Cubane derivatives 7. Synthesis and molecular structure of 4-bromo-1-hydroxymethylcubane

Abstract

The present study concerned with reduction of methyl 4 bromocubanecarboxylate (1) with lithium aluminum hydride and aluminum hydride in THF. An efficient procedure was devel oped for the synthesis of 4 bromo 1 hydroxymethylcubane (2) based on reduction of com pound 1 with aluminum hydride under mild conditions. The structure of 2 was established by X ray diffraction.Key words: methyl 4 bromocubanecarboxylate, 4 bromo 1 hydroxymethylcubane, hydroxymethylcubane, reduction, lithium aluminum hydride, aluminum hydride, X ray dif fraction study.Cubane derivatives attract considerable interest as po tential pharmaceuticals. 2-6 However, their synthesis in volves many steps. Hence, the development of efficient and selective methods for modifications of compounds containing the cubane fragment and investigation of their structures are of great importance.The present study continues our research on reduc tion of cubane derivatives containing different functional groups with light metal hydrides. 7-11The aim of the study was to develop a more efficient procedure (compared to a known method 12 ) for the syn thesis of 4 bromo 1 hydroxymethylcubane and establish its structure. This compound can be used as an intermedi ate for the synthesis of biologically active compounds, in particular, of nitrates of cubane containing alcohols.Since the synthesis of various cubane derivatives in volves many steps, it is necessary to elaborate procedures for the preparation of intermediates in high yields in indi vidual steps. Our attempts to increase the yield of carbinol 2 reported earlier (80%) in reduction of ester 1 with lithium aluminum hydride 12 by performing the reaction at higher temperature (65 °С) over a longer period of time with the use of an excess of LiAlH 4 failed. The yield of com pound 2 was no higher than 80%. When the reaction was performed for 48-300 h, the yield decreased due to hydrodebromination (Scheme 1).With the aim of developing a more efficient and selec tive procedure for the preparation of carbinol 2, we stud ied reduction of ester 1 with aluminum hydride. This reaction was found to occur under mild conditions (15-25 °С) and proceed much faster (4 h at 20 °С) than the reaction with LiAlH 4 to give the target product in higher yield (∼94%) (see Scheme 1). In addition, this process is highly selective. Thus, reduction of ester 1 with AlH 3 was not accompanied by hydrodebromination for several days.The structure of product 2 was established by X ray diffraction (Fig.

Not Your Usual Bioisostere: Solid State Study of 3D Interactions in Cubanes

“…Therefore, this linear stacking can only indicate the potential interactions between the cubane scaffolds. The structure of 4‐bromo‐1‐(hydroxymethyl)cubane ( 50 ) shows the alcohol moiety in a linear hydrogen bonding fashion (Figure S23) . This allows the bromine atoms to interact with the hydrogen of the cubane in the next layer to create a 3D lattice.…”

“…The structure of 4-bromo-1-(hydroxymethyl)cubane( 50)s hows the alcohol moietyi nalinear hydrogen bondingf ashion ( Figure S23). [25] This allows the bromine atoms to interact with the hydrogen of the cubane in the next layer to create a3 Dl attice.W hen substituting hydroxymethyl for a methyl nitrate (51)t he NO 2 group interacts with the cubane the CH 2 hydrogen atoms. [12a] This leaves bromine atoms close to each other to form ad irecth alogen-bonded network (Figure S24).…”

Cubane derivatives 10. Synthesis and molecular structures of nitroxymethylcubanes

“…Previously, 5, 6 it has been shown that the reduction of dimethyl cubane 1,4 dicarboxylate (1a) and methyl 4 bromocubane 1 carboxylate (2) afforded 1,4 bis (hydroxymethyl)cubane (3) and 4 bromo 1 hydroxy methylcubane (4). In the present work, 1,4 bis(nitroxy methyl)cubane (5) and 4 bromo 1 nitroxymethylcubane (6) (Scheme 1) were synthesized for the first time and characterized.…”