Nadezhda M. Svirskaya

Preparation of adamantyl derivatives of 1,4-; 1,6- and 1,7-dihydroxynaphthalenes and assignment of their NMR data

Adamantylation of dihydroxynaphthalenes with the hydroxyl groups on the same or different rings leads to compounds that are convenient starting materials in target‐oriented organic synthesis. Here, we report the 1H and 13C NMR assignments of eight 1‐adamantyl substituted derivatives of 1,4‐; 1,6‐ and 1,7‐dihydroxynaphthalenes. The data acquired and peculiarities of their molecular structure are useful for extrapolation for prompt characterization of compounds containing adamantane, dihydroxynaphthalenes or naphthoquinone units. Copyright

Reaction of phenols with 1-adamantanol in the presence of 1-bromoadamantane

A solvent-free reaction of phenol with 1-adamantanol in the presence of 1-bromoadamantane at ∼200 °C gives 2,4,6-tri(1-adamantyl)phenol. Pyrocatechol, o- and p-cresols, and p-halophenols under these conditions form diadamantylated derivatives.

Adamantylation of polysubstituted arenes in trifluoroacetic acid

A reaction of 2,3-xylenol, 2,3-dichlorophenol, and 1,3-disubstituted benzenes with 1-adamantanol in trifluoroacetic acid leads to the corresponding monoand diadamantylated products.

Spectral assignment of new adamantane derivatives of 1,3-; 1,5-dihydroxy- and 1,5-dimethylnaphthalenes

1,3(I) and 1,5-dihydroxynaphthalens (II) as well as 1,5dimethylnaphthalene (III) are considered and investigated as template for building up various derivatives due to specific arrangement of the hydroxyl groups in its molecule (orthoandmetafor I; orthoand perifor II-III). Furthermore, some compounds containing resorcinol moiety exhibit depigmentation activity. A wide applications of adamantane derivatives allows to suggest that containing in its structure above-listed compounds I-III are of definite practical interest. Also it should be noted that aromatic compounds with an adamantane at the ortho-position to the hydroxyl groups are the key skeletons of synthetic retinoid analogues and supporting ligands of many homogeneous transition-metal catalysts. Moreover, recently much attention has been heeded to dearomatization reactions of aromatic and heteroaromatic compounds due to the highly reactive intermediates opportunities. Current report is an ongoing research of determination structure and features of adamantyl derivatives of dihydroxynaphthalenes by NMR spectroscopy. We describe here assignments of H and C NMR spectra of synthesized 1-adamantyl substituted compounds I-III. Additionally, previously defined patterns on the effect of OH-group in the orthoormetaposition to adamantane for its H and C NMR spectra have been confirmed on the basis of found spectral data. Such information can be useful for unambiguous interpretation of more sophisticated adamantyl derivatives of various naphthalene-units contain compounds, including their dearomatized derivatives.

1H and 13C NMR spectral assignments of novel adamantyl and di-adamantyl derivatives of 1,2-dihydroxynaphthalenes, 1,8-dihydroxynaphthalenes, 2,3-dihydroxynaphthalenes, 2,6-dihydroxynaphthalenes and 2,7-dihydroxynaphthalenes

Despite the fact that since the discovery and development methods of preparation and isolation of various dihydroxynaphthalenes passed a long time, at present, each of the ten isomers continue to find more and more fields of application. Among them, 1,8-dihydroxynaphthalene and their derivatives take a special place because the peri-interactions in 1,8-substituted naphthalene skeleton have an influence on the physical and chemical properties of these compounds. In addition, currently, the properties of equatorenes [chiral polycyclic aromatic hydrocarbons containing bis(1-adamantyl) groups at the peri-positions] were actively investigated, and in the case of 1,8-bis(1-adamantyl)naphthalene, a distortion of an aromatic ring system was determined. Studies by NMR spectroscopy of various perieffects of naphthalene-containing compounds as well as analysis of influence of different-sized substituents on an aromaticity in hydroxynaphthalene system are an important topic in NMR literature. On the other hand, to date, numerous studies have reliably found that the adamantyl moiety generally increases the lipophilicity and positively modulates the therapeutic index of many experimental substances via various mechanisms. Many of these adamantylmodified compounds contain in their structure a variety of aromatic components. Beyond pharmaceutical chemistry, the most practical applications are discovered among hydroxyaromatic compounds with adamantane in the ortho-position relative to the hydroxyl groups. In addition, nuclear magnetic resonance properties of adamantane, its derivatives, and higher adamantalog series continue to be actively explored. We continue to describe adamantyl derivatives of the homologous series of different naphthalenediols and their NMR features. Previously, NMR spectra of 1,4-dihydroxynaphthalenes, 1,6-dihydroxynaphthalenes, 1,7-dihydroxynaphthalenes, 1,3dihydroxynaphthalenes and 1,5-dihydroxynaphthalenes with one or two adamantyl groups were characterized in details. In the current paper, we report complete H and C spectral assignments of mono-adamantyl and di-adamantyl-containing derivatives of 1,2-dihydroxynaphthalenes, 2,3-dihydroxynaphthalenes, 2,6-dihydroxynaphthalenes, 2,7-dihydroxynaphthalenes and 1,8-dihydroxynaphthalenes and 6-(1-adamantyl)-2,3-dihydroxynaphthalene synthesized previously. Some of these NMR spectra show expected features associated with the symmetry of the molecules. The obtained results, together with the data from previous articles, will expand information on the effect of bulky substituents on molecular constitution of hydroxynaphthalene systems and thus will be a useful resource in their structure elucidation by NMR spectroscopy.

Improved Synthesis of 2-(1-Adamantyl)-4-bromophenol and 2-(1-Adamantyl)-4-bromoanisole, Intermediates in Adapalene Synthesis

A new simple and environmentally friendly synthetic method for 2-(1-adamantyl)-4-bromophenol that did not use catalysts and solvents was developed. A new simplified preparation method for 2-(1-adamantyl)-4-bromoanisole in one step instead of two was proposed. Both compounds are intermediates in the first and second synthetic steps to 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid (adapalene).