Efficient and Convenient One-Pot Synthesis of Dioxadiazaphophepines

The reaction of vicinal dioxime with sodium hydride in dry THF followed by addition of dichlorophosphates or dichlorothiophosphates yields 2-oxo-1,3,4,7-dioxadiazaphosphepines and 2-thioxo-1,3,4,7-dioxodiazaphosphepines in moderate to good overall yields. The products are characterized by elemental analyses, molecular weights and spectral (IR, ¹H, ¹³C and ³¹P NMR) studies. A salt elimination route is used for the synthesis of titled heterocycles.     

Multicomponent Transformation of Isoindoline‐1,3‐diimine (=1H‐Isoindole‐1,3(2H)‐diimine), Acetylenic Esters,and Triphenylphosphine to Novel Dihydropyrimido[2,1‐a]isoindole Derivatives

The three‐component reaction of the zwitterions generated from dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates and triphenylphosphine (Ph₃P) with isoindoline‐1,3‐diimine (=1H‐isoindole‐1,3(2H)‐diimine) is described (Scheme 1). This reaction affords the corresponding special type of substituted dihydropyrimido[2,1‐a]isoindole derivatives in good yields without using any catalyst and activation (Table).     

Fluorescent Isoindole Crosslink (FlICk) Chemistry: A Rapid,User‐friendly Stapling Reaction

The stabilization of peptide secondary structure via stapling is a ubiquitous goal for creating new probes, imaging agents, and drugs. Inspired by indole‐derived crosslinks found in natural peptide toxins, we employed ortho‐phthalaldehydes to create isoindole staples, thus transforming inactive linear and monocyclic precursors into bioactive monocyclic and bicyclic products. Mild, metal‐free conditions give an array of macrocyclic α‐melanocyte‐stimulating hormone (α‐MSH) derivatives, of which several isoindole‐stapled α‐MSH analogues (K_i≈1 nm ) are found to be as potent as α‐MSH. Analogously, late‐stage intra‐annular isoindole stapling furnished a bicyclic peptide mimic of α‐amanitin that is cytotoxic to CHO cells (IC₅₀=70 μm ). Given its user‐friendliness, we have termed this approach FlICk (fluorescent isoindole crosslink) chemistry.     

Fluorescent Isoindole Crosslink (FlICk) Chemistry: A Rapid,User‐friendly Stapling Reaction

The stabilization of peptide secondary structure via stapling is a ubiquitous goal for creating new probes, imaging agents, and drugs. Inspired by indole‐derived crosslinks found in natural peptide toxins, we employed ortho‐phthalaldehydes to create isoindole staples, thus transforming inactive linear and monocyclic precursors into bioactive monocyclic and bicyclic products. Mild, metal‐free conditions give an array of macrocyclic α‐melanocyte‐stimulating hormone (α‐MSH) derivatives, of which several isoindole‐stapled α‐MSH analogues (K_i≈1 nm ) are found to be as potent as α‐MSH. Analogously, late‐stage intra‐annular isoindole stapling furnished a bicyclic peptide mimic of α‐amanitin that is cytotoxic to CHO cells (IC₅₀=70 μm ). Given its user‐friendliness, we have termed this approach FlICk (fluorescent isoindole crosslink) chemistry.     

Self-Assembled Binaphthyl-Bridged Amphiphilic AABB Phthalocyanines: Nanostructures for Efficient Antimicrobial Photodynamic Therapy

Herein, the photodynamic activity of phthalocyanine (pc)-assembled nanoparticles against bacterial strains is demonstrated. The photosensitizers (PS) studied in this work are two chiral Zn^IIPcs ( PS-1 and PS-2 ), with an AABB geometry (where A and B refer to differently substituted isoindole constituents). They contain differently functionalized, chiral binaphthyloxy-linked A isoindole units, which determine the hydrophobicity of the system, and cationic methyl pyridinium moieties in the other two isoindoles to embody hydrophilicity. Both compounds have the ability to self-assemble into nanoparticles in aqueous media and have proved efficient in the photo-inactivation of Staphylococcus aureus and Escherichia coli, selected as models of Gram-positive and Gram-negative bacteria. The average size of the nanoparticles was determined by substitution at the binaphthyl core and, in turn, influences the toxicity of the PS. Thus, PS-1 , presenting a nonsubstituted binaphthyl core, forms larger nanoparticles with a larger cationic surface than the octyl-functionalized PS-2 . Although both PSs present similar structure and photophysical features, the self-assembled nanostructures of PS-1 are more effective at killing both types of strain, showing an outstanding photo-inactivation capacity with the Gram-negative E. coli.     

Infrared spectra of phthalocyanine and naphthalocyanine in sandwich-type (na)phthalocyaninato and porphyrinato rare earth complexes. Part 3. The effects of substituents and molecular symmetry on the infrared characteristics of phthalocyanine in bis(phthalocyaninato) rare earth complexes

The infra-red (IR) spectroscopic data for a series of 45 homoleptic unsubstituted and substituted bis(phthalocyaninato) rare earth complexes M(Pc)2 and M(Pc*)2 [M=Y, La...Lu except Pm; H2Pc=phthalocyanine; H2Pc*=2,3,9,10,16,17,24,25-octakis(octyloxy)phthalocyanine (H2OOPc) and 2(3),9(10),16(17),24(25)-tetra(tert-butyl)phthalocyanine (H2TBPc)] have been collected with resolution of 2 cm(-1). The IR spectra for M(Pc)2 and M(OOPc)2 are much simpler than those of M(TBPc)2, revealing the relatively higher symmetry of the former two compounds. For M(Pc)2 the Pc-* marker band at 1312-1323 cm(-1), attributed to the pyrrole stretching, and the isoindole stretching band at 1439-1454 cm(-1) are found to be dependent on the central rare earth size, shifting slightly to the higher energy along with the decrease of rare earth radius. The frequency of the vibration at 876-887 cm(-1) is also dependent on the rare earth ionic size. The metal size-sensitivity of this band and theoretical studies render it possible to re-assign it to the coupling of isoindole deformation and aza vibration. The nature of another metal-sensitive vibration mode at 1110-1116 cm(-1), which was previously assigned to the C-H bending, is now re-assigned as an isoindole breathing mode with some small contribution also from C-H in-plane bending. These assignments are supported by comparative studies of the IR spectra of substituted bis(phthalocyaninato) analogues M(OOPc)2 and M(TBPc)2. By comparison between the IR spectra of unsubstituted and substituted bis(phthalocyaninato) rare earth analogues and according to the IR characteristics of alkyl groups, some characteristic vibrational fundamentals due to the Pc rings and the substituents can be separately identified. In conclusion, all the metal size-dependent IR absorptions are composed primarily of the vibrations of pyrrole or isoindole stretching, breathing or deformation or aza stretching of the Pc ring.     

A New and Convenient Synthesis of Amino‐phthalimide (1H‐Isoindole‐1,3(2H)‐dione) Derivatives and Their Photoluminescent Properties

A new and convenient synthesis for amino‐phthalimide (1H‐isoindole‐1,3(2H)‐dione) derivatives has been developed starting from an α,β‐unsaturated ketone. The ketones were reacted with amines to give aromatic amine products. This is the first time that substituted amine groups have been incorporated in aromatic rings. The mechanism of the product formation is rationalized by the 1,2‐addition of amines to ketones. All aromatic compounds exhibited high fluorescence properties at the blue‐green region.     

Synthesis of the 5H-pyrrolo[2,1-a]isoindole ring with 1,3-dipolar cycloaddition reactions

The 1,3-dipolar cycloaddition reaction between mesoionic oxazolines, formed from either 1,3-dihydro-2-substituted-2H-isoindole-1-carboxylic acids or 1,3-dihydro-1-oxo-α-substituted-2H-isoindole-2-acetic acids, and dimethylacetylene dicarboxylate has led to the synthesis of several 5H-pyrrolo[2,1-a]isoindole derivatives 9a-d .     

Two isomeric 2‐[4‐chloro‐2‐fluoro‐5‐(prop‐2‐ynyloxy)phenyl]hexahydro­isoindole‐1,3‐dione compounds

The molecular structures of 2‐[4‐chloro‐2‐fluoro‐5‐(prop‐2‐ynyloxy)phenyl]‐1,3,4,5,6,7‐hexahydro­isoindole‐1,3‐dione, C₁₇H₁₃ClFNO₃, (I), and the isomeric compound 2‐[4‐chloro‐2‐fluoro‐5‐(prop‐2‐ynyloxy)phenyl]‐cis‐1,3,3a,4,7,7a‐hexahydro­isoindole‐1,3‐dione, (II), are, as anticipated, significantly different in their conformations and in the distances between the farthest two atoms. The six‐membered ring of the 1,3,4,5,6,7‐hexahydro­isoindole‐1,3‐dione moiety in (I) adopts a half‐chair conformation. The dihedral angle between the five‐membered dione ring of (I) and the benzene ring is 50.96 (7)°. The six‐membered ring of the cis‐1,3,3a,4,7,7a‐hexahydro­isoindole‐1,3‐dione moiety in (II) adopts a boat conformation. The dihedral angle in (II) between the five‐membered dione ring and the benzene ring is 61.03 (13)°. In the crystal structures, the molecules are linked by C—H⋯O hydrogen bonds and weak π–π interactions. Compound (I) is a much more potent herbicide than (II). The Cl⋯H distances between the farthest two atoms in (I) and (II) are 11.37 and 9.97 Å, respectively.     

A Synthesis of an Isoindole Derivative

Isoindole or 1H-isoindole, where there is the possibility of tautoinerism, is too unstable to be isolated, and its existence is ascertained only by Diels-Alder addition products with maleic anhydride and N-phenylmaleinimide.¹⁾ Moreover, the systematic preparations of isoindole derivatives have not been confirmed.²⁾ However, several successful isoindole syntheses have been realized from ortho-disubstituted benzene derivatives. For instance,³⁾ catalytic reduction over Raney nickel of o-cyanobenzophenone gave 1-phenylisoindole, accompanied by the oxidative coupling product. We wish to report now a synthesis of an isoindole derivative (2) by the dimerization of o-tolunitrile and several reactions of the compound (2), and the physical data were also reported.     

Condensation du méthane disulfochlorure avec quelques diamines 1,2 et 1, 3 études des hétérocycles obtenus

Bis ehlorosulfonylmethane was condensed with several ortho-phenylendiamines in benzene at low concentration, yielding the corresponding bcnzo[e]-1,3,4,7-dithiadiazepine 2,2,4,4-lrtroxides. A similar heterocycle was obtained from bischlosulfonylmethane and 2-amino-5-chlorobenzhydrylamine. Mass spectrometry results were discussed with reference to one of the series.     

Photolysis and Pyrolysis of N-Methyl Isoindole

Near UV. irradiation of N-methyl isoindole ( 1 ) in deaerated solution has yielded two constitutionally isomeric [_π4_s+_π4_s] dimers 3 and 4 (Scheme 2). No transient or stable photoisomers of 1 were detected. The photodimers were reconverted to 1 both by pyrolysis and photolysis. The photocleavage of dimer 3 proceeds (predominantly) by anonadiabatic pathway yielding 1 in its electronic ground state. Prolonged pyrolysis of 1 afforded 11H-indeno [1,2-c]-isoquinoline ( 5 ) as a major product.     

Products formed by the reaction of o-diacylbenzenes with primary amines

The reactions of o-diacylbenzenes with primary amines or ammonia produced several isoindole derivatives in the presence or the absence of acid. From o-diacylbenzenes and hydroxylamine hydrochloride in the presence of triethylamine 1H-2,3-benzoxazine derivatives were obtained.     

Total 1H and 13C chemical shift assignment of indolizino[3,4,5-a,b]-isoindole and 2-methylthiobenz[f]imidazo[5,1,2-c,d]indolizine

The ¹H and ¹³C nmr spectral assignment of indolizino[3,4,5-a,b]isoindole and 2-methylthiobenz[f]-imidazo[5,1,2-c,d]indolizine are described. A concerted interpretation of the HMQC, HMQC-TOCSY, HMBC and nOe-difference experiments were used to assign the ¹H and ¹³C resonances of indolizino-[3,4,5-a,b]isoindole, whereas for 2-methylthiobenz[f]imidazo[5,1,2-c,d]indolizine a concerted interpretation of the COSY, HMQC and HMBC experiments were used to generate spectral assignments.     

Cycloaddition in Condensed Isoindoles. 2. Method for Obtaining New Derivatives of 2-Phenylpyridine

The reaction of pyrido[2,1-a]isoindole with maleimide derivatives has been investigated. A new rearrangement has been found, the products of which are 2-[2'-(1-R-2,5-dioxopyrrolidinidene)-2'-(1-R-2,5-dioxopyrrolidinyl)methyl]phenylpyridines. A probable mechanism for the rearrangement has been proposed. The existence of atropoisomerism for the compounds obtained has been demonstrated by ¹H NMR spectra.     

Synthesis of Novel Pyrazino[2,1‐a]isoindolediones via Intramolecular Hydroamination of 2,3‐Dihydro‐3‐oxo‐2‐(prop‐2‐yn‐1‐yl)‐1H‐isoindole‐1‐carboxamides

Novel derivatives of pyrazino[2,1‐a]isoindolediones were synthesized through 6‐exo‐dig intramolecular hydroamination of 2,3‐dihydro‐3‐oxo‐2‐(prop‐2‐yn‐1‐yl)‐1H‐isoindole‐1‐carboxamides followed by 1,3‐H shift, in the presence of sodium hydride in DMF at 80°. All products were obtained in good yields (60 – 80%) within short reaction time (40 – 60 min).     

Copper(I)‐Catalyzed Intramolecular Direct C‐Arylation of Azoles with Aryl Bromides

A concise route to access 5H‐imidazo[2,1‐a]isoindole heterofused compounds by copper(I)‐catalyzed intramolecular coupling of non‐activated aryl bromides with azoles is reported. With CuI as catalyst, 1,10‐phenanthroline as ligand, and K₃PO₄ as base, the reactions of 1‐(2‐bromobenzyl)‐1H‐imidazoles in DMF/o‐xylene (1:1, V:V) at 145°C afford the corresponding substituted 5H‐imidazo[2,1‐a]isoindoles in high yields via intramolecular C‐arylation.     

Isoindole derivatives from o-diacylbenzenes and aromatic amines

o-Acetylbenzophenone produced yellow 1,2-diaryl-3-(aryliminomethyl)isoindole by the reaction with aromatic amines in the absence of acid. On the reaction of o-diacetylbenzene under the similar condition, three types of yellow products were obtained. The structures of these isoindole derivatives were determined and their formation mechanism was proposed.     

Isoindolones from Lasiosphaera fenzlii Reich. and Their Bioactivities

Two new, 1 and 2 , along with one known isoindolone, 3 , were isolated from the AcOEt extract of Lasiosphaera fenzlii Reich . The structures of these compounds were determined as 4,6‐dihydroxy‐1H‐isoindole‐1,3(2H)‐dione ( 1 ), 4,6‐dihydroxy‐2,3‐dihydro‐1H‐isoindol‐1‐one ( 2 ), and clitocybin A ( 3 ) on the basis of chemical and spectroscopic evidences. The bioactivity assays revealed that all of them were devoid of significant cytotoxicities against tumor cells, whereas 1 exhibited potent antiangiogenic activity by inhibiting the secretion of vascular endothelial growth factor (VEGF) in A549 cells.     

Synthesis of 5H-imidazo[5,1-a]isoindole: Photocyclization of N,N′ -bis(o-chlorobenzyl)imidazolium chloride and N-(o-chlorobenzyl)imidazole

A N-heterocyclic compound containing two hetero atoms, imidazo[5,1-a]isoindole, was synthesized in 40% yield by the intramolecular photocyclization of N,N'-bis(o-chlorobenzyl)imidazolium salts 1 in water (neutral or pH ～4) or of N-(o-chlorobenzyl)imidazole 2 , in aqueous acid (pH ?4). However, the photocyclized compound 3 was not formed effectively in basic aqueous solution (3 equivalents of sodium hydroxide or pyridine) or in acetonitrile by the photochemical reaction of N,N'-bis(o-chlorobenzyl)imidazolium salts 1 or N-(o-chlorobenzyl)imidazole (2).