RU2252215C9 - Crystal form of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline and method for production thereof - Google Patents

Abstract

FIELD: organic chemistry, in particular nitrogen-containing heterocyclic compounds from class of hydrated quinolines.

SUBSTANCE: invention relates to compounds of general formula I

(m.p. 28-39°C) and method for production thereof. New compounds in crystal form have high antioxidant activity and are useful in production of oils, resin articles, tears, plastics, adhesives, etc. with improved quality.

EFFECT: new crystal compounds of high antioxidant activity.

2 cl, 13 dwg, 2 tbl, 2 ex

Description

The invention relates to the field of organic chemistry and relates to a little-known, nitrogen-containing heterocyclic compound from the class of hydrogenated quinolines, namely 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) in a crystalline form having a high antioxidant activity. Also disclosed is a method for producing this compound, which consists in the fact that 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline (III) is subjected to hydrogenation in an alcohol medium on a new catalyst with a composition of 1-8% titanium, 30-60 % nickel, 0.2-1.5% iron and 35-65% aluminum by its subsequent activation, as well as known nickel catalysts, other metals active in the hydrogenation reaction, followed by isolation of the target product in crystalline form from an alcohol medium immediately or after preliminary cleaning.

The invention can be used as a substance that improves the properties of oils, petroleum products, rubber-rubber products, tires, polymers, plastics, adhesives, paints, organic glasses, biological objects, as a biologically active substance, an analytical reagent, a trap for radicals.

Known 8-methoxy-2,2,4-trimethyl-1,2-dihydroquinoline (II), which is an analogue of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) and which was obtained in the form of a viscous mass by condensation of o-anisidine with acetone in the presence of iodine (Ivanov Yu.A. Dis. Candidate of Chemical Sciences, Moscow, 1983).

When comparing the relative antioxidant activity of 8-methoxy-2,2,4-trimethyl-1,2-dihydroquinoline with the well-known phenolic antioxidant ionol (2,6-di-tert-butyl-4-methylphenol), taken as a standard, in concentrations 1.5 · 10 ^-4 mol / l in the process of autooxidation of pollock liver fat at 70 ° C and determination of oxidation kinetics by oxygen absorption, it was found that the relative antioxidant activity of this compound was two times lower than that of ionol.

Known 6-ethoxy-2,2,4-trimethyl-1,2, -dihydroquinoline (III), which is analogue I, which was obtained in the form of a viscous mass by condensation of p-phenetidine with acetone in the presence of iodine or 4-toluenesulfonic acid [Tung S.S. 1,2-Dihydroqinoline studien. I. The structure of the arylamine-acetone condensation products, - tetrahedron, 1963, vol. 19, No. 11, p. 1685-1689; U.S. Patent No. 2,748,100 of May 29, 1956; Ivanov Yu.A. Dis. Cand. Chem. Sciences, Moscow, 1983].

When comparing the relative antioxidant activity of 6-ethoxy-2,2,4-trimethyl-1,2, -dihydroquinoline (III) with the well-known phenolic antioxidant ionol (2,6-di-tert-butyl-4-methylphenol), taken as standard, in the process of autooxidation of pollock liver fat at 70 ° C and determination of oxidation kinetics by oxygen absorption, it was found that the relative antioxidant activity of III was 0.6 relative units.

Known 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline (IV), which is an analogue of the compound 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I), obtained by boiling 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline (III) in concentrated hydrobromic acid (Ivanov Yu.A. Dis. Candidate of Chemical Sciences, Moscow, 1983).

Studies of the antioxidant activity of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline (IV) showed its relative antioxidant activity compared to the known antioxidant ionol (2,6-di-tert-butyl-4-methylphenol), accepted as a standard, in concentrations of 2.1 · 10 ^-4 mol / l during auto-oxidation of pollock liver fat at 70 ° C and determination of oxidation kinetics by oxygen absorption, the relative antioxidant activity of IV was 0.78 relative units.

Known 8-methoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (V), which is an analogue of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline ( I) obtained by hydrogenation of 8-methoxy-2,2,4-trimethyl-1,2-dihydroquinoline (II) on Raney nickel in the form of a viscous mass (Ivanov Yu.A. Dis. Candidate of Chemical Sciences, Moscow , 1983).

When comparing the relative antioxidant activity of 8-methoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (V) with the well-known phenolic antioxidant ionol (2,6-di-tert-butyl-4-methylphenol) accepted as a standard in concentrations of 1.5 · 10 ^-4 mol / l during autooxidation of pollock liver fat at 70 ° C and determination of oxidation kinetics by oxygen absorption, it was found that the relative antioxidant activity of V was 0.6 relative units.

Known 8-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (VI) which is an analogue of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I ) obtained from 8-methoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (V) by boiling it in hydrobromic acid and transferring the obtained hydrobromic salt VI to the base (Ivanov Yu.A. Dis. Cand Chemical Sciences, Moscow, 1983).

The study of the antioxidant properties of 8-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (VI) showed its relative antioxidant activity compared to the known phenolic antioxidant ionol (2,6-di-tert-butyl -4-methylphenol), taken as the standard, in concentrations of 1.5-10 ^-4 mol / l during the auto-oxidation of pollock liver fat at 70 ° C and determination of the oxidation kinetics by oxygen absorption, which amounted to 1.0 relative units.

Known 6-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (VII), which is an analogue of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline ( I) obtained by transferring the hydrobromic salt VII to the base (Ivanov Yu.A. Dis. Cand. Chem. Sciences, Moscow, 1983).

The study of the antioxidant properties of VII showed its relative antioxidant activity compared to the known phenolic antioxidant ionol (2,6-di-tert-butyl-4-methylphenol), adopted as the standard, in concentrations of 1.5 · 10 ^-4 mol / l in the process of autooxidation of pollock liver fat at 70 ° C and determination of oxidation kinetics by oxygen absorption, which amounted to 0.8 relative units.

Known 6-acetoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (VIII), which is the closest analogue in structure and properties and adopted by us for the prototype 6-ethoxy-2,2,4-trimethyl -1,2,3,4-tetrahydroquinoline (I) obtained from 6-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (VII) by acylating it with acetic acid chloride (Ivanov Yu. A. Dis. Candidate of Chemical Sciences, Moscow, 1983; A.E. Obodovskaya, Z.A. Starikova, Yu.A. Ivanov, I.E. Pokrovskaya. Journal of Structural Chemistry, 1985.v. 26, No. 5, pp. 99-102).

The study of the antioxidant properties of VIII showed its relative antioxidant activity compared to the well-known phenolic antioxidant ionol (2,6-di-tert-butyl-4-methylphenol), adopted as a standard, in concentrations of 1.5 · 10 ^-4 mol / l in the process of autooxidation of pollock liver fat at 70 ° C and determination of oxidation kinetics by oxygen absorption, which amounted to 1.1 relative units.

Comparison of the relative antioxidant activity of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) with ionol (2,6-di-tert-butyl-4-methylphenol), taken as the standard, in concentrations of 1.5 · 10 ^-4 mol / l during the autooxidation of pollock liver fat at 70 ° C and determination of the oxidation kinetics by oxygen absorption showed that the relative antioxidant activity of this compound I was 1.5 relative units.

In limited scientific sources of information, mention is sometimes made of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline as an intermediate or intermediate in the synthesis of certain substances (US Patent No. 3,991,042 of 11/11/1976 g.). However, convincing information proving its structure and other parameters is not provided, which does not give grounds to consider the previously given formula of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline as completely reliable. Previously available information does not confirm or characterize this substance itself, although it is known that not only its physicochemical properties, including its state of aggregation under ordinary conditions, but also other properties, for example, its inhibitory activity, depend on the purity of the compound.

The use of hydrogenation in the alcohol medium of 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline (III) on a nickel catalyst in the preparation of 6-ethoxy-2,2,4-trimethyl-1,2,3,4- tetrahydroquinoline (I), although it leads to the formation of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I), but below technical qualification, i.e. with a basic substance content of ≥49%, which does not give grounds to consider it an individual compound. It is known that the purity of a substance obtained by various methods can differ greatly in its properties depending on the method of its preparation, since even microimpurities present in it, which are difficult to detect by known methods, determine not only its state of aggregation under ordinary conditions, but also physicochemical properties, including its stabilizing activity, for example antioxidant.

The absence in the periodic literature, patents and other publications of reliable information on methods for producing 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) and its physicochemical properties gives every reason to consider it uncertain new.

An object of the present invention is to provide a new 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) having a highly effective antioxidant activity and to develop an optimal method for its preparation on a new catalyst using high-speed mixing.

The problem is achieved by the new 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I), which has highly effective antioxidant activity, and a method for its preparation, which consists in the fact that 6-ethoxy-2, 2,4-trimethyl-1,2-dihydroquinoline (III) is subjected to hydrogenation in an alcohol medium on a new catalyst, as well as known nickel catalysts, other metals active in the hydrogenation reaction with vigorous stirring, followed by isolation of the target product immediately or after preliminary fractional fractional distillation with p the following additional purification.

The present invention describes a method for producing I on a new catalyst with vigorous stirring, fully characterizes it with various physicochemical research methods, as well as physical and fire and explosion proof data.

The research results, methods for producing 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I), below, confirm, but do not limit the present invention.

NMR study of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I).

¹ H and ¹³ C NMR spectra of a solution of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline in DMSO-d6 were measured on a Broker AM-360 NMR spectrometer at 360 and 90 MHz, relative to the internal TMS standard.

In the spectrum of ¹ N (figure 1) there is a group of signals at 1.05-1.3 ppm the total intensity of 13H, they can be divided into the following components.

Two singles of 1.05 and 1.14 ppm. from protons of methyl groups at C ₂ superimposed on each other in the region of 1.18 and 1.28 ppm, a singlet from one of the protons at C ₃ , a triplet of protons CH ₃ - a fragment of the ethoxy group and a doublet of protons of the methyl group at C ₄ ;

At 1.25 ppm triplet of protons CH ₃ - a fragment of an ethoxy group; J (HH) = 6.7;

At 1.65 ppm there is a multiplet from another proton at C ₃ ; J (HH) = 5.7; J (HH) = 12.4;

At 2.75 ppm there is a multiplet from the proton at C ₄ ;

At 3.86 is the proton quadruplet of the methylene moiety of the ethoxy group;

J (H-H) = 6.7;

At 4.95 ppm poorly resolved proton signal NH;

At 6.36 ppm there is a proton doublet at C ₇ , J (HH) = 8.6;

At 6.46 ppm there is a double proton doublet at C ₈ ; J (HH) = 1.9 and 8.7;

At 6.64 ppm there is a proton doublet at C ₅ ; J (HH) = 1.9.

The ¹³ C NMR spectrum of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) was recorded with suppression of spin-spin interactions with protons. In the ¹³ C NMR spectrum (FIG. 2), chemical shifts belonging to the following carbon atoms are observed:

At 14.9 ppm - signal of methyl carbon of ethoxy group;

At 20.5 ppm - carbon signal of the methyl group at C ₄ ;

At 26.8 ppm - carbon signal C ₄ ;

At 27.4 and 30.8, the signals of the carbons of methyl groups at C ₂ ;

At 44.3 ppm - carbon signal C ₃ ;

At 48.2 ppm - carbon signal C ₂ ;

At 63.3 ppm - signal of methylene carbon of ethoxy group;

At 113.3 ppm - carbon signals C ₅ and C ₇ ;

At 125.0 - carbon signal C ₁₀ ;

At 138.6, the carbon signal is C ₉ ;

At 149.5 - carbon signal C ₆ ;

At 114.5, the carbon signal is C ₈ .

Thus, the ¹ H and ¹³ C NMR spectra completely confirm the chemical structure (the order of the atoms in the molecule) of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I).

Mass spectrometric studies of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I).

Mass spectrometric analysis (Fig. 3) was carried out on a Hewlett Packard HP 5973 quadrupole gas chromatography-mass spectrometer, on an HP-5MS quartz capillary column (30 m × 0.25 mm × 0.25 μ) in a temperature programming mode from 50 up to 300 ° C at a rate of 10 ° C / min; the injector temperature was 280 ° С, the scanning speed was 1 spectrum / s, the recorded mass range was 40–450 in the full ion current mode. The ionizing voltage is 70 V.

Based on the obtained chromatography-mass spectrogram data (Fig. 4), the content of the basic substance 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline is 100%.

The main fragmentation processes for bridging groups of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) are presented in the diagram at the end of the description.

(2-2) и образований ионов с m/е 174 (4,8%), m/е 175 (7,4%).As can be seen from the diagram, the molecular ion corresponds to the mass of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) (M 219), and the fragmentation processes occurring along the bridging groups confirm structure I. The main fragmentation ion corresponds to a fragment with a mass of m / e 204 (max. Int., 100%). It is formed when the methyl group is lost. The decay over bridging groups determines the formation of fragmentation ions on the scale of mass numbers corresponding to the loss of one ethyl group, with the formation of a fragment ion m / e 190 (16.1%) and its further decay, leading to the formation of fragmentation ions with m / e 176 (8 , 8%) and m / e 160 (9.4%), another group of ions on the scale of mass numbers corresponds to a bond break

(2-2) and ion formations with m / e 174 (4.8%), m / e 175 (7.4%).

Investigations of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) by IR spectrophotometry.

The IR spectrum was obtained on a SPECORD M80 spectrophotometer. The sample was pressed with KBr. 1 mg of the substance in 200 mg KBr. (figure 5);

sample in liquid paraffin, a thin layer between square KBr. (Fig.6).

Assignment of some absorption bands based on generalized literature data, v 1 / cm:

3368 (NH-val.col.), 3060, 3020 (= CH-val.col.), 2972, 2912.2872 (CH3, CH2-val.col.), 1576, 1500 (val.col. of aromatic ring) , 1472, 1444 (deformation numbers of methyl and methylene groups), 1388, 1380 (doublet characteristic of heme-dimethyl groups), 1280 and 1052 (val.col. Ph-OC groups), 876, 804 (non-flat deformations. number of H-atoms of the benzene ring corresponding to 1,2,4-substitution).

The main characteristic absorption frequencies correspond and confirm this structure of the 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) molecule.

Investigations of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) by UV spectrophotometry.

The UV spectrum of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) was obtained on an Agilent 8453 UV-Vis spectrophotometer from Agilent Technologies. The sample was dissolved in ethanol (Fig.7), in hexane (Fig.8). In the UV spectra, two main characteristic bands are observed:

- λ nm = 244.0 and λ nm = 313.0 (in ethanol) Fig.7;

- λ nm = 248.0 and λ nm = 320.0 (in hexane) Fig. 8.

Based on the generalized literature data, it can be assumed that the 244 nm (ethanol) and 248 nm (in hexane) bands are π → π * transition bands, while 313 nm and 320 nm are the n → π * transition bands.

Crystal and molecular structure of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) and its comparison with the structure of 6-acetoxy-2,2,4-trimethyl-1,2,3 , 4-tetrahydroquinoline (VIII) adopted as prototype I.

In order to establish the exact structure of the 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) molecule, an X-ray diffraction study of colorless single crystals I grown by slow evaporation of a hexane solution, T _pl. = 38-39 ° C.

An X-ray diffraction study was carried out on an Enraf Nonius FR 590 diffractometer at room temperature. The basic information about the X-ray diffraction experiment and the crystallographic parameters of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) are given in Table 1. The structure was solved using the direct method (SHELXL-97 software package). The positions of the hydrogen atoms are calculated from geometric considerations. Refinements were carried out in the anisotropic (for non-hydrogen atoms) and isotropic (for hydrogen atoms) full-matrix approximations in F2 (SHELXL-97 software package). Complete tables of atom coordinates, temperature factors, bond lengths, and bond angles are deposited at the Cambridge Structural Data Bank.

Table 1
Crystallographic data and refinement parameters of the crystal structure of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline PARAMETER VALUE Gross formula C14H21NO Molecular mass 219.32 T / ° K (calc.) 293 (2) Diffractometer Enraf Nonius FR 590 Scan type θ / 2θ Scan interval θ = 3.35 ° -74.86 ° Radiation CuKα wavelength / 1.54180 Crystal size 0.3 × 0.3 × 0.3mm Syngonia, space group Monoclinic P2 ₁ / c Crystal cell parameters A = 13.196 (4) α = 90.00 ° B = 8.865 (6) β = 90.77 (6) ° C = 11.330 (11) γ = 90.00 ° Cell volume 1325.3 (16) A ³ Density (calculated) 1.099 g / cm ³ The number of molecules in the cell 4 Absorption coefficient 0.580 cm. ^-1 F (000) 480 The total number of recorded reflections 5533 Total number of independent reflections 2717 The final R-factor [over 1805 reflections with I> 2σ (I)] R ₁ 0,0530 wR ₂ 0.1254

To study the molecular and crystalline structure of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) by X-ray diffraction analysis, its decoding was performed using the numbering of atoms included in molecule I, shown in FIG. .9. The main values of bond lengths and bond angles are shown in FIG. 10 and Table 2.

table 2
The values of the main interatomic distances and valence angles of the 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline molecule Communication d / a Valence angle ω / deg. N1-C10 1.399 (2) C10-N1-C2 118.3 (1) N1-C2 1.469 (2) C10-N1-H1 121.70) N1-H1 0.80 (2) C2-N1-H1 116.8 (1) C2-SZ 1.514 (2) N1-C2-C3 106.4 (1) C2-C22 1.521 (3) C22-C2-C21 109.5 (2) C2-C21 1.537 (2) C2-C3-C4 114.3 (1) SZ-S4 1.522 (3) C3-C4-C5 109.9 (1) C4-C41 1.514 (3) C41-C4-C3 111.3 (2) C4-C5 1.523 (2) C41-C4-C5 113.7 (1) C5-C6 1.388 (2) C4-C5-C10 120.8 (1) C5-C10 1.399 (2) C7-C8-C9 119.3 (1) C6-C7 1.390 (2) C8-C9-C10 121.9 (2) C7-C8 1.375 (2) C9-C10-C5 118.7 (1) S7-07 1.377 (2) C6-C5-C10 118.5 (1) 07-C71 1.413 (2) C5-C6-C7 122.3 (1) C71-C72 1.489 (3) C7-O7-C71 118.2 (1) C8-C9 1.386 (2) O7-C71-C72 108.3 (2) C9-C10 1.398 (2)

The bicyclic system of molecule I consists of two fragments - a flat benzene ring and a non-planar tetrahydropyridine ring. The standard deviation of the benzene ring atoms from the plane is 0.006 Å. The N1, C4, and O7 atoms bonded to the carbon atoms of the benzene ring lie in the same plane. The dihedral angles C8-C9-C10-N1, C4-C5-C6-C7 and C5-C6-C7-07 are respectively 176.8 °, 179.7 ° and 178.6 °. The carbon atoms C71 and C72 are also slightly deviated from this plane. The dihedral angle C7-O7-C71-C72 is 177.3 °. The bond lengths of the CC bond of the benzene ring are the same as in other substituted benzene molecules (Alien F. N., (2002). Acta Cryst. Sect. B, 58, 380).

The atomic radius of the sp ³ hybridized C71 carbon atom is greater than the atomic radius of the carbon C7 of the benzene ring; therefore, the C71-O7 bond is longer than the C7-O7 bond (1.413 (2) and 1.377 (2) Å). In the molecule of 6-acetoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (VIII), on the contrary, the C-O bond, similar to the C7-O7 bond in I, is longer than the next O-C bond ( 1,441 (8) and 1,335 (8) Å) (A.E. Obodovskaya, Z.A. Starikova, Yu.A. Ivanov, I.E. Pokrovskaya. Journal of Structural Chemistry 1985, v.26, No. 5, p. 99-102), although the atomic radii of the carbon to which acetyl oxygen is bound in VIII are approximately the same.

The benzene ring is linked by a common bond of C5-C10 to the tetrahydropyridine ring N1-C2-C3-C4-C5-C10. As noted above, this ring is non-planar. It has a distorted \ half-chair \ conformation (C2 and C3 atoms are located on opposite sides of the plane of the benzene ring). The torsion angles C3-C4-C5-C10 and C2-N1-C10-C5 are equal to 15.4 ° and 21.5 °, respectively. Due to A ^{1,2 of the} allylic stress existing in cyclohexene cycles (Johanson, F., 1968, Chem. Rev. p. 68. 4. 375.), carbon C41 occupies a pseudo-axial position. The nitrogen atom N1 has a flat bond configuration (the sum of the bond angles is 356.9 °). CC bond lengths are common for substituted tetrahydropyridines.

The structures of molecules I and VIII are largely similar to each other. The values of many homogeneous valence bonds, valence and torsion angles are very close to each other. Only the forms of tetrahydropyridine rings are significantly different. And in one and the other molecules, these rings have the conformation of a distorted \ half-chair \. But if in a molecule carbon C2 is located below the plane of the benzene ring, and carbon C3 is above this plane, then in molecule VIII, on the contrary, C2 is above this plane, and C3 is below it (see Fig. 11). The torsion angles C6-C5-C4-C3 and C9-C10-N1-C2 in I are -165.9 ° and -162.3 °, and in VIII + 171.8 ° and + 159.0 °. The reason for this is the different configuration of the bonds of nitrogen atoms.

As mentioned above, a flat configuration of these bonds is realized in molecule I; in VIII, the bond configuration is pyramidal (the sum of the bond angles is 341.7 °). With this configuration of bonds, a lone electron pair must exist at the nitrogen atom, occupying a certain region near the atomic space. Therefore, the minimum voltage energy of the tetrahydropyridine ring in I and VIII is achieved with different orientations of N-H relative to the (CH3) 2C-CH2 bond. In structure I, the torsion angle H-N-C (CH3) 2-CH2 is 151.8 °, in structure (VIII) it is - 176.7 °.

The various electronic states of the nitrogen atom (and the corresponding bond configurations) in molecules I and VIII most likely arise due to the fact that in the VIII crystals the N-H group is involved in the intermolecular hydrogen bond C = O ... H-N . (Fig. 12), but in crystals I (Fig. 13) there are no such bonds, the packing of molecules in the structure is determined only by the van der Waals interaction.

It is interesting to note that in crystals of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline (IV), where there are intermolecular hydrogen bonds Н-O ... HN (A.E. Obodovskaya, Z.A. Starikova, Yu.A. Ivanov, I.E. Pokrovskaya, Journal of Structural Chemistry 1985, vol. 26, No. 5, pp. 93-98), the configuration of the bonds of the nitrogen atom is also pyramidal (the sum of the bond angles -338.3 ° is almost same as in VIII).

Methods for producing 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) on new and known catalysts.

Many methods are known for producing tetrahydroquinolines (Ivanov Yu.A. Dis. Candidate of Chemical Sciences, Moscow 1983; Klare PA - In the book General Organic Chemistry, Chapter 16.4. Quinolines vol. 8 / edited by Academician Kochetkov N .K. M .: Publishing house \ Chemistry \. - 1985, p.229.), The simplest and most affordable is the hydrogenation of the corresponding quinolines on various catalysts, of which a relatively high selectivity in this reaction is manifested on nickel catalysts. However, the use of nickel catalysts in the process of hydrogenation of the corresponding quinolines to their tetrahydro derivatives occurs with a relatively low yield of the target product due to the hydrogenation reaction and in other directions leading to a mixture of different hydrogenation products, which is also influenced by the nature of the substituents in quinolines. (Ivanov Yu.A. Dis. Candidate of Chemical Sciences., Moscow 1983; Braun J., Petzold A., Seemann J. Katalytische Hydrierungen unter Druck bei Gegenwart von Nickelsalzen. IV. Chinolin-Basen. - Ber., 1922, Bd. 55, s.3779-3792; Braun J., Gmelin W., Schulteheiss A. Uber Bz-Tetrahydro-chinoline und ihre Derivate. - Ber., 1923, s.1338-1347; Braun J., Gmelin W. , Petzold A. Uber Bz-Tetrahydrochinoline und ihre Derivate. (IV) - Ber., 1924, Bd. 57, s. 382-391).

Therefore, the creation of new nickel-based catalysts is highly relevant. In order to increase the selectivity of the hydrogenation process on nickel-containing catalysts, the yield and quality of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I), we used a new nickel-containing catalyst composition: 1-8% titanium , 30-60% nickel, 0.2-1.5% iron and 35-65% aluminum.

The rate of mixing of the reaction mass during the hydrogenation of 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline (III) on a solid catalyst affects many factors of this reaction, including not only the concentration of hydrogen in the reaction mass, but also the contact time of the substance with the catalyst, which is also determined by the activity and selectivity of the catalyst itself.

The optimization of the hydrogenation process is determined by the activity and selectivity of the catalyst, hydrogen pressure, temperature, the rate of mixing of the reaction mass and the time it takes. These parameters are calculated in each case.

Preparation of a new catalyst for the hydrogenation process.

The alloy containing 1-8% titanium, 30-60% nickel, 0.2-1.5% iron and 35-65% aluminum, is ground in a rotary ball mill MRSh-150, or others, providing the required grinding. The initial alloy is ground to a powder with a particle size passing through a 125 micron sieve.

The preparation of the active catalyst was carried out in a five-liter reactor made of glass or coated with enamel. To 100 g of alloy powder is poured 1000 ml of distilled water. The system is thoroughly flushed with nitrogen. About 160 g of solid sodium hydroxide are then added in portions without cooling. The reaction sometimes begins with a small induction period of 0.5-1.0 minutes. And proceeds in a \ boiling \ mode. Gradually, the introduction of new portions of alkali ceases to cause a noticeable reaction (after the introduction of 150-160 g of caustic soda). The mixture is allowed to stand for 10 minutes, then kept using external heating at 70 ° C for 30 minutes. The active catalyst is deposited in the form of sludge at the bottom of the reactor. The catalyst is washed with distilled water to a pH of the last wash of 8-9 on a universal indicator paper (it is possible to use a continuous wash in a flow system with a mandatory pH control), and then with absolute ethanol. Obtain 52 g of a black catalyst. The resulting catalyst retains its activity for two weeks or more with proper storage (0 ÷ + 5 ° C).

EXAMPLE 1

.650 g of technical 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline (III) in the form of a thick black-brown liquid are purified by vacuum distillation in a Kleisen flask. Get 642 g (98.7%) of compound III, light yellow in color with so Kip. 131-132 ° C at 2 mm Hg. Art. (t. kip. 168-170 ° C at 12 mm Hg) and

.

(определен впервые), ρ=1,089 г/см³.642 g (2.95 mol) of 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline (III), 150 ml of absolute, are charged into a steel autoclave rotating at a speed of 40-60 rpm ethanol, 30 g of Raney nickel, prepared according to the method of G. Becker et al. Organikum (workshop on organic chemistry, translated from German. - M .: ed. \ Mir \, 1980, volume 2, p. 370), then served at room temperature, hydrogen until a pressure of ~ 150 atm is reached. The temperature is increased to 60 ° C, after 2 hours the pressure drops to 5 atm. It is again brought to 150 atm. After 2.5 hours, the pressure drops to 70 atm. And no longer changes due to the completion of hydrogenation. The reaction mixture is cooled, the catalyst is filtered off. Volatile are separated on a rotary evaporator. By distillation of the residue, 610 g (94.2% of theory) of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline I are obtained with a boiling point. 128-129 ° C at 3 mm Hg. Art. when stored in the cold (0 ÷ 5 ° C) during the day, the product forms light pink crystals. After recrystallization, first from isopropanol and then from hexane, 526 g (81.3% of theory) of colorless crystals of I are obtained with a melting point of 38-39 ° C,

(determined for the first time), ρ = 1,089 g / cm ³ .

Under similar conditions, reactions were carried out on catalysts W2, W3, W4, in an environment of ethanol, isopropanol, which slightly affected the reaction rate and the yield of the target product.

Elemental analysis

Found: C, 76.65; H 9.71; N, 6.43%; M + 219 (mass spectrum). C14H21NO.

Calculated: for C14H21NO: C 76.67; H, 9.65; N, 6.39%.

EXAMPLE 2

, ρ=1,089 г/см³.In a liter stainless steel reactor equipped with a mechanical stirrer (1000 rpm), a thermocouple is charged with 642 g (295 mol) of distilled santokhin, 30 g of a new catalyst prepared according to the procedure described above, and 150 ml of absolute ethanol and at the end of the reagent loading it is thoroughly purged with nitrogen, then at room temperature hydrogen is pumped to 15 atmospheres, for an hour, at 400 rpm, the pressure in the reactor decreases to 5 atmospheres, then the hydrogen pressure is brought to 15 atmospheres and the reaction mass is heated to 70 ° C, etc process of repeated until the hydrogen pressure after another swap does not change. The reactor is cooled to room temperature, the reaction mass is discharged onto a filter and the catalyst is filtered off in a stream of nitrogen. Then, the catalyst was washed twice with 50 ml ethanol. the filtrate is loaded into a distillation cube and distilled in vacuo, collecting ethanol as readily volatile products, and 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) as a high-boiling fraction, with a boiling point 128-130 ° C at a residual pressure of 2-3 mm Hg Yield 632 g (97% of theory). After recrystallization of isopropyl alcohol, the yield of I is 622 g (95.5% of theory) of colorless crystals of I with a melting point of 38-39 ° C,

, ρ = 1,089 g / cm ³ .

Elemental analysis

Found: C, 76.68; H, 9.64; N, 6.41%; M + 219 (mass spectrum). C14H21NO.

Calculated: for C14H21NO: C 76.67; H, 9.65; N, 6.39%.

Under similar conditions, reactions were carried out in an environment of ethanol, isopropanol, which slightly affected the reaction rate and the yield of the target product.

A sample for mixing 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) obtained by the above methods did not give a depression of the melting temperature, as well as NMR, Mass, IR, UV spectra and refractive indices are completely identical.

The fire hazard indicators 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) were determined using metrologically certified equipment: installation \ TV-1 \, \ TV-2 \, \ STS- 2A \, \ TP-ZP \. The test results showed that 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) in accordance with GOST 12.1.044-89 (clause 2.1.2) refers to flammable liquids ( since they have a melting point below 50 ° C) and has the following fire and explosion hazard indicators:

- The flash point in a closed crucible is 143 ° C according to GOST 12.1.044-89 (clause 4.4);

- Flash point and ignition temperature in an open crucible according to GOST 12.1.044-89 (items 4.5, 4.6) 147 ° C and 161 ° C, respectively;

- Auto-ignition temperature 330 ° С according to GOST 12.1.044-89 (Clause 4.8);

- The temperature limits of flame propagation through vapor-air mixtures according to GOST 12.1.044-89 (item 4.12): lower 146 ° С, upper 159 ° С.

Based on the foregoing, it was first obtained and completely investigated by spectral methods, X-ray diffraction analysis, elemental analysis of 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) in crystalline form, and also determined its melting point, refractive index and indicators of its fire and explosion hazard.

Claims (2)

1. 6-Ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I) in crystalline form (mp = 38-39 ° C), which has high antioxidant activity.

2. The method of obtaining 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (I), which consists in the fact that 6-ethoxy-2,2,4-trimethyl-1,2- dihydroquinoline (III) is subjected to hydrogenation in an alcohol medium at a temperature of 20-120 ° C and a hydrogen pressure of 2-170 atm., rotation speed of 20-3000 rpm, on a new catalyst obtained from an alloy of the composition: 1-8% titanium, 30- 60% nickel, 0.2-1.5% iron and 35-65% aluminum, by its subsequent activation, as well as known nickel catalysts, followed by isolation of the target product (I) immediately or after preliminary purification.

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