RESUMO
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.
Assuntos
Carbono/química , Cobalto/química , Nanopartículas de Magnetita/química , Sulfonas/síntese química , Alquilação , Ácidos Carboxílicos/química , Indicadores e Reagentes , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
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.
Assuntos
Alquilantes/química , Dióxido de Silício/química , Tiazepinas/síntese química , Alquilação , Aminas/síntese química , Aminas/química , Compostos de Benzil/síntese química , Indicadores e Reagentes , Óxidos , Fosfatos/química , Estereoisomerismo , Triazóis/síntese químicaRESUMO
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.
Assuntos
Alquilantes/química , Compostos de Benzil/síntese química , Compostos Heterocíclicos/síntese química , Dióxido de Silício/química , Triazóis/química , Boranos/química , Indicadores e Reagentes , Nióbio/química , Polimerização , Reprodutibilidade dos TestesRESUMO
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.
Assuntos
Compostos de Benzil/química , Fosfatos/química , Dióxido de Silício/química , Triazóis/química , Alquilação , Conformação Molecular , Tamanho da Partícula , Fosfatos/síntese química , Propriedades de SuperfícieRESUMO
An operationally simple method for the acylation of amines utilizing carbon-coated metal nanoparticles as recyclable supports is reported. Highly magnetic carbon-coated cobalt (Co/C) and iron (Fe/C) nanobeads were functionalized with a norbornene tag (Nb-tag) through a "click" reaction followed by surface activation employing Grubbs-II catalyst and subsequent grafting of acylated N-hydroxysuccinimide ROMPgels (ROMP=ring-opening metathesis polymerization). The high loading (up to 2.6 mmolg(-1) ) hybrid material was applied in the acylation of various primary and secondary amines. The products were isolated in high yields (86-99%) and excellent purities (all >95 % by NMR spectroscopy) after rapid magnetic decantation and simple evaporation of the solvents. The spent resins were successfully re-acylated by acid chlorides, anhydrides, and carboxylic acids and reused for up to five consecutive cycles without considerable loss of activity.
Assuntos
Cobalto/química , Ferro/química , Nanopartículas Metálicas/química , Succinimidas/química , Acilação , Carbono/química , Fenômenos Magnéticos , Norbornanos/química , Compostos Organometálicos/química , Polimerização , ReciclagemRESUMO
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.
Assuntos
Benzotiadiazinas/síntese química , Micro-Ondas , Óxidos/síntese química , Fosfatos/química , Bibliotecas de Moléculas Pequenas/síntese química , Triazóis/química , Benzotiadiazinas/química , Técnicas de Química Combinatória , Metilação , Estrutura Molecular , Óxidos/química , Bibliotecas de Moléculas Pequenas/química , EstereoisomerismoRESUMO
A novel one-pot sulfonylation/intramolecular thia-Michael protocol is reported for the synthesis of 1,5,2-dithiazepine 1,1-dioxides. Sulfonylation between cysteine ethyl ester/cysteamine and 2-chloroethanesulfonyl chloride, followed by in situ intramolecular thia-Michael addition, was achieved and afforded the titled 1,5,2-dithiazepine-1,1-dioxide scaffolds. Diversification was demonstrated for future library synthesis.
RESUMO
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.
Assuntos
Benzeno/química , Técnicas de Química Sintética/métodos , Tiadiazinas/química , Tiadiazinas/síntese química , Ciclização , Nanopartículas/químicaRESUMO
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.
Assuntos
Fosfatos/química , Triazóis/química , Estrutura Molecular , PolimerizaçãoRESUMO
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.
Assuntos
Polímeros/síntese química , Magnetismo , Nanopartículas Metálicas/químicaRESUMO
The combination of norbornenyl-tagged (Nb-tagged) silica particles and functionalized Nb-tagged monomers for the generation of hybrid Si-ROMP reagents and scavengers is reported. Specifically Si-ROMP-derived bis-acid chloride, dichlorotriazine, and triphenylphosphine scavenger/reagents have been grafted from the surface of silica particles utilizing surface-initiated, ring-opening metathesis polymerization (ROMP). These hybrid polymeric materials combine the physical properties of current immobilized silica reagents and represent a key advancement in load by merging the inherent tunable properties of the ROMP-derived oligomers with silica supports for application in a parallel synthesis.
Assuntos
Compostos de Silício/química , Microscopia Eletrônica de Varredura , Estrutura MolecularRESUMO
The development of new ROMP-based oligomeric benzyl phosphates (OBP(n)) is reported for use as soluble, stable benzylating reagents. These oligomeric reagents are readily synthesized from commercially available materials and conveniently polymerized and purified in a one-pot process, affording bench-stable, pure white, free-flowing solids on multigram scale. Utilization in benzylation reactions with a variety of nucleophiles is reported.
Assuntos
Compostos de Benzil/síntese química , Fosfatos/química , Compostos de Benzil/química , Conformação Molecular , EstereoisomerismoRESUMO
We describe herein a one-pot synthesis of novel tetracyclic scaffolds that incorporate a fusion of a proline, 1,2,3-triazole ring with [1,4]-benzodiazepin-8(4H)-one ring systems following click chemistry. The expected peptide bond formation followed by in situ 1,3-dipolar cycloaddition in absence of any catalyst led to the formation of new triazole fused benzodiazepine derivatives.
