2-trimethylammoniumchloride-4-methoxy-6-morpholyl-1,3,5-triazine as an intermediate for the synthesis of antioxidant
(57) Abstract:The invention relates to the field of organic chemistry and oil industry, specifically to the new derived contrasena-2-trimethylammoniumchloride-4-methoxy-6-morpholyl-1,3,5-triazine, which is an intermediate in the synthesis of active additives, inhibiting the oxidation of vegetable oils (antioxidant). table 1. The invention relates to the field of organic chemistry and oil industry, specifically to the new derived contrasena - 2-trimethylammoniumchloride-4-methoxy-6-morpholyl-1,3,5-triazine (TMT) structure:
< / BR>which is an intermediate in the synthesis of active additives, inhibiting the oxidation of oils (antioxidant).The increase in the production of cosmetic and oil industry requires the creation of new and expansion of existing affordable and effective antioxidants to extend shelf life of fats, creams, oils, lubricants, etc.Known 2-amino(amido)-4-morpholino-6-ethyl-1,3,5-triazine (AMT)structure:
< / BR>where R1and R2identical or different, are equal to H, alkyl, cycloalkyl, oxyalkyl, or derivatives of triazine, whitesky acceptable acid additive salts and potentialization choline-ergicheskoe effect, improving memory and learning ability [see A. C. the USSR , 1806142, 1822403 and 1838312 by M C 07 D 413/04/ Kossman E., J. Gaubert, Boaden R., Mathieu J. - publ. on 15.08.89] - (prototype structure).Also known methyl ester 4-oksibenzoynoy acid structure:
< / BR>Under the brand name "Nipagin" this connection is recommended for use as antioxidant additives (antioxidant) in creams and other cosmetics [see R. A. Friedman. Cosmetics and perfumes. - M.: Publishing house of the Food industry, 1968. - 487 S.] - (prototype).The disadvantages of using "Nipagina are relatively low antioxidant activity in relation to the ability to slow down the accumulation of peroxides and organic acids, as evidenced by the increase in the peroxide and acid numbers in time. Its use as an antioxidant in the composition of vegetable oils is unknown.Technical solution to the problem is the synthesis of more active and suitable for use in the composition of vegetable oil antioxidant.The task is achieved by the fact that to increase antioxidant activity are encouraged to use the newly synthesized polypropylene of the claimed invention is seen in that, what prompted the synthesis of a new compound - TMT, the use of which as an intermediate allows to synthesize the antioxidant, the use of which is composed of vegetable oil can significantly increase the stability of the oil to increase the acid and peroxide numbers in comparison with known antioxidant "Nipaginom".In this case, the placeholder for the application - "Nipagin used in the drug trade mark "chemically pure". The prototype structure - 2-ethylamino-4-morpholino-6-propyl-1,3,5-triazine (AMT) received in accordance with the patent [see A. C. the USSR 1822403 by M C 07 D 413/04/ Kossman E., J. Gaubert, Boaden R., Mathieu J. - Publ. on 15.08.89]. Source cyanuric chloride (technical product) purified twice by crystallization from CCl4(tPL=146oC). 2-Chloro-4-methoxy-6-morpholyl-1,3,5-triazine get known methods in accord with [G. M. Poghosyan, V. A. Pankratov, V. N. Zaplishny, S., Macayan. Policiesin. Yerevan: Publishing House.-in an AWS. SSR - 1987. - S.]. Chloroform purified and dried by [A. Gordon, R. Ford. Satellite chemist. M.: Mir, - 1976. - S.]. Methanol and morpholine immediately prior to use purified by fractional distillation; these constants correspond to the lit. data.Specific examples of the synthesis of the proposed>Example 1. 2-trimethylammoniumchloride-4-methoxy-6-morpholyl-1,3,5-triazine (TMT). Through a solution of 3 g (13 mol) of 2-chloro-4-methoxy-6-morpholyl-1,3,5-triazine in 20 ml of absolute benzene, in constant, slow current of dry nitrogen, with stirring and a temperature of 81oC for 1 h bubbled dry trimethylamine. Saturated with trimethylamine reaction mixture is left at 20oWith 12 h, the resulting abundant precipitate is filtered off, washed (315 ml) abs. benzene and dried in vacuum to constant weight. Get of 3.69 g (98%) TMT in the form of a white, crystalline powder with Tpl.145o(Melts with decomposition).Found, %: C 45,78; N 7,24; N 24,30; C1 12,47.WITH11H20N5lO2.Calculated, %: C 45,59; N. Of 6.96; N 24,17; C1 12,24.X , cm-1: 1620, 1570, 1510 (C=C and C=N-comp.); 1010, 1140 (C-O-C).The PMR spectrum , M. D.: 3,62...3,88 m (8H, -och2N-CH2); 3,47 m (N, N(CH3)3); 4,0 S. (3H, -och3).Example 2. 2-trimethylammoniumchloride-4-methoxy-6-morpholyl-1,3,5-triazine (TMT). Under conditions analogous to example 1, from the same quantities of the original, with the only difference that the bubbling of trimethylamine is carried out at 51oC for 1.5 h get to 3.73 g (99,06%) TMT in the form of a white t is 45,78; N 7,24; N 24,30; Cl 12,47.WITH11H20N5Cl2.Calculated, %: C 45,59; N. Of 6.96; N 24,17; Cl 12,24.X , cm-1: 1620, 1570, 1510 (C=C and C=N-comp.); 1010, 1140 (C-O-C).The PMR spectrum , M. D.: 3,62...3,88 m (8H, -och2N-CH2); 3,47 m (N, N(CH3)3); 4,0 S. (3H, -och3).Example 3. 2-Methoxy-4-morpholin-6-(-amoxici)-1,3,5-triazine (OATT). To a mixture of 1 g (of 0.003 mol) 2-trimethylammoniumchloride-4-methoxy-6-morpholyl-1,3,5-triazine and 0.47 g (0,006 mol) of mercaptoethanol in 30 ml of dry chloroform with stirring and the temperature 0-51oWith added in small portions 0.12 g (of 0.003 mol) of dry powdered sodium hydroxide. The mixture is stirred for further 3 h at the same temperature and left for 12 h at 6-10oC. the Solvent is evaporated in vacuo, the precipitate washed with water until the absence of chlorine in the wash water and dried to constant weight. Obtain 0.7 g (74%) OATT in the form of a white crystalline powder with so pl. 152-153oC.Found, %: From 44.3; H 6,01; N 20,79.WITH10H16N4SO3.Calculated, %: From 44.1; H Of 5.92, N 20,57.X , cm-1: 3410 (OH); 1560, 1510 (C=C and C=N-comp.); 1270 (-S-CH2); 1190, 1095, 1040 (C-O-C).PMR-spectrum , M. D.: 4,73...4,78 so (1H, Specific examples of the use of TMT as an antioxidant plant oils are presented in the table (see examples 3-7 at the end of the description). Thus the object of the study was svezhevyrabotannym refined sunflower oil production in the Krasnodar plant, with initial values peroxide and an acid number equal to 3.88 mmol O/kg and 0.21 mg KOH/g, respectively. Antioxidant OATT obtained on the basis of the claimed intermediate TMT and known connection "Nipagin" was introduced into the oil in the form of conc. solutions in chloroform in an amount of 0.001 to 0.01 wt.% based on DV. As control served the oil, not containing added antioxidants. Study of the process of oxidation of the oil was performed continuous accelerated kinetic method in isothermal conditions at 50oWith on the air in a quartz controlled open cuvettes for 50 days. At set time intervals for selected oil samples was determined values peroxide and krotovo numbers according to GOST 26593-85 and 5476-80 respectively. The stability of the oil to oxidation in % was determined by the formula:
where a and bivalues peroxide or acid number of control options and pilot, respectively. The results are summarized in table.As can be seen from these examples 3-7 table primeneniye stability of vegetable oil to increase the value peroxide value in comparison with control over time through 7, 15, 21 and 50 days 18,53-31,31; 23,26-32,48; 19,22-27,85 and 9,81-11,3%, respectively(39,0-35,26; 90,0-83,77; 140,18-130,85 and 912,6-900,3 mmol/kg, respectively) while in the presence of known antioxidant "Nipagina this indicator increases only by 11,22; becomes 9.97; 10.16 and 7.5%, respectively. Resistance to increasing values of the acid number of vegetable oil in time after 7, 15, 21 and 50 days in the presence of additives proposed OATT increased by 23,59-32,91; 31,14-26,05; 26,7-32,94 and 26,56-29,25% respectively(0,3225-0,299; 0,369-0,355; 0,382-0,364 and 1,4513-1,421 mg KOH/g, respectively), while in the presence of known antioxidant "Nipagin" this indicator has increased by only 10.5; 13,25; 14,96 and 20,09%, respectively. The analogue of the construction of the AMT in these conditions as an antioxidant is inactive (example 8).Thus the application of the proposed TMT as an intermediate for the synthesis of antioxidant enables you to get a connection OATT the use of which as an antioxidant plant oils, can significantly increase the stability of the oils to ascending values of the peroxide and acid numbers in time, and also extends the range of known antioxidants. 2-Trimethylammoniumchloride-4-methoxy-6-morpholyl-1,3,5-triazine structure
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to a new method for preparing 5-(4-fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxotetrahydropyran-2-yl)ethyl]-2-isopropyl-4-phenyl-1H-pyrrol-3-carboxylic acid phenylamide that involves conversion of methylcyano acetate to the end compound for 8 or less stages. Also, invention relates to value intermediate compounds that are synthesized as result of realization of above indicated stages of the claimed method. 5-(4-Fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxotetrahydropyran-2-yl)ethyl]-2-isopropyl-4-phenyl-1H-pyrrol-3-carboxylic acid phenylamide is a value intermediate compound used in synthesis of the drug atorvastatin calcium that is used as hypolipidemic and/or hypocholesterolemic agent. Proposed method allows avoiding usage of expensive chiral parent substances and to reduce the synthesis process time.
EFFECT: improved preparing method.
12 cl, 3 ex