Waste‐Free and Facile Solid‐State Protection of Diamines, Anthranilic Acid, Diols, and Polyols with Phenylboronic Acid

Abstract

Phenylboronic acid (2) reacts quantitatively by ball-milling in the solid state with o-phenylendiamine, 1,8-diaminonaphthalene, anthranilic acid, pyrocatechol, pyrogallol, pinacol, bicyclic cis-diols, mannitol, and inositol to form the five- or six-membered cyclic phenylboronic amides or esters. Catalysts or other auxiliaries are strictly excluded as they are not required and would have to be removed after the reactions. These varied model reactions provide pure protected products without the necessity of further purifying workup and the potential for protection chemistry is demonstrated. Some of the reactions can also be quantitatively performed if stoichiometric mixtures of the reactants are co-ground or co-milled and heated to appropriate temperatures either below the eutectics or above the melting points. The temperatures are much higher in the latter case. Similar reactions in solution suffer from less than 100 % yield of the mostly sensitive compounds that are difficult to purify and thus create much waste. The hydrolysis (deprotection) conditions of the products are rather mild in most cases. Therefore, this particularly easy access to heteroboroles, heteroborolanes, heteroborinones, heteroborines, and heteroborinines is highly valuable for their more frequent use in protective syntheses.

Organic Solid-State Reactions

“…The crystal packing of the components allow for the necessary molecular migrations. Similar solid-state reactions of diamines and amino acids with phenylboronic acid have also been realized [208]. The topic of solid-state ligand exchange at metals or metal ions surpasses the scope of this review and is thus not covered here.…”

“…One of these is the reaction of cholesterol [208] (Scheme 27). Numerous comillings of phenylboronic acids with solid 1,2-diols lead to phenylborolic esters in quantitative solid-state reactions.…”

“…The so protected hydroxyl groups are easily deprotected under neutral conditions. For example, 1-benzoyl-pyrogallol is synthesized by quantitative protection of two of the three vicinal phenolic OH groups of pyrogallol by stoichiometric milling with phenylboronic acid, so that benzoylation of the remaining OH group becomes possible and the other two hydroxyl groups can be deprotected by substitution of mannitol by the borolic ester [208]. Extraordinary specificities have been found with the polyols d-mannitol or myo-inositol and phenylboronic acid.…”

“…All six OH groups are protected and the water of reaction is taken up by the tris-borolic ester crystals. It can be removed at 80 ∘ C in a vacuum [208]. The crystal packing of the components allow for the necessary molecular migrations.…”

Organocatalytic clean synthesis of densely functionalized 4H-pyrans by bifunctional tetraethylammonium 2-(carbamoyl)benzoate using ball milling technique under mild conditions

“…Subsequently, some specific books and review papers have been published on the topic. Some typical examples include the carbon-carbon or carbon-heteroatom bond formation, oxidation by solid oxidants, asymmetric organocatalytic reactions, dehydrogenative coupling, and peptide or polymeric material synthesis (9,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). Furthermore, organocatalysis, namely the use of small organic molecules to catalyze organic transformations, is a relatively new and popular field within the domain of organic synthesis.…”