Method of producing n-arylpyrrolidines and n-arylpiperidines

FIELD: chemistry.

SUBSTANCE: method includes reacting anilines of general formula R-C6H4NH2 (where R=H, o-, m-, n-CH3, o-C2H5, o-, m-, n-Cl, n-F) and α,ω-diols (1,4-butanediol, 1,5-pentanediol) in the presence of a catalyst FeCl3·6H2O in the medium of tetrachloromethane at 180°C for 4-8 hours with molar ratio [FeCl3·6H2O]:[RC6H4NH2]:[diol]:[CCl4]=0.2-0.5:100:100-400:20-100. At 180°C and reaction duration of 6 hours, output of N-arylpyrrolidines reaches 45-88%, and output of N-arylpiperidines reaches 33-85%. Synthesis is carried out in an argon atmosphere.

EFFECT: method reduces reaction time and enables to use more affordable catalyst.

1 tbl, 33 ex

 

The present invention relates to the field of organic synthesis, in particular to method of obtaining N-arylpyrimidines and N-arylpiperazines.

Cyclic amines of the number of N-arylpyrimidines and N-arylpiperazines are widely used in the manufacture of pharmaceuticals, agrochemicals, herbicides, fungicides, dyes, etc. [Tan W., Li C, Zheng J., Shi L., Sun Q., He Y. Nat. Gas Chem.,2008, 17 (4), 383].

N-Vinylpyrrolidone and N-phenylpiperidine prepared by reacting aniline with 1,4-butane - and 1.5-pentanedione in the presence of 1,3,5-triaza-2,4,6-trilastin-2,2,4,4,6,6-hexanamide (TAPC the trimer of phosphonitrilic, cost 5 g 38€ [http://www.acros.com]). The reaction takes place under severe conditions: 200°C, 36 h in 1,2,4-trimethylbenzene [Y. Du, S. Oishi, S. Saito Chem. Eur. J., 2011, 17, 12262].

Disadvantages of the method:

1. Significant duration of the reaction (36 h).

2. Conducting the reaction at elevated temperature (200°C).

3. Use as a high-boiling solvent 1,2,4-trimethylbenzene, which creates difficulties in the separation and purification of target products.

4. The use as the catalyst a highly toxic and expensive 1,3,5-triazo-2,4,6-trilastin-2,2,4,4,6,6-hexanamide (TAPC).

In [Tan W., Li CM., Zheng J., Shi L., Sun Q., He Y. H. J. Nat. Gas Chem., 2008, 17 (4), 383; Li S. M., Miao Z. L., Shi L., Sun Q., He Y. H. Chin. Chem. Lett., 2006, 17(12), 1540] synthesis of N-fenilpiperidina implemented communication�esteem of aniline with 1,5-pentanediol in the presence of γ-Al 2O3. The catalyst is γ-Al2O3(SBET=290 m2/g, 20-40 mesh) is obtained by calcining active alumina at 500°C for 4 hours. The yield depends on the microstructure of Al2O3it is higher for the catalyst with a large total pore volume.

Disadvantages of the method:

1. The need to conduct the reaction at elevated temperature (300°C).

2. Activation of Al2O3before use is carried out by calcination at high temperature (500°C), resulting in large power consumption.

3. The reaction takes place under pressure.

To reduce the temperature of the reaction is possible through the use of applied catalysts. So, cyclic amines were obtained N-heterocyclization anilines with α,ω-dialami under the influence of a heterogeneous catalyst Pt-Sn/γ-Al2O3(0.5 wt % Pt, Pt/Sn ratio=1:3), which has dehydrating properties [Not W., Wang L, Sun, K. Wu, S., J. Chen, P. Wu, Z. Yu, Chem. Eur. J., 2011, 17, 13308].

For the synthesis of N-arylpyrimidines and N-arylpiperazines widely used homogeneous catalysts. Thus, the interaction of anilines with 1,4-butanediol under the action pentamethylcyclopentadienyl iridium complex Cp∗Ir in the presence of base NaHCO3(equimolar amount relative to the catalyst) leads to N-fenile�rolidone and N-(4-methoxyphenyl)pyrrolidine with the release of 70% and 90% respectively. Elektromotory the substituent in the phenyl ring of aniline contributes to a significant increase in the yield of the target product [Fujita, K. - I., Fujii, T., Yamaguchi, R. Org. Lett., 2004, 6 (20), 3525].

Disadvantages of the method:

1. The need for expensive iridium catalyst.

2. Significant duration of response (17-40 h).

For the synthesis of cyclic amines of the number of pyrrolidine and piperidine by heterocyclization anilines with dialami widely used ruteniisoderzhashchii catalysts.

Thus, N-phenylpiperidine obtained by reaction of aniline with 1,5-pentanediol. The reaction is catalyzed by ruthenium complexes RuCl2(PPh3)3[Tsuji Y., Huh, K. - T., Ohsugi Y., Watanabe Y., J. Org. Chem., 1985, 50 (9), 1985].

N-vinylpyrrolidone and N-phenylpiperidine obtained by reaction of aniline with 1,4-butanediol and 1,5-pentanediol under the action of complexes of ruthenium(II) RuCl2(PPh3)3and RuCl3·xH2O/3PPh3[Abbenhuis, R., Boersma, J., Koten G. J. Org. Chem., 1998, 63, 4282].

Disadvantages of the method:

1. The high cost ruteniysoderzhaschim catalysts.

2. The necessity of carrying out the process under pressure.

Cyclic amines (N-vinylpyrrolidone and N-phenylpiperidine) were obtained by the interaction of aniline with dialami in the presence of a catalyst [Ru(p-cymene)Cl2]2, aktivirovannogo� bidentate phosphine ligand is bis [(2-diphenylphosphino)phenyl] ether (DPEphos), [Hamid M. H. S. A, C. L. Allen, G. W. Lamb, A. C. Maxwell, H. C. Maytum, Watson AJ.A. Williams J. M. J. J. Am. Chem. Soc, 2009, 131, 1766].

The use of microwave radiation allows to reduce the reaction duration from 24 to 1.5 h. the Excess diol increases the yield of the target product. [A. Watson, A. Maxwell,J. Williams, J. Org. Chem., 2011, 76, 2328].

N-phenylpiperidine obtained by reaction of 1,5-pentanediol with aniline under the action of ruteniysoderzhaschim catalyst [Ru(p-cymene)Cl2]2activated ligand 1,1'-bis(diphenylphosphino)ferrocene (dppf) in the presence of molecular sieves. When using the catalyst of less than 5 mol.% along with a N-phenylpiperidine formed lactones and other by-products [Hamid M., Williams J. Chem. Commun., 2007, 725].

Disadvantages of the methods:

1. Significant duration of the reaction (24 h).

2. The need for expensive ruthenium catalyst.

3. The use of expensive ligands: dppf - and DPEphos.

4. Difficulty scaling due to the use of microwave radiation.

The authors propose a method of producing cyclic amines that do not have the above drawbacks.

The method consists in the interaction of anilines of the General formula R-C6H4NH2(where RH, o-, m-, n-CH3, o-(C2H5, o-, m-, n-Cl, n-F) with α,ω-dolami (1,4-butanediol, 1,5-pentanediol in the presence of a catalyst FeCl3·6H2O in the environment of carbon tetrachloride at 180°C for 4-8 h at a molar ratio of [FeCl3·6H2O]:[RC6H4NH2]:[diol]:[CCl4]=0.2-0.5:100:100-400:20-100. Optimal for the reaction are in the ratio of catalyst and reagents: [FeCl3·6H2O]:[RC6H4NH2]:[diol]:[CCl4]=0.5:100:200:30. At a temperature of 180°C and duration of the reaction 6 hours, the yield of N-arylpyrimidines (1-9) reaches 45-88%, and N-arylpiperazines (10-18) - 33-85%. The synthesis is carried out in an argon atmosphere.

In the absence of catalyst and CCl4the reaction fails.

Optimal reaction conditions were fulfilled on the interaction of aniline with 1,5-pentanediol under the action of FeCl3·6H2O in the environment of CCl4. Examples of the method are shown in table 1.

Significant differences of the proposed method from the prototype.

To obtain cyclic amines from substituted anilines and α,ω-diols are used, the catalyst is FeCl·6H2O, the reaction is conducted in an environment CC14.

The advantages of the proposed method.

1. High yields of products.

2. The selectivity of the process.

3. The availability and low cost of initial reagents and cat�of lysator.

4. Cheapening the cost and simplify the technology in General by reducing energy and labor costs.

The structure of the obtained N-arylpyrimidines (1-9) and N-arylpiperazines (10-18) is proved using the methods of NMR, mass spectrometry, and by comparison with known samples and literature data.

The proposed method is illustrated by examples:

EXAMPLE 1. Obtaining N-fenilpiperidina (10).

In a vial under a stream of argon was loaded 2.9 mg (0.5 mmol) of FeCl3·H2O, 0.2 ml (100 mmol) of aniline, 0.45 ml (200 mmol) of 1,5-pentanediol, 0.06 ml (30 mmol) of CCl4. Sealed ampoule was placed in an autoclave, the autoclave was tightly closed and heated at 180°C for 6 hours, then the autoclave was cooled to ~20°C, the ampoule was opened, the reaction mass is neutralized with 10% aqueous solution of Na2CO3the organic layer was extracted with methylene chloride and filtered. The solvent was distilled, the residue was distilled under vacuum.

N-Phenylpiperidine (10)

A yield of 85%. Bestv. oil, Kip. 73-74°C/0.4 mm Hg.PT. (TKip86°C/1 mm Hg.PT. [Abbenhuis, R., Boersma, J., Koten G. J. Org. Chem., 1998, 63, 4282-4290]).

The NMR spectrum13C (δ, M. D.): 152.22 (C-1), 129.04 (C-3, C-5), 119.36 (C-4), 116.66 (C-2, C-6), 50.81 (C-2', C-6'), 25.88 (C-3', C-5'), 24.34 (C-4'). The NMR spectrum1H (CDCl3d, M. D.): 7.25-7.35 m (2H, C3,5H), 7.00 (2H, C2,6H, J 8.0 Hz), 6.80-6.96 m (1H, C4H), 3.15-3.26 m (4H, C2',6'H2), 1.70-1.80 m (4N, C3',5'H2), 1.55-1.68 m (2H, C4� H2).

EXAMPLES 2-16 (see tab.1). Analogously to example 1.

EXAMPLE 17. Obtaining N-(2-methylphenyl)piperidine (11).

Analogously to example 1, but instead of aniline used 0.2 ml (100 mmol) of 2-methylaniline.

N-(2-methylphenyl)piperidine (11)

The yield of 42%. Light yellow. oil. W., so Kip. 96-97°C/2 mmHg.PT. (TKip274.8°C/760 mm Hg.PT. [http://www.lookchem.com]).

The NMR spectrum13C (δ, M. D.): 149.87 (C-1), 131.56 (C-3), 126.74 (C-5), 132.41 (C-2), 124.31 (C-4), 119.32 (C-6), 18.31 (C-7), 54.08 (C-2', C-6'), 25.74 (C-3', C-5'), 23.76 (C-4'). The NMR spectrum1H (CDCl3d, M. D.): 6.80-6.92 m (1H, C5H), 7.08-7.20 m (1H, C3H), 7.09-7.28 m (1H, C4H), 6.91-7.05 m (1H, C6H), 2.41 (3H, C7H3), 2.99 ush with (4H, C2',6'H2), 1.86 ush with (4H, C3',5'H2), 1.50-1.70 m (2H, C4'H2).

Mass spectrum, m/z (IRel.(%)): 175 [M]+(86), 176 (11), 174 (100), 146 (28), 134 (12), 132 (18), 130 (7), 120 (15), 119 (21), 118 (86), 117 (12), 91 (38), 77 (8), 65 (22), 55 (6).

EXAMPLE 18. Obtaining N-(3-methylphenyl)piperidine (12).

Analogously to example 1, but instead of aniline used 0.2 ml (100 mmol) 3-methylaniline.

N-(3-methylphenyl)piperidine (12)

The yield of 47%. Light yellow. oil. W., so Kip. 95-97°C/0.5 mm Hg.PT.

The NMR spectrum13C (δ, M. D.): 148.34 (C-1), 139.45 (C-3), 129.32 (C-5), 124.56 (C-4), 119.90 (C-2), 115.62 (C-6), 53.49 (C-2', C-6'), 24.69 (C-3', C-5'), 23.18 (C-4'), 21.64 (C-7). The NMR spectrum1H (CDCl3d, M. D.): 7.05-7.30 m (1H, C5H), 6.80-6.90 m (1H, C6H), 6.53 (1H, C2H), 6.45-6.70 m (1H, C4H), 3.23-3.26 m (4H, C2',6'H2), 2.33 (3H, Csup> 7H3), 2.14-2.25 m (4H, C3',5'H2), 1.48-1.73 m(2H, C4'H2).

Mass spectrum, m/z (IRel.(%)): 175 [M]+(81), 174 (100), 160 (7), 146 (12), 134 (15), 120 (9), 119 (36), 118 (28), 91 (38), 65 (16).

EXAMPLE 19. Obtaining N-(4-methylphenyl)piperidine (13).

Analogously to example 1, but instead of aniline used 0.2 g (100 mmol) of 4-methylaniline.

N-(4-methylphenyl)piperidine (13)

The yield of 61%. Light yellow. oil. W., so Kip. 106-107°C/1 mm Hg.PT.

The NMR spectrum13C (δ, M. D.): 142.18 (C-1), 137.94 (C-4), 129.92 (C-3, C-5), 120.42 (C-2, C-6), 56.15 (C-2', C-6'), 23.17 (C-3', C-5'), 21.94 (C-4'), 20.86 (C-7). The NMR spectrum1H (CDCl3d, M. D.): 7.56 (1H, C3,5H, J 8.0 Hz), 7.11 (1H, C2,6H, J 8.0 Hz), 3.30-3.45 m (4H, C2',6'H2), 2.24 (3H, C7H3), 1.70-2.15 m (4H, C3',5'H2), 1.52-2.05 m (2H, C4'H2).

Mass spectrum, m/z (IRel.(%)): 175 [M]+(98), 174 (100), 160 (12), 146 (9), 134 (13), 120 (9), 119 (32), 118 (24), 91 (29), 64 (10).

EXAMPLE 20. Obtaining N-(2-ethylphenyl)piperidine (14).

Analogously to example 1, but instead of aniline used 0.2 ml (100 mmol) of 2-ethylaniline.

N-(2-ethylphenyl)piperidine (14)

The yield of 38%. Yellow. oil. W., so Kip. 75-77°C/0.3 mm Hg.PT.

The NMR spectrum13C (δ, M. D.): 152.29 (C-1), 139.26 (C-2), 128.87 (C-3), 126.36 (C-5), 123.62 (C-4), 119.85 (C-6), 54.36 (C-2', C-6'), 26.60 (C-3', C-5'), 24.36 (C-7), 23.44 (C-4'), 14.89 (C-8). The NMR spectrum1H (CDCl3d, M. D.): 7.27 m (1H, C5H), 7.19 m (1H, C3H), 7.10 m (1H, C4H), 6.81 m (1H, C6H), 3.51-3.69 kV (2H, C7H2), 2.69-3.02 m (4H, C2'6' H2), 1.69-1.93 m (4H, C3',5'H2), 1.51-1.69 m (2H, C4'H2), 1.30 (3H, C8H3, J 7.6 Hz).

EXAMPLE 21. Obtaining N-(2-chlorophenyl)piperidine (15).

Analogously to example 1, but instead of aniline used 0.16 ml (100 mmol) of 2-Chloroaniline.

N-(2-chlorophenyl)piperidine (15)

The yield of 33%. Light yellow. oil. W., so Kip. 89-90°C/0.2 mm Hg.PT.

The NMR spectrum13C (δ, M. D.): 148.74 (C-1), 130.49 (C-3), 128.87 (C-4), 127.48 (C-5), 123.22 (C-2), 120.55 (C-6), 52.89 (C-2', C-6'), 26.25 (C-3', C-5'), 24.26 (C-4'). The NMR spectrum1H (CDCl3d, M. D.): 7.33 m (1H,C3H, J 8.0 Hz), 7.15-7.22 m (1H, C5H), 7.04 (1H, C6H, J 8.0 Hz), 6.92 t (1H, C4H), 2.75-3.18 m (4H, C2',6'H2), 1.65-1.88 m (4H, C3',5'H2), 1.45-1.88 m (2H, C4'H2).

EXAMPLE 22. Obtaining N-(3-chlorophenyl)piperidine (16).

Analogously to example 1, but instead of aniline used 0.17 ml (100 mmol) 3-Chloroaniline.

N-(3-chlorophenyl)piperidine (16)

The yield of 35%. Light yellow. oil. W., so Kip. 115-116°C/0.08 mm Hg.PT.

The NMR spectrum13C (δ, M. D.): 152.80 (C-1), 134.85 (C-3), 130.26 (C-5), 118.95 (C-4), 116.16 (C-6), 114.49 (C-2), 50.34 (C-2', C-6'), 25.52 (C-3', C-5'), 24.14 (C-4'). The NMR spectrum1H (CDCl3d, M. D.): 7.15 t (1H, C5H, J 8.0 Hz), at 6.84 (1H, C4H, J 8.0 Hz), 6.92 (1H, C2H), 6.79 (1H, C6H, J 8.0 Hz), 3.10-3.22 m (4H, C2',6'H2), 1.53-1.78 m (4H, C3',5'H2), 1.53-1.63 m (2H, C4'H2).

EXAMPLE 23. Obtaining N-(4-chlorophenyl)piperidine (17).

Analogously to example 1, but instead anili�and used 0.2 g (100 mmol) 4-Chloroaniline.

N-(4-chlorophenyl)piperidine (17)

The yield of 40%. Light yellow. oil. W., so Kip. 92-94°C/0.5 mm Hg.PT.

The NMR spectrum13C (δ, M. D.): 144.90 (C-1), 128.95 (C-3, C-5), 123.07 (C-4), 118.11 (C-2, C-6), is at 51.19 (C-2', C-6'), 25.46 (C-3', C-5'), 23.94 (C-4'). The NMR spectrum1H (CDCl3d, M. D.): 6.93 (2H, C3,5H, J 8.0 Hz), 6.60 (2H, C2,6H, J 8.0 Hz), 3.07-3.20 m (4H, C2',6'H2), 1.69-1.83 m (4H, C3',5'H2), 1.52-1.66 m (2H, C4'H2).

Mass spectrum, m/z (IRel.(%)): 195.5 [M]+(91), 197 (36), 196 (41), 194 (100), 154 (25), 141 (16), 140 (30), 139 (42), 138 (37), 125 (14), 111 (50), 77 (18), 75 (32), 56 (15), 55 (39).

EXAMPLE 24. Obtaining N-(forfinal)piperidine (18).

Analogously to example 1, but instead of aniline used 0.17 ml (100 mmol) 4-foronline.

N-(forfinal)piperidine (18)

The yield of 35%. Light yellow. oil. W., so Kip. 100-101°C/2 mmHg.PT.

The NMR spectrum13C (δ, M. D.): 143.02 (C-1), 160.09 (C-4, J13C19F 244 Hz), 116.28 (C-3, C-5, J13C19F 22 Hz), 121.47 (C-2, C-6), 55.00 (C-2', C-6'), 24.20 (C-3', C-5'), 22.35 (C-4'). The NMR spectrum1H (CDCl3d, M. D.): 7.46 ush with (2H, C3,5H), 6.59 ush with (2H, C2,6H), 3.22 ush with (4H, C2',6'H2), 1.93 ush with (4H, C3',5'H2), 1.59 ush with (2H, C4'H2). The NMR spectrum19F (CDCl3d, M. D.): 116.13.

EXAMPLE 25. Obtaining N-phenylpyrrolidine (1).

Analogously to example 1, but instead of the diol used 0.38 ml (200 mmol) of 1,4-butanediol.

N-phenylpyrrolidine (1)

Yield 88%). Bestv. oil. W., so Kip. 89-90°C/1 mm Hg.PT. (T. Kip. 81°C/0.5 mmHg.PT [Abbenhuis, R., Boersma J., Koten G. J. Org. Chem., 1998, 63, 4282-4290]).

The NMR spectrum13C (δ, M. D.): 148.06 (C-1), 129.22 (C-3, C-5), 115.53 (C-4), 111.81 (C-2, C-6), 47.72 (C-2', C-5'), 25.56 (C-3', C-4'). The NMR spectrum1H (CDCl3d, M. D.): 7.30-7.38 m (2H, C3,5H), 6.74-6.82 m (1H, C4H), 6.69 (2H, C2,6H, J 8.0 Hz), 3.30-3.40 m (4H, C2',5'H2), 2.05-2.15 m (4H, C3',4'H2).

Mass spectrum, m/z (IRel.(%)): 147 [M]+(94), 148 (10), 146 (100), 119 (9), 118 (7), 104 (25), 92 (6), 91 (72), 77 (46), 65 (7), 51 (19).

EXAMPLE 26. Obtaining N-(2-methylphenyl)pyrrolidine (2).

Analogously to example 25, but instead of aniline used 0.2 ml (100 mmol) of 2-methylaniline.

N-(2-methylphenyl)pyrrolidin (2)

The yield is 50%. Light yellow. oil. W., so Kip. 122-124°C/10 mm Hg.PT. (So Kip. 255°C/760 mm Hg.PT. [http://www.lookchem.com]).

The NMR spectrum13C (δ, M. D.): 148.14 (C-1), 131.92 (C-3), 129.20 (C-5), 126.56 (C-2), 121.68 (C-4), 116.59 (C-6), is at 49.74 (C-2', C-5'), 24.52 (C-3', C-4'), 20.35 (C-7). The NMR spectrum1H (CDCl3d, M. D.): 7.12-7.30 m (1H, C5H), 6.98-7.12 m (1H, C3H), 6.88-6.98 m (1H, C4H 6.60-6.80 m (1H, C6H), 3.25-3.45 m (4H, C2',5'H2), 1.96-2.15 m (4H, C3',4'H2).

EXAMPLE 27. Obtaining N-(3-methylphenyl)pyrrolidine (3).

Analogously to example 25, but instead of aniline used 0.2 ml (100 mmol) 3-methylaniline.

N-(3-methylphenyl)pyrrolidin (3)

Yield 63%). Light yellow. oil. W., so Kip. 93-95°C/0.08 mm Hg.PT.

The NMR spectrum13C (δ, M. D.): 148.15 (C-1), 138.83 (C-3), 129.11 (C-5), 116.61 (C-4), 112.53 (C-2), is at 109.14 (C-6), 47.79 (C-2', C-5'), 25.55 (C-3', C-4'), 21.98 (C-7). The NMR spectrum1/sup> H (CDCl3d, M. D.): 7.20-7.35 m (1H, C5H), 6.63 (1H, C6H, J 8.0 Hz), 6.53 C (H, C2H), 6.52 (1H, C4H J 8.0 Hz), 3.37-3.40 m (4H, C2',5'H2), 2.45 (3H, C7H3), 2.08-2.11 m (4H, C3',4'H2).

Mass spectrum, m/z (IRel.(%)): 161 [M]+(72), 160 (100), 118 (22), 117 (9), 105 (69), 91 (56), 89 (11), 77 (14), 65 (34), 63 (10), 51 (11).

EXAMPLE 28. Obtaining N-(4-methylphenyl)pyrrolidine (4).

Analogously to example 25, but instead of aniline used 0.2 g (100 mmol) of 4-methylaniline.

N-(4-methylphenyl)pyrrolidin (4)

A 75% yield. Light yellow. oil. W., so Kip. 108-110°C/0.1 mm Hg.PT. (So Kip. 274.1°C/760 mm Hg.PT. [http://www.weiku.com/chemicals/]).

The NMR spectrum13C (δ, M. D.): 145.85 (C-1), 129.68 (C-3, C-5), 124.98 (C-4), 112.19 (C-2, C-6), is at 48.26 (C-21, C-5'), 25.39 (C-3', C-4'), 20.36 (C-7). The NMR spectrum1H (CDCl3d, M. D.): 7.07 (2H, C3,5H, J 8.0 Hz), 6.56 (2H, C2,6H, J 8.0 Hz), 3.20-3.40 m (4H, C2',5'H2), 2.28 (3H, C7H3), 2.01 m (4H, C3',4'H2).

Mass spectrum, m/z (IRel.(%)): 161 [M]+(76), 160 (100), 118 (31), 117 (12), 105 (79), 91 (64), 89 (16), 78 (9), 77 (18), 65 (38), 63 (10), 51 (13).

EXAMPLE 29. Obtaining N-(2-ethylphenyl)pyrrolidine (5).

Analogously to example 25, but instead of aniline used 0.2 ml (100 mmol) of 2-ethylaniline.

N-(2-ethylphenyl)pyrrolidin (5)

The yield of 47%. Yellow. oil. W., so Kip. 88-90°C/0.8 mmHg.PT.

The NMR spectrum13C (δ, M. D.): 148.40 (C-1), 135.60 (C-2), 129.46 (C-3), 126.27 (C-5), 121.42 (C-4), 116.88 (C-6), 52.03 (C-2', C-5'), 25.31 (C-3', C-4'), 24.91 (C-7), 14.49 (C-8). The NMR spectrum1H (CDCl3 d, M. D.): 7.22 (1H, C3H, J 7.2 Hz), 7.14 (1H, C6H, J 8.0 Hz), 6.94-7.01 m (1H, C4H), 6.63-6.77 m (1H, C5H), 3.12-3.40 ush with (4H, C2',5'H2), 2.68-2.85 kV (2H, C7H2), 1.90-2.12 ush with (4H, C3',4'H2), 1.29 t (3H, C8H3, J 7.6 Hz).

Mass spectrum, m/z (IRel.(%)): 175 [M]+(80), 174 (100), 160 (7), 146 (12), 134(15), 120 (9), 119(35), 118 (27), 91 (37), 65 (16).

EXAMPLE 30. Obtaining N-(2-chlorophenyl)pyrrolidine (6).

Analogously to example 25, but instead of aniline used 0.16 ml (100 mmol) of 2-Chloroaniline.

N-(2-chlorophenyl)pyrrolidine (6)

The yield of 51%. Light yellow. oil. W., so Kip. 115-117°C/0.6 mm Hg.PT.

The NMR spectrum13C (δ, M. D.): 146.98 (C-1), 131.29 (C-3), 127.29 (C-5), 126.44 (C-2), 123.59 (C-4), 120.91 (C-6), area from 51.26 (C-2', C-5'), 25.20 (C-3', C-4'). The NMR spectrum1H (CDCl3d, M. D.): 7.28-7.40 m (1H, C3H), 7.11-7.22 m (1H, C5H), 6.92-7.08 m (1H, C6H), 6.75-6.90 m (1H, C4H), 3.32-3.51 ush with (4H, C2',5'H2), 1.88-2.08 ush with (4N, C3',4'H2).

Mass spectrum, m/z (IRel.(%)): 181.5 [M]+(100), 182 (29), 180 (95), 140 (24), 138 (42), 124 (85), 118 (17), 117 (37), 111 (45), 90 (29), 88 (31), 77 (36), 74 (25), 73 (20), 62 (16), 50 (30).

EXAMPLE 31. Obtaining N-(3-chlorophenyl)pyrrolidine (7).

Analogously to example 25, but instead of aniline used 0.17 ml (100 mmol) 3-Chloroaniline.

N-(3-chlorophenyl)pyrrolidin (7)

The yield is 50%. Light yellow. oil. W., so Kip. 120-122°C/0.4 mm Hg.PT.

The NMR spectrum13C (δ, M. D.): 148.83 (C-1), 134.78 (C-3), 129.98 (C-5), 114.95 (C-4), 111.27 (C-2), 109.89 (C-6), 47.57 (C-2', C-5'), 25.41 (C-3', C-4'). Speck�p NMR 1H (CDCl3d, M. D.): 7.04-7.08 m (1H, C5H), 6.55 (1H, C4H, J 8.0 Hz), 6.46 (1H, C2H), 6.37 (1H, C6H, J 8.0 Hz), 3.05-3.32 ush with (4H, C2',5'H2), 1.85-2.05 nl (4H, C3',4'H2).

EXAMPLE 32. Obtaining N-(4-chlorophenyl)pyrrolidine (8).

Analogously to example 25, but instead of aniline used 0.2 g (100 mmol) 4-Chloroaniline.

N-(4-chlorophenyl)pyrrolidin (8)

The yield was 60%. Light yellow. oil. W., so Kip. 132-134°C/0.3 mm Hg.PT. (So Kip. 288.4°C/760 mm Hg.PT. [http://www.lookchem.com]).

The NMR spectrum13C (δ, M. D.): 146.51 (C-1), 128.90 (C-3, C-5), 120.04 (C-4), 112.73 (C-2, C-6), 47.78 (C-2', C-5'), 25.56 (C-3', C-4'). The NMR spectrum1H (CDCl3d, M. D.): 7.14 (2H, C3,5H, J 8.0 Hz), 6.46 (2H, C2,6H, J 8.0 Hz), 3.17-3.31 m (4H, C2',5'H2), 1.96-2.09 m (4H, S3',4'H2).

Mass spectrum, m/z (IRel.(%)): 181.5 [M]+(88), 183 (23), 182 (30), 180 (100), 138 (37), 127 (17), 125 (66), 111 (19), 110 (46), 91 (16), 89 (19), 75 (20), 63 (18), 52 (19), 51 (18).

EXAMPLE 33. Obtaining N-(4-fluorophenyl)pyrrolidine (9).

Analogously to example 25, but instead of aniline used 0.17 ml (100 mmol) 4-foronline.

N-(4-fluorophenyl)pyrrolidin (9)

The yield of 45%. Light yellow. oil. W., so Kip. 92-94°C/1 mm Hg.PT.

The NMR spectrum13C (δ, M. D.): 144.83 (C-1), 154.83 (C-4, J13C19F 232 Hz), and 112.14 (C-3, C-5, J13C19F 8 Hz), 115.43 (C-2, C-6, J13C19F 22 Hz), 48.18 (C-2', C-5'), 25.53 (C-3', C-4'). The NMR spectrum1H (CDCl3, 5, M. D.): 6.91-7.00 m (2H, C3,5H), 6.44-6.53 m (2H, S2,6H), 3.18-3.32 m (4H, C2',5'H 2), 1.92-2.10 m (4H, C3',4'H2).

The NMR spectrum19F (CDCl3d, M. D.): - 130.73.

Mass spectrum, m/z (IRel(%)): 165 [M]+(94), 164 (73), 136 (11), 124 (15), 123 (19), 122 (63), 111 (12), 110 (21), 109 (100), 95 (10), 94 (46), 75 (14), 64 (9). 50 (10).

Table 1
The results of experiments on the synthesis of N-phenylpiperidine reaction of aniline with 1,5-penttila under the action of FeCl·6H2O in the environment of carbon tetrachloride∗
№ p/pThe molar ratio of [Fe]:[aniline]:[diol]:[CCl4]Duration of reaction, hThe yield of N-fenilpiperidina, %
10.5:100:200:30685
20:100:200:10060
30.2:100:200:100654
40.5:100:200:100669
50.5:100:100:100 12
60.5:100:120:100638
70.5:100:150:100644
80.5:100:160:100657
90.5:100:180:100666
100.5:100:200:100669
110.5:100:300:100633
120.5:100:400:100627
130.5:100:200:20656
140.5:100:200:50638
150.5:100:200:30445
160.5:100:200:30876
* All reactions were carried out at a temperature of 180°C.

A method of producing N-arylpyrimidines and N-arylpiperazines

the interaction of anilines with dialami in the presence of a catalyst, characterized in that the anilines used aniline of the General formula R-C6H4NH2(where R=H,about-,m-,p-CH3,about-C2H5,about-,m-,p-Clp- (F), the catalyst is FeCl3·6H2O, the reaction is carried out at a molar ratio of [FeCl3·6H2O]:[aniline]:[diol]:[CCl4]=0.2-0.5:100:100-400:20-100, in the environment of CCl4at a temperature of 180°C for 4-8 hours in an inert atmosphere.



 

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< / BR>
< / BR>
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39 cl, 7 tbl

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New ketoenamine // 2190599
The invention relates to new ketoenamine formula (1), where R1means phenyl, naphthyl, hinely, pyridyl, chinadoll, Minoxidil, benzothiazyl, isoquinoline, tetrahydroisoquinoline or tetrahydroquinolin, which may be unsubstituted or substituted, R2means hydrogen or alkyl, R3means alkyl, which may carry phenyl ring, X is a bond, -(CH2)m-, -(CH2)m-O-(CH2)0-, -(CH2)n-S-(CH2)m-, -CH= CH-, -CO-CH=CH-, -(CH2)m-NHCO-(CH2)0-, -(CH2)m-CONH-(CH2)0-, -(CH2)m-NHSO2-(CH2)0-, -(CH2)m-SO2NH-(CH2)0-; R4means group OR6, NR7R8; n is a number from 0 to 2

The invention relates to new compounds of the formula I

Y-(CmH2m-CHR1)n-CO- (NH-CHR2CO)r-Z

where Y denotes

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or

< / BR>
Z denotes

< / BR>
or if Y

< / BR>
also means

< / BR>
R1, R2and R7each means-CtH2t-R9,

R3means H or H2N-C(=NH)-,

R4and R6each means (H,H) or =O,

R5means H2N-C(=NH) -, or H2N-C(=NH)-NH,

R8means OH or OA,

R9denotes H or COOH,

A denotes alkyl with 1-4 C-atoms,

m and t each is 0, 1 or 2,

n and r each denotes 0 or 1 and

p is 0, 1 or 2,

and their salts

The invention relates to new cycloalkenes and cycloalkanes, suitable as pharmaceutically active substances, more particularly to derivatives of 1,3-substituted of cycloalkene and cycloalkane formula (I)

Z-CH2-Y (I)

where Z stands for a group

< / BR>
where

where R is aryl, 2-, 3 - or 4-pyridinyl, unsubstituted or substituted lower alkyl, lower alkoxyl, hydroxyl or halogen, 2-, 4 - or 5-pyrimidinyl, unsubstituted or substituted lower alkyl, lower alkoxide, hydroxyl or halogen, 2-pyrazinyl, unsubstituted or substituted lower alkyl, lower alkoxyl, hydroxyl or halogen, 2 - or 3-thienyl, unsubstituted go substituted lower alkyl or halogen, 2 - or 3-furanyl, unsubstituted or substituted lower alkyl or halogen, 2-, 4 - and 5-thiazolyl, unsubstituted or substituted lower alkyl or halogen, 3-indolyl, 2-, 3 - or 4-chinoline, and m is the number 1, 2, or 3, or group

< / BR>
in which R and m have the above meanings;

Y - group

< / BR>
where R is the specified value,

mixtures of their isomers or the individual is

The invention relates to the field of chemistry, to a method for the chemical substance that manifests anthelminthic properties, and can be used in agriculture to treat animals

The invention relates to organic chemistry, and in particular to methods obtain 1-ethyl-6-fluoro-7-(piperazinil-1)-4-oxo-1,4-dihydro-3-quinoline-carboxylic acid (norfloxacin) formula 1

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FIELD: chemistry.

SUBSTANCE: present invention provides a method of producing a conjugated diene polymer. Also disclosed is the make-up of the used catalytic composition. The method of producing a conjugated diene polymer involves polymerisation of a conjugated diene monomer in the presence of a catalytically effective amount of the catalytic composition formed by mixing: (a) a nickel-containing compound; (b) an alkylating agent; (c) a fluorine-containing compound; (d) a carboxylic acid; and (e) an alcohol selected from a group consisting of aliphatic alcohols, cyclic alcohols, unsaturated alcohols, aromatic alcohols, heterocyclic alcohols and polycyclic alcohols, said polymerisation being carried out in a nonpolar solvent; molar ratio of the alkylating agent to the nickel-containing compound (alkylating agent/Ni) ranges from approximately 1:1 to 200:1; molar ratio of the fluorine-containing compound to the nickel-containing compound (F/Ni) ranges from approximately 7:1 to 500:1; molar ratio of the carboxylic acid to the nickel-containing compound (COOH/Ni) ranges from approximately 0.1:1 to 2:1; and molar ratio of the alcohol to the nickel-containing compound (OH/Ni) ranges from approximately 0.4:1 to 80:1; and said polymerisation is carried out using from about 0.01 to about 0.1 mmol of the nickel-containing compound per 100 g of the conjugated diene monomer.

EFFECT: obtaining a nickel-based catalytic composition and a polymer obtained using said composition.

18 cl, 2 tbl, 9 ex

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