DE181510C - - Google Patents

Description

IMPERIAL

PATENT OFFICE.

PATENT LETTERING

CLASS 12y ?. GROUP

Dr. MARTIN FREUND in FRANKFURT a. M.

Process for the preparation of derivatives of thebaine.

Patented in the German Empire on October 7, 1905.

Of the three oxygen atoms in thebaine, two are contained as methoxyl groups. The type of binding of the third is still unclear. Until recently it was believed that this third oxygen atom was an oxazine ring
O

while in recent times the prevailing view is that it is similar to
Diphenylene oxide

in the

be bound. In any case, the type of bond with that of the oxygen is im Ethylene oxide cannot be compared.

It is therefore surprising that as found that thebaine is able to react with Grignard solutions in a similar way as ethylene oxide (cf. Compt. rend. Vol. 136, 1903, p. 1261, paras. 5 and 6). One brings the alkaloid together with organometallic magnesium compounds are stored in this way the latter to the third oxygen atom.

Intermediate products are formed which, when decomposed with water, create new bases deliver. When using a solution prepared from bromobenzene, magnesium and ether, the reaction proceeds, for example as follows:

(CH ₃ Ok > [C ₁₇ H ₁ , N] <0+ C ₆ H ₅ Mg Br = (CH _S O) ₂ > [C ₁₇ H ₁₆ N]

(CH ₈ O) ₂ > [C ₁₇ H ₁₅

^V 6 - "5

^Br

OH

55

Just like the organomagnesium compounds of the aromatic series react Grignard solutions, which BEZW by means of haloalkyl. Haloaralkyl are prepared. This behavior of thebaine is all the more remarkable than morphine and codeine, which like the third oxygen atom Thebaine contains bound, does not react with Grignard solutions.

The new compounds, which have both basic and acidic properties, should be used as medicinal products.

Example I.

In order to achieve the most quantitative possible conversion of the alkaloid, one works expediently with an excess of the organometallic magnesium compound. 50 g of bromobenzene are combined with 8 g of magnesium and about 400 ecm of absolute ether reacted and 50 g of 7Q

powdered thebaine in portions while stirring registered. The bulk of the new product is contained in the semi-solid sediment, of which the essential Solution is poured off. This is shaken with dilute acid, preferably acetic acid, by and adds the separated solution to the sediment, which has previously been decomposed with water, whereby a clear solution

ίο is obtained. The new base can easily be obtained from this in the form of its salts in various ways; Either the sparingly soluble and readily crystallizing iodine hydrate (C ₂₅ H ₂₁ NO _S · HJ, melting point 230 to 232 ⁰ ) is precipitated directly with potassium iodide, or it is first supersaturated with ammonia, filtered, the precipitate is extracted with strong alcohol, filtered again and separates the hydrochloric acid from the concentrated filtrate with alcoholic hydrochloric acid (C. _2i H ₂₇ NOg. H Cl + C ₂ H ₆ O, melting point 145 to 147 ⁹ ). The yield is almost quantitative. The product provides, decomposed with ammonia, the free base C ₂₅ H ₂₁ NO _3, which is readily soluble in almost all organic Solventienen and is obtained from a little alcohol in columns of melting point 62 to 65 ^0th It is soluble in alkali; the sodium salt can easily be obtained in crystallized form.

The bromine hydrate, crystallized from water, forms tablets that foam up at 190 to 195 °.

Example II.

If one carries thebaine (6.2 parts) into one of benzyl chloride (10.12 parts), magnesium (2 parts) and ether (50 parts), almost everything dissolves during digestion. Man decomposes with water, then adds hydrochloric acid (specific gravity 1.1), separates the Hydrochloric acid layer from the ether, the new base falls through ammonia and shakes it in ether. When it evaporates, it remains oily; by recording again in dilute hydrochloric acid and cases with ammonia it appears as almost white Powder received. In the pure state it is in a dilute alkali with a yellowish color soluble, ν

Claims (1)

Patent claim: Process for the preparation of derivatives of thebaine, consisting therein that on thebaine organometallic magnesium compounds are allowed to act in an ethereal solution and those obtainable in this way Intermediate products decomposed with water.