Concise Synthesis of [1,1′‐Biisoquinoline]‐4,4′‐diol via a Protecting Group Strategy and Its Application for Potential Liquid‐Crystalline Compounds

Abstract

The [1,1′‐biisoquinoline]‐4,4′‐diol (4a), which was obtained as hydrochloride 4a⋅2 HCl in two steps starting from the methoxymethyl (MOM)‐protected 1‐chloroisoquinoline 8 (Scheme 3), opens access to further O‐functionalized biisoquinoline derivatives. Compound 4a⋅2 HCl was esterified with 4‐(hexadecyloxy)benzoyl chloride (5b) to give the corresponding diester 3b (Scheme 4), which could not be obtained by Ni‐mediated homocoupling of 6b (Scheme 2). The ether derivative 2b was accessible in good yield by reaction of 4a⋅2 HCl with the respective alkyl bromide 9 under the conditions of Williamson etherification (Scheme 4). Slightly modified conditions were applied to the esterification of 4a⋅2 HCl with galloyl chlorides 10a–h as well as etherification of 4a⋅2 HCl with 6‐bromohexyl tris(alkyloxy)benzoates 11b,d–h and [(6‐bromohexyl)oxy]‐substituted pentakis(alkyloxy)triphenylenes 14a–c (Scheme 5). Despite the bulky substituents, the respective target 1,1′‐biisoquinolines 12, 13, and 15 were isolated in 14–86% yield (Table).

1,1′-Biisoquinolines—Neglected Ligands in the Heterocyclic Diimine Family That Provoke Stereochemical Reflections

“…The reaction of 1-bromoisoquinoline with either sodium or magnesium does not yield 3 [ 79 ]. The coupling of 1-haloisoquinolines has been achieved with Zn–[NiBr 2 (PPh 3 ) 2 ] [ 47 , 82 ], Zn–[NiBr 2 (PPh 3 ) 2 ]–(Et 4 N)I [ 70 , 83 ], Zn–NiCl 2 –PPh 3 [ 43 , 44 , 45 , 46 , 84 , 85 , 86 , 87 ] or In–[Pd(PPh 3 ) 4 ] [ 88 ] catalysts. Substituted derivatives of biiq which have been prepared using this approach include 3,3′-Me 2 biiq [ 84 ], 8,8′-Me 2 biiq [ 45 , 46 ], 3,3′-Et 2 biiq [ 84 ], 8,8′-Et 2 biiq [ 45 , 46 ], 3,3′-( i Pr) 2 biiq [ 84 ], 8,8′-( i Pr) 2 biiq [ 45 , 46 ], 8,8′-( t Bu) 2 biiq [ 45 , 46 ], 3,3′-Ph 2 biiq [ 84 ], 3,3′-(2-py) 2 biiq [ 84 ], 6,6′-(MeO) 2 biiq [ 84 ], 3,3′-(MeO 2 C) 2 biiq [ 83 ], 3,3′-(HO 2 C) 2 biiq [ 83 ], 4,4′-(C n H 2 n +1 O) 2 biiq ( n = 1–11, 13, 17) [ 86 ], 4,4′-{ n ROC 6 H 4 O(CH 2 ) n O} 2 biiq ( R = C 6 H 13 , C 8 H 17 ; n = 4, 6) [ 86 ].…”

The crystal structure of 1,1′-bisisoquinoline, C18H12N2

“…For enhancing the transannular steric hindrance a series of 8,8′-dialkylsubstituted 1,1-bisisoquinolines were synthesized, whereby dihedric angles between both isoquinoline moieties of 77.68°(Me) and 86.27°( Et) can be observed [19]. Introducing ethoxy substituents in the 4,4′-positions leads to a dihedral angle of 66.20° [20]. During complexation reaction the isoquinoline subunits can forced into a more planar position depending on the requirements of the metal centre [13].…”