Chemistry of aporphines. III. Mechanism of carbon-carbon cleavage with potassium borohydride. Reduction products of nitrobenzylisoquinolinium salts

Neumeyer, John L.; McCarthy, Monica; Levins, P.L.

doi:10.1021/jo01271a062

Cited by 17 publications

(6 citation statements)

References 1 publication

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“…to the corresponding benzyltetrahydroisoquinoline (5). Despite reaction conditions favoring cleavage, no scission of the exocyclic linkage was observed.…”

Section: Resultsmentioning

confidence: 94%

“…5 In the limited number of 2-nitrobenzylisoquinolinium salts examined in these earlier experiments, we concluded that cleavage occurs when the nitro group is coplanar with the benzene ring and is able to stabilize the transition state for the nitrotoluene anion (i.e., la and lg).4•5 However, when the nitro group is sterically hindered and forced out of the plane of the benzene ring as in the case of le and If only reduction to the tetrahydrobenzylisoquinoline derivative takes place. 5 In an extension of these earlier studies several positional isomers of nitrobenzylisoquinolinium salts 1 were synthesized or were available in our laboratory and subjected to conditions known to lead to fragmentation. The quaternary salts 1 were prepared by refluxing the appropriate nitrobenzylisoquinoline1 with either methyl iodide or 1-iodopropane and were then subjected to borohydride reduction as described in the Experimental Section.…”

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confidence: 99%

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Aporphines. 20. Chemically induced fragmentation of nitrobenzylisoquinolinium salts

Neumeyer¹,

Dafeldecker²

1977

J. Org. Chem.

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“…to the corresponding benzyltetrahydroisoquinoline (5). Despite reaction conditions favoring cleavage, no scission of the exocyclic linkage was observed.…”

Section: Resultsmentioning

confidence: 94%

mentioning

confidence: 99%

Aporphines. 20. Chemically induced fragmentation of nitrobenzylisoquinolinium salts

Neumeyer¹,

Dafeldecker²

1977

J. Org. Chem.

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“…2-Benzoyl-l-(2-nitro-4-methoxylbenzyl)-l,2-dihydroquinaldonitrile (8). A solution of 2.62 g (10 mmol) of 7 in 40 ml of dry dimethylformamide was cooled to -15°and equimolar amounts of 6 and sodium hydride (50% mineral oil suspension) were added.…”

Section: Methodsmentioning

confidence: 99%

Aporphines. 14. Dopaminergic and antinociceptive activity of aporphine derivatives. Synthesis of 10-hydroxyaporphines and 10-hydroxy-N-propylnoraporphine

Neumeyer¹,

Reinhard²,

Dafeldecker³

et al. 1976

J. Med. Chem.

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The synthesis of racemic 10-hydroxyaporphine [(+/-)-2a] and 10-hydroxy-N-n-propylnoraporphine [(+/)-2b] is described. The method involved a Reissert alkylation-Pschorr cyclization route. The dopaminergic activity of (+/-)-2b was evaluated in comparison with L-Dopa, (-)-apomorphine (1a), (+/-)-N-n-propylnorapomorphine (NPA) (1b), and (+/-)-11-hydroxy-N-n-propylnoraporphine [(+/-)-11-OH-PNA] by the behavioral model of rotational behavior in animals after unilateral lesion of the ascending DA pathways. The dopaminergic activity of NPA and 11-OH-PNA is essentially equivalent to L-Dopa and (-)-apomorphine, and both are more active than (+/-)-2b. Furthermore, (+/-)-NPA (threshold doses, 5 mug/kg) appears to be even more potent that (-)-apomorphine (threshold doses, 25 mug/kg). The duration of action of NPA and 11-OH-PNA is considerably longer than that obtained with L-Dopa. The antinociceptive activity of (+/-)-2b was evaluated by the tail-flick procedure and compared with 1a, 2b, morphine, and L-Dopa. Weak but significant antinociceptive activity was shown by (+/-)-2b and by (+/-)-1b but not by (-)-apomorphine. This effect was not antagonized by naloxone. The finding that (+/-)-2b and particularly (+/-)-11-OH-PNA are active in doses from 500 to 50 mug/kg, respectively, in causing rotational behavior further supports previous studies indicating that N-n-propyl derivatives of monohydroxylated aporphines were more active than the corresponding parent N-methyl derivatives as DA receptor agonists and that a catechol system is not an absolute requirement for dopaminergic activity in such aporphines.

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“…The Bischler-Napieralski product 1- 19,20 This subsequent reduction would have given 2-methylisoquinoline and 3,4-dimethoxy-2-nitrotoluene.…”

Section: N-methylation and Reductionmentioning

confidence: 99%

Application of the Bischler–Napieralski–Pschorr radiosynthesis of (R)-(-)-[6a-14C]apomorphine, a non-selective D1/D2 dopamine receptor agonist

Kitson¹,

Knagg²

2006

J Label Compd Radiopharm

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A method has been developed for the carbon‐14 radiosynthesis of non‐narcotic morphine derivative (R)‐(‐)‐[6a‐14C]apomorphine (1) from the starting material 3,4‐dimethoxy‐2‐nitrophenyl‐N‐phenethyl[carboxyl‐14C]acetamide (5). The key to this synthesis was the application of the Bischler–Napieralski cyclodehydration to 1‐(3,4‐dimethoxy‐2‐nitrobenzyl)dihydro[1‐14C]isoquinoline (4), followed by N‐methylation and reduction to 1‐(3,4‐dimethoxy‐2‐nitrobenzyl)‐2‐methyl‐1,2,3,4‐tetrahydro[1‐14C]isoquinoline (3). A final Pschorr reductive ring closure followed by chiral separation to give (R)‐(‐)‐[6a‐14C]apomorphine dimethyl ether (2) and O‐demethylation led to (R)‐(‐)‐[6a‐14C]apomorphine (1) with a specific activity of 55 mCi/mmol, radiochemical purity of >98% and chiral purity of >99%. Copyright © 2006 John Wiley & Sons, Ltd.

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Chemistry of aporphines. III. Mechanism of carbon-carbon cleavage with potassium borohydride. Reduction products of nitrobenzylisoquinolinium salts

Cited by 17 publications

References 1 publication

Aporphines. 20. Chemically induced fragmentation of nitrobenzylisoquinolinium salts

Aporphines. 20. Chemically induced fragmentation of nitrobenzylisoquinolinium salts

Aporphines. 14. Dopaminergic and antinociceptive activity of aporphine derivatives. Synthesis of 10-hydroxyaporphines and 10-hydroxy-N-propylnoraporphine

Application of the Bischler–Napieralski–Pschorr radiosynthesis of (R)-(-)-[6a-14C]apomorphine, a non-selective D1/D2 dopamine receptor agonist

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