SYNTHESIS OF ADAMANTYL-CONTAINING AMID ALKYLING AGENTS AND NITROGEN-CONTAINING HETEROCYLES BASED ON THEM

Norwegian Journal of development of the International Science No 166/2025 19 SYNTHESIS OF ADAMANTYL-CONTAINING AMID ALKYLING AGENTS AND NITROGENCONTAINING HETEROCYLES BASED ON THEM Koshchii I. PhD in Chemistry, Associate Professor Department of Organic Chemistry and Technology of Organic Substances National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute” Klimko Yu. PhD in Chemistry, Senior Lecturer Department of Organic Chemistry and Technology of Organic Substances National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute” Vasilkevich O. PhD in Chemistry, Associate Professor Department of Organic Chemistry and Technology of Organic Substances National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute” Levandovskii I. PhD in Chemistry, Associate Professor Department of Organic Chemistry and Technology of Organic Substances National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute” https://doi.org/10.5281/zenodo.17352695 Abstract Methods have been developed for the synthesis of adamantyl-containing amidoalkylating reagents: adamantyl-1-carboxy-N-(1-hydroxy-2,2,2-trichloroethyl)amide, adamantyl-1-carboxy-N-(1-chloro-2,2,2-trichloroethyl)amide, adamantyl-1-carboxy-N-(2,2,2-trichloroethylidene)amide, adamantyl-1-carboxy-N-(2,2-dichloro-1cyanovinyl)amide, 2-(adamantyl-1-carboxamido)-3,3-dichloroacrylamide, and 2-(adamantyl-1-carboxamido)- 3,3-dichloroacrylic acid. Using these reagents, 2-(adamantan-1-yl)-4-(dichloromethylene)oxazol-5(4H)-one and 2-(adamantan-1-yl)-4-(dichloromethylene)-1H-imidazol-5(4H)-one were obtained via cyclocondensations in 73% and 76% yields, respectively. All products were identified by IR and 1H NMR spectra. Keywords: 2,2,2-trichloroacetaldehyde, adamantyl-1-carboxamide, amidoalkylating reagents, oxazoles, imidazoles, cyclocondensations. Introduction The chemistry of nitrogen heterocyclic derivatives has attracted the attention of many researchers. They are finding increasing application in the production of polymeric materials, dyes, pharmaceuticals, insecticides, herbicides, and plant growth regulators. Therefore, the search for new regioselective heterocyclizations based on readily available reagents is highly relevant. Such promising reagents include various amidoalkylating agents suitable for a number of characteristic cyclizations that cannot be achieved with aminoalkylating agents. Preparation of Reagents. Typical amidoalkylating agents with the characteristic >C(OH)NHCOR fragment are usually prepared by reacting carboxylic acid amides, alkyl carbamates, and ureas with aldehydes, ketones, or α-dicarbonyl compounds [1-8]. Most aliphatic and aromatic aldehydes do not form stable N-1-hydroxyalkyl derivatives with amides. The stability of the latter is significantly increased by the introduction of electron-withdrawing substituents into the alkyl residue. The most important of these are the products of the reaction of chloral with primary amides of the general formula RCONHCH(OH)CCl3, which are readily formed by heating equimolecular quantities of the reagents without a catalyst or in the presence of sulfuric or hydrochloric acid [3]. Most of these condensation products have proven suitable for the preparation of even more pronounced amidoalkylating agents containing an N-1-chloroalkyl fragment. The latter react particularly readily with various nucleophiles, which is widely used for the synthesis of a number of N-alkylamide derivatives containing various oxygen-, nitrogen-, sulfur-, or phosphorus-containing functional groups at the α-position of the N-alkyl residue. When considering the reactivity of amidoalkylating agents, their electrophilic nature should be taken into account first [4, 57]. The lone electron pair of the nitrogen atom, although conjugated with the carbonyl group, still has a significant effect on the C–X bond (X = OH, Hal, and N-, S-, P-containing groups) due to the α-effect. Intramolecular condensations. Cyclizations without the participation of an electrophilic center at position 1 of the N-alkyl fragment have been successfully achieved when the amidoalkylating agents contain one or two halogen atoms at position 2. Easily accessible N-substituted amides of carboxylic and thiocarboxylic acids with the general formula CHCl2CH(X)NHC(Y)R undergo dehydrochlorination (dehydration) when treated with alkalis, alcoholates, or triethylamine, and are converted into oxazole, 2-oxazoline, or thiazole derivatives. Dehydration of synthons of the RC(O)NH-C(>C=)C(O)NHR' type, depending on their structure and condensation conditions, yields 2imidazolin-5-one derivatives, which have been studied in greatest detail and are a convenient preparative method for the synthesis of substituted imidazolin-5ones [5, 6, 7, 8, 9, 10-17]. One of the simplest cases of 20 Norwegian Journal of development of the International Science No 166/2025 such cyclization was discovered back in 1900 by E. Erlenmeyer during the treatment of amide of α-benzoylaminocinnamic acid with sodium hydroxide. However, acetic acid in the presence of sodium acetate was more often used as the condensing agent [11, 13-15]. Aim of the work. It is widely known that the presence of a framework fragment in a heterocycle exhibiting pharmacophoric properties often enhances these properties. Therefore, the aim of this study was to introduce an adamantyl (framework) fragment into the heterocycle structure. At the initial stage of the study, as noted above, the use of adamantyl-1-carboxamide for the synthesis of the corresponding amidoacylating agent seemed the simplest. Materials and methods IR spectra were obtained on a Specord 75IR spectrometer for samples in KBr tablets containing 0.25% of the substance . 1H NMR spectra (400 MHz and 500 MHz) were taken on Varian Mercury-400 and Bruker Avance DRX 500 NMR spectrometers with TMS in accordance with the internal standard. Mass spectra were obtained on a GCMS-TQ8040 Shimadzu instrument. GLC analysis was carried out on a Tsvet-500 M device, glass column 1000x3 mm, 5% Apiezon L on Inerton N-AW-HMDS carrier, temperature 150-260 oC (10 deg/min), carrier gas – helium (40 ml/min ). Adamantyl-1-carboxamide was obtained according to the method of [18]. Adamantyl-1-carboxy-N-(1-hydroxy-2,2,2-trichloroethyl)amide (3) [6]. A mixture of 0.2 mol of amide (1), 0.22 mol of chloral (2) and 1 ml of concentrated sulfuric acid is heated to boiling in 50 ml of chloroform and boiled for 6 hours. The formed precipitate after cooling the reaction mixture is filtered off, washed with benzene, water and dried in vacuo over P2O5. The yield of amide (3) is 87%. M.p. 154-155 °C (benzene). IR spectrum (КBr, cm-1): 850 (C-Cl, ν), 1100 (C-O, ν), 1300 (OH, δ), 1570 (NH, δ), 1640 (C=O, ν), 2910 (CH, ν), 2840 (CH, ν), 3440 (NH, ν), 3625 (OH, ν). 1Н NMR (δ, ppm): 4.5 (ОH, s, J=4.8 Hz), 7.3 NH, d, J=6.5 Hz), 7.6 (CH, m), 0-8-1.1 (15H, m). MS (m/z): 325 (M•+), 307, 289, 271, 135. Adamantyl-1-carboxy-N-(1-chloro-2,2,2-trichloroethyl)amide (4) [19]. To a suspension of 0.05 mol of amide (3) in 50 ml of anhydrous CCl4 is added 0.15 mol of SOCl2 over 0.5 h. The mixture is stirred for another 1 h. The precipitate is separated, washed with CCl4 and dried in vacuo. The yield of chloramide (4) is 89%. M.p. 171-172 °C (CCl4). IR spectrum (KBr, cm-1): 870 (C-Cl, ν), 970 (C-Cl, ν), 1130 (C-O, ν), 1290 (OH, δ), 1580 (NH, δ), 1650 (C=O, ν), 2830 (CH, ν), 2920 (CH, ν), 3450 (C-O, ν), 3640 (OH, ν). 1H NMR (δ, ppm): 7.4 (NH, d, J=6.8 Hz), 6.2 (CH, d, J=6.8 Hz), 0.8-1.1 (15H). MS (m/z): 343 (M•+), 308, 307, 261, 135. Adamantyl-1-carboxy-N-(2,2,2-trichloroethylidene)amide (5) [20]. A solution of 0.03 mol of triethylamine in 20 ml of benzene is added dropwise with stirring to a solution of 0.03 mol of amide (4) in 180 ml of benzene. After 30 min, the triethylamine salt is filtered off, and the benzene is removed in vacuo. The residue is crystallized from hexane-ethyl acetate (10:1). Yield of imine (5) 75%. M.p. 116-117 oC. IR spectrum (KBr, cm-1): 990 (C-Cl, ν), 1710 (C=O, ν), 2850 (CH, ν), 2890 (CH, ν). 1H NMR (δ, ppm): 9.2 (CH, s), 0.8-1.1 (15H). MS (m/z): 307 (M•+), 225, 190, 135. Adamantyl-1-carboxy-N-(2,2-dichloro-1-cyanovinyl)amide (6) [2]. A solution of 0.02 mol of amide (5) in 70 ml of ether is added dropwise over 0.5 h with vigorous stirring and ice-cooling to a mixture of 0.042 mol of triethylamine and 0.04 mol of hydrocyanic acid in 50 ml of ether. The mixture is stirred for 1 h at room temperature. The precipitate is filtered off and suspended in 100 ml of water. The insoluble portion is filtered off, washed with water, dried in vacuo over P2O5 and recrystallized from benzene. The yield of amide (6) is 73%. M.p. 121-122 °C (with decomposition). IR spectrum (KBr, cm-1): 950 (C-Cl, ν), 1570 (NH, δ), 1645 ( =C-CN, ν), 1660 (C=O, ν), 2210 (>N-C=C-CN, ν), 2840 (CH, ν), 2910 (CH, ν), 3440 (NH, ν). 1H NMR (δ, ppm): 9.6 (NH, s), 0.8-1.1 (15H). MS (m/z): 332 (M•+), 250, 135, 42. 2-(Adamantyl-1-carboxamido)-3,3-dichloroacrylamide (7) [22]. To a suspension of 0.5 mol of nitrile (6) in 250 ml of 80% aqueous acetic acid solution, 1 mol of activated zinc dust is added in small portions over 3 hours with vigorous stirring at a mixture temperature no higher than 40 °C. The mixture is kept under stirring for 5 hours, the zinc salts are filtered off and washed with acetic acid. The filtrate is evaporated in vacuo at 30-40 °C. The residue is triturated with water to obtain a crystalline mass. After filtration, the crystals are dried in vacuo over P2O5 and recrystallized from hexane-ethyl acetate (1:1). Yield 71%. M.p. 186-187 °C. IR spectrum (KBr, cm-1): 780 (C=C-CCl2), 835 (CCl, ν), 929 (C-Cl, ν), 1660 (C=O, ν), 1677 (C=O, ν), 2840 (CH, ν), 2910 (CH, ν), 3180 (NH, ν), 3350 (NH, ν), 3440 (NH, ν). 1H NMR (δ, ppm): 8.3 (NH2, m), 10.1 (NH, s), 0.8-1.1 (15H). MS (m/z): 352 (M•+), 270, 135, 44. 2-(Adamantyl-1-carboxamido)-3,3-dichloroacrylic acid (8) [23]. A suspension of 0.3 mol of nitrile (6) in 800 ml of concentrated hydrochloric acid is quickly heated until the precipitate dissolves and boiled for 15-20 min. Cooled with ice. The precipitate is filtered off, washed with water and added in small portions to 1.5 l of saturated sodium bicarbonate solution. The mixture is shaken until the evolution of carbon dioxide ceases. Insoluble amide of the acid (8) is filtered off. The filtrate is acidified with concentrated hydrochloric acid to pH ~ 2. The precipitate is filtered off, washed with water and dried in vacuum over P2O5. The yield of acid (8) is 62%. M.p. 195-196 oC. IR spectrum (KBr, cm-1): 950 (C-Cl, ν), 1635 (C=O, ν), 1640 (C=O, ν), 1715 (C=C-CO2H, ν), 2840 (CH, ν), 2910 (CH, ν), 3300 (OH, ν). 1H NMR (δ, ppm): 9.9 (NH, s), 12.8 (COOH, s), 0.8-1.1 (15H). MS (m/z): 353 (M•+), 336, 308, 271, 135, 45. 2-(Adamantan-1-yl)-4-(dichloromethylene)oxazol-5(4H)-one (9). a) To a solution of 0.01 mol of acid (8) in 50 ml of methylene chloride is added 0.015 mol of dicyclohexylcarbodiimide (DCC). The mixture is boiled for 5 hours. The mixture is cooled and filtered to remove the urea precipitate. The filtrate is evaporated in vacuo. The residue is crystallized from hexane – ethyl acetate (1:1). The yield of oxazole (9) is 76%. Norwegian Journal of development of the International Science No 166/2025 21 M.p. 147-148 °C. IR spectrum (KBr, cm-1): 1240 (C-O, ν), 1700 (C=CCl2, ν), 1820 (C=O, ν), 2840 (CH, ν), 2910 (CH, ν). 1H NMR (δ, ppm): 0.8-1.1 (15H). MS (m/z): 299 (M•+), 217, 135, 44, 42. b) [24]. A solution of 0.03 mol of sodium methoxide in 5 ml of methanol is added to a solution of 0.01 mol of acid (8) in 30 ml of methanol. The mixture is kept at 20-25 °C for 10-12 days. Sodium chloride is filtered off. Methanol is removed in vacuo. To the residue are added 30 ml of water and ether. The aqueous layer is additionally extracted twice with 50 ml of ether. The combined ethereal extracts are dried over sodium sulfate. The ether is removed in vacuo. The residue is crystallized from hexane – ethyl acetate (1:1). The yield of oxazole (9) is 53%. M.p. 148–149 °C. IR spectrum (KBr, cm-1): 1240 (C-O, ν), 1700 (C=CCl2, ν), 1820 (C=O, ν), 2840 (CH, ν), 2910 (CH, ν). 1H NMR (δ, ppm): 0.8–1.1 (15H). MS (m/z): 299 (M•+), 217, 135, 42, 44. 2-(Adamantan-1-yl)-4-(dichloromethylene)-1Himidazol-5(4H)-one (10) [11]. To a solution of 0.01 mol of amide in 30 ml of acetic acid is added 0.01 mol of sodium acetate. The mixture is heated at 60 °C for 7 hours. After cooling, the mixture is diluted with 100 ml of water and made alkaline with 10% NaOH solution. The solution is extracted with 3x50 ml of chloroform. Dry over anhydrous sodium sulfate. The extract is evaporated. The residue is triturated with water until a crystalline mass is formed. Filtered and dried in vacuo over P2O5. The yield of imidazole (10) is 73%. M.p. 183-184 °C. IR spectrum (КBr, cm-1): 800 (NH, δ), 930 (C=CCl2, ν), 1330 (C-N, ν), 1465 (NH, δ), 1715 (C=O, ν), 2840 (CH, ν), 2910 (CH, ν). 1H NMR (δ, ppm): 8.5 (NH, s), 0.8-1.1 (15H). MS (m/z): 298 (M•+), 297, 216, 135, 42, 27. Results and discussion. Synthesis of reagents. As can be seen from the scheme, to obtain the target heterocycles (9) and (10), it was necessary to go through several stages of synthesis of the starting reagents - acid (8) and amide (9), respectively. The first synthesis, common to both reagents, was the synthesis of adamantyl-containing amide (3). To obtain it, it was necessary to make changes to the original method [6], since amide (1) had limited solubility in benzene even when heated. The reaction was carried out in chloroform. The time was increased to 6 hours. Identification of product (3) was carried out based on the IR spectrum. The presence of characteristic deformation and stretching vibrations of NH, OH bonds, as well as stretching vibrations of C=O, C-Cl, CH bonds confirms the composition of amide (3). In addition, the PMR spectrum contains signals of NH and CHOH protons with characteristic shifts and splitting constants. The presence of the adamantyl fragment is confirmed by a multiplet integrating over 15 protons in the range of 0.8-1.1 ppm. The mass spectrum confirms the mass of the product and the presence of characteristic fragments formed by the elimination of water molecules, dichlorocarbene, and the adamantyl cation (m/z 135) [25]. The yield of amide (3) was 87%. The next step was the conversion of the amido alcohol (3) to the amido chloride (4) [19]. For this, a suspension of the amide (3) in CCl4 was treated with thionyl chloride. The yield of amide (4) was 89%. The structure of chloride (4) is confirmed by the following spectra IR: 870 (C-Cl, ν), 970 (C-Cl, ν), 1130 (C-O, ν), 1290 (OH, δ), 1580 (NH, δ), 1650 (C=O, ν), 2830 (CH, ν), 2920 (CH, ν), 3450 (C-O, ν), 3640 (OH, ν), 1H NMR (δ, ppm): 7.4 (NH, d, J=6.8 Hz), 6.2 (CH, d, J=6.8 Hz), 0.8-1.1 (15H), MS (m/z): 343 (M•+), 308, 307, 261, 135. 22 Norwegian Journal of development of the International Science No 166/2025 Imine (5) was obtained by treating a solution of chloride (4) in benzene with triethylamine [20]. The reaction proceeded at room temperature for 30 minutes, as evidenced by the precipitation of triethylamine hydrochloride. The yield of the product was 75%. The product was identified by IR: 990 (C-Cl, ν), 1710 (C=O, ν), 2850 (CH, ν), 2890 (CH, ν), 1H NMR (9.2 (CH, s), 0.81.1 (15H)) and MS spectra (307 (M•+), 225, 190, 135). The next step was the synthesis of the key product, nitrile (6), from which the starting compounds for the synthesis of heterocycles, amide (7) and acid (8), were obtained [21]. A solution of amide (5) in ether was added dropwise with cooling to a solution of triethylamine and HCN. The reaction mixture was kept at room temperature for 1 hour. As a result, nitrile (6) was formed in 76% yield. IR, PMR and mass spectrometry served as evidence of the structure. spectra. So, in the IR spectrum there are characteristic signals of bond vibrations: stretching C-Cl at 950 cm-1, =C-CN at 1645 cm-1, C=O at 1660 cm-1, >N-C=C-CN at 2210 cm-1, CH at 2840 and 2910 cm-1. The next step was the conversion of the amido alcohol (3) to the amido chloride (4) [19]. For this, a suspension of the amide (3) in CCl4 was treated with thionyl chloride. The yield of amide (4) was 89%. The structure of chloride (4) is confirmed by the following spectra: IR: 870 (C-Cl, ν), 970 (C-Cl, ν), 1130 (C-O, ν), 1290 (OH, δ), 1580 (NH, δ), 1650 (C=O, ν), 2830 (CH, ν), 2920 (CH, ν), 3450 (C-O, ν), 3640 (OH, ν), 1H NMR (δ, ppm): 7.4 (NH, d, J=6.8 Hz), 6.2 (CH, d, J=6.8 Hz), 0.8-1.1 (15H), MS (m/z): 343 (M•+), 308, 307, 261, 135. Imine (5) was obtained by treating a solution of chloride (4) in benzene with triethylamine [20]. The reaction proceeded at room temperature for 30 minutes, as evidenced by the precipitation of triethylamine hydrochloride. The yield of the product was 75%. The product was identified by IR 990 (C-Cl, ν), 1710 (C=O, ν), 2850 (CH, ν), 2890 (CH, ν), 1H NMR (9.2 (CH, s), 0.8-1.1 (15H)) and MS spectra (307 (M•+), 225, 190, 135). The next step was the synthesis of the key product, nitrile (6), from which the starting compounds for the synthesis of heterocycles, amide (7) and acid (8), were obtained [21]. A solution of amide (5) in ether was added dropwise with cooling to a solution of triethylamine and HCN. The reaction mixture was kept at room temperature for 1 hour. As a result, nitrile (6) was formed in 76% yield. IR, PMR and mass spectrometry served as evidence of the structure. spectra. So, in the IR spectrum there are characteristic signals of bond vibrations: stretching C-Cl at 950 cm-1, =C-CN at 1645 cm-1, C=O at 1660 cm-1, >N-C=C-CN at 2210 cm-1, CH at 2840 and 2910 cm-1, NH at 3440 cm-1; deformation vibrations of NH at 1570 cm-1. In the PMR spectrum, proton signals were observed: NH, a broad singlet at 9.6 ppm and 15 protons of the adamantane nucleus at 0.8-1.1. The mass spectrum showed a molecular ion mass of 298 m/z, which corresponds to the butto formula of compound (6), as well as signals of fragments with masses of 297 (-H•), 216 (-CCl2), 135 (Ad+), 42 (NCO+), 27 (CN+). Nitrile (6) is reduced to amide (7) using the procedure described in [22]. As a result, amide (7) was obtained in 71% yield. The product was identified by IR, PMR, and mass spectra. IR spectrum: 780 (C=C-CCl2), 835 (C-Cl, ν), 929 (C-Cl, ν), 1660 (C=O, ν), 1677 (C=O, ν), 2840 (CH, ν), 2910 (CH, ν), 3180 (NH, ν), 3350 (NH, ν), 3440 (NH, ν). 1H NMR (δ, ppm): 8.3 (NH2, m), 10.1 (NH, s), 0.8-1.1 (15H). MS (m/z): 352 (M•+), 270, 135, 44. The procedure in [23] was used to convert nitrile (6) into acid (8). The yield of product (8) was 62%. The standard set of signals in the IR, PMR, and mass spectra of acid (8), proving its structure, is given in the experimental section. Synthesis of heterocycles. Two methods were used to synthesize oxazolone (9). The first of them was "traditional" and described in the article [24]. The synthesis consisted of treating acid (8) with sodium methylate in a methanol solution, followed by prolonged incubation of the reaction mixture at room temperature. After isolation and purification of the product, the yield of oxazolone (9) was 53%. The IR, PMR, and MS spectra contained all the signals necessary to prove the structure: IR spectrum: 1240 (C-O, ν), 1700 (C=CCl2, ν), 1820 (C=O, ν), 2840 (CH, ν), 2910 (CH, ν). The latter parameters indicated the presence of an adamantane core in the product. This is also evidenced by the only proton signals in the 1H NMR spectrum: 0.8-1.1 (15H). The mass spectrum shows the molecular weight of oxazolone (9), 299 D (M•+), a low-intensity molecular ion, which corresponds to the gross formula. As well as fragments corresponding to the departure of the CCl2 (217 D), Ad (135 D), NCO (42 D), CO2 (44 D) groups. The second method involved the use of dicyclohexylcarbodiimide (DCC) as a condensing agent in equimolar quantities. Product (9) was formed by boiling the reagent mixture in methylene chloride. The yield of oxazolone (9) was significantly greater than in the first method and amounted to 76%. The product had spectra similar to those of the product obtained in the first method. The synthesis of imidazole (10) consisted of heterocyclization by intramolecular condensation of amide (7) [11]. The reaction took place in acetic acid in the presence of sodium acetate at 60 °C for 7 hours. Such a long heating was required to achieve the maximum degree of conversion - 73%. Identification of product (10) was carried out using IR and PMR spectroscopy, mass spectrometry. Thus, the following characteristic bond signals were observed in the IR spectrum: 800 (NH, δ), 930 (C=CCl2, ν), 1330 (C-N, ν), 1465 (NH, δ), 1715 (C=O, ν), 2840 (CH, ν), 2910 (CH, ν). PMR spectroscopy shows the presence of a broad singlet at 8.5 ppm, indicating the presence of a proton at the nitrogen atom. The presence of a group of signals in the product at 0.8-1.1 ppm, integrating on 15H, indicates the presence of a damantan substituent. The mass spectrum proved to be quite informative. The mass of the product according to the MS spectrum was 298 D, which corresponded to the molecular formula C14H16Cl2N2O2 and indicated the presence of two nitrogen atoms. The presence of fragments 297, 216, 135, 42, 27 D confirmed the structure of imidazole (10)., NH c at 3440; deformation vibrations of NH at 1570 cm-1. In the PMR spectrum, proton signals were observed: NH, a broad singlet at 9.6 ppm and 15 protons of the Norwegian Journal of development of the International Science No 166/2025 23 adamantane nucleus at 0.8-1.1. The mass spectrum showed a molecular ion mass of 298 m/z, which corresponds to the butto formula of compound (6), as well as signals of fragments with masses of 297 (-H•), 216 (- CCl2), 135 (Ad+), 42 (NCO+), 27 (CN+). Nitrile (6) is reduced to amide (7) using the procedure described in [22]. As a result, amide (7) was obtained in 71% yield. The product was identified by IR, PMR, and mass spectra. IR spectrum: 780 (C=C-CCl2), 835 (C-Cl, ν), 929 (C-Cl, ν), 1660 (C=O, ν), 1677 (C=O, ν), 2840 (CH, ν), 2910 (CH, ν), 3180 (NH, ν), 3350 (NH, ν), 3440 (NH, ν). 1H NMR (δ, ppm): 8.3 (NH2, m), 10.1 (NH, s), 0.8-1.1 (15H). MS (m/z): 352 (M•+), 270, 135, 44. The procedure in [23] was used to convert nitrile (6) into acid (8). The yield of product (8) was 62%. The standard set of signals in the IR, PMR, and mass spectra of acid (8), proving its structure, is given in the experimental section. Synthesis of heterocycles. Two methods were used to synthesize oxazolone (9). The first of them was "traditional" and described in the article [24]. The synthesis consisted of treating acid (8) with sodium methylate in a methanol solution, followed by prolonged incubation of the reaction mixture at room temperature. After isolation and purification of the product, the yield of oxazolone (9) was 53%. The IR, PMR, and MS spectra contained all the signals necessary to prove the structure: IR spectrum: 1240 (C-O, ν), 1700 (C=CCl2, ν), 1820 (C=O, ν), 2840 (CH, ν), 2910 (CH, ν). The latter parameters indicated the presence of an adamantane core in the product. This is also evidenced by the only proton signals in the 1H NMR spectrum: 0.8-1.1 (15H). The mass spectrum shows the molecular weight of oxazolone (9), 299 D (M•+), a low-intensity molecular ion, which corresponds to the gross formula. As well as fragments corresponding to the departure of the CCl2 (217 D), Ad (135 D), NCO (42 D), CO2 (44 D) groups. The second method involved the use of dicyclohexylcarbodiimide (DCC) as a condensing agent in equimolar quantities. Product (9) was formed by boiling the reagent mixture in methylene chloride. The yield of oxazolone (9) was significantly greater than in the first method and amounted to 76%. The product had spectra similar to those of the product obtained in the first method. The synthesis of imidazole (10) consisted of heterocyclization by intramolecular condensation of amide (7) [11]. The reaction took place in acetic acid in the presence of sodium acetate at 60 °C for 7 hours. Such a long heating was required to achieve the maximum degree of conversion - 73%. Identification of product (10) was carried out using IR and PMR spectroscopy, mass spectrometry. Thus, the following characteristic bond signals were observed in the IR spectrum: 800 (NH, δ), 930 (C=CCl2, ν), 1330 (C-N, ν), 1465 (NH, δ), 1715 (C=O, ν), 2840 (CH, ν), 2910 (CH, ν). PMR spectroscopy shows the presence of a broad singlet at 8.5 ppm, indicating the presence of a proton at the nitrogen atom. The presence of a group of signals in the product at 0.8-1.1 ppm, integrating on 15H, indicates the presence of a damantan substituent. The mass spectrum proved to be quite informative. The mass of the product according to the MS spectrum was 298 D, which corresponded to the molecular formula C14H16Cl2N2O2 and indicated the presence of two nitrogen atoms. The presence of fragments 297, 216, 135, 42, 27 D confirmed the structure of imidazole (10). Conclusions 1. Methods for producing adamantyl-containing amidoadkylating reagents in high yields have been developed. 2. Adamantylimidazole and adamantyloxazolone have been synthesized using adamantyl-containing amidoadkylating reagents. 3. Approaches for the synthesis of a variety of framework-containing nitrogen heterocycles have been discovered. References: 1. Heilmann H. // Angew. Chem., - 1957. - 69, # 13/14. - S. 463-471. 2. Adams P., Baron F. A. // Chem. Revs. - 1965. - 65, # 5. - P. 567-602. 3. Zaugg G., Martin V. // Organic Reactions / Ed. by I. F. Lutsenko. - Moscow: Mir, 1967. - Vol. 14. - P. 65-286. 4. Speckamp W. N., Hiemstra H. // Tetrahedron. - 1985. - 41, # 2. - P. 4367-4416. 5. Campbell R. D., Behr F. 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