DE2164847C3 - 1- (2-Hydroxybutoxy) -3-hydroxybutane and process for its preparation - Google Patents

Description

2. A method for producing the compound according to claim 1, characterized in that nvan 1,2-hulylene oxide in the presence of sodium alcoholate, Potassium alcoholate, sodium acetate, sodium hydroxide or potassium hydroxide with 1,3-butanediol implements.

3. Medicament, characterized in that it is the compound according to claim 1 as an active ingredient as well contains an inert diluent, carrier material or adjuvant.

N- (p-hydroxyphenyl) salicylanide has long been used (Oxaphenumid) of the formula

OH

CONH -

OH

used as a cholagogue. Oxaphenaniid is however Regardless of its therapeutic effectiveness, it is questionable as it is quite toxic.

The object of the invention is to find a chemical compound that can also be used as a cholagogue suitable, but has a lower toxicity than oxaphenamide.

It has now surprisingly been found that _K2 .Hvdroxybutoxy) -3-hydroxybu.an with the general formula

_C H, C \ L CW CH,

_clis ClI CH, CH,

on

very XK-I linger toxic than Oxaphenannd, m dice, _"ch i" his Aktiv.tal as Cholago.um

^ f ₁ ;, V ^T Z Ket VH ^P. ι, Λ. , ml -5 t r

t for mice is be, oral Vuab-υ. as Oxaphenamids l, -> tg and im droxvbutovv) -3-hydroxybuian, ö, riu g ^ ch. and be, intravenous administration - / η "! O ¹ H For rats, the r--; .c;" id «be, oral administration; _P ! K-nan, ids 2.38 g and in the case of the u "^"-.'-h> Jr "xybutane _S 8, .Og and for p 0.26 g compared to 2 ν g. Most effective from 1- (2. _;> N was on Gru.u,, er

cLllensekai,:, w Kalten concerned. O.e attempts were carried out like foiüi:

0 rats J ^ before the l-xpcrimentjs hours run Food received were treated with Ethylurethan, Nästhes.ert and ... back position fastened. Then became • in each RjHe on lSauchschn.tt carried out a cannula connected to the ememamen biliary duct. The amount of (iallensckret.on was all "Ό minutes / uemul measured (their mean as The base index in the table below is gle.ch 100 set / t). and / was starting 30 minutes after

Intervention. . .. ,,,,.

Then 0.4 ml of a solution containing 100 mg l-C-Hydroxybuto \ v) -3-h> droxybutane or oxaphane

amide or saline as a control substance containing, inserted into the upper part of the duodenum, and the amount of bile was determined in intervals of ¹ O per minutes for 5 hours. The results are summarized in the table, and the numbers listed there indicate the volume of bile secretion based on the value 100 before administration of the above-mentioned solution in each group.

Test subscription 20th 40 60 80 100 120 Min
140 jten
160 180 200 220 240 260 280 300 total l- (2-hydroxy-
butoxy) -
3-hydroxy
butane. 129
138
110 132
138
104 129
132
100 121
120
100 121
104
100 ILl
104
97 107
96
93 100
104
97 96
88
93 93
76
86 89
100
86 82
88
86 82
88
85 79
88
86 79
88
86 1550
1552
1409 Oxaphenamide
Table salt ....

Base 100; Number of test animals 10.

The test results show that l- (2-hydroxybutoxy) -3-hydroxybutane significantly better pharmacological activity and extremely lower toxicity has as oxaphenamide.

L- (2-Hydroxybutoxy) -3-hydroxy butane can be passed through Reaction of 1,2-butylene oxide with 1,3-butanediol in the presence of sodium alcoholate, potassium alcoholate, Synthesize sodium acelate, sodium hydroxide, or potassium hydroxide or potassium hydroxide. The two Last compounds are particularly effective.

The reaction can be carried out at room temperature. However, your speed will increase and l- (2-Hydroxybuioxy) -3-hydroxybutane can be obtained in good yield by adding the reaction mixture is heated.

If 1,3-butanediol is used in excess,

fvagiert it little by little with 1,2-butylene oxide, whereby good results can be achieved.

That with the fractional distillation of the reaction solution recovered 1,3-butanediol can be obtained from new to be used in the process.

Details of the method of preparation are given in Examples 1 to 3 below.

After filtering off the insoluble salts
the filtrate is distilled under reduced pressure, wherein
41.2 g of pure 1- (2-hydroxybutoxy) -3-hydroxybiitan were obtained.

The yield was 50.8% (boiling point 96 to 98 ° C./1 mm Hg). The substance was colorless, viscous liquid, which lends itself very well to water, Ether or alcohol, but only slightly dissolved in Pelrolath Example 1. The results of the elemental analysis were

ίο assuming the gross formula C _s H _ltt O _{: l} :
36 g of 1,2-butylene oxide was added to a solution of

3.0 metallic sodium in 270 g of 1,3-butanediol at Calculated C 59.23'Vo- ^H H.IS ¹¹ O,

a temperature of 60 to 7O ^'J C to-measured under stirring.'. '.'. C 59.41%, H 10.96%.

given.

The reaction was 5 hours at this temperature-15th, _r

_fil luv unier stirring continued, and then the compound was the solution tralisicrt to Harm their Inlrarotwurde by adding tartaric acid new spectrum in dilute carbon tetrachloride-Losunt. ^{like fo |} g ^l identified:

free secondary hydroxyl groups ... SO - H

Methyl and methylene groups C-H

Methyl groups SC-H

aliphatic ^ ether groups as C-OC-

3627 cm '
2950-2850 cm ¹
1370 cm- '
1110 cm " ^l

Example 2

360 g of 1,2-butylene oxide were added to a solution of 5.6 g of potassium hydroxide in 540 g of 1,3-butanediol were added. This mixture was stirred at 70 ° C. for 6 hours and then neutralized with sulfuric acid.

After filtration, 1,603 g of pure 1- (2-hydroxybutoxy) -3-hydroxybutane were obtained by fractional distillation in vacuo. The yield was 74.5% (boiling point 100 to 102 ° C. / 1.3 mm Hg). Analysis values for C ₈ H ₁₈ O ₃ :

Calculated ... C59.23%, H 11.18%; measured .... C 59.38%, H 11.23%.

The physical and chemical properties of this compound and those obtained by IR spectroscopy in The values obtained from a dilute carbon tetrachloride solution were the same as in Example 1.

Example 3

360 g of 1,2-butylene oxide was added to a solution of 8.2 g of sodium acetate in 540 g of 1,3-butanediol. The mixture was then 6 hours at 85 C

30 stirs.

The fractional distillation of the reaction mixture gave 392 g of pure 1- (2-hydroxybutoxy) -3-hydroxybutane. The yield was 48.4% (boiling point 94 up to 96 ° C / 0.7mm Hg).

_{Analysis values} for C _s Ii llt O.,:

C 59.23%. H 11.18%;
C 59.21%, H 11.07%.

Calculated measured.

The physical and chemical properties of this compound and those obtained by IR spectroscopy in The values obtained from a dilute carbon tetrachloride solution were the same as in Example 1.

Claims (1)

Patent claims: 1. 1- (2-Hydroxybutoxy) -3-hydroxybuian
CH., CH ₂ -CH -CH ₁ OH CH, CH -CH ₂ -CH ₃ OH