Patent GB-694738-A (GB)
Title: Improvements in or relating to quinone compounds and the preparation thereof
IPC: C07D211/08
Filed: 1950-10-03
Abstract: The invention comprises (a) quaternary ammonium compounds of the general formula <FORM:0694738/IV (b)/1> (wherein R represents hydrogen or a methyl radical, -N(tert) represents a tertiary amine radical containing not more than 20 carbon atoms and devoid of aryl radicals directly attached to the nitrogen atom, Y represents an alkylene bridge interposing 2-5 carbon atoms between the nitrogen atoms connected thereby, Z represents hydrogen, an alkylamino or dialkylamino, or a second (identical or different) iminoalkyl-(quaternary ammonium) radical of the formula <FORM:0694738/IV (b)/2> An represents a non-toxic anion, and X1 and X2 are identical and each represent hydrogen or, when Z is an iminoalkyl-(quaternary ammonium) radical, may represent chlorine or bromine; (b) tertiary amines of the general formula <FORM:0694738/IV (b)/3> (wherein -N = B represents a di-(lower alkyl)-amino, piperidino or pyrrolidino radical, Y1 represents an alkylene bridge interposing 3-5 carbon atoms between the nitrogen atoms connected thereby, Z3 represents hydrogen, a mono- or di-(lower alkyl)-amino radical or a second (identical or different) radical -NH-Y1-N = B, and "lower alkyl" means an alkyl radical of 1-5 carbon atoms), and their salts (e.g. hydrochlorides, hydrobromides, sulphates, tartrates, nitrates and citrates); (c) the manufacture of compounds of the general formula <FORM:0694738/IV (b)/4> (wherein R2 and R3 represent aliphatic, cycloaliphatic or araliphatic radicals or jointly form, with the nitrogen atom to which they are attached, a saturated 5 or 6-membered heterocyclic ring, and Z1 represents hydrogen, an alkylamino or dialkylamino radical or a second radical -NR-Y-NR2R3) by reacting p-benzoquinone under conditions of mild oxidation with a diamine or diamines of the formula HNR-Y-NR2R3 or with one molecular proportion of such a diamine and then with one of a mono- or di-alkylamine; (d) the manufacture of compounds of the general formula <FORM:0694738/IV (b)/5> (wherein each X represents chlorine or bromine) by reacting chloranil or bromanil with two molecular proportions of an amine HNR-Y-NR2R3; (e) the manufacture of the quaternary ammonium compounds defined in (a) by treating the appropriate (tertiary amino) alkylamino-p-benzoquinone with a quaternizing agent.  The compounds defined in (a) and (b) are useful as pharmaceutical agents, the former having strong and the latter moderate curarimimetic activity.  The residue represented by -N(tert) in the compounds of (a) is preferably of the form -NR1R2R3 wherein R1 is an aliphatic radical (e.g. an alkyl radical such as methyl, ethyl, n-butyl or n-heptyl or an alkenyl radical such as allyl or methallyl) or an aralkyl radical which may carry inert substituents, such as alkyl, alkoxy or halogen, in the ring (e.g. benzyl, p-methoxybenzyl, 2 : 4 : 6-trimethoxybenzyl, p-chlorobenzyl or methylbenzyl), and R2 and R3 are as defined in (c), e.g. they may be alkyl radicals such as methyl, ethyl, n- or isopropyl, n-butyl or isohexyl, alkenyl radicals such as allyl or methallyl, aralkyl radicals such as benzyl, phenethyl, p-chlorobenzyl, p-methoxybenzyl or o-ethoxybenzyl, cycloalkyl radicals such as cyclohexyl or cyclopentyl, or cycloalkenyl radicals such as 2-cyclohexenyl or 2-cyclopentenyl, or they may form with the nitrogen atom a piperidino, 2-methylpiperidino, morpholino, thiamorpholino or pyrrolidino radical.  In the process of (c), the introduction of only one group -NR-Y-NR2R3 may be ensured by using not more than about one mol. of diamine per mol. of p-benzoquinone, or by carrying out the reaction in concentrated solution so that the monosubstituted compound precipitates as it is formed, or by working at comparatively low temperatures (e.g. 20-25 DEG  C.).  The conditions of mild oxidation may be provided by passing air or preferably oxygen through the reaction mixture, or p  when introducing only one -NR-Y-NR2R3 group, by using excess of p-benzoquinone to act as an oxidizing agent. Suitable quaternizing agents for the process of (e) are esters of (preferably primary) aliphatic or araliphatic alcohols with strong organic or inorganic acids, e.g. methyl or ethyl iodide or p-toluenesulphonate, methyl bromide, dimethyl sulphate, ethyl chloroacetate, n-propyl iodide, allyl chloride or bromide, n-hexyl bromide, benzyl chloride or bromide, or p-methoxy- or p-chloro-benzyl chloride.  Examples describe the preparation of: (1) 2 : 5 - bis - (31-diethylaminopropylamino)-p-benzoquinone and its dihydrochloride, bis-(benzyl chloride) and bis-methobromide; (2) 2 - (21 - diethylaminoethylamino) - p - benzoquinone and its methobromide; (3) 2 : 5-bis-(21 - diethylaminoethylamino) - p - benzoquinone and its bis-(benzyl chloride); (4) 2 : 5-bis - (21 - morpholinoethylamino) - p - benzoquinone and its bis-methobromide; (5) 2-(31-dimethylaminopropylamino) - p - benzoquinone; (6) 2-(31-piperidinopropylamino)-p-benzoquinone and its methobromide; (7) 2-(N-31-piperidinopropyl - N - methylamino) - p - benzoquinone; (8) 2 : 5-bis-(31-dimethylaminopropylamino) - p - benzoquinone and its bis - (benzyl chloride); (9) 2 : 5 - bis - (31 - di - n - propylaminopropylamino)-p-benzoquinone and its bis-(benzyl chloride) and bis-methobromide; (10) 2 : 5 - bis - (31 - piperidinopropylamino) - p-benzoquinone and its bis-methobromide and bis - (benzyl chloride); (11) 2 : 5 - bis - (N - 31-piperidinopropyl - N - methylamino) - p - benzoquinone and its bis-methobromide; (12) 2 : 5-bis - (31 - morpholinopropylamino) - p - benzoquinone and its bis-methobromide; (13) 2-(41 - diethylaminobutylamino) - p - benzoquinone and its methobromide; (14) 2-(41-diethylaminobutylamino) - 5 - methylamino - p-benzoquinone; (15) 2 : 5 - bis - (41 - diethylaminobutylamino) - p - benzoquinone and its bis-methobromide and bis-(benzyl chloride); (16) 2 : 5 - bis - (51 - diethylaminoamylamino)-p-benzoquinone and its bis-methobromide; (17) 2 : 5 - bis - (51 - piperidinoamylamino) - p-benzoquinone and its bis-methobromide; (18) 2 - (51 - diethylaminoamylamino) - p - benzoquinone and its methobromide; (19) 2-(51-piperidinoamylamino)-p-benzoquinone and its hydrobromide; (20) 2 : 5-bis-(31-diethylaminopropylamino) - 3 : 6 - dichloro - p - benzoquinone and its bis-(benzyl chloride).  Reference is also made to 2 : 5-bis-(31-ethylmethylaminopropylamino) - p - benzoquinone, 2 - (31 - (211-methylpiperidino) - propylamino) - p - benzoquinone, 2 - (31 - pyrrolidinopropylamino) - p-benzoquinone and 2 - (41 - diethylaminobutylamino) - 5 - dimethylamino - p - benzoquinone.