Process for the preparation of arylalkylamines and substituted arylalkylamines

A method for the preparation of tyramine hydrochloride, which comprises the steps of:

• a) providing p-hydroxy-.alpha.-isonitrosoacetophenone;
• b) reacting said p-hydroxy-.alpha.-isonitroso-acetophenone with hydrogen in an essentially nonalcoholic aqueous reaction medium comprising hydrochloric acid in the presence of a palladium on carbon catalyst, wherein the hydrochloric acid is present in an initial amount ranging from about 2% by weight to about 37% by weight of said reaction medium, and wherein said palladium is present in an amount ranging from about 0.0005% by weight to about 1.5% by weight of the initial amount of said p-hydroxy-.alpha.-isonitroso-acetophenone;
• and
• c) recovering tryamine hydrochloride from said reaction medium.

A process for the preparation of the hydrochloride salt of an arylalkylamine, which comprises the steps of:

• a) providing a compound of the formula ##STR7## wherein P.sub.1 =hydroxyl radical, alkyl, or alkyloxy
• R2=hydrogen or a C.sub.1 -C.sub.8 alkyl or cycloalkyl, and
• Ar=an unsubstituted phenyl, or a phenyl substituted only at the ortho position, the para position or both the ortho and para positions, or an unsubstituted naphthyl radical, or a naphthyl radical substituted only at one or more of the 3, 3, 6, and 7 positions, wherein the substituents are selected from the group consisting of amino, alkylamino, dialkylamino, hydroxyl, alkoxy, alkyl, phenyl, benzyl, sulfonic acid, and sulfinic acid radicals, wherein the alkyl components is a branched or unbranched C.sub.1 -C.sub.8 alkyl radical and wherein any of said alkyl, phenyl, and benzyl radicals are optionally substituted with one or more substituents selected from amino, hydroxyl, sulfonic acid, and sulfinic acid radicals, and said phenyl and benzyl substituents are optionally substituted with a C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkoxy radical, or both;
• b) reacting said compound with hydrogen in an aqueous reaction medium which comprises about 90% by weight or less of a lower alkyl alcohol, wherein said aqueous reaction medium also comprises hydrochloric acid present in an initial amount of from about 2% by weight to about 37% by weight of said reaction medium, and a hydrogenation catalyst comprising a transition metal on an inert substrate, wherein sufficient of said catalyst is present in said reaction medium for the amount of said transition metal present to range from about 0.0005% by weight to about 5.0% by weight of the initial amount of said compound for which the formula is given in step a), and wherein said transition metal is selected from the group consisting of platinum, palladium, nickel, rhodium, and combinations thereof;
• and
• c) recovering the hydrochloride salt of a compound of the formula Ar-CH.sub.2 CHR.sub.2 NH.sub.2, wherein R.sub.2 and Ar are the same as in the compound of step a).

A method for the preparation of tyramine hydrochloride, which comprises the steps of:

• a) providing p-hydroxy-.alpha.-isonitrosoacetophenone;
• b) reacting said p-hydroxy-.alpha.-isonitroso-acetophenone with hydrogen in an aqueous reaction medium which comprises about 90% by weight or less of a lower alkyl alcohol, wherein said reaction medium also comprises hydrochloric acid present in an initial amount of from about 2% by weight to about 37% by weight of said reaction medium, and from about 5% by weight to about 25% by weight of a palladium hydrogenation catalyst comprising palladium on an inert support, wherein said palladium is present in said reaction medium in an amount of from about 0.0005% by weight to about 5.0% by weight of the initial amount of said p-hydroxy-.alpha.-isonitrosoacetophenone;
• and
• c) recovering tyramine hydrochloride from said reaction medium.

A method of preparing a salt of a substituted or unsubstituted arylalkylamine from an arylalkylketone, comprising the steps:

• a) providing an arylalkylketone of the formula ##STR8## wherein, R=represents hydrogen, a C.sub.1 -C.sub.8 alkyl or cycloalkyl, and
• Ar=represents an aromatic phenyl radical which is unsubstituted, substituted only at the ortho position, substituted only at the para position, or substituted only at both the ortho and para positions, or
• Ar=represents a naphthyl radical which is unsubstituted, or substituted only at one or more of the 1, 3, 6, and 7 positions, where the substituent is selected from the group consisting of amino, alkylamino, dialkylamino, hydroxyl, alkoxy, alkyl, phenyl, benzyl, aryloxy, sulfonic acid, and sulfinic acid radicals, wherein the alkyl in the alkyl-containing substituent is a branched or unbranched C.sub.1 -C.sub.8 alkyl radical and wherein said alkyl radical as well as said phenyl and benzyl radicals may be optionally substituted with one or more substituents selected from amino, hydroxyl, sulfonic acid, and sulfinic acid radicals, said phenyl and benzyl substituents also or alternatively being optionally substituted with one or more C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkoxy, or both radicals;
• b) reacting said arylalkylketone with a lower alkyl nitrite in the presence of hydrogen chloride and in the presence of a dipolar aprotic solvent to produce a reaction mixture which includes an aryl-alphaoximinoalkylketone reaction product;
• c) removing protic by-products of the dipolar aprotic solvent of step b) when such protic by-product is capable of interfering with a hydrogenation catalyst used in step d) below;
• d) reacting the aryl-alpha-oximinoalkylketone of step b) with hydrogen in an essentially nonalcoholic aqueous reaction medium comprising water, hydrochloric acid present in an initial amount of from about 2% by weight to about 37% by weight of said reaction medium, and a hydrogenation catalyst comprising a transition metal on an inert support, wherein sufficient of said catalyst is present in said reaction medium for the amount of said transition metal to range from about 0.0005% by weight to about 1.5% by weight of the initial amount of said compound for which the formula is given above, and wherein said transition metal is selected from the group consisting of platinum, palladium, nickel, rhodium, and combinations thereof;
• and
• e) recovering the hydrochloride salt of a compound of the formula Ar-CH.sub.2 CHR.sub.2 NH.sub.2, wherein R.sub.2 and Ar are the same as in the compound of step a).

A method of preparing a salt of a substituted or unsubstituted amine from an arylalkylketone comprising the steps of:

• a) providing an arylalkylketone of the formula ##STR9## wherein, R represents hydrogen, a C.sub.1 -C.sub.8 alkyl or cycloalkyl, and
• Ar represents an aromatic phenyl radical which is unsubstituted, substituted only at the ortho position, substituted only at the para position, or substituted only at both the ortho and para positions, or
• Ar represents a naphthyl radical which is unsubstituted, or substituted only at one or more of the 1, 3, 6 and 7 positions, where the substituent is selected from the group consisting of amino, alkylamino, dialkylamino, hydroxyl, alkoxy, alkyl, phenyl, benzyl, aryloxy, sulfonic acid, and sulfinic acid radicals, wherein the alkyl in the alkyl-containing substituent is a branched or unbranched C.sub.1 -C.sub.8 alkyl radical and wherein said alkyl radical as well as said phenyl and benzyl radicals may be optionally substituted with one or more substituents selected from amino, hydroxyl, sulfonic acid, and sulfinic acid radicals, said phenyl and benzyl substituents also or alternatively being optionally substituted with one or more C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkoxy, or both radicals;
• b) reacting said arylakylketone with a lower alkyl nitrite in the presence of hydrogen chloride and in the presence of a dipolar aprotic solvent to produce a reaction mixture which includes an aryl-alphaoximinoalkylketone reaction product;
• c) removing protic by-products of the dipolar aprotic solvent of step b) when such protic by-product is capable of interfering with a hydrogen catalyst used in step d) below;
• d) reacting the aryl-alpha-oximinoalkylketone of step b) with hydrogen in an aqueous reaction medium which comprises about 90% by weight or less of a lower alkyl alcohol, wherein said aqueous reaction medium also comprises hydrochloric acid present in an initial amount of from about 2% by weight to about 37% by weight of said reaction medium, and a hydrogenation catalyst comprising a transition metal on an inert substrate, wherein sufficient of said catalyst is present in said reaction medium for the amount of said transition metal present to range from about 0.0005% by weight to about 5.0% by weight of the initial amount of said compound for which the formula is given in step a), and wherein said transition metal is selected from the group consisting of platinum, palladium, nickel, rhodium, and combinations thereof;
• and
• e) recovering the hydrochloride salt of a compound of the formula Ar-CH.sub.2 CHR.sub.2 NH.sub.2, wherein R.sub.2 and Ar are the same as in the compound of step a).

A method of preparing the hydrochloride salt of an arylalkylamine, which comprises the steps:

• a) providing a compound of the formula ##STR10## wherein, R.sub.1 =hydroxyl radical, alkyl, or alkyloxy
• R.sub.2 =hydrogen or a C.sub.1 -C.sub.8 alkyl or cycloalkyl, and
• Ar=an unsubstituted phenyl, or a phenyl substituted only at the ortho position, the para position or both the ortho and para positions, or an unsubstituted naphthyl radical, or a naphthyl radical substituted only at one or more of the 1, 3, 6, and 7 positions, wherein the substituents are selected from the group consisting of amino, alkylamino, dialkylamino, hydroxyl, alkoxy, alkyl, phenyl, benzyl, sulfonic acid, and sulfinic acid radicals, wherein the alkyl component is a branched or unbranched C.sub.1 -14 C.sub.8 alkyl radical and wherein any of said alkyl, phenyl, and benzyl radicals are optionally substituted with one or more substituents selected from amino, hydroxyl, sulfonic acid, and sulfinic acid radicals, and said phenyl and benzyl substituents are optionally substituted with a C.sub.1 -C.sub.8 alkyl or a C.sub.1 -C.sub.8 alkoxy radical, or both;
• b) reacting said compound with hydrogen in an aqueous reaction medium comprising hydrochloric acid present in an initial minor weight percent of said reaction medium and a hydrogenation catalyst comprising a transition metal of an inert support, wherein said transition metal is selected from the group consisting of platinum, palladium, nickel, rhodium, and combinations thereof;
• and
• c) recovering the hydrochloride salt of a compound of the formula Ar-CH.sub.2 CHR.sub.2 NH.sub.2, wherein R.sub.2 and Ar are the same as in the compound of step a).