CN102952026B

CN102952026B - Preparation and synthetic method for chirality (S)-benzene ammonia alcohol hydrochloride

Info

Publication number: CN102952026B
Application number: CN2012103183645A
Authority: CN
Inventors: 罗梅
Original assignee: Individual
Current assignee: Individual
Priority date: 2012-09-02
Filing date: 2012-09-02
Publication date: 2013-12-04
Anticipated expiration: 2032-09-02
Also published as: CN102952026A

Abstract

The invention discloses a novel chirality (S)-benzene ammonia alcohol hydrochloride. A chemical formula of the S-benzene ammonia alcohol hydrochloride is formed by the following synthetic steps of: carrying out a reaction on N-(2-cyanoethyl)-N-(2-ethoxyl) aniline, (S)-D-phenylglycinol and chromium chloride hexahydrate at the ratio of 1:4.2:1.5 in chlorobenzene solution for 1 day; and standing the reaction liquid for 3 days to obtain the product of chirality clear crystal (S)-benzene ammonia alcohol hydrochloride. The compound has good catalysis performance in nitrile silicide reaction and henry reaction of benzaldehyde, and the yield is respectively up to 77.5 percent and 99.2 percent.

Description

Preparation and the synthetic method of a kind of chirality (S)-benzene glycinol hydrochloride

One, technical field

The present invention relates to a kind of preparation and synthetic method of quaternary ammonium salt, is exactly preparation and the synthetic method of a kind of chirality (S)-benzene glycinol hydrochloride.

Two, background technology

The synthetic method of quaternary ammonium salt has many bibliographical informations.As far back as 1956, change the synthetic method that institute periodical has reported some quaternary ammonium salts, nineteen fifty-nine, American Chemical Society has also reported the synthetic method of quaternary ammonium salt,

Reference:

1. Surrey, Alexander R.; Lesher, George Y.; Mayer, J. Richard; Webb, Wm. G. Journal of the American Chemical Society (1959), 81 2894-7;

2 . Davis, M. Journal of the Chemical Society (1956), 337-43.。 [0003]The applicant, in the experiment of synthetic N-and six hydration Samarium chloride title complexs, does not obtain the target product title complex, has but obtained another kind of novel chiral compound (S)-benzene glycinol hydrochloride.

Three, summary of the invention

The present invention aims to provide chirality (S)-benzene glycinol hydrochloride, and technical problem to be solved is that one-step synthesis obtains target product.

Alleged a kind of (the S)-benzene glycinol hydrochloride of the present invention be by N-(2-cyanoethyl)-N-(2-hydroxyethyl) aniline, (S)-benzene glycinol and six hydrated chromium trichlorides, prepared by the compound shown in following chemical formula:

（Ⅰ）

Chemical name: (S)-benzene glycinol hydrochloride, be called for short compound (I).

This synthetic method comprises synthesizes and separates, the N-of described synthetic 1:4.2:1.5 (2-cyanoethyl)-N-(2-hydroxyethyl) aniline, (S)-benzene glycinol react one day with six hydrated chromium trichlorides in chlorobenzene solution, by standing 3 days of reaction solution, obtain product chirality clear crystal (S)-benzene glycinol hydrochloride.

Its reaction mechanism can be speculated as N-(2-cyanoethyl)-N-(2-hydroxyethyl) aniline or (S)-benzene glycinol under strong lewis acid effect, with the effect of 146mol% chromium trichloride, form hydrogenchloride, then, with excessive (S)-benzene glycinol salify, form

(S)-benzene glycinol hydrochloride.

This synthetic method one step obtains target product, and technique is simple, easy to operate.

Four, accompanying drawing explanation

Fig. 1 is the X-diffraction analysis figure of (R)-α-phenylethylamine hydrochloride.

Five, embodiment

1. the preparation of chirality (R)-α-phenylethylamine hydrochloride

In the 100mL flask, under the anhydrous and oxygen-free condition, add six hydrated chromium trichloride 3.0g (15.3mmol), N-(2-cyanoethyl)-N-(2-hydroxyethyl) aniline 2.0g(10.5mmol), (S)-benzene glycinol 6.1(44.2mmol), chlorobenzene 40mL, by the mixture 48h that refluxes, stopped reaction, by standing 3 days of reaction solution, obtain product chirality clear crystal (S)-benzene glycinol hydrochloride, productive rate: 30%; M.p.:98-100 ° of C, [a] ⁵ _D=-33.69 o (c=0.148, CH ₃OH), ¹H NMR (500MHz, CDCl ₃) 8.45(s, br, 1H), 7.30 – 7.49 (m, 5H), 5.74 – 5.82 (m, 1H), 4.14 (d, J=4.5Hz, 1H), 2.40 (s, br, 1H). ¹³C NMR (75 MHz, CDCl ₃) 130.1,123.0 (x2), 122.1,122.0 (x2), 57.4,50.5, results of elemental analyses is as follows: theoretical value: C, 55.34%; H, 6.97%; N, 8.07; Measured value: C, 55.26%; H, 6.58%; N, 8.05%.; HRMS (EI): m/z – Cl ^-(%): calcd for C ₈H ₁₂NO:138.0919; Found:138.0921. IR (KBr): 3125,3005,2930,2878,2751,2658,2637,1615,1535,1495,1455,1194,1057,1194,1057,770,705,661,540.

The match crystal volume data is as follows:

Empirical formula(empirical formula) C8 H12 Cl N O

Formula weight(molecular weight) 173.64

Temperature (temperature) 173 (2) K

Wavelength (Wavelength) 0.71073 A

Crystal system, space group (crystallographic system, spacer) Orthorhombic(rhombic system), P2 (1) 2 (1) 2 (1)

Unit cell dimensions(unit cell parameters) a=6.4263 (7) A alpha=90 deg.

b = 7.2598(8) A beta = 90 deg.

c = 19.860(2) A gamma = 90 deg.

Volume (volume) 926.53 (18) A^3

Z, Calculated density) (electric density) 4,1.245 Mg/m^3

Absorption coefficient(absorption correction parameter) 0.358 mm^-1

F (000) (number of electrons in unit cell) 368

Crystal size (crystallographic dimension) 0.32 x 0.22 x 0.17 mm

Scope 2.05 to 30.50 deg. at Theta range for data collection (scope at Theta angle) q angle

The index capture range of Limiting indices(HKL)-9<=h<=8 ,-10<=k<=10 ,-28<=l<=24

Reflections collected/unique(collection/independent diffraction data) 9052/2820 [R (int)=0.0200]

Completeness to theta=30.50 (the data integrity degree of theta=30.5) 99.8 %

Absorption correction (the method Semi-empirical from equivalents(Multi Slice Mode of absorption correction)

Max. transmitance 0.9416 and 0.8940 of and min. transmission minimax

The Matrix least square method of Refinement method (method that refine is used) Full-matrix least-squares F^2

Number/the number of parameters of Data/restraints/parameters(data number/use restriction) 2820/0/102

The consistence factor of Goodness-of-fit on F^2(point diffraction) 1.063

Final R indices [I > 2sigma (I)] (the identical factor of observable diffraction) R1=0.0255, wR2=0.0667

R indices [all data] (the identical factors of all data diffraction) R1=0.0288, wR2=0.0685

Absolute structure parameter (absolute configuration parameter)-0.01 (4)

Maximum summit and peak valley on Largest diff. peak and hole(difference Fourier figure) 0.267 and-0.151 e.A^-3

The typical bond distance's data of crystal:

N(1)-C(2) 1.5004(14)

N(1)-H(1C) 0.9100

N(1)-H(1D) 0.9100

N(1)-H(1E) 0.9100

O(1)-C(1) 1.4164(13)

O(1)-H(1) 0.8400

The typical bond angle data of crystal:

C(2)-N(1)-H(1C) 109.5

C(2)-N(1)-H(1D) 109.5

H(1C)-N(1)-H(1D) 109.5

C(2)-N(1)-H(1E) 109.5

H(1C)-N(1)-H(1E) 109.5

H(1D)-N(1)-H(1E) 109.5

C(1)-O(1)-H(1) 109.5

O(1)-C(1)-C(2) 112.17(9)

O(1)-C(1)-H(1A) 109.2

C(2)-C(1)-H(1A) 109.2

O(1)-C(1)-H(1B) 109.2

2. nitrile silicification reaction application

2-phenyl-2-(tri-silyloxies) preparation of propionitrile

0.20mmol Compound I, phenyl aldehyde 0.1mL, TMSCN 0.3 ml (3.3mmol) adds in succession under 20 ~ 30 C, after 19h, add the shrend (sherwood oil/methylene dichloride: 5/1), obtain colourless oil liquid after column chromatography that goes out, productive rate: 77.5 % ¹H NMR (300MHz, CDCl3) 7.56 – 7.59 (m, 0.9 Hz, 2H), 7.31 – 7.34 (m, 3H), (5.43 s, 1H), 0.16 (s, 9H). 13C NMR (75 MHz, CDCl3) 136.1,128.8 (x2), 126.2 (x2), 119.1,63.5 ,-0.39 (x3).

3. Henle reaction application:

1. 2-nitro-1-phenylethyl alcohol

Catalyst I (0.20mmol), phenyl aldehyde 0.10 mL (0.986 mmol) and Nitromethane 99Min. (0.50 mL, 9.255 mmol) at room temperature stir 72 h, and with the nuclear-magnetism monitoring, transformation efficiency is not: 99.2 %.

Nitroethylene base benzene

Transformation efficiency is 41.1 %.

Claims

1. one kind has (the S)-benzene glycinol hydrochloride synthetic method shown in following chemical formula (I), comprise and synthesize and separate, it is characterized in that: the N-of 1:4.2:1.5 (2-cyanoethyl)-N-(2-hydroxyethyl) aniline, (S)-benzene glycinol react one day with six hydrated chromium trichlorides in chlorobenzene solution, by standing 3 days of reaction solution, obtain product chirality clear crystal (S)-benzene glycinol hydrochloride