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26/4/2018 CN1562961A - Method for preparing procaine - Google Patents

 Patents CN 1562961

Method for preparing procaine

Abstract
CN1562961A
This invention relates to a process for preparing procaine, by using p-nitrobenzoic acid and
CN Application
diethylamino ethanol as raw materials, by esteri cation to produce nitrocaine, which is then reduced
by reductant of hydrogenin xylene solvent with catalyst of nicket compound (Leininie) in suitable
temp. and pressure to produce nal product-procaine. Advantages are simple process, high Download PDF Find Prior Art Similar
transforming rate, high yield, high pureness, short process, reutilization of catalyst, no three wastes.
Other languages: Chinese

Inventor: 李方实, 贾志刚, 祝清兰, 周禾

Original Assignee: 南京工业大学

Priority date : 2004-04-02

Family: CN (1)

Date App/Pub Number Status

2004-04-02 CN 200410014538

2005-01-12 CN1562961A Application

2005-12-28 CN1233620C Grant

Info: Cited by (1), Legal events, Similar documents, Priority and


Related Applications

External links: Espacenet, Global Dossier, Discuss

Claims (2) translated from Chinese

1. 1. A method for the preparation of procaine, comprising the steps of: (a) Ni-Al alloy was weighed, added portionwise successively temperature 55 ~ 65 ℃ 1 ~ 1.5h time in
a concentration of 18 to 20% after the NaOH solution, the addition was complete warmed to 85 ~ 95 ℃, and maintained for 2 ~ 3 hours discharge, and then allowed to
stand, the solution decanted, washed rst with 70 ~ 80 ℃, at room temperature and then washed with water until the PH value 8 ~ 9, to obtain Raney nickel catalyst and
preservation with absolute ethanol; (b) p-nitrobenzoic acid in ethanol as a raw material and diethylamino esteri cation nitro tetracaine in xylene solvent; (c) Raney Nickel
as catalyst, hydrogen as a reducing agent, reduction of the nitro tetracaine in xylene solvent, the hydrogen pressure is 2.0 ~ 3.0MPa, reaction temperature is 80 ~ 130 ℃,
the reaction time is 5 to 8 hours, and then the material was cooled, ltered through extraction , adjusting the PH value of the ltrate, the precipitate was ltered and dried
to give a solid procaine.

2. 2. Preparation procaine according to claim 1, wherein the step (c) is the wet weight of Raney nickel catalyst in an amount of nitro group of 5 to 15% lidocaine.

Description translated from Chinese

Procaine preparation

FIELD

The present invention relates to a method for preparing an ester anesthetics, and more particularly relates to a method for preparing a catalytic hydrogenation procaine.

Background technique

Procaine (p-aminobenzoate -β- diethylamino ethyl) ester is a common local anesthetic, the drug is one of the basic clinical widely used at home and abroad. The clinical
application of irritation and toxicity are smaller, better and faster absorption and short duration of anesthesia. In recent years, the clinical use of new increasing market
demand has risen, increasing concern.

Procaine synthetic methods are indirect and direct esteri cation esteri cation.

Currently in production procaine most direct esteri cation method. Speci c routes are as follows: In direct esteri cation diethylamino-nitrobenzoic acid and ethanol as a
raw material, in xylene as solvent, azeotropic dehydration, esteri cation nitro lidocaine (p-nitrobenzoic acid diethylamine -β- ethyl group). Aqueous sodium hydroxide and
extracted with unreacted p-nitrobenzoic acid, the organic phase is the base resolution nitro lidocaine (lidocaine nitro xylene solution). Analysis of the base with
hydrochloric acid and extracted nitro tetracaine, lidocaine is the acid precipitating nitro (nitro tetracaine HCl solution). The reduction iron powder cocaine nitro group is
reduced to acid precipitation procaine.

Preparation procaine iron reduction by containing a large amount of mature technology, low equipment requirements, higher yield, but lower the purity, the product
remains in the process of iron and sul de ions, plasma, and the production process aromatic amines iron sludge and wastewater, serious environmental pollution and
equipment corrosion, and physical strength.

U.S. Patent No. (US3728376) reported the direct esteri cation method, catalytic hydrogenation was prepared procaine. Using a noble metal catalyst Pd / C direct
reduction of nitro cocaine base analysis. Reducing effect is good, high yield, less waste, recyclable solvent such as xylene. But Pd / C catalyst market more expensive,

https://patents.google.com/patent/CN1562961A/en?oq=CN+1562961 1/4
26/4/2018 CN1562961A - Method for preparing procaine - Google Patents
which limits its application in industrial production. And the process employed continuously added over 7 hours a solution of xylene nitro lidocaine autoclave, during the
addition operation with pressure increases the risk of operation and equipment requirements.

SUMMARY

The present invention overcomes the disadvantages of the prior art, there is provided a catalyst for cheap, low cost, easy to operate simple process, conversion and yield
and high purity preparation of procaine.

Mingpuluka present invention by the preparation method aspect comprises the steps of: (a) Ni-Al alloy was weighed, added portionwise successively temperature 55 ~
65 ℃ 1 ~ 1.5h time in a concentration of 18 to 20% after the NaOH solution, the addition was complete warmed to 85 ~ 95 ℃, and maintained for 2 ~ 3 hours discharge,
and then allowed to stand, the solution decanted, washed rst with 70 ~ 80 ℃, at room temperature and then washed with water until the PH value 8 ~ 9, to obtain Raney
nickel catalyst and preservation with absolute ethanol; (b) p-nitrobenzoic acid in ethanol as a raw material and diethylamino esteri cation nitro tetracaine in xylene
solvent; (c) Raney Nickel as catalyst, hydrogen as a reducing agent, reduction of the nitro tetracaine in xylene solvent, the hydrogen pressure is 2.0 ~ 3.0MPa, reaction
temperature is 80 ~ 130 ℃, the reaction time is 5 to 8 hours, and then the material was cooled, ltered through extraction , adjusting the PH value of the ltrate, the
precipitate was ltered and dried to give a solid procaine.

Step (c) is the wet weight of Raney nickel catalyst in an amount of 5 to 15% Nitro cocaine.

Compared with the prior art, the bene cial effects of the present invention are: good catalytic activity used in the present invention are cheap, easy to prepare the
activated and can be recycled or directly applied to remain in the reactor, the production cost can be greatly reduction; reduction according to the present invention is
implemented in a base resolution nitro tetracaine in xylene solution after the esteri cation, without the introduction of other solvents, eliminating the nitro acid was
precipitated by cocaine iron reduction step, and since without introducing ferric ions, so that greatly improved product quality, and without substantial aromatic amine-
containing waste water and sludge generating iron, process route is short, no waste; while the present invention uses a feeding mode, and does not require pressurized
operation, the operator more convenient; hydrogenation conversion of the present invention is 99.4% procaine purity 98%, yield of 83.5%.

detailed description

Example 1 was weighed 20g of nickel alloy, the material was added portionwise successively at a temperature of 60 ℃, 160mLNaOH concentration of 19% solution, the
addition, the temperature was raised to 90 ℃, and held 2.5 hours after the time of 1.2h , then allowed to stand, the solution decanted, washed twice with 75 deg.] C, and
then washed with water to pH 8.5 at room temperature, to obtain Raney nickel catalyst with absolute ethanol and stored.

In 500ml three-necked ask equipped with a stirrer, thermometer, water separator, were added 46.4g (0.278mol) p-nitrobenzoic acid, 150ml of xylene, 31g (0.264mol) N,
N- diethylethanolamine, heating re uxing. 19 h after the reaction was stopped, deg.] C cooling to about 60, transferred to a separatory funnel, of NaOH was added
solution preheated% to about 100 ml of 5 60 ℃, standing layer, the aqueous layer was discarded, to obtain a xylene solution of tetracaine nitro 184ml containing
tetracaine nitro 0.204mol, 73.4% yield (to p-nitro benzoic acid).

Nitro tetracaine obtained xylene solution 120mL, 130mL xylene and wet weight of 3.4g Raney nickel catalyst into a reactor, sealed and replaced with nitrogen three times,
three times replacement with hydrogen, heated to 80 deg.] C under stirring, hydrogen pressure 3.0MPa, 7H maintained, the temperature was cooled to 50 ℃, pressure
relief, the material; measured hydrogenation conversion was 92.6%, with a concentration of 10% hydrochloric acid solution ltrate was extracted aqueous layer, add
activated carbon 0.4g heated to 60 ℃, kept 10min, ltered; the ltrate was 10.0 to 10.5, the precipitate was ltered with saturated sodium carbonate solution was
adjusted to pH value, weighed and dried, to obtain 24.7 g of a light yellow solid procaine, yield 78.5% purity of 97.6%.

Example 2 The embodiment nitro lidocaine 120mL xylene solution obtained in Example 1, 130mL xylene, and Raney nickel catalyst was added 4.2g wet weight reactor,
sealed, maintaining the temperature 100 ℃, a hydrogen pressure of 3.0MPa, with other operations Example 1; measured hydrogenation conversion was 93.1%, pale
yellow solid procaine 24.9g, yield 79.2%, purity 97.8%.

Example 3 The nitro embodiment lidocaine 120mL xylene solution obtained in Example 1, 130mL xylene, and Raney nickel catalyst was added 1.8g wet weight reactor,
sealed, maintaining the temperature at 130. deg.] C, a hydrogen pressure of 2.0MPa, with other operations Example 1 measured hydrogenation conversion was 90.3%, to
obtain 24.5 g of a light yellow solid procaine, yield 77.8%, purity 97.6%.

Example 4 The xylene solution 120mL nitro lidocaine obtained in Example 1, 130mL xylene, and Raney nickel catalyst was added 1.8g wet weight reactor, sealed,
maintaining the temperature at 130. deg.] C, a hydrogen pressure of 2.5MPa, with other operations Example 1 measured hydrogenation conversion was 92.6%, to obtain
24.6 g of a light yellow solid procaine, yield 78.4%, purity 97.6%.

Example 5 The nitro lidocaine 120mL xylene solution obtained in Example 1, 130mL xylene, and Raney nickel catalyst was added 5.3g wet weight reactor, sealed,
maintaining the temperature at 130. deg.] C, a hydrogen pressure of 3.0MPa, embodiments with other operations Example 1, hydrogenation conversion was measured at
98.2 %% to give 26.3 g of a light yellow solid procaine, 83.5% yield, 98.0% purity.

Example 6 left reaction kettle catalyst in Example 1 obtained in Example 1 was added lidocaine nitro xylene solution 120mL and 130 mL of xylene, sealed embodiment,
other operations as in Example 5, hydrogenation conversion was measured 99.4%. Procaine pale yellow solid 27.4 g, 87.3% yield, 97.4% purity.

Cited By (1)

Publication number Priority date Publication date Assignee Title

CN101823928A * 2010-05-17 2010-09-08 无锡宏瑞生物医药科技 Clean production process for derivatives of para aminobenzoic acid by reactor
有限公司 coupled simulated moving bed

Family To Family Citations

* Cited by examiner, † Cited by third party, ‡ Family to family citation

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Priority And Related Applications

Priority Applications (1)

Application Priority date Filing date Title

CN 200410014538 2004-04-02 2004-04-02 Method for preparing procaine

Applications Claiming Priority (1)

Application Filing date Title

CN 200410014538 2004-04-02 Method for preparing procaine

Legal Events

Date Code Title Description

2005-01-12 C06 Publication

2005-03-09 C10 Request of examination as to substance

2005-12-28 C14 Granted

2009-06-03 C19 Lapse of patent right due to non-payment of the annual fee

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