US2046947A - Process for the production of diamino-alcohols of the aromatic series - Google Patents
Process for the production of diamino-alcohols of the aromatic series Download PDFInfo
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- US2046947A US2046947A US708517A US70851734A US2046947A US 2046947 A US2046947 A US 2046947A US 708517 A US708517 A US 708517A US 70851734 A US70851734 A US 70851734A US 2046947 A US2046947 A US 2046947A
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- methyl
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- diethylaminoethyl
- alcohols
- diamino
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/22—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
- C07C215/28—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
- C07C215/30—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
Definitions
- the present invention relates to a process for the production of diamino-alcohols of the arcmatic series of the type:
- R4 hydrogen or a hydrocarbon radicle.
- the pro-v duction of said diamino-alcohols is efiected by treating aliphatic aromatic compounds, having one or two oxygen atoms in the side chain, with diamines in which 1 nitrogen atom is in tertiary, and the other in primary or secondary combination, the resulting reaction products being -re-" Jerusalem if necessary.
- the operations are performed in the manner customary for the production of the monoamino alcohols, such as ephedrin.
- the monoamines 1- phenyl-2(methyl-(diethylammoethyl))-aminopropane-l-ol 2.
- an aliphatic-aromatic a-dioxide compound, of the type R.CO.CO.X (in which R denotes an aromatic radicle and X hydrogen or methyl) be caused to react with diamines containing one nitrogen atom in tertiary, and the other in primary, combination, water is split off and a condensation product is obtained which furnishes the desired diamino-alcohol on reduction.
- the double linkage of the azornethine is saturated by hydrogen and, at the same time, the keto-group is converted into a secondary-alcohol group. 7
- Phenylpropandione brought into reaction in the aforesaid case are replaced by diamines, so that amino-alcohols with 2 nitrogen atoms result.
- the procedure according to the present invention consists in introducing the diamine, either in compounds already possessing alcohol character, or else'in compounds containing keto-groups which are afterwards reduced to alcoholgroups.
- the two working stages maybe combined, if the condensation of the keto-alcohol with the diamine be effected in presence of reducing agents.
- EXAlVl'PLE 2 (1 p-Methoxy-w- (methyl- (diethylaminoethyl) AMINOETHYL) )-AMINOETHANE-1-0L
- p-methoacy-w- (methyl- (diethylaminoethyl) aminoacetophenone 18.5 grams of p-methoxy-w-chloracetophenone (Ber. deutsch.chem.Ges., 30 (1897), p. 1715) are distributed in 50 cc. of benzene and gradually treated with 26 grams of a-methylamino-p-diethylaminoethane.
- the salt is very sparingly soluble in acetone. It is crystallized from a mixture of acetone with a small amount of alcohol, and melts, with decomposition, at 170-471 C. Yield: 25 grams of dihydrochloride (71% of the theoretical).
- the liquid is 11- tered and acidified, the methanol being distilled off and the solution repeatedly extracted with ether in order to remove non-basic constituents.
- the new base is taken up with ether and fractionated under a good vacuum. Under a pressure of about 0.5-1 mm. the racemic 1-phenyl-2- (diethylaminoethyl)aminopropane-1-ol passes over at about 140 C.
- the very sparingly soluble oxalate (melting point 180-182 C.) being precipitated.
- the free base is regenerated from the oxalate by means of alkali, then neutralized with hydriodic acid, brought to dryness and recrystallized from isopropyl alcohol. It melts at FIG-178 C.
- the residue is taken up with dilute hydrochloric acid, the aqueous acid solution is extracted with ether, to remove non-basic constituents, and after being rendered strongly alkaline with caustic potash, is again repeatedly extracted with ether.
- the liquid After the ether has been distilled oif, the liquid is heated at 100 C. for 1 hour with a threefold quantity of hydrobromic acid saturated at 0 C. When the liquid has cooled down, it is rendered alkaline, and the liberated base is fractionated in vacuo.
- the constituent passing over at 130- 135 C., under a pressure of about 1 mm., represents the desired racemic I-phenyl-Z-(methyl- (diethylaminoethyl) -aminopropane-1-ol.
- R denotes one element of the group consisting of phenyl and mono methoxy phenyl
- X one element of the group consisting of hydrogen and methyl
- R5 represents one element of the group consisting of hydrogen and methyl and subjecting the diamino-ketones thus obtained to a reduction.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Patented July 7, 1933 UNITED" STATES PATENT OFFICE PROCESS FOR THE PRODUCTION OF DI-' AMINO -ALCOHOLS SERIES OF THE AROMATIC Gustav Heilner, Berlin-Fichtengrund, Post Friedrichsthal, Germany,
assignor to Chemische Fabriken Dr. Joachim Wiernik & (30., Aktiengesellschaft, Berlin-Waidmannslust Germany No Drawing. Application January 26, 1934, Serial No. 708,517. In Germany February 1, 1933 1 Claim.
The present invention relates to a process for the production of diamino-alcohols of the arcmatic series of the type:
in whichRi denotes an aromatic radicle, R2 hydrogen or methyl, R3 a diaminoalkyl radicle and C H C O-CHB1'CH:+2CH:NHCHz-CH:N(CZH5):)
u-bromopropiophenone 1 methylamino 2 diethylamino ethane CHa N 1-phenyl-2-(metby1-(diethylaminoethyl-aminopropane-l-one.
l-phenyl-2-(methyl-(diethylaminoethyl))-aminopropane-l-one.
R4 hydrogen or a hydrocarbon radicle. The pro-v duction of said diamino-alcohols is efiected by treating aliphatic aromatic compounds, having one or two oxygen atoms in the side chain, with diamines in which 1 nitrogen atom is in tertiary, and the other in primary or secondary combination, the resulting reaction products being -re-" duced if necessary.
The operations are performed in the manner customary for the production of the monoamino alcohols, such as ephedrin. According to the present invention however, the monoamines 1- phenyl-2(methyl-(diethylammoethyl))-aminopropane-l-ol 2. If an aliphatic-aromatic a-dioxide compound, of the type R.CO.CO.X (in which R denotes an aromatic radicle and X hydrogen or methyl) be caused to react with diamines containing one nitrogen atom in tertiary, and the other in primary, combination, water is split off and a condensation product is obtained which furnishes the desired diamino-alcohol on reduction. In this reduction, the double linkage of the azornethine is saturated by hydrogen and, at the same time, the keto-group is converted into a secondary-alcohol group. 7
Phenylpropandione brought into reaction in the aforesaid case are replaced by diamines, so that amino-alcohols with 2 nitrogen atoms result.
The procedure according to the present invention, consists in introducing the diamine, either in compounds already possessing alcohol character, or else'in compounds containing keto-groups which are afterwards reduced to alcoholgroups.
lamino-24iethylamino-ethane These two processes can also be performed in a single Working stage, by effecting the condensation in the presence of reducing agents CoHsC 0-C OCH3+NH2C H2OHzN(C2H5)2 Phenylpropandione. l-amino-2-diethylaminoethane EXAMPLE I' RACEMIC l-PHENYL-Z- (METHYL- (DiETHYLAMINO- ETHYL) )-AMINOPROPANE-1-OL (1) 1 -phenyZ-2- (methyl- (diethylaminoethyl) aminopropanone A solution of 21.3 grams of u-bromopropiophenone in 50 cc. of ether is treated with 26 grams of a methylamine p diethylaminoethane, accompanied by cooling. The precipitation of a-meth'yL amino-fi-diethylaminoethane-hydrobromide commences after a short time. After leaving the mixture at rest for several hours in the cold, the reaction is completed by gentle heating. The precipitated salt is separated by filtration, and the oily'residue is distilled in vacuo. Under a pressure of about 1 mm. the 1-pheny1-2-(methyl-(diethyl- Phenylpropanolone.
1-phenyl-2-(diethylaminoethyl)-aminopropane-l-ol In this case also, the two working stages maybe combined, if the condensation of the keto-alcohol with the diamine be effected in presence of reducing agents.
Phenylpropanolone I-aminQ-Z'dicthylaminoethane 4. If I a fatty-aromatic halogenalcohol R.CH(OI-I)'.'CH (halogen) X (in which R denotes an aromatic radicle, and X hydrogen or methyl) be caused to react with diamines containing l'nitrogen atom in tertiary combination, the desired diamino-alcohol will be formed.
In such case','however, it is preferable to start, not with halogen-alcohols, but with the corresponding ethers, the ether being subsequently split up. V c
aminoethyl))-aminopropanone passes over at 132-13 4 0., as a yellowish oil, which darkens on being lefte'xposed in the air. The yield of pure product is zi'gmms (i. e. about of theory).
(2) Racemic 1 phenyZ-Z-(methyl (diethylaminoethyl) -aminopropane-1-ol A solution of 13.1 grams of the keto-base, (obtained as in 1) in the calculated quantity of dilute aqueous hydrochloric acid, is treated with 25 grams of a palladium and barium sulphate catalyst, containing 0.5 grams of metallic palladium, and agitated in presence of hydrogen. After the calculated amount of hydrogen has been absorbed, the catalyst is filtered ofi" and the reducl-methylamino-2 diethylaminoethane.
CHr-CHr-N(C2H5)2 1-phenyl1-methoxy-2- (methyl- (diethylaminoethyl) -aminopropane.
1-phenyl-2-(methyl-(diethylaminoethyl))-an1inopropane-l-ol- I hydrobromide The resulting products possess valuable therapeutic properties, and are intended for the treatment of asthma.
ti'on prpauais set free by addition of alkali.
Under apressure of 1.5-2 mm; the racemic 1- phnyI-Z- (methyl- (diethylaminoethyl) aminopropane-l-ol boils at 140-141" C. An almost theoretical yield is obtained. The dihydrochlorlde obtained by precipitating the ethereal solution of the base with ethereal hydrochloric acid, is a hygroscopic crystalline mass. Analysis showed 20.8 of chlorine (theory 21.04% Cl).
EXAlVl'PLE 2 (1 p-Methoxy-w- (methyl- (diethylaminoethyl) AMINOETHYL) )-AMINOETHANE-1-0L (1) p-methoacy-w- (methyl- (diethylaminoethyl) aminoacetophenone 18.5 grams of p-methoxy-w-chloracetophenone (Ber. deutsch.chem.Ges., 30 (1897), p. 1715) are distributed in 50 cc. of benzene and gradually treated with 26 grams of a-methylamino-p-diethylaminoethane. Spontaneous heating, tempered by intermittent cooling, occurs, the halogenketone passing into solution, whilst a-methylamino-p-diethylaminoethane hydrochloride is precipitated. After standing for several hours at room temperature, followed by a brief moderate heating, the reaction mixture is agitated with water, whereupon the precipitated salt redissolves. The benzene solution is freed from the solvent in vacuo', the residue is taken up with acetone and treated with ethereal hydrochloric acid until the reaction solution is acid to Congo solution as indicator. The dihydrochloride of the methoxy-w- (methyl-diethylaminoethyl) aminoacetophenone thereupon separates as a rapidly solidifying oil. The salt is very sparingly soluble in acetone. It is crystallized from a mixture of acetone with a small amount of alcohol, and melts, with decomposition, at 170-471 C. Yield: 25 grams of dihydrochloride (71% of the theoretical).
(2) 1 (methozcyphenyl) -2- (methyl (diethylaminoethyl) -aminoethane-1 -Z 20 grams of the dihydrochloride obtained in 1, are dissolved in water and agitated with hydrogen, under a slight positive pressure, in presence of palladinized charcoal. After the theoretical amount of hydrogen has been absorbed, the catalyst is filtered off, the liquid being rendered alkaline and extracted with ether, and the extraction residue distilled in vacuo. The l- (p-methoxyphenyl) -2- (methyl- (diethylaminoethyl))-aminoethane-1-ol passes over at 185- 190 C. (pressure mm.). The dihydrochloride melts at 158160 C.
EXAMPLE 3 I'PHENYL- (DIETHYLAMINOETHYL) 'AMINOPM PANE-l-OL 23.2 grams of 1-amino-2-diethylaminoethane (Berichte, 29, p. 2526) in 100 cc. of methyl alcohol are mixed with a solution of 6.4 grams of sulphurous acid in 150 cc. of methyl alcohol, 20 grams of zinc dust being added and the whole actively stirred. The mixture is heated to boiling, under a reflux condenser. In the course of about 2 hours, 20 grams of phenylpropandione, dissolved in 100 cc. of methanol, are dropped in, 11 grams of sulphurous acid in 170 cc. of water, and a further 20 grams of zinc dust being added at the same time.
When reduction is complete, the liquid is 11- tered and acidified, the methanol being distilled off and the solution repeatedly extracted with ether in order to remove non-basic constituents. After the solution has been rendered alkaline, the new base is taken up with ether and fractionated under a good vacuum. Under a pressure of about 0.5-1 mm. the racemic 1-phenyl-2- (diethylaminoethyl)aminopropane-1-ol passes over at about 140 C. For further purification it is taken up with alcohol and treated with alcoholic oxalic acid, the very sparingly soluble oxalate (melting point 180-182 C.) being precipitated. In order to prepare the dihydroiodide, the free base is regenerated from the oxalate by means of alkali, then neutralized with hydriodic acid, brought to dryness and recrystallized from isopropyl alcohol. It melts at FIG-178 C.
EXAMPLE 4 1-PHENYL-2- (DIETHYLAMINOETEYL) -AMINO- PROPANE-L01.
15 grams of phenylpropanolone in 30 cc. of ether are treated with 12 grams of l-amino-2- diethylaminoethane, and the whole is warmed under the reflux condenser for a short time. A condensation product with the character of an azomethine is formed, which can be subjected to reduction without further purification. After addition of palladium catalyst, the ethereal solution is agitated with hydrogen under pressure until the calculated amount of hydrogen has been absorbed. The reduction is then stopped, the catalyst filtered off, and the solution rendered alkaline in order to remove non-basic constituents. The further treatment is performed in the same manner as set forth in Example 3.
EXAMPLE 5 1-PHENYL- METHYL- (DIETHYLAMINOETHYL) AMINOPROPANE-l-OL 23 grams of 1-phenyl-l-methoxy-2-bromopropane (Berichte, 58 (1925) pp. 1260-1270) and 26 grams of 1-methylamino-2-diethylaminoethane are left in contact for a short time, being then gradually heated and maintained for several hours at 100 C. The reaction mixture is diluted with ether, separated from the precipitated 1- methylamino-2-diethylamino-ethane hydrobromide, and the ether is distilled off. The residue is taken up with dilute hydrochloric acid, the aqueous acid solution is extracted with ether, to remove non-basic constituents, and after being rendered strongly alkaline with caustic potash, is again repeatedly extracted with ether. After the ether has been distilled oif, the liquid is heated at 100 C. for 1 hour with a threefold quantity of hydrobromic acid saturated at 0 C. When the liquid has cooled down, it is rendered alkaline, and the liberated base is fractionated in vacuo. The constituent passing over at 130- 135 C., under a pressure of about 1 mm., represents the desired racemic I-phenyl-Z-(methyl- (diethylaminoethyl) -aminopropane-1-ol.
What I claim and desire to secure by Letters Patent of the United States is:
The process which consists in causing fattyaromatic halogen ketones of the type:
in which R denotes one element of the group consisting of phenyl and mono methoxy phenyl, X one element of the group consisting of hydrogen and methyl, to react with wherein R5 represents one element of the group consisting of hydrogen and methyl and subjecting the diamino-ketones thus obtained to a reduction.
GUSTAV HEILNER.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE431786X | 1933-01-12 | ||
| DEC47477D DE629699C (en) | 1933-01-12 | 1933-02-02 | Process for the preparation of benzene series diamino alcohols |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2046947A true US2046947A (en) | 1936-07-07 |
Family
ID=25926314
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US708517A Expired - Lifetime US2046947A (en) | 1933-01-12 | 1934-01-26 | Process for the production of diamino-alcohols of the aromatic series |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US2046947A (en) |
| DE (1) | DE629699C (en) |
| FR (1) | FR781017A (en) |
| GB (3) | GB431848A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5250546A (en) * | 1984-09-28 | 1993-10-05 | Nippon Chemiphar Co., Ltd. | Amino-alcohol derivatives and processes for their preparation |
-
1933
- 1933-02-02 DE DEC47477D patent/DE629699C/en not_active Expired
-
1934
- 1934-01-12 FR FR781017D patent/FR781017A/en not_active Expired
- 1934-01-12 GB GB10001/35A patent/GB431848A/en not_active Expired
- 1934-01-12 GB GB1171/34A patent/GB431786A/en not_active Expired
- 1934-01-26 US US708517A patent/US2046947A/en not_active Expired - Lifetime
-
1936
- 1936-08-05 GB GB21574/36A patent/GB461866A/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5250546A (en) * | 1984-09-28 | 1993-10-05 | Nippon Chemiphar Co., Ltd. | Amino-alcohol derivatives and processes for their preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| GB431848A (en) | 1935-07-12 |
| GB461866A (en) | 1937-02-25 |
| DE629699C (en) | 1936-05-09 |
| GB431786A (en) | 1935-07-12 |
| FR781017A (en) | 1935-05-08 |
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