxylic acid chloride with ethoxymag nium methyl ester followed by decarboxylation and saponification in 94-.9b% 2

Another method for producing 1-adamantylmethyl ketone is multistage from 1-acetylenalanmantane with a minor input 3.

1-Adamanty ethyl ketone is also obtained by condensation of ethyl methyl magnesium malonic acid ester and adamantane-1-carboxylic acid chloride in 50% yield 4.

However, the expansion of a number of representatives of alkyladelamine ketones due to the fact that normal and branched alkyladelamine ketones can be found as starting compounds for obtaining rimantadine, which exhibits antiviral activity, is an urgent task.

They propose a method of obtaining new

o higher alkyl-1-adamantylamine formula

-G.

five

where Ad - 1 is adamantyl;

R is alkyl, H — C — tH; 1-SzN7 / 1 st. And -

,

phenyl; g i-CjH .;

ns, n

0

from 1-adamantylcarboxylic acid chloride and the corresponding Grignard reagents in the presence of copper monochloride. The proposed method

5 provides a small process time, available starting materials and provides a high yield of the target products.

Example 1. Getting 1-adamantylamine.

0

To a solution of 20 g (0.1 mol) of the acid chloride.. -Adamantanecarboxylic acid, 0.1 g (0.0005 mol) CCCC3 in 60 ml of dry ether was added a Grignard reagent obtained from 2.43 g (0.1 mol ) magnesium and 15.7 g (0.1 mol of bromobenzene in 50 ml of dry ether. The reaction mixture is boiled for 1.5 hours in a water bath, cooled and treated with 5% hydrochloric acid. The ether solution is separated, washed with a solution of metabisulphite and water. After removing the ether, the obtained mass to remove the starting acid chloride is heated with stirring with 5% sodium hydroxide solution for 5-10 m N. The cooled mixture is extracted with ether, the ether solution is washed with water until neutral, dried with calcium chloride. The ether is removed, 15.3 g (62%) of crystalline substance are obtained, mp 55-5bc (from hexane).

Found,%: C 84.49. H 8.39.

--I- 24

Calculated,%: C 84.96; H 8.38.

M.p. 2,2-dinitrophenyl hydrazone 233-235 ° C (from ethanol-dioxane). The structure is confirmed by the PMR- (M, D. SSe4, TMS) spectra: 8.01 (singlet, 9H, ie, Hfj, and N. adamantyl); 8.26 (singlet, 6H-H adamantyl); 2.34- 2.85 (multiplet, 5H-phenyl group, with a maximum at 2.67). The addition of europium trisdipivaloylmethanate causes a significant shift of the ortho-proton-phenyl group and (b-protons of the adamantyl group towards weak fields, which indicates the presence of a carbonyl group.

In addition, in the presence of Her (DPM), the Hp signal appears as a doublet, and the Hn-triplet signal, as it should be for adamantyl. The presence of a carbonyl group in the molecule is also confirmed by the IR spectrum of 1680 cm ().

Similarly, using the appropriate halide derivatives to prepare Trinir reagents, I get the following ketones, the structure of which is confirmed by IR and PMR spectra, the IR spectra were taken on a UP-20 instrument, the PMR spectra were obtained on a Pevkin E6mev R-12, 60 MHz, in a CCl solution with an internal TMS standard, the place of the signals is given on the t-scale, Hp, H, Hjj are the corresponding protonated adons. Her application (PMD) allows the purity of ketones isolated directly from the reaction medium to be detected using PMR spectroscopy.

Example 2. 1-Adamantylamine, yield 80%, BP. 117I9 C / 3 mmHg, 1.5020; m.p. 2,4-dinitrophenylhydrazone 146-148 C (from ethanol-dioxane) 1710cm- () IR spectrum, so pl. oxime 178-180 ° C. PMR spectrum: 8.24 (Hp,

H); 7.98 (); 7.63 (CH triplet, -C 0); 9.13 (CH3, triplet); 8.40-8.80 (multiplet, SND).

Example 3. 1-Adamantylamine, yield 78%, liquid, BP. 115120s / 2 mmHg, 1.4975, so pl. 2,4-dinitrophenylhydrazone 175177C (ethanol-dioxane); PMR spectrum: 8.24 (Hp, H); 8.0 (H), 7.66 (triplet, CH,); 9.1 (CH, tri-. Plet); 8.4-8.8 (multiplet) IR spectrum 1700 cm- ().

Example 4. 1-Adamantylamine ketone, yield 79%, liquid, IR spectrum 1705 cm- (); PMR spectrum: 8.24

(Hp) 8.0 (); 7.68 (CH2-C 0,

triplet); 9.11 (CH-e ,, trippet); 8.74 (6H, CH, -CH, j, -CH2, broad multiplet).

P - meerp 5. 1-Adamantane isopropyl ketone, yield 75%, so pl. 5657 ° C, so pl. 2,4-dinitrophenylhydrazone 206-207С, PMR spectrum: 8.22 (H Hff) ;. 7.96 (H); 6.6-7.2 (1H, septuplet); 9.08 (6H, doublet, isopropyl group).

Example 6. 1-Adamantylamine, 55% yield, PMR spectrum:

8.21 (Hp, H); 8.0 (H, j-); 7.66 (CH,); 9.11 (6H, doublet of isopropyl group); 8.5-8.8 (СНа, multiplet); IR spectrum: 1700 cm- ().

Example 7. 1-Adamantylamine butone, yield 60%, spectrum PMR:

8.22 (Hf. ,, Hjf, doublet); 7.95 (H-j-); 7.79, triplet); 9.12 (duplicate isopropyl group); IR spectrum: 1700 cm ().

Example 8. 1-Adamantyltret. butyl ketone, yield 40%, so pl. 93-, spectrum nMPi 8.02 (9H, Hp ,,); 8.29 (6H, Hj); 8.80 (9H, t-butyl group); IR: 1680 ().

In a similar way, methyl (or ethyl) -1-adamantyl ketones can be obtained in 82% yield.

Claims (4)

1. On adamantane and its derivatives, message VI On the new production of I-ethyladamantane and its properties, Hala S., Landa S., Cott, Czech., Chem. Conunun, 25,, 19Ш 2. Stetter H., Rauscher E. About obtaining ethyl ester ft - (1-adamantyl) -p-oxopropionic acid, 5 Chem. Veg., 93, 2054, I960. 3. Stetter N., Goebe R., f mantil-1-acetylene Chem. Veg., 95, J.UJ, 1962. 4. Stepanov F.N., Isaev SD, Vasilieva Z.P. Chemistry of General Science