SU578869A3 - Method of preparing 4-oxy-3-nitrocarbostyryls - Google Patents

Description

(54) METHOD FOR PRODUCING 4-.OXY 3-NITROCARBOSTYRILES

Claims (2)

one The invention relates to a process for the preparation of novel 4-hydroxy-3-nitrocarbostyryl, which can be used as a medicine. Methods are known for the preparation of 1-hydroxy-3-nitrocarbostyril i, 3,6-dinitro-.4-oxycarbostyril and 4-hydroxy-3,6,8-trinitrocaron bostyril f by nitration with concentrated nitric acid or a mixture of anhydrogen sulfide with sulfuric acid. However, the biological activity of these compounds is not specified. A method is proposed for the preparation of novel 4-hydroxy-nitrocarboxy groups of the general formula RI OH (} where RJ, R, I, and P, is hydrogen or alkyl, alkoxy, aryloxy, araloxy, aryl, aralkyl, heterocyclic, oxy, nitro, or halogen or any two groups of P and R, I and K. together with the carbon atoms to which they are attached, form a substituted or unsubstituted carbocyclic ring; Rj is hydrogen, alkyl, aryl or aralkyl, provided that 1, P., 1, R, and 5 are not all hydrogen; R2 is not a nitro group, eslt R., R, R, and Rg is hydrogen; Rg and R are not nitro, if R, Rj and R are hydrogen, that is, the compound: Kenya of the general formula: where R, - R, has the abovementioned nitriding followed by removal. target compounds in free- jaoM form or in the form of salt. The lowest apkyl in these rasysals contains from 1 to 6 carbon atoms and means such groups as methyl, ethyl, H - and isopropyl, M -.frmajo-and mpem-butyl, methoxy, ethoxy-, n- and isopropoxy-, H, L shr - and t-butoxy or ilif (shoxy-, benzyloxygroup, phenyl, benep, pyridyl, fluorine, chlorine, bromine iodine. In addition, R, and R. or R, and R. together with carbon atoms to which they are attached, may form a condensed phenyl or condensed 1,2-cyclohexenipene nucleus, which may have one or more of these substituents. would be R, was hydrogen and R. each is a methyl, ethyl, K uj methoxy, ethoxy or H-propoxy propyl group. Compounds of the general formula (1) are also obtained in the form of salts formed by a cross-metal, such as aluminum and magnesium, and, in addition, salts formed by organic bases such as amines or amine compounds. 4 Oxy 3-nitrocarboxyrypides can exist in a number of tautomeric forms. The initial products of the general formula (I) are RC, -hydrogen is obtained in a known manner, for example, in the Patel and Mehta method, when the mixed anipin is condensed diethyl malonate, followed by conducting hydrolysis and cyclization with monoanilida on. lipophosphate acid. In the case of symmetrically mixed anilines or anilines, zamvshchenny in the ortho-position, get only one product as a result of cyclization. In the case of asymmetric anilines, in which the freedoms of the two ortho-positions are free, 5 "and 7" are obtained, and the oxycarboxyd in varying proportions; x Thus, in the presence of 3,4-dimet; nilin receive a mixture of two possible isomers in a 1: 1 ratio, and in the presence of more complex substituents, the ratio influences on part of the newly formed C – C bond, dropped from the most complex substituent or substituents. Thus, 3,4-.dn-. Ethylaniline results predominantly in the preparation of 6,7-Diatilcarbostyril with only minor amounts of the 5,6-diethyl isomer. Source products of general formula (il). where R, -apkyl, aryl, or aralkyl, get 113 substituted N-alkyl-, N-aryl-N-aralkylanthronic acid by condensation by reaction with acetic anhydride in a medium of acetic acid, M-alkylthiranic acid is obtained by quantizing anthranilic acids with a medium of acetic anhydride in a medium of acetic acid; x In these beams, products are not obtained due to the fact that the sites for the formation of a new nickel are defined. Example. 6 Haor-4-hydroxy-3-nitro, arbostiril. A suspension of 6-chloro 4.oxycarbostyril, 1.82 g, 0, OO93 mol) in ped-acetic acid (10 ml) was shaken with concentrated nitric acid (2.5 ml; d 1.42). The mixture is heated in a water bath at 10 ° C until a clear solution appears. After the orange solution has cooled, it releases a bright yellow solid, which is filtered, thoroughly washed with lactic acid and ethanol. Drying in vacuum over phosphorus pentaoxide and sodium hydroxide gives an analytically pure product that decomposes at 200 ° C. N 11.93; Found,% t C 45.31; H 2.31; CE 14.78 O Calculated,%; C, 44.93; H 2, O9; N11.64; All 14.74. The sodium salt is prepared by treating nit rosinamide with 1 eq. sodium hydroxide in aqueous solution, shaking, followed by recrystallization, shaking, and subsequent recrystallization from water. Found,%: C 41.00; H 1.60; CE 13.11; N10.75; Na 9.48 SdNDSEM. OMA Calculated,%: C 41.17; H 1.54; Cei 3.50; N 10.67; Ma 8.76. PRI mme R 2. 4-Oxy-6-methyl-3-nitrocarboxy. A suspension of 4-hydroxy-6-methylcarbostyril (l, 63 g, 0.0093 mol) in icic acid and hydrochloric acid (10 ml) is nitrated similarly to Trimer 1. The dried material with m.p. 239 C is recrystallized from a mixture of acetic acid and ethanol to obtain a solid product, which decomposes at 245 C. Found:% C 54.51; H 3 J2 N 13,13 Sle P Calculated,%: C 54.55; H 3.66; N 12.75. EXAMPLE 3, 6-Ethyl-4-Oxy-3-Yitrocarbostyryl. Concentrated nitric acid (2.5 ml, d 1.42) is added to a stirred suspension of 6-ethyp-4-hydroxycarbostyryl (1.76 g, OOOOS mol) and the mixture is heated at 100 ° C until isolation from the original ( After cooling, the solid is filtered off, washed with acetic acid, then with ethanol and recrystallized.Text 220-222 ° C (acetic acid). Found D: C 56.67; H 4, 38; No. 11.64. Deducted,%: C 56.41; H 4.30; f 11.96 The sodium salt is prepared by dissolving the free nitro compound in an equivalent amount diluted About an aqueous solution of sodium hydroxide followed by neocrystallization from water, a solid yellow substance is obtained. Found: C 49.98; H 3.82; N 10.78; ttt 8.67 C ll aO -l / 2H Calculated: C 49.82; H 3.8 O; N 10.56 Wa 8.67. PRI me R 4. 4-Oxy.5 methyl-.3 nitro carbostyryl and 4 oxy-7-methyl- 3-nitrocarbostyril. By nitration of a mixture (l: l) of 4-yuxi.5.methylcarbostyril and 4 hydroxy-7-methylcarboyl reel (1.68 g, 0.0093 mol), analogously to example 1, a mixture of two derivatives, so pl. 231.232 C, Found,%: C 54.18; H 3.73; M12.87, .04 Calculated,%: C 54.55; H 3.66; N12.75 Fractionated recrystallization from acetic acid gives 5 methyl derivative with m.p. 231 C as a less soluble isomer. Found,%: C 54.43; H 3.715 N 12.47 s. Calculated,%: C 54.55; H 3.66; N and 7-methyl derivative with so pl. 207-210 ° C As; more soluble isomer. Found,%: C 54.03; H 3.76; N12.25 Calculated,%: C 54.55; H 3.66; N 12.75. PRI me R 5. 4-Oxy 8.methyl-8-nitro carbostyryl. A suspension of 4-hydroxy-8 methylcarbosterine (l, 63 g; 0.0093 mol) in glacial acetic acid (10 ml) is stirred by adding concentrated nitric acid (2.5 ml d 1.42), the mixture is heated for 8 minutes at 10O With the release of a clear solution from the transparent solution of the yellow nitro derivative. After cooling, ethanol is added, the solid is filtered off and washed thoroughly with ethanol. After drying over a mixture of phosphorus pentoxide and sodium hydroxide, the product is obtained with m.p. 266-267 C. Found,%: C 54.41; H 3,6O; M 12.51 C, Calculated,%: C 54.55; H 3.66; N 12.75. EXAMPLE 6. 6-Bromo 4-hydroxy-3-nitro carbostyryl. Suspension of 6-bromo-4-hydroxycarboxylic Prg1: pa (2 (23 g, O, Q093 mop) in glacial acetic acid (l5 ml) is stirred, added concentrated h nitric acid (2.5 ml, (1.42), After heating at 100 ° C for several minutes, the solid yellow solid is isolated. After cooling, ethanol (40 ml) is added and the mixture is filtered; the solid is completely washed from nitric acid with ethanol. Dry in vacuum over phosphoric anhydride to give 213- 214 C (times.). A variety of products with a mp of 1.74; N 9.77; Found, C: 37.83; WU, 28.33 1.77; N 9.83; Calculated,%: C 37.92;, O3. The solution is an NSR ineip in sylvolysis solution of sodium hydroxide (o, 01 N), taken with a slight excess, followed by recrystallization from the same solution, the sodium salt is obtained in the form of a yellow crystalline compound. After drying 70 to 90 ° C, an anhydrous product is obtained in the form of a solid , Dect MA easily spreading on. Found,%: C 34.72; H 1.74; M 8.92 Bb 411sleio,%: C 35.20; H 1.31; M N 9D2. Example f. 3, .3 Dimethyl-.4 "-Oxy 3, -nitrocarbostyryl. A suspension of 5,8-dimethyl-4-hydroxy 3 Oxy carbostyryl (1.76 g, 0, O093) in glacial acetic acid (10 ml) is not stirred up, quickly added with terminated nitric acid (2.5 mp, d 1.4-2). Heating on the steam bath for several minutes gives a solid yellow substance in the form of flakes, which after cooling is diluted with ethanol, filtered and thoroughly washed with ethanol. Dried in 1 pd thioxide of foss1zor n receive 3 "Hydroderivative with m.p. , C. (dec). Found,%: C 56.55; H 4.33; M 11, SO. C3, HioNp4 Calculated,%: C, 56.41; H 4.30; N 11.96. Example 8. 5.8 Dimethyl-.4-hydroxy ™ 3 nitrocarbostyril. Nitration of 5.8 dimethyl-d4. -Oxencarbol styryl (l, 76 g, 0.0093 mol) analogously to example 7 gives the title compound as a yellow crystalline substance with mp. 226 ° C (decomp.). Found,%: C 56.09; H 4, ZO; N 11.72 C «H ,, Calculated th,%: C 56.41; H 4, ZO; N 11.9 EXAMPLE 9 9.8 Dimethyl-4-hydroxy. 3-nitrocarbostyryl. Concentrated nitric acid (2.5 ml, d 1.42) is quickly added to a suspension of 6,8-dimvtil-4-hydroxycarbostyryl (1.76 g, 0, OO93 mol) in glacial acetic acid (10 MP), the mixture was heated at 1 ° C with a yellow colored product; then it was filtered and by recrystallization of the acetic acid, the desired compound was obtained with m, pl. 290 ° C (decomp.). Found,%: With 56.41; H 4.17; N 11.94 4lW L1 number,%: C 56.41; H 4.30; N 11.96. EXAMPLE 1. 7,8-Dimethyl 4 ox-3-nitrocarbostyril .. By nitration of 7,8-dimethyl 4-yuxicarbo-. styryl concentrated nitric acid analogously to example 7, a 3-nitro isopropane with m.p. 284-285 C (decomp.). Found,%: C 56.51; H 4, ZO; N 11.79. & 1num,%: C 56.41; H 4, ZO; K 11.96 Example 11, 8-Bromo-4-hydroxy-.3 nit “rocarbostiril. Concentrated nitric acid (2.5 ml, oil, 42) is added to a suspension of 8-bromo-4-hydroxycarbostyril (2.23 g, 0, OO93 mol) in acetic acid (Yu ml), the mixture is heated for steam bath until the termination of release of yellow 3 nitro-derivatives. Ethano and the filtered product are carefully added to the cooled mixture: selected with ethanol, dried under vacuum over phosphorus pentoxide and sodium hydroxide. T, pl. 191 C (dec,). Found,%: C 38.24; H 1.91; N 9.65 Bf27.97. CgHjBrHp Calcd.,%: C 37.92} H 1.77; N 9.8 Bp28, OZ. A suspension of the nitro compound in water is treated with 1 eq. a dilute solution of sodium hydroxide and yellow sodium salt is recrystallized from water; Found: C 35.86; H 1.51; К 9.37 Вг2в, 42; Ма 7, О9 CgHjj BrNgMaO Calculated,%: С 35.2О; H 1.31; N 9.1 Br26, O3; Na 7.49. Example 2. 8-Chloro-4 hydroxy-3-nitro carbostyril. A suspension of 8-chloro-4-hydroxycarbostyril (1.82 g, O, O093 mol) in glacial acetic acid (10 ml) was nitrated as in Example 11, yielding a 3-nitro derivative with m.p. 2OOu2O2 ° C. (different). Found,%: C 44.92; H 2.72; N 11.5 ce 14.68. . Calculated,%: C, 44.93; H 2, O9; N 11, se 14.74. 57 9 -Dimethyl-4-yuxi- Example 3. nitrocarbostyril. By nitration (l: l) of a mixture of 5,6-dimethi. -4 -oxycarbostyril and 6,7 -dimethyl-4-hydroxy-. Carbostyril analogously to Example 1, a mixture of 3-nitro derivatives is obtained. 6.7-dimethyl isomer is isolated by fractional crystallization from acetic acid as the more soluble isomer; m.p. 221-225 C. Found,%: С 56.46; H 4.51; N 11.86 P1% VD Calculated,%: C 56.41; H 4.30; N 11.86. Example 14. 7-Chlo1.4-hydroxy-3-nitrocarbostyril, A suspension of 7-chloro-4-hydroxycarbostyryl (0.5 g) in glacial acetic acid (4 ml) is nitrated with concentrated nitric acid (0.7 ml) at 1OO C and treated in the usual way, obtaining a compound with m. pl. 166-187 C (total ethanol). Example 15, A. Mono (3,4-diethyl) -anilyl malonic acid. A mixture of 3,4-diethylaniline (39.0 g, O | 263 mol) and diethyl malonate (73.2 g) 0.458 mol) is carefully heated for 1 rt when refluxing for 45 minutes. The ethanol formed is removed through an air-cooled 127 mm diameter isolated column. After cooling and adding a double volume of ethanol, the precipitate is filtered off and the diamide is filtered off and the filtrate is distilled off on the steam bath for 1 hour in the presence of sodium carbonate (40 g) in water (350 ml). The flasks are cooled, filtered to remove residual amide and,. monoanilide is precipitated with - concentrated hydrochloric acid; m.p. 120-121 ° C (water). Found%: C 65,97; H 7.9; N 5.89. CjjHj MOj Calculated,%: C, 66.36 ;, H, 7.28; N, 5.95; B. A solution of mono- (3,4-diethyl-) - anilide of malonic acid (54 g, 0.23 mol) in polyphosphoric acid obtained from phosphorus pentoxide (230 g) in syrup-like phosphoric acid. (140 ml), stirred at 14 ° C for 3 hours, then housed and hydrochloric acid solution (B90 ml) was added. After adjusting the pH to 4 with a solution of sodium hydroxide, the hydroxycarbostyryl is filtered off, washed thoroughly with water and recrystallizing from glacial acetic acid the product is obtained with a melting point. above 300 ° C. c 71.69; H 6.88; N 6.26 Found 9 q, H, No 9 Calculated,%: C, 71.87; H 6.96; M6.45. The NMR spectrum showed the presence of minor amounts of 5,6-diethyl isomer. p, 6,7-Diethyl-4-.oxy-3-nitrocarbostyril. By nitration of 6,7-diethyl-4-hydroxycarboyl reel (3.9 g, 0, O18 mol), as described. previously, a 3-nitroderivative is obtained in the yellow solid crystalline suspension with a melting point of mp. 248-250 ° C (decomp.; Ethanol). d Original product -Oxy-.7 methoxycarbostyryl 4-hydroxy-7-methoxy-6-methylcarbostyryl 8-Ethoxy-4-hydroxy-6-n-propylcarbostyryl 4-Oxy-7-methyl-8-H-Propoxcarbostyryl 4-Oxy-7-phenoxycarbostyryl 7 Benzyloxy-4-hydroxy-6-methyl-carbostyryl 7-Ethyl 4-hydroxy-b-fbnylcarbo- stiril 8-Benzyl-4-hydroxy-6-methylcarbostyryl 4-Oxy-6-methyL-7- {3-pyridyl " -carbostyril 4-Oxy-8- (3-pyridyl) -carbostyryl 4,7-Dioxycarbostyryl 4-.OXI-7-H-Propoxycarbostyryl Example 16 A. 1-Ethyl-4-hydroxycarbostyryl, A solution of N-ethyl anthranilic acid (l2.0 g, 0.073 mol) in acetic acid (37 ml) and acetic anhydride (37 ml) is heated under the action of a reflux condenser for 4 hours. Red the solution is cooled, poured onto crushed ice and brought to reaction with an alkaline aqueous solution of sodium hydroxide. After filtration, the yellow filtrate is neutralized with concentrated hydrochloric acid (pH 5), the solid yellow substance is filtered and washed with doi. Recrystallization from acetic acid 10 Found,%: C 59.28; And 5.60; N 10.56, , t Calculated,%: C 59.53; H 5.38; N 1O 68 Spectrum NMR showed the absence of 5, in the di ethylnomer. Analogously to Example 1, the following were prepared by nitrating the starting products of general form 1b (I) in glacial acetic acid with concentrated nitric acid (Compounds Target product 4-Oxy-7 methoxy-3-nitrocarbostyryl 4-Oxy-7-.methoxy-6-methyl-3-nitrocarbostyryl 8-Ethoxy-4-hydroxy 3 nitrs-6. n-proplcarbostyril 4 Oxy-.7-methyl-propoxy-3-nitrocarbostyryl 4-Oxn-3-nitro 7-phenoxparbosti-. reel 7-Benzyloxy-4 hydroxy-b-methyl-3-nntro carbostyryl 7 tyl-4-hydroxy-3-nitro-6-4enylcar. Bostyril 8-Benzyl-4-.oxy "6-.methyl-3 nitrocarbostyryl 4-Oxy-6-methyl 3-nitro-7- (3-pyridine-carboxytyl 4 "Oxy-3-.nitro 8- (3-pyr11Dil) -carbostyryl 4,7-Dioxy-3-nitrocarboxyrnl 4 Oxy-.3 nitro-.7. N-propoxycage-boctcryl in the presence of activated carbon, you give an orauke-colored substance with m. pl. 273-275 ° C, Found,%: C 69.85; H 6.04; K 7.29 Calculated,%: C 69.83; And 5.86; M 7.40, B. 1-Ethyl 4 hydroxy 3 nitrocarbostyril. A suspension of 1. ethyl-4-oxycarbostyril (1.09 g, 0.00575 mol) in glacial acetic acid (5 ml) is stirred, quickly added concentrated nitric acid (1, 25 ml, d 1.42) and a dark liquid heat for 5 minutes at 100 C. A yellow, solid substance released on cooling. filtered and washed thoroughly with this NOLA, so pl. 154.155 ° C (decomp.). FoundDg C 56,54; H 4.52; K 11.56 / Г1 М ГЛ. О1,%: С 56.41 g Н 4.30-, N 11.96. Example 17. A, 4 Oxy-1-mtitilcarbostyril is obtained from N-methyl anthranilic acid (22.04 g of 0.146 mol) as in Example 16 A, so pl. a70-273 ° C (ethanol). Found,%: C 68.59; H 5.44; M 7.73 & 1 number,%: C 58.56; H 5.18; W 8, OO B. 4-Oxy 1-methyl-3 nitrocarbostyryl. A suspension of 4 Oxy-1-methi carbostyril (1.63 g, 0, O09 mol) in glacial acetic acid (10 ml) was stirred by adding concentrated nitric acid (2.5 ml d 1.42), the mixture was heated several metgut per steam bath. After cooling, the caste material in the form of yellow crystals, which are diluted with ethanol, is filtered off and thoroughly washed with ethanol. 159-161 ° C. Found; %: C 54.2 Oj H 3.71; M 12.4 SyuNeH O C 54.55; H 3.66; N 12.72 Calculated, Example 18b A, 1,6-Dimethyl-4-hydroxycarboxyrip, Reaction L, 5-dimethyl anthranilic acid (19 g, 0.115 mol) B with acetic JfflC lot (58 ml) and acetic anhydride (58 ml) is similar Example 16A 1, a compound with m.p., C (ethanol) is obtained. Found,%: C, 70.16; H 6.15; M 7.04 C., Calculated,%: C 69.88; H 5.86; N 7.40 B, 1,6-.Dimethyl-.4- "ox 3 - nitrocarboyl reel. . To a stirred suspension of 1,6.dime "gil-4 oxycarbostyril (l, 70 g, 0.009 mol) in glacial acetic acid (10 ml) was added concentrated nitric acid (2.5 ml, d 1.42) with a vortex-like stirring. The solid is dissolved by heating to 100 ° C, to obtain a red solution, from which, upon cooling, the yellow crystals of 3-nit ™ roso compound are isolated as yellow crystals. Mp, 185 ° C; Found,%; C 56.05; H 4.33; M 11.86 C HjpMjO Calculated,%: C 56.41; H 4, ZO; N 11.9 PRI me R 19. A. 1-Ethyl-4-hydroxy 6-methylcarbostyryl. N-ethyl-5-methyl anthranilic acid (17.6 g 0, OO98 mol), mp, 159 ° C, is heated under the action of reverse cooling of kica in acetic acid (43 ml) and vinegar anhydride (43 ml) for 12 hours, The dark red {cooling solution is cooled and poured onto crushed ice. The mixture is made alkaline, the resinous product is filtered off and neutralized with hydrochloric acid. The yellow crystalline product is filtered off, washed thoroughly with water, and recrystallized from ethanol, mp 235280 ° C; Found,%: C, 70.87; H 6.34} N 7.17 C, H.1MO. Calculated,%: C, 70.88; H 6.44; M 6.89. B. Tyl 4-hydroxy-6.methyl "3-.nitrocarbostyril, Concentrated nitric acid (2.5 ml, d 1.42) was added to a suspension of 1 ethyl" .4-hydroxy-6.methylcarbostyril (1.82 g , 0.009 mol.) In glacial acetic acid (10 ml) and the mixture is heated to 100 ° C. The solid is dissolved and isolated 3-nitro-derivative as a yellow solid, which is cooled, filtered, thoroughly rinsed with water and dried in vacuum over phosphorus pentoxide; t, pl, 192-194 C. Found / o; C 58.16; H 5.02; N 11.29 ,, Calculated,%: C 58, O6; H 4,87; M 11,29, Example 20, A. 6-Chloro-4-Oxy ”1 methylcarbostyryl. 5-Chloro "M. Methylanthranilic acid (15 g, 0.81 mol) is dissolved in acetic acid (41 ml) and acetic anhydride (41 ml) and the dark mixture is heated under reflux for 12 hours. After cooling, the red solution is poured on crushed ice, alkalinized with 2.5 N, sodium hydroxide solution and filtered from AMOID impurities. The filtrate is acidified to pH 5 and the carbostyryl is obtained as a yellow solid with m.p. 317 "318 C (1 suslota islota). Found,%: C 57.39; H 3.98; M 6.83; se 16.69 Calculated,%: C 57.29; H 3.85; N 6.68; All 16.91 B, 6-. Chloro-4. Oxy-1-methyl-3-nitrocarbostyryl ,. A suspension of 6 chlorine 4-hydroxy-1-methylcarbostyril (1.0 g, O, O048 mol) in acetic acid (5 ml) is treated with concentrated nitric acid (l, 25 ml, 14O d 1.42; and heated to 1OO From 2 minutes, the red solution is cooled, a yellow solid is obtained. Then it is diluted with ethanol, filtered, washed with ethanol, and I get a 3-nitro derivative with m, mp, (melt. 13 Found,%; C, 46.85; And 2.86; M 10.96; CP 13.78 qHNjCIO Calculated,%: C 47.11; And 2.77; N 11.0 ce 13.92. The sodium salt is obtained by dissolving the free nitro compound in a slight excess of the diluted sodium hydroxide solution and recrystallizing the product. Salt - yellow solid hydroscopic crystalline substance, Found,%: C 43.57; And 2.32; N 10.04; All 12.84; Na 8.31. claims 1. Method for preparing 4-hydroxy-.3-nitrocarbostyril of formula: where R,, F ,, and Kd is hydrogen or alkyl, alkoxy, aryloxy, aralkoxy, arn ar-1, heterocyclic, hydroxy, nitro or halogen , or any two groups of H, and Rp, R, and R, together with the carbon atoms to which they are attached, form a substituted or unsubstituted carbocyclic ring; RC is hydrogen, alkyl, aryl or aralkyl, provided that R, R, R, R, and R are not all hydrogen; is not a nitro group if R ,, F, R and Rg are hydrogen; K, and Rjj are not a nitro group, if P, and R is hydrogen, o, tl and h and y and the fact that the compound of the general formula 14 where P - h have the indicated values, submits nitration with the release of the target product in free form or in the form of a syrup, 2, The method according to claim 1, which is ill, and the nitration is carried out with concentrated nitric acid in the presence of phosphorus acid and a mixture of uksuoic acid with concentrated nitric acid, and and nitric laicnoToii fume in chloroform, or with nitric acid nitrification. Priority on the grounds: 19.05.73 at T J - Rd hydrogen, alkyl, alkoxy, aryl, aralkyl, arnloxy group, heterocyclic group, window-, nitro group or halogen of either of the two groups. T, and T, are substituted or unsubstituted carboxylic ring and are alkyl, arnl, or aralkyl; 05/22/73 with T. - T. - hydrogen, alkyl. alkoxy, aryl, aralkyl, aryloxy group, heterocyclic group, window-, nitro group or halogen to any of the two groups, T. Ti t is a substituted or non-hydroxyl carbocyclic ring. Sources of information taken into consideration in the examination: 1.GabrJieS &. liur Ken-nH: “is cinioep ttitnoEl-iaKol. - „Cliem.Ber-. ; i9l8,51, LOO. 2.AshEej a, N., W.H., Ro ii so-nR, Sti ych "iiie and-. Poi X. Ppepav at oi of Some IJsoirjei-sides of Dinitpost I - oE awd TnH-nitra stiTycl oC .- „J. A“ t CViervi. Soc. 1930, Zos-ZE5,