1,8-Bis(bromomethyl)naphthalene in the synthesis of 1,5-diazacyclodecane and benz[de]isoquinoline proton sponges

Simultaneous Formation of Isomeric and Polycyclic Proton Sponges Derived from 1,8‐Diaminonaphthalenes and Xylylene Dibromides

“…Indeed, during the deprotonation of out ‐cation 10H + , the deprotonating agent does not need to overcome obstacles in the form of bulky and hydrophobic alkyl groups, nor does it need to break the intramolecular hydrogen bond, as in cation 9H + . Nevertheless, both 9 and 10 are weaker bases than unsubstituted DMAN 1 (p K a =18.6, MeCN), [22] which quite naturally follows from the introduction of benzyl‐type substituents to the amine nitrogens [16,23] …”

“…By inspecting several reactions with unsubstituted 1,8-diaminonaphthalene, we wondered why some products are formed in high yields, while similar or even simpler ones are not. For example, excellent isolated yields using the appropriate dibromides are observed in the case of bi-heterocycles 7 (86 %) [15] and 8 (94 %), [16] while the reported yield for quite simple di(isoindoline) 9 was only 5 %. [8] This discrepancy forced us to repeat the interaction of diaminonaphthalene with o-xylylene dibromide.…”

“…Nevertheless, both 9 and 10 are weaker bases than unsubstituted DMAN 1 (pK a = 18.6, MeCN), [22] which quite naturally follows from the introduction of benzyl-type substituents to the amine nitrogens. [16,23] Of principal importance turned out to be the fact that both isomers 9 and 10 remain unchanged on boiling them for many hours in acetonitrile in the presence of hydrobromic acid. This excludes the possibility of their interconversion (isomerization) and confirms the independence of formation in the reaction depicted in Scheme 3.…”

“…The outcome depends on the length of the hydrocarbon moiety in the organic dihalide. For example, in the case of 1,2-dibromoethane and 1,3-dibromopropane, bridged compounds (A, e. g. 5) [8] are formed, but if the halogens are separated by 4-6 atoms, then this gives fiveto-seven-membered heterocycles (B, e. g. 3) [8,[14][15][16] exclusively (Scheme 2).…”