PL214511B1 - Chromophore derivatives of [(2S)-1-phenylpyrrolidine-2-yl] methanol and process for the preparation thereof - Google Patents

Description

(12) PATENT DESCRIPTION (19) PL (11) 214511 (13) B1 (21) Application number: 394753 ^{(51) Int.Cl.}

C07D 207/08 (2006.01) C07D 403/10 (2006.01) C07D 403/12 (2006.01) (22) Date of notification: 04.05.2011 C07D 413/10 (2006.01) C07D 413/12 (2006.01)

Chromophore derivatives of [(2S) -1-phenylpyrrolidin-2-yl] methanol and the method of their preparation (73) The patent holder:

POLITECHNIKA WROCŁAWSKA, Wrocław, PL (43) Application was announced:

November 21, 2011 BUP 24/11 (45) The following was announced about the grant of the patent:

30.08.2013 WUP 08/13 (72) Inventor (s):

SONIA ZIELIŃSKA, Kędzierzyn-Koźle, PL KRZYSZTOF KOLMAN, Kuźnia Raciborska, PL STANISŁAW KUCHARSKI, Wrocław, PL (74) Representative:

item. stalemate. Anna Meissner

PL 214 511 B1

Description of the invention

The subject of the invention are chromophore derivatives of [(2S) -1-phenylpyrrolidin-2-yl] methanol and the method of their production applicable in nonlinear optics as well as optical recording and processing of information.

Polish patent specification no. PL 195540 describes bi-functional ethylcarbazole chromophores which contain a chromophore group and a photoconductive fragment in one chemical structure. The description also describes a method of producing these bi-functional ethylcarbazole chromophores, which consists in 4-amino-N- (pyrimidin-2-yl) benzosulfonamide, 4-amino-N- (2,6-dimethylpyrimidin-4- yl) benzosulfonamide, 2-amino-6-nitro-1,3-benzothiazole or 2-amino-5 ((4-nitrophenyl) sulfonyl) -1,3-thiazole are diazotized to the corresponding diazonium salts in a dilute aqueous medium hydrochloric acid solution and glacial acetic acid at a temperature of 0 ° C to 4 ° C, and the obtained diazonium salts are then subjected to a coupling reaction with N-ethylcarbazole in the presence of sodium acetate and at a temperature of 0 ° to 4 ° C.

The Polish patent application No. 380843 describes a new nonlinear-optical monomer named 3- (4'-N, N-di (2-hydroxyethyl) phenylazo) -5-methylisoxazole. The subject of the application is also a method of producing this compound, which consists in diazotizing 3-amino-5-methylisoxazole with a mixture of concentrated sulfuric acid and aqueous sodium nitrate (III), and then the obtained diazonium salt is coupled with N, N-di (2-hydroxyethyl) aniline.

From the publication of K. Hofmann, K. Schreiter. A. Seifert, S. Spange. T. Rueffer, H. Lang, New Journal of Chemistry, 32 (2008) 2180 - 2188 azo dyes containing a donor-acceptor system in the structure, such as 2 - ({4 - [(E) - (2,4- dinitrophenyl) diazenyl] -2-nitrophenyl} amino) propane-1,3-diol, (2S) -1- (4 - [(E) - (2,4-dinitrophenyl) diazenyl] -2-nitrophenyl] pyrrolidine-2- acid methyl carboxyl and methyl (2S) -1- {4 - [(E) - (2,4-dinitrophenyl) diazenyl] -2-nitrophenyl} pyrrolidine-2-carboxylate, which were obtained by one-step nucleophilic aromatic substitution (E ) -1- (2,4-dinitrophenyl) -2- (4-fluoro-3-nitrophenyl) diazene with 2-aminopropane-1,3-diol, (S) -proline and (S) -proline methyl ester. The publication describes the synthesis and solvatochromism of dyes that undergo reversible equilibrium protonation-deprotonation in the presence of hydrochloric acid with a concentration ranging from 5 to 12 M.

So far, the chromophore derivatives of [(2S) -1-phenylpyrrolidin-2-yl] methanol and the method of their preparation, which are the subject of the invention, are unknown in the literature.

The invention relates to chromophore derivatives of [(2S) -1-phenylpyrrolidin-2-yl] methanol of the general formula I, in which R is 4-benzonitrile, 4-N- (5-methylisoxazol-3-yl) benzenesulfonamide or 4-N - (4,6-dimethyl-pyrimidin-2-yl) benzenesulfonamide.

The invention also provides a method for the preparation of chromophore derivatives of [(2S) -1-phenylpyrrolidin-2-yl] methanol of general formula I, wherein R is 4-benzonitrile, wherein 4-aminobenzonitrile is diazotized with nitrate (III ) of sodium in a mixture of concentrated hydrochloric acid and water, and then the obtained diazonium salt in the form of 4-cyanobenzenediazonium chloride is coupled with [(2S) -1-phenylpyrrolidin-2-yl] methanol and then neutralized with aqueous sodium acetate solution.

Preferably, the coupling reaction is carried out with a molar ratio of the diazonium salt to [(2S) -1-phenylpyrrolidin-2-yl] methanol ranging from 4: 5 to 5: 4.

The invention also provides a process for the preparation of chromophore [(2S) -1-phenylpyrrolidin-2-yl] methanol derivatives of general formula I, in which R is 4-N- (5-methylisoxazol-3-yl) benzenesulfonamide or 4-N- (4,6-dimethylpyrimidin-2-yl) benzenesulfonamide characterized by 4-amino-N- (5-methyl-isoxazol-3-yl) benzenesulfonamide or 4-amino-N- (4,6-dimethyl-pyrimidine -2-yl) benzenesulfonamide is subjected to diazotization with sodium nitrate (III) in a mixture of concentrated hydrochloric acid, water and glacial acetic acid, and then the resulting diazonium salt is coupled with [(2S) -1-phenylpyrrolidin-2-yl] methanol and neutralizes.

Preferably the diazotization reaction of 4-amino-N- (5-methylisoxazo-3-yl) benzenesulfonamide and 4-amino-N- (4,6-dimethyl-pyrimidin-2-yl) benzenesulfonamide is carried out in a mixture of concentrated hydrochloric acid, water and glacial acetic acid containing from 6 to 10% by volume of concentrated hydrochloric acid and from 50 to 60% by volume of glacial hydrochloric acid.

Preferably, from 1.00 mole to 1.30 mole of sodium nitrate per mole of the benzenesulfonamide derivative are used in the diazotization reaction.

PL 214 511 B1

Preferably, the coupling reaction is carried out with a molar ratio of the diazonium salt to [(2S) -1-phenylpyrrolidin-2-yl] methanol ranging from 4: 5 to 5: 4.

Preferably, the coupling solution is neutralized with sodium acetate, potassium acetate or sodium carbonate.

Preferably, the obtained coupling reaction products, after isolation and drying, are purified by crystallization from a water-N, N-dimethylformamide mixture.

Preferably, the obtained coupling reaction products, after isolation and drying, are purified by crystallization from a water-tetrahydrofuran mixture.

Preferably, the obtained coupling reaction products, after isolation and drying, are purified by crystallization from a pyridine-water mixture.

The subject of the invention is described in the examples of the preparation of azo derivatives of [(2S) -1-phenylpyrrolidin-2-yl] methanol.

P r z k ł a d 1

Preparation method of 4 - [(E) - [4 - [(2S) -2- (hydroxymethyl) pyrrolidin-1-yl] phenyl] azo] benzonitrile of general formula 1, wherein R is 4-benzonitrile.

₃

The beaker is placed 1.18 g (10 mmol) 4-aminobenzonitrile and 5.9 cm ³ of concentrated hydrochloric acid _3, thoroughly mixed, and then the resulting dispersion is added to 5.9 cm ³ of distilled water.

The mixture is cooled to a temperature of about 0 ° C and treated with small portions of aqueous azo ₃ methane (III) sodium [0.759 g (11 mmol) NaNO2 in 5 cm ³ of distilled water] with stirring, keeping the system temperature below 7 ° C. After the dropwise addition of the sodium nitrate solution, the mixture was stirred for minutes while still keeping the system temperature below 7 ° C. After this time, a solution of 1.77 g (10 mmol) [(2S) -1-phenylpyrrolidin-2 _{3 cooled to a temperature of about 10 ° C is added to the mixture.}

-yl] methanol in 5 cm ³ of methyl alcohol. The mixture is stirred for another 30 minutes and then neutralized with an aqueous sodium acetate solution. The mixture was left for 24 hours in the refrigerator to allow the dye sediment to coagulate. The precipitate of the product is then filtered off, washed several times with water and dried at 45 ° C. The dried, crude product is dissolved in tetrahydrofuran and then precipitated from the solution by dropwise addition of distilled water and left in the refrigerator for several hours. The precipitate formed is filtered off, washed with water and dried at 45 ° C. The yield of the dye thus obtained is 90%.

¹ H NMR (solvent: CDCl 3, pattern: TMS): 1.79 ppm, bs, 1H (OH); 2.15 ppm, m, 4H (protons on the (2S) -1-phenylpyrrolidin-2-yl ring at C3 and C4); 3.36 ppm, d, 1H (proton on the (2S) -1-phenylpyrrolidin-2-yl ring at the C5 position); 3.61 ppm, m, 1H (proton on the (2S) -1-phenylpyrrolidin-2-yl ring at the C5 position); 3.68 ppm, m, 1H (proton on the (2S) -1-phenylpyrrolidin-2-yl ring at C2 position); 3.73 ppm, m, 1H (CH2O); 4.07, m, 1H (CH2O); 6.76 ppm, d, 2H (protons on the phenylene ring ortho to the amino group); 7.74 ppm, d, 2H (protons in the phenylene ring meta to amino); 7.89 ppm, d, 4H (protons in the phenylene ring in ortho position and meta to the cyano group).

P r z k ł a d 2

Preparation method of 4 - [(E) - [4 - [(2S) -2- (hydroxymethyl) pyrrolidin-1-yl] phenyl] azo] -N- (5-methylisoxazol-3-yl) benzenesulfonamide of general formula 1 wherein R is 4-N- (5-methylisoxazol-3-yl) benzenesulfonamide.

The beaker is placed 2.53 g (10 mmol) of 4-amino-N- (5-methyl-isoxazol-3-yl) benzenesulfonic Polymorph Form ₃ and 3 cm ^{3 of} concentrated hydrochloric acid and heated until a clear solution. Then 23.2 cm ³ of distilled water and 30 cm ^{3 of} glacial acetic acid are added. The mixture is cooled to a temperature of about 0 ° C and treated with small portions of aqueous nitrate solution (III) sodium ₃ [0.83 g (12 mmol) NaNO2 in 5 cm ³ of distilled water] with stirring, keeping the system temperature below 7 ° C. After all the sodium nitrate solution has been added dropwise, the mixture is stirred for 30 minutes while still keeping the system temperature below 7 ° C. After this time, a cooled solution to a temperature of about 10 ° C containing 1.77 g (10 mmol) [(2S) -1-phenylpyrrolidines ₃

-2-yl] methanol in 5 cm ³ of methyl alcohol. The mixture is stirred for another 30 minutes and then neutralized with an aqueous sodium acetate solution. The mixture was left for 24 hours in the refrigerator to allow the dye sediment to coagulate. The precipitate of the product is then filtered off, washed several times with water and dried at 45 ° C. The dried, crude product is dissolved in Ν, Ν-dimethylformamide, and then precipitated from the solution by the addition of small portions of distilled water and left for several hours. The precipitate formed is filtered off, washed with water and dried at 45 ° C. The yield of the dye thus obtained is 80%.

PL 214 511 B1 ή

¹ H NMR (solvent: DMSO-d6, standard: TMS): 2.04 - 2.15 ppm, m, 4H (protons of the ring (2S) -1-phenylpyrrolidin-2-yl anion at C3 and C4); 2.30 ppm, s, 3H (CH3); 3.22 - 3.47 ppm, bs, 4H (protons on the (2S) -1-phenylpyrrolidin-2-yl ring at C2 and C5 positions and CH-O); 3.91 ppm, m, 1H (CH-O); 4.90 ppm, bs, 1H (OH); 6.16 ppm, s, 1H (proton in a 5-methylisoxazol-3-yl ring); 6.78 ppm, d, 2H (protons on the phenylene ring ortho to the amino group); 7.80 ppm, d, 2H (protons in the phenylene ring meta to amino); 7.90 ppm, d, 2H (protons on the phenylene ring ortho to the SO2 group): 7.97 ppm, d, 2H (protons on the phenylene ring meta to the SO2 group).

P r z k ł a d 3

Preparation method of N- (4,6-dimethylpyrimidin-2-yl) -4 - [(E) - [4 - [(2S) -2- (hydroxymethyl) pyrrolidin-1-yl] phenyl] azo] benzenesulfonamide of general formula The compound of claim 1, wherein R is 4-N- (4,6-dimethylpyrimidin-2-yl] benzenesulfonamide.

The beaker is placed 2.78 g (10 mmol) of 4-amino-N- (4,6-dimethyl-pyrimidin-2-yl) benzenesulfonic fonamidu ₃ and 5.5 cm ^{3 of 2 1} concentrated hydrochloric acid and heated until a clear solution . 33

Then 23.2 cm ³ of distilled water and 32.9 cm ^{3 of} glacial acetic acid are added. The mixture is cooled to about 0 ° C and an aqueous solution of sodium nitrate ₃ (III) [0.83 g (12 mmol) NaNO 2 in 5 cm ³ of distilled water] is added in small portions while keeping the system temperature below 7 ° C. After all the sodium nitrate solution has been added dropwise, the mixture is stirred for 30 minutes while still keeping the system temperature below 7 ° C. After this time, a cooled solution to a temperature of about 10 ° C containing 1.77 g (10 mmol) [(2S) -1-phenylpyrrolidines ₃

-2-yl] methanol in 5 cm ³ of methyl alcohol. The mixture is stirred for another 30 minutes and then neutralized with an aqueous sodium acetate solution. The mixture was left for 24 hours in the refrigerator to allow the dye sediment to coagulate. The precipitate of the product is then filtered off, washed several times with water and dried at 45 ° C. The dried, crude product is dissolved in N, N-dimethylformamide, and then precipitated from the solution by the addition of small portions of distilled water and left for several hours. The precipitate formed is filtered off, washed with water and dried at 45 ° C. The yield of the dye thus obtained is 80%.

₁ ¹ H NMR (solvent: DMSO-d6, standard: TMS): 2.10 ppm, bs, 4H (protons of the ring (2S) -1-phenylpyrrolidin-2-yl anion at C3 and C4); 2.37 ppm, s, 6H (CH3); 3.17 ppm, t, 1H (proton on the (2S) -1-phenylpyrrolidin-2-yl ring at the C5 position); 3.34 ppm, d, 1H (proton on the (2S) -1-phenylpyrrolidin-2-yl ring at the C5 position); 3.50 ppm, m, 1H (proton on the (2S) -1-phenylpyrrolidin-2-yl ring at C2 position); 3.63 ppm, m, 1H (CH2O); 3.75 ppm, m, 1H (CH2O); 4.20 ppm, bs, 1H (OH); 6.64 ppm, t, 2H (protons on the phenylene ring ortho to the amino group); 6.74 ppm, t, 2H (protons in the phenylene ring at the meta position of the amino group; 7.25 ppm, t, 2H (protons in the phenylene ring at the ortho position to the SO2 group): 7.90 ppm, t, 2H ( protons on the phenylene ring meta to the SO2 group) 8.24 ppm, d, 1H (proton on the 4,6-dimethylpyrimidin-2-yl ring at C5).

Claims (13)

Patent claims 1. Chromophore [(2S) -1-phenylpyrrolidin-2-yl] methanol derivatives of general formula I, in which R is 4-benzonitrile, 4-N- (5-methylisoxazol-3-yl) benzenesulfonamide or 4-N - (4,6-dimethyl-pyrimidin-2-yl) benzenesulfonamide. 2. A method for producing chromophore derivatives of [(2S) -1-phenylpyrrolidin-2-yl] methanol of the general formula I, in which R is a 4-benzonitrile group, characterized in that 4-aminobenzonitrile is subjected to diazotization with sodium nitrate (III) in a mixture of concentrated hydrochloric acid and water, and then the obtained diazonium salt in the form of 4-cyanobenzenediazonium chloride is coupled with [(2S) -1-phenylpyrrolidin-2-yl] methanol and then neutralized with aqueous sodium acetate solution. 3. The method according to p. 2. The method of claim 2, wherein the coupling reaction is carried out with a molar ratio of the diazonium salt to [(2S) -1-phenylpyrrolidin-2-yl] methanol ranging from 4: 5 to 5: 4. 4. A method for the preparation of chromophore derivatives of [(2S) -1-phenylpyrrolidin-2-yl] methanol of general formula 1, in which R is a 4-N- (5-methylisoxazol-3-yl) benzenesulfonamide group or 4-N- ( 4,6-dimethylpyrimidin-2-yl) benzenesulfonamide, characterized in that 4-amino-N- (5-methyl isoxazol-3-yl) benzenesulfonamide or 4-amino-N- (4,6-dimethyl- pyrimidin-2-yl) benzenesulfonamide is subjected to the diazotization reaction with sodium nitrate (III) in a mixture of concentrated hydrochloric acid, water and glacial acetic acid, and then the obtained diazonium salt is coupled with [(2S) -1-phenylpyrrolidin-2-yl ] with methanol and neutralizes. 5. The method according to p. 4. The process according to claim 4, characterized in that the diazotization reaction of 4-amino-N- (5-methylisoxazo-3-yl) benzenesulfonamide and 4-amino-N- (4,6-dimethyl-pyrimidin-2-yl) benzenesulfonamide is carried out in a mixture of concentrated hydrochloric acid, water and glacial acetic acid containing from 6 to 10% by volume of concentrated hydrochloric acid and from 50 to 60% by volume of glacial hydrochloric acid. 6. The method according to p. 4. The process of claim 4, wherein the diazotization reaction uses from 1.00 mole to 1.30 mole of sodium nitrate per mole of benzenesulfonamide derivative. 7. The method according to p. 4. The process of claim 4, wherein the coupling reaction is carried out with a molar ratio of the diazonium salt to [(2S) -1-phenylpyrrolidin-2-yl] methanol ranging from 4: 5 to 5: 4. 8. The method according to p. The process of claim 4, wherein the coupling solution is neutralized with sodium acetate. 9. The method according to p. The process of claim 4, wherein the coupling solution is neutralized with potassium acetate. 10. The method according to p. The process of claim 4, wherein the coupling solution is neutralized with sodium carbonate. 11. The method according to p. A process as claimed in claim 4, characterized in that the obtained coupling reaction products, after separation and drying, are purified by crystallization from a water-N, N-dimethylformamide mixture. 12. The method according to p. The process of claim 4, characterized in that the obtained coupling reaction products, after separation and drying, are purified by crystallization from a water-tetrahydrofuran mixture. 13. The method according to p. A process according to claim 4, characterized in that the obtained coupling reaction products, after separation and drying, are purified by crystallization from a water-pyridine mixture. Drawing