Series Of Benzoxazines Research Articles

Synthesis, ring-opening polymerization, and properties of benzoxazines based on o- and p-hydroxybenzyl alcohols

Two series of bifunctional benzoxazines were synthesized from o- and p-hydroxybenzyl alcohols ( oHBA and pHBA), three aliphatic diamines containing ether linkage (Jeffamines D230 and D400 and 4,7,10-trioxa-1,13-tridecanediamine (TTDDA)), and paraformaldehyde. The chemical structures of the benzoxazines were confirmed by 1H and 13C nuclear magnetic resonance and Fourier transform infrared (FTIR) spectroscopy. The ring-opening polymerization of the benzoxazines was studied by differential scanning calorimetry and FTIR, respectively. oHBA-based benzoxazines respectively exhibit lower onset temperatures of ring-opening polymerization than pHBA-based counterparts due to the O–H∙∙∙O intramolecular hydrogen-bonding interaction between the hydrogen of ortho-methylol group and the oxygen in oxazine ring, and oHBA-based polybenzoxazines respectively show lower glass transition temperatures ( Tgs) than pHBA-based counterparts due to the difference in crosslinking density caused by the steric hindrance effect of the position of methylol group on the polymerization of benzoxazine monomers. In each of the two series of benzoxazines, the onset temperature of ring-opening polymerization of D230-based benzoxazine is close to that of TTDDA-based analogue and lower than that of D400-based counterpart owing to the steric effect of the chain length and chain volume of the bridging structure between the oxazine rings on the polymerization, and the Tg of D230-based polybenzoxazine is close to that of TTDDA-based analogue and much higher than that of D400-based counterpart owing to the difference in crosslinking density caused by the steric hindrance effect of the bridging structure on the polymerization of benzoxazine monomers. In addition, all the polybenzoxazines exhibit thermally induced shape memory effect. In each of the two series of polybenzoxazines, the shape recovery rate and ratio of D400-based polybenzoxazine are respectively close to those of D230-based counterpart and higher than those of TTDDA-based analogue due to the difference in network architecture.

Synthesis, ADMET predictions, molecular docking studies, and in-vitro anticancer activity of some benzoxazines against A549 human lung cancer cells.

This study aims to synthesize a series of benzoxazines (1-5) to be examined as an epidermal growth factor receptor (EGFR) inhibitor by in-silico study. The overexpression of EGFR causes the growth of normal lung cells to become uncontrollable, which may lead to cancer formation. We also conducted the absorption, distribution, metabolism, excretions and toxicity (ADMET) properties evaluation and also examined in vitro anticancer assay on human lung cancer cells line, which is A549. Benzoxazines (1-5) were synthesized by reacting anthranilic acid and benzoyl chlorides. The structures of the compounds were determined with 1H, 13C-NMR, HRMS, UV and FT-IR spectrometric methods. Prediction of ADMET was using online pkCSM, and the molecular docking studies were using MVD with EGFR-TKIs as the target (PDB ID: 1M17). In vitro assay of anticancer activity was performed by MTT assay. Compounds 1-5 were successfully synthesized in good yields (71-84%). The ADMET prediction showed that benzoxazines are able to be absorbed through GIT, metabolized by CYP 450, and not hepatotoxic. The title compounds have a greater Moldock Score than Erlotinib, and 3 has the highest activity against A549 compared with other benzoxazines, IC50=36.6μg/mL. Compound (3) more active as anticancer against Human cancer cells line compared with other benzoxazines.

Effect of methoxy position on dynamic mechanical and shape memory properties of methoxyphenol-based polybenzoxazines

Two series of benzoxazines were synthesized from o-, m-, and p-methoxyphenols, two polyetheramines with different molecular weights, and formaldehyde. The glass transition temperatures (T gs) of m-methoxyphenol-based polybenzoxazines are respectively higher than those of o- and p-methoxyphenol-based counterparts. The polybenzoxazines exhibit thermally induced one-way dual-shape memory behavior based on T g, and the o- and p-methoxyphenol-based polybenzoxazines exhibit higher shape memory performance than m-methoxyphenol-based counterparts under motion constraints.

Synthesis, dynamic mechanical properties, and shape memory effect of polybenzoxazines based on monofluorophenol isomers and polyetheramines

Two series of benzoxazines are synthesized from a set of isomeric monofluorophenols (o-, m-, and p-fluorophenols), two polyetheramines (Jeffamine D230 and D400), and formaldehyde. The chemical structures of the benzoxazines are confirmed by nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy. For m-fluorophenol-based benzoxazines, the two sets of data appeared in the 13C, DEPT-135, and 19F NMR spectra indicate that each product obtained is a mixture of two isomers. The ring-opening polymerization temperatures for ortho, meta, and para isomers in the two series of benzoxazines are in descending order para > ortho > meta. The glass transition temperatures (Tgs) of the resultant polybenzoxazines are in ascending order ortho < para < meta. The polybenzoxazines exhibit thermally induced one-way dual-shape memory effect based on Tg, and the shape memory performance are excellent in tensile, bending, and twisting tests. Under motion constraints in a tensile deformation mode, the D400-based polybenzoxazines show higher shape recovery ratios compared with the corresponding D230 counterparts.

Two homochiral organocatalytic metal organic materials with nanoscopic channels

Two homochiral organocatalytic MOMs were prepared using tetra- and octa-carboxylate ligands, respectively. The nanoscopic channels in these MOMs are lined by organonocatalytic chiral phosphoric acid derivatives of binol and ocMOM-1 exhibited improved enantioselectivity over the parent ligand in the context of transfer hydrogenation of a series of benzoxazines.

Benzoxazine Series of Histidine Kinase Inhibitors as Potential Antimicrobial Agents with Activity against Enterococci

Background: Antibacterial activity of three members of a benzoxazine series of histidine kinase inhibitors (4a, 4b and 6) was studied on standard strains, and with 4b also on clinical isolates of enterococci. Methods: Susceptibility to each compound was tested using a broth macrodilution method with a range of dilutions from 0.016 to 128 μg/ml on four standard strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212) and in the case of 4b also on 52 clinical isolates of enterococci (7 vancomycin-susceptible E. faecalis, 15 vancomycin-susceptible Enterococcus faecium and 30 vancomycin-resistant E. faecium), and on two additional standard strains (S. aureus ATCC 43300 and E. faecalis ATCC 51299). Results: Neither of the compounds inhibited the growth of E. coli ATCC 25922 or P. aeruginosa ATCC 27853. Compound 4b inhibited the growth of S. aureus ATCC 29213 at 8 μg/ml, S. aureus ATCC 43300 at 32 μg/ml, E. faecalis ATCC 29212, and E. faecalis ATCC 51299 at 16 μg/ml, while 4a and 6 did so at higher concentrations. For clinical isolates of enterococci, the minimal inhibitory concentrations of 4b were in the range of 0.5–16 μg/ml. Conclusions: Compound 4b promises to be a potentially useful antimicrobial agent for vancomycin-susceptible and -resistant enterococci.

The Effect of Tb and Sm Ions on the Photochromic Behavior of Two Spiropyrans of Benzoxazine Series in Solution

The photochromism of [7′-hydroxy-8′-formyl-3-methyl-4-oxospiro[1,3-benzoxazin-2,2′-[2H-1]benzopyran],SP(I),[7′-hydroxy-8′-formyl-3-benzyl-4-oxospiro[1,3-benzoxazin-2,2′-[2H-1]benzopyran] SP(II) and their coordination with Tb3+and Sm3+ ions have been studied in DMF. UV/vis induced-color development due to heterolytic bond cleavage of SP(I) and SP(II) is greatly influenced by complexation with the lanthanide ions. The irradiation-induced color enhancement due to ring opening and thermal decoloration of the open forms of SP(I), SP(II) follows first-order kinetics. Physical characteristics of the studied systems such as colorability and relaxation time of thermal bleaching parameters were determined. Moreover, light-energy transfer-induced luminescence of lanthanide ions via coordination with the two spirobenzoxazines was monitored.

Dissociated Nonsteroidal Glucocorticoid Receptor Modulators; Discovery of the Agonist Trigger in a Tetrahydronaphthalene−Benzoxazine Series

The tetrahydronaphthalene-benzoxazine glucocorticoid receptor (GR) partial agonist 4b was optimized to produce potent full agonists of GR. Aromatic ring substitution of the tetrahydronaphthalene leads to weak GR antagonists. Discovery of an "agonist trigger" substituent on the saturated ring of the tetrahydronaphthalene leads to increased potency and efficacious GR agonism. These compounds are efficacy selective in an NFkB GR agonist assay (representing transrepression effects) over an MMTV GR agonist assay (representing transactivation effects). 52 and 60 have NFkB pIC(50) = 8.92 (105%) and 8.69 (92%) and MMTV pEC(50) = 8.20 (47%) and 7.75 (39%), respectively. The impact of the trigger substituent on agonism is modeled within GR and discussed. 36, 52, and 60 have anti-inflammatory activity in a mouse model of inflammation after topical dosing with 52 and 60, having an effect similar to that of dexamethasone. The original lead was discovered by a manual agreement docking method, and automation of this method is also described.

Binuclear Copper(II) Complexes with Hydrazones Containing Spiropyran Fragment

New hydrazones were prepared by the reaction of new spiropyran of benzoxazine series and aliphatic acid hydrazides; their binuclear complexes were synthesized.

Studies on the benzoxazine series. Part 3—Preparation and 13C NMR structural Study of γ Effects of Some N‐substituted 3,4‐dihydro‐2H‐1,3‐benzoxazines

AbstractSeventeen N‐substituted 3,4‐dihydro‐2H‐1,3‐benzoxazines [N‐substituent = Et, Pri, But, CH2C6H5 or CH(CH3)C6H5] were prepared and their structures studied in the light of 13C chemical shifts. The γ effects caused by C(α)‐methyl or C(α)‐phenyl substitution at the heterocyclic ring carbons were found to be valuable structural parameters. By using N‐tert‐butyl derivatives as models, and by dividing γtot effects into their components, the rotamer populations due to the rotation around the NC(α) bond could be evaluated. The method also allows the configurational assignment of diastereomeric N‐α‐methylbenzyl derivatives. The effect of the half‐chair structure on the 13C NMR parameters is discussed.

Studies on the benzoxazine series. 2—Preparation and1H and13C NMR structural study of some substituted 1,2‐dihydro‐4H‐3,1‐benzoxazines

AbstractIn addition to the parent compounds, nine methyl‐substituted 1,2‐dihydro‐4H‐3,1‐benzoxazines with and withoutN‐methyl substitution were prepared. The chain tautomer could only be detected in the case of 1,2‐dihydro‐2‐(p‐nitrophenyl)‐4H‐3,1‐benzoxazine in solution. The configurational and conformational assignments were based on1H and13C NMR data. The calculations of the methyl substituent effects on the heterocyclic ring (half‐chair structure) carbons gave a good fit between the observed and calculated shifts and made in possible to estimate that 1,2‐dihydro‐4‐methyl‐4H‐3,1‐benzoxazine is a 75:25 and itsN‐methyl derivative a 69:31 mixture of the 4eq′‐ and 4ax′‐ forms. 1,2‐Dihydro‐trans‐1,2,4‐trimethyl‐4H‐3,1‐benzoxazine is also not conformationally homogeneous, but is a 43:57 mixture of the 2eq,4ax′‐ and 2ax,4eq′‐ forms. A comparison of the13C chemical shift correlations with those of 3,4‐dihydro‐2H‐1,3‐benzoxazines also improves the structural knowledge about the latter series. Whereas theN‐methyl groups in 3,4‐dihydro‐2H‐1,3‐benzoxazines are axially orientated, model calculations reveal that theN‐methyl substitutions in the title compounds can be orientationally heterogeneous.

ChemInform Abstract: Studies on the Benzoxazine Series. Part 1. Preparation and 1H and 13C NMR Structural Study of Some Substituted 3,4‐Dihydro‐2H‐1,3‐benzoxazines.

ChemInformVolume 19, Issue 30 Physical Organic Chemistry ChemInform Abstract: Studies on the Benzoxazine Series. Part 1. Preparation and 1H and 13C NMR Structural Study of Some Substituted 3,4-Dihydro-2H-1,3-benzoxazines. K. NEUVONEN, K. NEUVONEN Dep. Chem., Univ. Turku, SF-20500 Turku, Finl.Search for more papers by this authorK. PIHLAJA, K. PIHLAJA Dep. Chem., Univ. Turku, SF-20500 Turku, Finl.Search for more papers by this author K. NEUVONEN, K. NEUVONEN Dep. Chem., Univ. Turku, SF-20500 Turku, Finl.Search for more papers by this authorK. PIHLAJA, K. PIHLAJA Dep. Chem., Univ. Turku, SF-20500 Turku, Finl.Search for more papers by this author First published: July 26, 1988 https://doi.org/10.1002/chin.198830064AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume19, Issue30July 26, 1988 RelatedInformation

Studies on the benzoxazine series. Part 1. Preparation and 1H and 13C nuclear magnetic resonance structural study of some substituted 3,4-dihydro-2H-1,3-benzoxazines

In addition to the parent compounds nine methyl-substituted 3,4-dihydro-2H-1,3-benzoxazines with and without N-methyl substitution were prepared. The former contain usually but minor amounts of the open-chain tautomer, too. The conformations and configurations of the oxazine rings were solved on the basis of 1H and 13C n.m.r. data which were best explained by assuming the N-methyl group predominantly axial in 3,4-dihydro-3-methyl-2H-1,3-benzoxazines. The oxazine ring prefers a half-chair form where the 4ax′-and 4eq′-methyl groups are practically equally stable. Hence, 3,4-dihydro-4-methyl-2H-benzoxazine is a 54 : 46 and the corresponding 3-methyl derivative an 8 : 92 mixture of the 4eq′ and 4ax′ forms. The 2,2,3,4-tetramethyl derivative is not conformationally homogeneous either. Substituent effects on 13C n.m.r. chemical shifts were found to be especially useful in configurational and conformational analysis and gave an excellent fit between observed and calculated shift values.

Rearrangement and reactions of allylthioimidate in the benzoxazine series

Journal of Heterocyclic ChemistryVolume 9, Issue 4 p. 943-945 Note Rearrangement and reactions of allylthioimidate in the benzoxazine series Sunil K. Roy, Sunil K. Roy Department of Chemical Research, G. D. Searle & Co., Skokie, Illinois, 60076Search for more papers by this author Sunil K. Roy, Sunil K. Roy Department of Chemical Research, G. D. Searle & Co., Skokie, Illinois, 60076Search for more papers by this author First published: August 1972 https://doi.org/10.1002/jhet.5570090436Citations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume9, Issue4August 1972Pages 943-945 RelatedInformation