DEP0012561DA - Process for the preparation of a thymol ester - Google Patents

Description

Process for the production of a ^ ghymolestere.

Numerous compounds have been proposed for combating human oxyuriasis ₈ which have the disadvantage of either a relatively large toosity for the patient / or an uncertain effectiveness against the parasites. These disadvantages are avoided when using the previously unknown N-isoamyl-oarbamic acid thymol @ ®t @ rs * produced according to the invention. This ester has a pronounced vermifuge effectiveness against oxyurs with excellent compatibility, which enables it to be used safely in children's practice g / kg reactiveloe, higher® dose cannot be administered in terms of quantity = it is similar with rats, guinea pigs and cats, who can tolerate 3 g / kg without reacting. In adults, are 3 times 2 g tägli'oh without discomfort tolerated "With strong Oxyurenbefall a very annoying itch noticeable j and it is a particular advantage d © s N» Isoamyl ~ earbaminsäur® # thymolesters that he, at therapeutic dose administered, the unpleasant itching suddenly disappears »

The present invention then consists in reacting the isoamyl derivative of the formula (CH ^) ₂ ^s GH-CH ₂ -GHg-X with a derivative of the thymol of the formula YOO ^ qH ₁₅ sur * where X and I are chosen so ,, that in the conversion the acid amide group -NH-GO- (with the nitrogen ^ m isoamyl radical) arises «I and I are therefore such reactive ^ groups and the reaction in question is such as it is for the production of other N-substituted garbamic acid esters are known β

duroli gain that isoamylamine is reacted with easily cleavable esters of thymol »Preferably, one uses the chloroformic acid ^ thymol ester or the carbonic acid ester of thymol« or work in an aqueous medium in the presence of lye »In the latter case, it is advantageous to use water-soluble salts of xsoamy! amine _? ZoB * from the hydrochloride. In addition, after what has been said, the following conversions, for example, can be carried out

Reaction of isoamyl isocyanate with thymol, reaction of isobutylacetamide first with halogen and then with thymol sodium or »thymol, action of isocaproic acid azide on thymol reaction of isoamyl halide with carbamic acid t & y» aL ester *

N-Isoamyl / carbamic acid ^ thymol ester of the formula

CI

GH ₉ -MH-CO-O

is a colorless crystallized substance with a melting point of 57 ° $ 9 which is practically insoluble in water (solubility in water at room temperature less than 1 ι 50,000). Is the preparation treated with normal methyl alcoholic lye at 40 ° _? so after 30 days about $ 86 are saponified.

Examples

I ₉ ) A solution of 904 g of chloroformic acid thymolestex in 4a5 liters of absolute ether is slowly introduced into a solution of 780 g of laoamylamine in 4 liters of absolute ether, while stirring and cooling with ice water. The whole thing is boiled under reflux and then freed from the precipitated isoamylamine hydrate after cooling by filtration. The filtrate is evaporated and the residue which crystallizes immediately as a part by volume of low-boiling P@trolaetb.er recrystallized Aasbeates 850 g of colorless® needles with a melting point of 57 ° »

2 ») 2s, 12 kg of chloroformic acid thymolestei ¹ are suspended in a Löeong Yon I ₉ 24 kg of isoamylamine carbohydrate in 2.48 liters of warm water. with vigorous stirring ein® solution of 880 g in 2.64 liter üatriumhydroxyd Lasser train @ give @ n _s is cooled during the Heaktionsgefäss with fli @ @ m ssen.d water is in a quarter of an hour. At an initial temperature of 35 ° dia Dempgra ™ tur dee reaction mixture terminated at about 55 ° ₀ After ¹ B @ action is cooled with vigorous lührea at 15 °, the reaction product is filtered off almost geworden® rises!; downsized? Washed well with water and air-dried ο The crude product is recrystallized from a volume part of low-boiling petroleum ether «yield®I -2.1 kg, melting point 57 ° *

Claims (1)

Claims I ₉ ) Process for the preparation of a thymol ester * characterized in that an isoamyl derivative of the formula (GH,) 2 ■ CH-OH ₂ = GHg = I with a derivative of thymol of the form! YOG ₁₀ H ₁ , aur reacts, where 1 and I are chosen like this? that at the Ums et sang the acid amide grouping -BH-CO- (with the nitrogen on the isoamyl residue) is formed;> 2 «) Process for the preparation of a thymolesterg, characterized in that one isoamy! Derivative of the formula (CHa) ₂ ^β GH-OH ₂ -CH ₂ -I with a derivative of the shymol of the formula YQ-CiqH} * ^{2ar Seak} ^ ^ion brings , where I and Ϊ are such groups as they are used for the preparation of other! »substituted carbamic acid esters in known processes» 3 ») Method according to claim 1 u = 2, characterized in that xsoamylamine is based on easily cleavable esters of Shymcüa preferably on the carbonic acid ester or "the chi" - formic acid ester ^ "lets act" 4 ') The method of claim 1 · α 2, characterized in that _s Isoemylisocyanat with thymol reacted. 5 ') The method of claim 1 and ° 2 ₉ characterized in that one brings ^ Isobutylacetsmid züx first with halogen and then with fhymal-Hatriom or thymol implementation. 6 ») Method according to claim 1 α. 2, characterized ₉ that isocaproic acid amide is allowed to act on thymol « 7 ») Process according to claim 1 12.0 2 ₉ dad arch gekennseichss t ₉ that isoamyl halide is« reacted »with carbamic acid thymol ester 8 «,) N ~ IsQamyl = carbamic acid ~ ihyiao! Es" fcer vöii the! Formula CH, CH a colorless crystallized substance _P which scisinizes at about 57 C, is practically insoluble in water and, in the case of alkaline saponification, yields xsoamyiamine and thymol (non-carbonic acid).