Patent GB-978281-A (GB)
Title: Tetrahydro-and decahydro-isoquinolinium compounds
Inventor: COPP FREDERICK CHARLES
Filed: 1960-02-11
Abstract: The invention comprises quaternary ammonium compounds containing a cation of the formula <FORM:0978281/C1/1> (wherein R1 is methyl, ethyl, 2-hydroxyethyl or amino; R2 is ethyl or 2-hydroxyethyl; and A= N+ is the 1,2,3,4-tetrahydro- or the cis- or transform of the decahydroisoquinolinium nucleus, optionally substituted in the 8-position with a halogen atom), but excluding 2-ethyl-2-methyl-1, 2, 3, 4-tetrahydroisoquinolinium iodide and 2-(2-hydroxyethyl)-2-methyl-1, 2, 3, 4-tetrahydroisoquinolinium iodide and bromide.  The invention also comprises the preparation of these compounds by reacting a tertiary amine R3R4R5 N with a compound R6X, wherein two of R3, R4, R5 and R6 are each as appropriate an R1 and R2 group and the other two of R3, R4, R5 and R6 are a 1, 2, 3, 4-tetrahydro- or a decahydroisoquinoline nucleus, and X is a reactive atom or group. Suitable anions are halides, sulphate, methylsulphate and p-toluenesulphonate, and suitable reactants for use in the process are a tertiary amine A=NR3 and a molecular proportion of a compound R6X wherein R3 and R6 are each as appropriate, and not necessarily as respective, an R1 and an R2 group. Anions may be exchanged by metathesis. Examples are given, one product being isolated as a picrate.  8-Bromo-2-methyl-1, 2, 3, 4-tetrahydroisoquinoline is prepared from 8-bromoisoquinoline and methyl iodide.  In the third Provisional Specification R1 and R2 are additionally defined as isopropyl and allyl; and the isoquinolinium nucleus may be optionally substituted at the 8-position with a methyl or nitro group. Another method of preparation viz. the cyclization of a 1-CH2X-2-CH2CH2X-benzene or -cyclohexane with the amine NHR R2, or the intramolecular quaternization of the intermediate tertiary amine, is also described. In the fourth Provisional Specification R2 is defined as an alkyl, hydroxyalkyl or alkenyl group, R1 being an amino group.ALSO:Pharmaceutical compositions contain quaternary ammonium compounds containing a cation of the formula <FORM:0978281/A5-A6/1> (wherein R1 is methyl, ethyl, 2-hydroxyethyl or amino; R2 is ethyl or 2-hydroxyethyl; and A = N+ is the 1,2,3,4-tetrahydro- or the cis or trans form of the decahydro-isoquinolinium nucleus, optionally substituted in the 8-position with a halogen atom) and a carrier. They have a sympatholytic action, and may take the form of powders, granules, capsules, cachets, tablets, solutions, suspensions, emulsions, suppositories or pessaries, which may contain dispersing, surface-active, suspending, flavouring, preserving or emulsifying agents, and antioxidants, buffers, bacteriostats or solutes to render the compound isotonic.  Tablets, capsules and injection solutions containing 2-ethyl-2-methyl-1,2,3,4 - tetrahydroisoquinolinium iodide, 2-(2 - hydroxyethyl) - 2 - methyltetrahydroisoquinolinium bromide or iodide and 2-amino-2-ethyl - 1,2,3,4 - tetrahydroisoquinolinium iodide are described.  Other anions referred to are sulphate, methyl-sulphate and p-toluenesulphonate anions.  In the third Provisional Specification R1 and R2 are additionally defined as isopropyl and allyl; and the isoquinolinium nucleus may be optionally substituted at the 8-position with a methyl or nitro group.  In the fourth Provisional Specification R2 is defined as an alkyl, hydroxyalkyl or alkenyl group, R1 being an amino group.