DE1115239B - Process for the production of acetylenically unsaturated ethanolamines - Google Patents

Description

The invention relates to a method of manufacture acetylenically unsaturated ethanolamines of the following structural formula:

R ₅ R ₇

R ₃ -N

C- R ₄ R ₂ C- -C-OH R ₆ -C-CR

In the above formula, R ₁ , R ₂ and R ₄ to R _{7 are} hydrogen or alkyl groups, aryl groups, alkaryl groups or aralkyl groups, where either R ₁ or R _{2 is} hydrogen. R ₃ represents an alkyl, aryl, alkaryl, aralkyl or oxyalkyl group.

R ₈ denotes hydrogen or an alkyl, alkenyl, aryl, aralkyl, alkaryl group or an oxyalkyl group.

The new compounds are made by reacting a compound that has an acetylene bond and contains at least one active hydrogen atom, made with an oxazolidine. This implementation is proceeding according to the following equation:

R ₆

Method of manufacture
acetylenically unsaturated ethanolamines

Applicant:

Miles Laboratories, Inc.,
Elkhart, Ind. (V. St. A.)

Representative: E. Maemecke, Berlin-Lichterfelde West, and Dr. W. Kühl, Hamburg 36, Esplanade 36 a,

Patent attorneys

Claimed priority:
V. St. v. America July 18, 1957 (No. 672 571)

Willard Joseph Croxall, Elkhart, Ind. (V. St. A.),
has been named as the inventor

C-C = CRo

where the R substituents have the above meanings.

In general, the reaction conditions for this reaction are as follows:

The respective oxazolidine is in a suitable solvent, preferably dioxane or dimethylformamide, dissolved, with dimethylformamide being preferred. Although the response even in the absence of one Solvent, it has been found to be smoother and better under control can hold when working with a solvent. The amount of solvent depends up to to some extent on the equipment used. In general, however, one works with about 1 to 5 parts of solvent per part of the oxazolidine. If you use dioxane as a solvent, it works one preferably with 2 to 3 parts of dioxane per part of the oxazolidine. If one uses dimethylformamide as Solvent, it is preferably used with 1 to 5 parts of the same per part of the oxazolidine.

The reaction is exothermic and is preferably carried out at temperatures ranging from about 0 to 60 ° C. A preferred temperature range is between 5 and 10 ^0. C. These temperature limits, however, are not critical. However, the reaction can be guided by suitable temperature control.
The reactions according to the invention can be carried out within a wide pressure range from underpressure to overpressure. There also seems to be some relationship between the speed and

109 709/418

3 4

the smooth course of the reaction and the pressure as well as the formation of salts, of quaternary ammonia

exist; However, this is not yet fully ammonium compounds.

clarified. The reactions usually proceed smoothly.
Hg, with overpressures of 203 to 254 mm preferred 5 The acetylenically unsaturated ethanolamines are measured according to the invention are also considered pharmacological

Since the acetylene compound usually gaseous means utilizable. Some derivatives, especially the

if gases such as nitrogen and other hydrochlorides are used, they have soporific and calming

inert gases used as diluents to avoid explosive effects when administered to animals

or overloading with the acetylene compound 10 The compounds according to the invention are also

to avoid. valuable hardeners and can be used to harden

One of the essential features of the invention of epoxy resins and other resinous substances

proper implementations is the presence of this type use.
Cuproions. These cuproions form with the

Acetylene compound a catalytically active copper Example 1

complex connection. As a source of the cuprous ions N-isobutyl-N- (propin-2-yl) -ethanolamine

can serve any cupro salt, which in the React _TT . ,. ",. ,, ....

tion mixture with elimination of the necessary reaction of acetylene with 3-isobutyloxazolidm

Cuproionen dissociated, e.g. B. Cuprochlorid, Cupro- Ein with stirrer, inlet pipe for acetylene and

sulfate. 20 one to an open U-tube mercury manometer

When the oxazolidine in the solvent became attached to the 1-1 flask

Solution has gone, the cuprous ions are present with 109 g of 3-isobutyloxazolidine, 250 ecm of dioxane and

and charged temperature and pressure to the desired 5 g of powdered cuprous chloride. The GE-

Values are set, the acetylene mixture is passed through, stirring was carried out and acetylene was added

bond is introduced into the reaction 25 50 to 75 mm Hg overpressure with stirring. During the

mix in until the desired amount is added. Introducing the acetylene was the temperature by means of

Normally a glowing ice bath is formed during this process, kept at around 20 to 25 ° C. Within

colored precipitate of the copper-acetylene complex - 2 hours a total of 20 g of acetylene were absorbed,

link. This is from the reaction mixture The catalyst was from the reaction mixture

filtered off. Sulfur is then preferably filtered off and the dioxane is filtered off under reduced pressure

hydrogen through the reaction mixture, around which is distilled off and the residue is fractionated. There were

to precipitate permanent cuproions. Of course, 59 g of product can be obtained; Bp _{0) 7 mm} = 59 ^° C; Refractive

Lich also use other known methods to index nf = 1.4545. The non-aqueous titration showed

to bind the excess of cuprous ions and to ensure that 98.8% ^{of the product consists of} N-isobutyl-N- (propyne-

distant. After removing the remaining cupro-35 2-yl) -ethanolamine,

ions is the solvent from the reaction.

mixture distilled off. After the solvent, example 2

the product ab- N-tert-butyl-N- (propyn-2-yl) -ethanolamine at a certain temperature

distilled, which is usually located within a loading A flask was filled with 65 g of 3-tert-butyl oxazolidine,

changes from no more than 2 to 10 ° C. The full 40 200 ecm of dimethylformamide and 5 g of cuprous chloride

Continuous work-up then takes place on the per se loaded. Over the course of 6 hours,

Known type, e.g. by redistillation, at 15 to 25 ° C 16 g of acetylene are introduced. The mixture

crystallize, etc. The product is not treated with hydrogen sulfide, charcoal and a

Treated aqueous titration, hydrogenation to control the filter aid and filtered. From the

Amount of hydrogen absorbed and after 45 filtrate, the dimethylformamide was removed by distillation

other methods known per se analyzed. tion on the water jet pump removed; the return

For the acetylenically unsuitable according to the invention, 41 g of N-tert-butyl-

Saturated ethanolamines there are a large number of N- (propin-2-yl) -ethanolamine; Kp. _{0, 24} mm = 63 to

Applications, both technical and 70 ° C. Redistillation was a material

also pharmacological applications. The compound 50 obtained, which has a boiling point of 15 mm Hg

fertilizers are possessed to produce a large number of 98 to 101 ° C. This material showed in the

Technically valuable compounds can be used since they were 97.3% pure and possessed by non-aqueous titration

three strongly reactive groups in the molecule have a refractive index »ff = 1.4665.
keep. Both the acetylene group and the

The amino group and the hydroxyl group can be compared with Example 3

various reactants in for this N-tert.Butyl-N- (l-n-propyl-propyn-2-yl) -ethanolamine

classical reactions known per se r ij rr

implemented. A flask was filled with 86 g of 2-n-propyl-3-tert.butyl-

If z. B. R ₈ in the above formula is hydrogen, oxazolidine, 200 ecm dimethylformamide and 10 g

so you can load with the acetylenically unsaturated 60 cuprous chloride. In the mixture was under

Ethanolamines initiated all classic reactions of stirring acetylene. In the course of 3 hours

Run acetylene, such as B. the ethynylation, the 8.5 g were absorbed, whereupon another 100 ecm

Vinylation, carbonylation and the like. If R _{8 is} an orga- Dimethylformamide has been added and again

A radical radical, such as methyl, ethyl, propyl, acetylene can be introduced. The mixture then took off

addition reactions with the compounds, such as the 65 in the course of 5 hours a further 7.5 g of acetylene,

Halogenation, hydrogenation, perform. Desired - a total of 16 g of acetylene on. The copper catalyst

if you can with the connections also the sator was filtered off and the remaining copper out

carry out classic reactions of tertiary amines, the filtrate by introducing hydrogen sulfide,

Addition of filter aids and filtration removed. After the dimethylformamide had been completely distilled off using the water jet pump, a solid separated out in the still. This was filtered off, washed with a petroleum hydrocarbon solvent, and the washing liquid was combined with the filtrate. The solvent was distilled off from the filtrate, and the residue gave 28.5 g of N-tert-butyl-N- (in-propyl-propyn-2-yl) -ethanolamine during the distillation; Kp _0, s = 80 mm ° to 83 ° C., a content of the material of the above compound of 101% was determined by non-aqueous titration. the refractive index was n ² i = 1.4635.

Example 4 N-tert-Butyl-N- (propyn-2-yl) -j9-phenylethanolamine

A flask was charged with 77 g of 3-tert-butyl-5-ph.enyloxazolidine, 250 ml of dimethylformamide and 5 g of cuprous chloride. Acetylene was passed in at room temperature over the course of 8 hours. A total of 17 g of acetylene was absorbed. The mixture was worked up in the usual manner and yielded 50 g on distillation; Bp. ₀ , _{aB mm} = 130 ⁰ C. The purity of the product
n% ⁵ = 1.5185.

Example 5 N-Benzyl-N- (propyn-2-yl) -ethanolamine

A. Reaction of 3-benzyloxazolidine with acetylene at room temperature

A flask equipped as in Example 1 was charged with 83 g of 3-benzyloxazolidine, 200 ecm of dioxane and 5 g of cuprous chloride. Acetylene was passed into this mixture at 20 to 30 ^{° C.} 15 g of acetylene were absorbed within 3 hours. The mixture was left to stand for about 2 days, then the catalyst was filtered off, the dioxane was distilled off under reduced pressure and the residue was distilled. 54 g of product (bp. _{1> 5} mm = 124 ^° C.) and 20 g of a higher-boiling material [bp. _{li5 mm} = 124 to 150 ° C (decomposition)].

ίο The product obtained as the first fraction turned out to be according to a non-aqueous titration as N-benzyl-N- (propin-2-yl) -ethanolamine.

This compound, a base in liquid form, was effective when administered intraperitoneally to mice a sleep effect of short duration is produced (W. R. 7-4-56). It therefore became the hydrochloride of these Compound and tested for efficacy when administered intravenously. The salt was obtained as a 9.18% strength aqueous solution. The test results were as follows:

(a) Acute intraperitoneal toxicity to mice

was 96.3%> the refractive index

effect Hyp
nose IP YOU mortality Be Sub- 5/5 dose 0.5 * quiet
supply hyp-
nose 5/5 mg / kg 0.5 * Time
(Number of mice) 5/5 5/5 5/5 577 5/5 * 5/5 5/5 5/5 751 5/5 * 5/5 5/5 976 20 minutes (5) 5/5 5/5 1269 10 minutes (5)

7/30/56 A-LD ₅₀ = 856 mg / kg (5/20 MauIP; 28 g).

b) Acute oral toxicity to rats

Subhypnosis effect TP
Vo I Mon 0/5 Oral YOU mortality Reassurance 0/5 hypnosis 0/5 0/5 dose
mg / kg 0/5 Time
(Number of rats) 0/5 1/5 0/5 0/5 5/5 400 0/5 4/5 5/5 0/5 5/5 5/5 600 0/5 5/5 5/5 5/5 5/5 5/5 900 0/5 5/5 5/5 5/5 5/5 5/5 1350 0/5 5/5 5/5 5/5 5/5 2025 4/5 * 5/5 5/5 3040 (5/5) * 12 minutes (4) 4550 Accepted

7/30/56 A-LD ₅₀ = 2690-219 SD mg / kg (5/30 RatOR; 111-20 g), 48.5 SE mg / kg.

At non-lethal doses, all rats were euthanized within 10 minutes and recovered within 30 minutes. It should be noted that numbness occurred in the rats at a dose of 900 mg / kg. The estimated oral dose sufficient for anesthesia (Anas D 50) is 735 mg / kg or 27% A-LD ₆₀ (RatOR).

B. Reaction of 3-benzyloxazolidine with acetylene at low temperature

83 g of 3-benzyloxazolidine, 200 ecm of dioxane and 5 g of cuprous chloride were placed in a 1-1 flask equipped according to Example 2. The mixture was cooled to about 10 ° C. in an ice bath, and acetylene was passed in at this temperature. 16 g of acetylene were absorbed over the course of 5 hours. The catalyst was then filtered off, the dioxane was distilled off under reduced pressure and the product was distilled. 68.5 g of product were obtained; Bp.j., 5 _mm = 124 to 128 ° C.

C. Reaction of acetylene with 3-benzyloxazolidine g using acetone as solvent

83 g of 3-benzyloxazolidine, 250 ecm of acetone and 5 g of cuprous chloride were placed in a device according to Example 1 1-1 flask abandoned. Before initiating

of the acetylene, the reaction mixture was cooled in an ice bath, whereupon 15 g Acetylene were added. The catalyst was filtered off, the acetone under reduced pressure Distilled off pressure and the product distilled. The yield was 41 g.

D. Reaction of acetylene with 3-benzyloxazolidine

using dimethylformamide

as a solvent

A flask was charged with 87 g of 3-benzyloxazolidine, 250 ml of dimethylformamide and 5 g of cuprous chloride. Acetylene was passed into this mixture under a pressure of 76 to 152 mm Hg with rapid stirring. The temperature was kept between 5 and 10 ^° C. There was an extremely rapid uptake of acetylene, and after 1 hour the mixture had taken up 22 g of acetylene. A filter aid was then added to the mixture, the mixture was filtered and the filter cake was washed with a small amount of acetone. The filtrate was treated with hydrogen sulfide, added with charcoal and then filtered again to remove the charcoal and copper sulfide. A clear, colorless filtrate was obtained, from which acetone and dimethylformamide were distilled off under reduced pressure. The high boiling point was then distilled to give 82 g of product; Kp. _{0, 25mm} = 106 to 110 ⁰ C. Yield = 82% of theory.

E. Reaction of acetylene with 3-benzyloxazolidine; Removal of the catalyst with hydrogen sulfide

35

A 1-1 flask equipped according to Example 2 was charged with 83 g of 3-benzyloxazolidine, 200 ecm of dioxane and 5 g of cuprous chloride. The mixture was cooled in an ice bath to about 10 ⁰ C and it was introduced for 4 hours at 5 to 10 ° C acetylene. Then the mixture was left to stand at room temperature overnight. 15.5 g of acetylene were absorbed. The catalyst was filtered off through a bed of filter aid. The catalyst cake was washed out with dioxane, the washing liquid was combined with the filtrate and copper sulfide was precipitated from the filtrate with hydrogen sulfide. The copper sulfide was filtered off. However, the filtrate was not clear. Therefore, more hydrogen sulfide was introduced, activated charcoal was added and filtered again. A light orange-colored filtrate was obtained. The dioxane was distilled off under reduced pressure and 70 g of product were obtained from the residue by distillation; Kp. _{0, 27} mm = 104 to 106 g. No decomposition occurred during this distillation.

Example 6

N-Benzyl-N- (1-phenyl-propyn-2-yl) -ethanolamine
Reaction of acetylene with 2-phenyl

3-benzyloxazolidine

This reaction was carried out according to Example 1 using 119 g of 2-phenyl-3-benzyloxazolidine, 250 ecm of dioxane, 10 g of cuprous chloride and 12 g of acetylene. After the batch had been worked up in the usual manner, 75 g of product were obtained; Kp _{0, 25} mm = 151 to 155 ° C. n ² i = 1.5695. This product showed the following pharmacological effects:

effect Ataxia Pseudo cramps IP YOU mortality do-
hyp-
nose dose
mg / kg 0/5 - - 100 0/5 Time
(Number of mice) - - - 372 0/5 - - - 629 0/5 - - - 818 2/5 { - 1063 1/5 - - 1382 1/5 10 minutes (1)
24 hours (1) - - - 1797 2/5 10 minutes (1) - 4/5 2/5 2326 3/5 10 minutes (1) - 4/5 5/5 3024 5/5 30 minutes (2) 3913 30 minutes (3) 10 minutes (5)

7/23/56 A-LD ₅₀ = 2576-311 SD mg / kg (5/40 MauIP; 23.9 g) 68 SE mg / kg.

Example 7
N-Benzyl-N- (In-propyl-propyn-2-yl) -ethanolamine

Implementation of 2-n-propyl-3-benzyloxazolidine
with acetylene

Following the procedure of Example 4, 95 g of the desired product were obtained from 103 g of the oxazolidine, 200 ecm of dioxane, 10 g of cuprous chloride and 15 g of acetylene; Kp = _3mm 115 to 117 ⁰ C. «Ff = 1.5155. This compound showed the following pharmacological effects:

effect Be
quiet
supply Sub-
hyp-
nose Hyp
nose IP YOU mortality 5/5
5/5 5/5
5/5
5/5 3/5
3/5
5/5 dose
mg / kg 0/5
1/5 *
1/5 * Time
(Number of mice) - 5/5 5/5 1063
1382
1797 5/5 * 48 hours (1)
24 hours (1) - 5/5 5/5 2326 4/5 * { 3 hours (2)
24 hours (2)
48 hours (1) 3024 3 hours (2)
24 hours (2)

7/30/56 AOLD ₅₀ = 1877-216SD mg / kg (5/25 MauIP; 27.7 g). 48 SE mg / kg.

Example 8
N-oxyethyl-N- (l-ethyl-propyn-2-yl) -ethanolamine

One with stirrer, gas inlet pipe, gas outlet with connection to an open mercury manometer and A flask equipped with a thermometer was filled with 143 g of 3-uS-oxyethyl) -2-ethyloxazolidine, 350 ecm of dimethylformamide and 8 g cuprous chloride charged. The mixture was cooled to 3 ° C with stirring, and after Acetylene purging was initiated at a temperature of -3 to 4 ° C over 4 hours with acetylene. A total of 24 g of acetylene was absorbed. The copper catalyst was filtered off and that Dilute the filtrate with 500 ecm acetone and add hydrogen sulfide saturated. The copper sulfide was filtered off and the acetone and dimethylformamide out the filtrate is distilled off at the water jet pump.

9 10

When distilling the residue in vacuo, left to stand overnight. It was done in the usual way

85 g of N-oxyethyl-N- (l-ethyl-propyn-2-yl) -ätha- were worked up. After the dioxane has been distilled off

get nolamine; Kp _ll3 mm = 122 to 128 ⁰ C. nff at the water jet pump delivered the distillation of the

= 1.4895. A non-aqueous titration gave a residue 65 g of N-isopropyl-N- (4-oxy-4-methyl-

Value of 102.8% ⁵ hexyn-2-yl) ethanolamine. According to this material possessed

D _e ; _c _.i _a i ο a non-aqueous titration a purity of

N-Benzyl-N- (4-oxy-4-methyl-hexin-2-yl) -ethanolamine ' ^{/ 0} ' ° '

In a similar experiment, the piston was marked with ^ _TT , _ _T ",. ,. ,. . ",,
48 g of 3-benzyloxazolidine, 200 ecm of dioxane and 5 g of 10 N-isopropyl-N- [3- (2-cyclohexanol) -propm-2-yl] -

Cuprous chloride charged. Then at 35 ⁰ C 25 g of atnanolamm were

Methyläthyläthinylcarbinol added. The Mixture In a similar experiment, a flask was made with

was stirred for 2 hours and then left to stand overnight - 85 g of 3-isopropyloxazolidine, 200 ecm of dioxane and 5 g

calmly. Hydrogen sulfide was then added and cuprous chloride was charged. Then the drip line turned Added charcoal and filtered. The dioxane 15 funnel with stirring a solution of 62 g ethynyl

was added to the water jet pump under reduced cyclohexanol in 20 ecm of dioxane. The addition

Distilled off pressure, and the residue provided in the case of the solution of ethynylcyclohexanol lasted 20 Mi-

Distillation 54g product; bp _{0, 2e} mm = 175bisl80 ° C. with a maximum temperature of 38 ° C

This material consisted of a non-aqueous range. The mixture was stirred for 2 ¹ ₂ hours I titration to be 99.8% ^of N-benzyl-N- (4-oxy-4-methyl-20 and then worked up in the usual manner.

hexin-2-yl) ethanolamine; n% ⁵ - 1.5366. 65 g of N-isopropyl-N- [3- (2-cyclohexanol) -

_. . . propin-2-yl] ethanolamine; Kp. _0j5mm = 158 ⁰ C. The

Example iu refractive index of the product was raf = 1.5057

N-Benzyl-N- (heptin-2-yl) -ethanolamine _and the purity according to a non-aqueous titration

A with stirrer, thermometer, dropping funnel and 25 99%
1-1 three-necked flask equipped with a reflux condenser.
was with 86 g of 3-benzyloxazolidine, 250 ecm of dioxane Example 14
and charged 5 g of cuprous chloride. Then in the N-isopropyl-N- (4-oxy-4-methyl-hexin-2-yl) process of 20 minutes, 46 g of n-butylacetylene were added ethanolamine
puts. When the butyl acetylene was added, a 30 A reaction with a reflux condenser, dropping funnel, stirrer and a slightly exothermic reaction took place. The reaction thermometer equipped 1-1 flask was charged with mixture was stirred for 5 hours, overnight stand- 60 g of 3-isopropyloxazolidin and 200 cc dioxane begelassen, then heated to 5O ⁰ C and sends a further 60 STUN and the mixture to 70 ⁰ C heated. Then the stirring at 40 to 50 ⁰ C. It was then filtered, and 50 g of methylethylethinylcarbinol were added. The filtrate was treated with hydrogen sulfide, and the filter was used without a catalyst. Auxiliaries were added to the mixture and filtered again. The dioxane was kept 7 hours to 75 to 8O ⁰ C, then was cooled from the filtrate of the water jet pump and distilled. Only isopropyl was distilled off, and the residue yielded 86 g of N-benzyl-N- (heptin-2-yl) -ethanol- in the oxazolidine, dioxane and methylethylethinylcarbinol distillation. A higher boiling product had amine; n% ⁵ = 1.5202. The purity of the product 40 not formed,
was 97% · Example 15 by non-aqueous titration

Example 11 N-Isopropyl-N- (butyn-2-yl) -ethanolamine

N-Isopropyl-N- (propin-2-yl) -ethanolamine _{Hn Kolh} ^ _{as he for the reactions} ^

Reaction of acetylene with 3-isopropyloxazolidine ₄₅ acetylene had been used with 60 g

A flask was charged with 77.5 grams of 3-isopropyloxazolidine, 3-isopropyloxazolidine, 250 cubic centimeters of dioxane, and 5 grams of 200 cubic centimeters of dioxane and 5 grams of cuprous chloride. Cuprous chloride charged. In this mixture was Upon initiation of acetylene in this mixture at 25 to 30 ° C in the course of 10 hours of a 10 to 20 ⁰ C in the course of 8 hours, 17 g reservoir methylacetylene (propyne-1) were initiated at, (theoretical 19 g) absorbed. The catalyst became 50 with 34 g of methyl acetylene being absorbed. The filtered off, the filtrate saturated with hydrogen sulfide catalyst was filtered off and the filtrate in and with activated charcoal was added and the mixture was filtered. treated with hydrogen sulphide in the usual way. The dioxane was distilled off in vacuo and the water product after distilling off the dioxane was distilled off in vacuo. 46.5 g of a jet pump were obtained, distillation of the residue yielded the desired product; _{B.p. iem} m = 96 to 55 of the 63 g of N-isopropyl-N- (butin-2-yl) -ethanolamine; 98 ° C. A higher boiling fraction (.. _{Mm ll5} Kp = Kp _0j6 64 _mm = 64 °; nf - 1.4728, which, according to a ⁰ to 145 C) was not identified. non-aqueous titration a purity of 97.3%

_,. . , .- owned.

Example 12. .

N-isopropyl-N- (4-oxy-4-methyl-hexyn-2-yl) - 60 _χτ τ ι -nt r * \ t. 1 i. λ ■ -, η

Ethanolamine N-Isopropyl-N- (4-methyl-penten-4-m-2-yl) -

T- -u 1 · u λτ u α τ λ ethanolamine

In a similar experiment, 74g _{TT OT} ,,.,. . _T ,

80% 3-isopropyloxazolidine, 200 ecm dioxane and reaction of 3-isopropyloxazolidine with isopropenyl-10 g cuprous chloride run out. In the course of acetylene

30 minutes, 50 g Methyläthyläthinylcarbinol 65 This experiment was similar to the added under Vertropfenweise, wherein the temperature change of butylacetylene experiment performed hooves was maintained under an ice bath 4O ⁰ C. That done. A 1-1 flask was stirred with 120 g of 3-iso mixture for 2 hours and then poured over propyloxazolidine, 200 ecm of dioxane and 7.5 g of cupro

chloride charged. A solution of 68 g of isopropenyl acetylene in 100 ecm of dioxane was then slowly added. An exothermic reaction took place, the temperature rising to 35 ° C. The temperature was then kept at 30 to 35 ° C. by cooling during the further addition, which lasted 25 minutes. The mixture was stirred for 3 hours, during which it gradually cooled. It was then left to stand overnight and worked up in the customary manner by filtering, passing in hydrogen sulfide and distilling off the low-boiling solvent using a water jet pump. 136 g of product were obtained; _{Bp 0.125} mm = 72 ° C., which, according to a nonaqueous titration, consisted of 98% N-isopropyl-N- (4-methyl-penten-4-yn-2-yl) -ethanolamine.

Example 17

N-Isopropyl-N- (heptin-2-yl) -ethanolamine
According to the method described above, 120 g of 3-isopropyloxazolidine, 400 ecm of dioxane and 10 g of cuprous chloride were reacted with 86 g of butylacetylene. The temperature during the addition of the Butylacetylens was 33 to 40 ° C. The mixture was stirred for 2 hours, heated in the course of 20 minutes at 6O ⁰ C and then warmed up in the course of 45 minutes at 68 ⁰ C. Thereafter, heating was turned off, the and the batch is allowed to cool to room temperature with stirring. The catalyst was filtered off and the filtrate was treated with hydrogen sulfide, treated with activated charcoal and filtered again. After the dioxane had been distilled off using a water jet pump, the residue gave 165 g of N-isopropyl-N- (heptin-2-yl) -ethanolamine on distillation in a high vacuum; Kp _{0, 5} mm = 88 to 90 ° C;. Nf = 1.4678. .

Example 18
N-Isopropyl-N- (1-oxy-butyn-2-yl) -ethanolamine

A 2-liter flask equipped with a stirrer, condenser, thermometer and dropping funnel was filled with 800 ecm Dioxane and 130 g (1.13 moles) of N-isopropyloxazolidine loaded. After the addition of 40 g of cuprous chloride, a weakly exothermic reaction also took place Temperature rise to 35 ° C. From the dropping funnel were in the course of 45 minutes 125 g (2.23 mol) Propargyl alcohol added. The reaction was exothermic and the temperature peaked of 49 ° C. The mixture was stirred for 2 hours, whereupon the yellow solid body (the copper salt of propargyl alcohol) was filtered off. The filtrate was treated with hydrogen sulfide and that precipitated copper sulfide filtered off. The now orange-colored filtrate became the dioxane and the excess propargyl alcohol is distilled off. The distillation on the vacuum pump went first a small head of unreacted propargyl alcohol over. The product distilled at 0.75 mm Hg at 147 to 150 ° C above. Yield = 91 g; «F = 1.4974, 48 g of a resinous remained in the flask Residue.

Example 19

N-methyl-N- (1-phenyl-2-propyn-2-yl) -ethanolamine
Implementation of 2-phenyl-3-methyloxazolidine with

acetylene

According to the process described above, 41 g of the desired product were obtained from 81 g of 2-phenyl-3-methyloxazolidine, 200 ecm of dioxane, 10 g of cuprous chloride and 8.5 g of acetylene; Kp. _{0, 26 mm} = 103 ° C.

Example 20

N-oxyethyl-N- (propyn-2-yl) -ethanolamine

Reaction of acetylene with 3 - (/? - Oxyäthyl) -

oxazolidine

According to the process described above, 32 g of product were obtained from 58.5 g of 3 - (/ 3-oxethyl) -o-oxazolidine, 200 ecm of dioxane, 7 g of cuprous chloride and 14.5 g of acetylene; Bp. _{0> 5 m} m = 113 to 116 ° C. The product solidified on standing and was 96% pure according to analysis by non-aqueous titration.This compound showed the following pharmacological activity:

effect
Reassurance

3/5
5/5

5/5
5/5

1382
1797

2326

3024

YOU

mortality

Time
(Number of mice)

0/5
0/5 *

3/5 *
3/5 *

24 hours (1) 48 hours (2)

24 hours (2) 72 hours (1)

10/12/56 A-LD ₅₀ = 2527-230 SD mg / kg (5/20 Mau IP; 26.5 g) 51 SE mg / kg.

Example 21

N-phenyl-N- (propyn-2-yl) -ethanolamine
Reaction of 3-phenyloxazolidine with acetylene
According to the process described above, 11 g of product were obtained from 75 g of 3-phenyloxazolidine, 200 ecm of dioxane, 8 g of cuprous chloride and 10 g of acetylene. _Bp . 0.5 mm = 115 ° C. The product had a refraction exponent of nff = 1.5730.

The product was 104% by non-aqueous titration. This compound showed the the following pharmacological values:

effect Hyp-
nose IP YOU mortality Be
quiet
supply 3/5 dose
mg / kg 1/5 * Time
(Number of mice) 4/5 3/5 372 2/5 * { 24 hours (1) 5/5 3/5 484 3/5 * 24 hours (1)
48 hours (1) -5/5 5/5 629 5/5 * 24 hours (3) 5/5 5/5 818 5/5 * 6 minutes (5) 5/5 1063 5 minutes (5)

10/8/56 A-LD ₅₀ = 534-64 SD mg / kg (5/25 Mau IP; 28.1 g), 14 SE mg / kg.

Example 22

N-tert-octyl-N- (propyn-2-yl) -ethanolamine
Reaction of 3-tert-octyloxazolidine with acetylene

In a similar experiment, acetylene was passed into a mixture of 136.5 g of 3-tert-octyloxazolidine with 250 ecm of dioxane and 5 g of cuprous chloride at room temperature with stirring. 15 g of acetylene were absorbed over the course of 8 hours. The mixture was worked up in the usual way and, on distillation, yielded 78.5 g of N-tert-octyl-N- (propyn-2-yl) -ethanolamine; Kp. _{117 to 2j0 mm} = 104 to 112 ° C. This material had a refraction exponent of Rf = 1.4722 and gave a purity value of 101% in the non-aqueous titration.

Example 23

N-tert-octyl-N- (l-n-propyl-2-propyn-2-yl) -ethanolamine

114 g of 2-n-propyl-3-tert.octyloxazolidine, 300 ecm of dimethylformamide and 7 g of cuprous chloride were treated with acetylene in the usual way. 16 g of acetylene were absorbed over a period of 4 hours at 15 to 25 ° C. The catalyst was then filtered off and the filtrate was used without further ado, since it was no longer colored and consequently no longer contained any copper. The dimethylformamide was distilled off using a water pump, and the residue yielded 76 g of product on distillation; _{Bp 0.175 mm} = 81 to 85 ° C; «F? = 1.4561.

Briefly summarized, the invention relates to new, acetylenically unsaturated ethanolamines which are obtained by reacting the corresponding oxazolidines with an acetylene compound using cuprous ions as a catalyst. A solvent such as dioxane or dimethylformamide, at a temperature in the range from 10 to 3O ⁰ C and pressures in the range of 127 to 254 mm Hg pressure is ao the reaction in the presence of.

25th

Claims (1)

PATENT CLAIM: Process for the preparation of acetylenically unsaturated ethanol flame of the formula
R ₅ R ₇ R ₃ -N 35 40 wherein R ₁ , R ₂ and R ₄ to R _{7 are} hydrogen or alkyl, aryl, alkaryl or aralkyl groups and where either R ₁ or R _{2 is} hydrogen, while R _{3 is} an alkyl, oxyalkyl, aryl, alkaryl - Or aralkyl group, characterized in that an oxazolidine of the structural formula Rs Re ρ ρ ρ I I R ₃ -NO Ko Ki wherein R ₁ to R _{7 have} the above meaning with an acetylenically unsaturated compound of the formula wherein R _{8 represents} hydrogen or an alkyl, alkenyl, aryl, aralkyl, alkaryl or oxyalkyl group, in the presence of a solvent for the oxazolidine and in the presence of a cupro salt at a temperature between 0 and 30 ⁰ C and a pressure between atmospheric pressure and 356 mm Hg overpressure is reacted, the unreacted fractions are removed from the reaction mixture and the desired end product is distilled off. 109 709/418 10.61