NO132931B - - Google Patents

Description

The present invention relates to new alkylT4-halophenyl-ether derivatives for use as starting materials in the production of therapeutically active benzamides, and which correspond to the

general formula:

0

where R 1 is a nitro group or a lower alkanoylamino group, R 2 is a lower alkyl group or a lower alkanoyl group, R 2 is a lower alkyl group and X is a halogen atom.

These new compounds can be prepared by reacting a 4-halogenphenol derivative with the general formula: where R 1 , R 2 and X have the meanings given above, with a compound of the general formula:

where R3 is an alkylidene group, and one of the symbols R4 and R5 denotes a hydrogen atom, while the other denotes a halogen atom or

the group -S03R7where R? is hydrogen or an alkyl group, or R 4 and R 4 together can be =N,,.

Examples of the above-mentioned lower alkanoyl group are acetyl, propionyl, butyryl and valeryl. Examples of usable lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl and pentyl. Examples of usable alkylidene groups are methylene, ethylidene, propylidene, isopropylidene, 2-methyl-propylidene, butylidene and pentylidene and examples of the halogen atoms are chlorine and bromine.

The compounds (i) are new compounds, and some of them, e.g. 4-chloro-5-nitro-orthodecresol can be prepared by adding sodium nitrite to a strongly acidic solution of 4-chloro-5-ortho-toluidine and heating the mixture. 2-hydroxy-4-acetamido-5-chloroacetophenone can be prepared by reacting 3-acetamido-4-chlorophenylacetate with anhydrous aluminum chloride in the presence of carbon disulphide. The other compounds (i) can also be prepared using these methods.'

The new starting materials (III) are usually prepared by reacting 4-halogenophenols, the water (I) with a compound of the general formula (II).

The compounds (II) are mono- or di-alkyl sulfates, alkyl halides or diazoalkanes. Examples of the mono- or di-alkyl sulfates are mono- or dimethyl sulfate, mono- or di-ethyl sulfate, mono- or dipropyl sulfate. ■ Examples of the alkyl halides are methyl chloride, ethyl bromide, propyl chloride and butyl bromide. Examples of the diazoalkanes are diazomethane, diazoethane and diazo-propane. If mono- or di-alkyl sulphates or alkyl halides are used as starting materials, it is preferred to carry out the reaction in the presence of a basic condensing agent such as an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal carbonate and an alkaline earth metal carbonate. The reaction can be carried out in the presence or in the absence of a solvent. If the reaction is carried out in a solvent, solvents such as acetone, ether, aromatic hydrocarbons and drmethylformamide are preferably used, depending on the nature of the compounds (II). Acetone or ether is preferably used when mono- or di-alkyl sulfates are used as compounds of formula (II), while aromatics, hydrdearboner- or dimethylformamide; used, when there,, as forT bi. compounds with the general formula (II) alkylhalogen is used there. When a diazoalkane is used as the compound of formula (II), ether is preferably used. The reaction is usually carried out under heating under reflux when mono- or di-alkyl sulfates or alkyl halides are used, and usually at room temperature when a diazoalkane is used.

The new alkyl-4-halophenyl ether derivatives (III) are useful as starting materials in the preparation of benzamides such as, for example N-(2-Dialkylaminoalkyl)-2-Alkoxy-4-amino-5-halobenzamides which have valuable therapeutic properties, such as analgesic, antispasmodic, sedative, anesthetic and antiemetic action.

Thus N-(diethylaminoethyl)-2-methoxy-4-amino-5-chlorobenzamide can be prepared from 2-methyl-4-chloro-5-nitroanisole by oxidation of this compound to 2-methoxy-4-nitro-5-chlorobenzamide zoic acid, esterification of this acid, conversion of the obtained ester to amide with diethylaminoethylamine and reduction of the thereby obtained N-(diethylaminoethyl)-2-methbxy-4-nitro-5-chlorobenzamide to the corresponding 4-aminobenzamide.

The following examples further illustrate how the new starting materials (III) can be produced.

Example 1

A solution of 0.8 g of 2-hydroxy-4-acetamido-5-chloro-acetophenone in 50 ml of absolute acetone was added with stirring to 0.57 g of anhydrous potassium carbonate. 0.52 g of dimethyl sulfate was added to the resulting solution, and the mixture was heated under reflux and stirring for 15 hours. After the reaction was complete, the reaction mixture was filtered and the filtrate evaporated, whereby 0.7 g of 2-m<:thoxy-4-acetamido-5-chloro-acetophenol was obtained in the form of white crystals. t-ied melting point 148 - .150°C.

Yield: 84

Analysis: Calculated for C^H^NC^Cl: C 54, 67;' H 5, Ol

Found: C 54.99; H 5.00

Example 2

A reading of 1.85 g of 4-chloro-5-nitro-orthocresol i

15 ml of absolute acelone were added, while stirring and with exclusion of moisture, to 3.38 g of anhydrous potassium carbonate and then immediately 1.39 g of dimethyl sulfate. They we ; .-held mixture was heated under reflux for 16 hours, after which 60 ml of absolute acetone was added and then filtered. This resulted in a residue which was washed 3 times with 10 ml portions of acetone. The filtrate and the washing liquids were mixed, after which the acetone was distilled off under reduced pressure, whereby slightly yellow, needle-shaped crystals were separated. These crystals were washed with 50 ml of water and then recrystallized from 50 ml of 60% ethanol. 1.89 g of 2-methyl-4-chloro-5-nitroanisole with melting point 87 - 89°C was then obtained. Yield: 95%.

Analysis; Calculated for CQH O NC1:

o p3

C 47.66; H 4.00; N 6.95; Cl 17.59 Found: C 47.97; H 4.06j N 6.90; Cl 17.51

Claims (1)

Disconnect switch which is self-locking in the inserted position, where the contact pressure is self-regulating and which is made with a movable contact arm and a stationary spring counter contact, which contact arm contains a first link which at one end is pivotally stored in a first storage point on a stand, another link which at one end is rotatably stored in another storage point on said stand, a third link which is pivotably stored in a third storage point at the other end of the first link and in a first storage point at the other end of the second link, the third link with its free end forming a movable contact part, characteristic in that the storage points (3, 4, 6, 7) are arranged in such a way that the contact point (5-9) between the movable contact part (9) and the fixed counter contact (5), as well as the fourth storage point (7) and the second storage point (4) ) in the closed position of the disconnector, when the movable contact part has hit the counter contact (5) and a spring force, which is at least partially caused by the spring counter contact, has been overcome, equal to essentially on a straight line while the third storage point (6) lies inside the triangle formed by the straight lines between the contact point (5-9), the first storage point (3) and the fourth storage point (7).