ABSTRACT
The development and application of high-load, recyclable magnetic Co/C hybrid ROMP-derived benzenesulfonyl chloride and analogues is reported. The regeneration and utility of these reagents in the methylation/alkylation of various carboxylic acids is demonstrated via efficient retrieval of the magnetic reagent with a neodymium magnet. Additional reactions employing the analogue sulfonic acid and in situ generated magnetic benzenesulfonyl azide are also reported.
Subject(s)
Carbon/chemistry , Cobalt/chemistry , Magnetite Nanoparticles/chemistry , Sulfones/chemical synthesis , Alkylation , Carboxylic Acids/chemistry , Indicators and Reagents , Particle Size , Surface PropertiesABSTRACT
Applications of silica-ROMP reagents in a one-pot, sequential protocol have been developed for the synthesis of a variety of diverse benzoxathiazepine 1,1-dioxides. This protocol includes sulfonylation, intramolecular SNAr, alkylation with silica-supported oligomeric benzyl (Si-OBPn) and triazole (Si-OTPn) phosphates, and intermolecular SNAr addition with a number of secondary amines in one-pot to afford a variety of unique benzoxathiazepine 1,1-dioxides sultams in good to excellent yields.
Subject(s)
Alkylating Agents/chemistry , Silicon Dioxide/chemistry , Thiazepines/chemical synthesis , Alkylation , Amines/chemical synthesis , Amines/chemistry , Benzyl Compounds/chemical synthesis , Indicators and Reagents , Oxides , Phosphates/chemistry , Stereoisomerism , Triazoles/chemical synthesisABSTRACT
The development of new ROMP-derived silica-immobilized heterocyclic phosphate reagents and their application in purification-free protocols is reported. Grafting of norbornenyl norbornenyl-functionalized (Nb-tagged) silica particles with functionalized Nb-tagged heterocyclic phosphate monomers efficiently yield high-load, hybrid silica-immobilized oligomeric heterobenzyl phosphates (Si-OHBP) and heterotriazolyl phosphates (Si-OHTP) as efficient alkylation agents. Applications of these reagents for the diversification of N-, O-, and S-nucleophilic species, for efficient heterobenzylation and hetero(triazolyl)methylation have been validated.
Subject(s)
Alkylating Agents/chemistry , Benzyl Compounds/chemical synthesis , Heterocyclic Compounds/chemical synthesis , Silicon Dioxide/chemistry , Triazoles/chemistry , Boranes/chemistry , Indicators and Reagents , Niobium/chemistry , Polymerization , Reproducibility of ResultsABSTRACT
The syntheses of silica-supported oligomeric benzyl phosphates (Si-OBP(n)) and triazole phosphates (Si-OTP(n)) using ring-opening metathesis polymerization (ROMP) for use as efficient alkylating reagents is reported. Ease of synthesis and grafting onto the surface of norbornenyl-tagged (Nb-tagged) silica particles has been demonstrated for benzyl phosphate and triazole phosphate monomers. It is shown that these silica polymer hybrid reagents, Si-OBP(n) and Si-OTP(n), can be used to carry out alkylation reactions with an array of different nucleophiles to afford the corresponding benzylated and (triazolyl)methylated products in good yield and high purity.
Subject(s)
Benzyl Compounds/chemistry , Phosphates/chemistry , Silicon Dioxide/chemistry , Triazoles/chemistry , Alkylation , Molecular Conformation , Particle Size , Phosphates/chemical synthesis , Surface PropertiesABSTRACT
A combination of MACOS scale-out and ROMP-derived oligomeric triazole phosphates (OTP(n)) have been successfully utilized for the preparation of a 106-member library of triazole containing benzothiaoxazepine-1,1-dioxides. This report demonstrates the utilization of a suite of soluble OTP(n) reagents for facile (triazolyl)methylation of 10 MACOS-derived sultam scaffolds in purification-free process for parallel synthesis of small molecule collections for HTS.
Subject(s)
Benzothiadiazines/chemical synthesis , Microwaves , Oxides/chemical synthesis , Phosphates/chemistry , Small Molecule Libraries/chemical synthesis , Triazoles/chemistry , Benzothiadiazines/chemistry , Combinatorial Chemistry Techniques , Methylation , Molecular Structure , Oxides/chemistry , Small Molecule Libraries/chemistry , StereoisomerismABSTRACT
The utilization of a monomer-on-monomer (MoM) intramolecular Mitsunobu cyclization reaction employing norbornenyl-tagged (Nb-tagged) reagents is reported for the synthesis of benzofused thiadiazepine-dioxides. Facile purification was achieved via ring-opening metathesis (ROM) polymerization initiated by one of three metathesis catalyst methods: (i) free metathesis catalyst, (ii) surface-initiated catalyst-armed silica, or (iii) surface-initiated catalyst-armed Co/C magnetic nanoparticles.
Subject(s)
Benzene/chemistry , Chemistry Techniques, Synthetic/methods , Thiadiazines/chemistry , Thiadiazines/chemical synthesis , Cyclization , Nanoparticles/chemistryABSTRACT
Soluble, high-load ring-opening metathesis polymerization (ROMP)-derived oligomeric triazole phosphates (OTP) are reported for application as efficient triazolating reagents of nucleophilic species. Utilizing a "Click"-capture, ROMP, release protocol, the efficient and purification-free, direct triazolation of N-, O-, and S-nucleophilic species was successfully achieved. A variety of OTP derivatives were rapidly synthesized as free-flowing solids on a multigram scale from commercially available materials.
Subject(s)
Phosphates/chemistry , Triazoles/chemistry , Molecular Structure , PolymerizationABSTRACT
A monomer-on-monomer (MoM) Mitsunobu reaction utilizing norbornenyl-tagged (Nb-tagged) reagents is reported, whereby purification was rapidly achieved by employing ring-opening metathesis polymerization, which was initiated by any of three methods utilizing Grubbs catalyst: (i) free catalyst in solution, (ii) surface-initiated catalyst-armed silica, or (iii) surface-initiated catalyst-armed Co/C magnetic nanoparticles.
