SU909934A1 - Method of producing adamanthyl-containing 2,3-dihydrofuranons - Google Patents

Abstract

METHOD FOR OBTAINING ADAMANTIL-CONTAINING 2,3-DGHYDROPHTHANONE General formulas I, II, III: -l /, (iii). (one)

Description

9099 The invention relates to the chemistry of adamantane derivatives, in particular to a new method of producing new adaman-tkl-containing 2,3-dihydrofuranones, which can be used to synthesize various compounds containing an adamantyl radical, and as potential biologically active substances.10 Known methods for the preparation of various substituted adamantane containing furan cycle. Thus, 2,5-di (1-adamant 1) Furan is obtained by the action of a sulfuric acid (de-5 hydration) on / 1,4-di (1-adamantyl) butane, 4, -dione. An acid of the p (1-adamantoyl) -acrylic acid ethyl ester is obtained by preparing the corresponding acid, at the 20th cyclization of which the hydroxy-U-lactone is formed. In these synthesis methods, alkaline or acidic agents are commonly used to form the Unsaturated A-Lactone Ring from various carbonyl compounds. Therefore, even with the presence of the necessary acids or their derivatives, the action of certain agents will result in the elimination of the substituents in the de-adamantane due to the ease of formation of the I-adamantylcation, which makes the obtained halo-nitroxy-substituted adamantane impossible. In addition, it should be noted that there is a known method for producing 3,5-disubstituted 2,3-dihydrofuran-2-ones, by reacting diazoketones with keneta in absolute xylene or toluene at a temperature from minus 60 to room temperature, for example; scheme:

-to

Product output ranges from 18 to 90% depending on the starting compounds. This method is limited due to the lack of acceptable methods for the synthesis of aroipketones.

. Further, it is known to obtain disubstituted digkiruuran-2 and 3-bases by intramolecular cyclisiossnsena. As is apparent from this scheme, the preparation by this method leads to two parallelly formed products, which in the case of α-admantane substituted products does not allow one to predict the structure of the resulting compounds. The goal and the inventor is to develop a method for producing new adamantletsociation of p-diazoketones of the formula: N CHCOCH (K) COOK, where K is Phenyl, K ethyl, in the presence of Copper sulphate in boiling diclohexane or in the presence of the complex salt (CH3) 5P.- Si1. in benzene at 20 ° G with a yield of 13-40%. Reaction Scheme:

BUT

holding 2,3-dihydrofuranov from available substances. The goal set is achieved by a new method of obtaining adamantyl-containing 2,3-dihydroFuranone general) Formulas G, 11.111:

where X is hydrogen or bromine according to the compounds of the general Formulas II to IIG, and bromine or nitroxy group according to the compounds of the general formula I,

by the interaction of the appropriately substituted (J-admantosh1) di4eo) ethane with 5-fench1-2,3-digi; crofuian-2, 3, 1 dioa at. boiling the JB environment with absolute benzene i for h, the reaction scheme is as follows

As vvdno from this scheme in the process parallel reactions occur with the formation of Z-benzoyl-5-adamantoyl-2, 3-dihydrofuran-2-it n 2-diazo-1-adamantoyl-3 Phenyl-1,3,5-pantantry which at heating decomposes. Carrying out the process for less than 3 hours does not provide complete carbonylation, and heating above 4 hours dramatically reduces the yield of the target product.

According to the invention, four compounds are synthesized:

1) 2-O-adamantoyl) -5- (benyl-2,3-dihydrofuran-3-one,

2) 2- (3-bromo-1-adamantoyl) -5-phenyl-2, 3-digvdrofuran-3-one,

3) 3- (3-bromo-1-adamantoyl) -5-fench1-2, 3-dig1zdroFuran-2-one,

4) 3- (3-nitroxy-1-adamantoyl) -5-Phenyl-2, 3-digtsroFuran-2-one.

The synthesized compounds I and II are white crystalline high-melting substances, poorly soluble in most organic solvents. In the IR spectra of 2,3-dihydrofuran-3-onrv, taken in vaseline oil, there are intense absorption bands, corresponding to vibrations of conjugated 1660 and enolized (1570 cm) carbonyl groups. The intense and slightly broadened absorption band in the region of 1630–1625 cm is referred to: by C C bond associated with the carbonyl group. There is also a weak broad absorption band of the OH group in the region of 2700-2650 characteristic of enol systems. T.O. IR spectroscopic data correspond to the 2 - (- - adamantoyl) -5-phenyl-2,3-dihydrofuran-3-ones structure and suggest their existence in enolic Forms A and B:

Synthesized 3,5-disubstituted | 2,3-Dihydrofuran-2-ones, where X is VU, are light yellow crystalline, water-insoluble, poorly melted substances. hexane, ether, cyclohexane, pentane and soluble in chloroform, benzene and acetone. Their identification was performed by single element analysis, IR and WR spectroscopy. The 3,5-disubstituted 2,3-digi / RrFuran-2-ones in the four-carbon carbon solution are fully enolized, which is confirmed by the PMR data, in which the CH-group proton singlet is present at position 4 at. 6.55-6.72 ppm, the singlet of the proton of the CH-group in position 3 is absent, and the HaiiyjKiffl is absent from the Ingle-t of the HE-g rototone in 12.8 0-1 2.70 ppm:

cfX

Ov IR spectra of compounds. in the area of 1610-1600 cm there is one wide and intense or bifurcated absorption band, which characterizes the vibrations of the conjugated carbonyl group and C-C bond in the chelate cycle, as well as the intense absorption band of lactone carbonyl in the region of 1700-1695, shifted to low frequencies due to mating and chelation. Example 1. 2- (1-Adamantoyl) -5-Phenyl-2, 3-dihydrofuran-3-one (I). A solution of 1.02 g (0.005 mol) (1-ada mantoyl) diazomethane and 0.87 g (0.005 m L) of 5-phenyl-2,3-dihydrofuran-2,3-di it in 30 ml of a dry solution of benzene is boiled t for 3 h. The solution is cooled, the precipitate is filtered, pro. The yield of 0.11 g (7%) is washed with ether. The output of 0.11 g (7%). M.p. 286-8 0 I, Found,%: C 78.31; H 6.80. e „n„ o. Vyagisleno,%: C 78.28; H 6.83 Mv. 322.71. IR (, cm, petrolatum mae. Lo): 1630, 1 660 (), 1400 () 570 (, 2650-2630 (OH). The residue is non-crystallizing oil. P im im 2. 2- (3-bromo-1 -amantuloyl) -5-phenyl-2,3-dihydrofuran-3-one (II) and 3- (3-bromo-1-adamantosh1) -5-phenyl-2, 3-dihydrofuran-2-one (III) Solution 1.42 g (0.005 mol) of 1-diazo-2- (3-bromo-1-adamantoyl) titan-2-one and 0.87 g (0.005 mol) of 5-phenyl-2,3-di hydrofuran-2 , 3-it in 20 ml of absolute abs. The ash is boiled for 3 hours. The solution is cooled and 2 .- (3-bromo-1-adamantoyl) 5-phenyl-2,3-dihydrofuran-3-one (II) is filtered off. yield 0.2 g (10%). Mp 255-7C Found: C 62.75J H 5.27 Bg 19.97. 21 2.1 - E Calculated,% C 62.88; H 5 , 24; Br 19.92; MW 401.21. IRS S. cm-d. oil): 1625, 1660 (), 1400 (); 1570 (), 2620-2700 (OH). Mass spectrum: M 400 and M 402. The filtrate is evaporated, the residue is taken up with 2-3 ml of ether, the precipitate is filtered and 3- (3-bromo-1-adamantoyl) -5-phenyl-2,3-dihydrofuran-2- is recrystallized. it is (iii) carbon tetrachloride. The yield is 0.76 g "(38%). So pl. 175-6 (cyclohexane). Mv 401.11. Found,%: - C 62.80; H5.27, Br 19.79. CjjH jjBrOj. Calculated,%: C 62.88 {H 5.24, Br 19.92. same (CHClj, -), cm-): 1705, 1600 () i 1605 (). PMR (SCC, MD): 2.22 m (Ad), 6.72 s (CF); 7.55 m (C, HJ, 12.8 s (OH). Example 3. 3- (3-nitroxy-1-adamantoyl) -5-phenyl-2,3-dihydrofuran-2-one (IV). Solution 1.32 g (0.005 mol) of 1-diazo-2- (3-nitroxy-1-adamanthoyl) ethan-2-one and 0.87 g (0.005 mol) of 5-Fensch1-2,3-dihydrofuran-2, 3 -dione in 20 ml of abs. benzene is boiled for 3-3.5 hours. Cool the solution. Filter, evaporate the filtrate, wash the residue with ether and obtain 0.50 g (26%) 3- (3-nitroxy-α-admantoyl) -5-phenyl-2, 3-dihydrofuran-2-one (IV), mp 148-50 C (cyclohexane), MW 383.21. Found: C 65.65; H 5; 47i N 3.56. Cr. Ng. Y 9099 with 10 4 X (CHCli, 9, cm-): 1610 $ 1695 (), 870, 1284, 1640 ONOji 1640 (). PNR (CCb.J, ppm .): 2.33 m (Ad), 6.55 s (CH), 7.38 m (C, F), 12.7 s (OH). Connected and III and IV at a dilution of 1: 8000 inhibit the growth of Staphylococcus aureus, and at a dilution of 1: 4000 (for III) and 1: 2000 (for IV) inhibit the growth of intestinal sticks.

Claims (1)

METHOD FOR PRODUCING ADAMANTYL-CONTAINING 2,3-DIHYDROFURANONES OF GENERAL FORMULAS I X (I), where X is hydrogen or bromine according to the compounds of formulas II and III, and bromine or nitroxy group according to the compounds of general formula I, characterized in that the corresponding substituted (1-adamantoyl) diaheoketone is reacted with g • 5-phenyl- 2,3-dihydrofuran-2,3-dione when boiling in absolute benzene for .3-4 hours.