Pyrylium Research Articles

Reactions of 1,3-Substituted Benzothieno[2,3-c]pyrylium Salts with Primary Amines

We have studied the reactions of benzothieno[2,3-c]pyrylium salts with primary amines. We have shown that recyclization occurs in two directions, and whether benzothieno[2,3-c]pyridinium salts or 1-aminodibenzothiophenes are formed is determined by the nature of the primary amine.

Pyridinium cationic lipids in gene delivery: a structure-activity correlation study.

Three series of pyridinium cationic lipids useful as nonviral gene delivery agents were prepared by reaction of pyrylium salts with aminodiols, followed by acylation with fatty acyl chlorides. On the basis of this set of compounds, we undertook a comprehensive structure-activity relationship study at the level of the linker, hydrophobic anchor, and counterion in order to identify the structural elements that generate the highest transfection efficiency for this new type of cationic lipid. The results revealed that when formulated with cholesterol at a 1:1 molar ratio, the 1-(1,3-dimyristoyloxyprop-2-yl)-2,4,6-trimethylpyridinium, under the form of hexafluorophosphate (5AMyr) or chloride (5DMyr), was able to transfect NCI-H23 lung carcinoma with efficiencies surpassing classic DOTAP-based formulations and with lower cytotoxicity. Subsequent tests on other malignancies yielded similarly promising results.

Ortho-5-Methylfuran- and Benzofuran-Substituted η3-Allyl(α-diimine)nickel(II) Complexes: Syntheses, Structural Characterization, and the First Polymerization Results

Two representatives of a new family of ortho-furan-substituted N,N-phenyl α-diimine ligands [(Ar−NC(Me)−(Me)CN−Ar) Ar = 2,6-bis(5-methylfuran-2-yl)-4-phenylphenyl, 9; Ar = 2,6-bis(benzofuran-2-yl)phenyl, 17] have been synthesized by two alternative synthetic methodologies. 3,5-Bis(5-methylfuran-2-yl)biphenyl-4-ylamine (7) was prepared through a classical pyrylium salt approach. 2,6-Bis(5-methylfuran-2-yl)-4-phenylpyranylium tetrafluoroborate (4) was converted to 2,6-bis(5-methylfuran-2-yl)-4-phenylnitrobenzene (5) by reaction with nitromethane. Reduction of nitro compound 5 by zinc dust afforded aniline 7. The palladium-catalyzed cross-coupling reaction between 2,6-dibromophenylamine 13 and 2-benzofuranboronic acid 14 was used to prepare 2,6-bis(benzofuran-2-yl)phenylamine 15. The condensation of 2,2,3,3-tetramethoxybutane 8 with anilines 7 and 15 afforded α-diimines 9 and 17. The reaction of π-allylnickel chloride dimer 10, α-diimines 9 and 17, and sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (B...

478. Preinjection of Free DiC14-Amidine Liposome and Dexamethasone Synergistically Enhance the Intravenous Transfection Efficiency of Cationic Lipid/DNA Lipoplex

A new approach for generating cationic lipids for gene delivery bearing pyridinium polar heads was described recently 1. It is based on the reaction of pyrylium salts with primary amines thus generating the polar head and the linker of the non-viral transfection vector in a single, high yield step. The versatility of the synthesis allows the choice of a large variety of aliphatic or aromatic linkers, yielding cationic lipids such as 1–4, some of which act better than commercial transfection systems. The method also allows the easy access to the class of gemini surfactants such as 5 and congeners, and the facile choice of the counterion of the final positively charged species. Additionally, the use of styryl pyrylium salts can yield fluorescent transfection systems and membrane markers such as 6. Detailed insights into their chemical synthesis and transfection properties on different tumor cell lines are presented, together with a complete structure - activity relationship study for each class of lipophilic pyridinium compounds Figure 1.

Electron‐Transfer Cycloreversion of 2,3‐Diaryloxetanes: Influence of the Substitution and the Photosensitizer on the Regioselectivity

AbstractThe regioselectivity in the oxidative electron‐transfer cycloreversion (CR) of 2,3‐diaryloxetanes depends on the substitution of the aryl groups and on the nature of the electron‐transfer photosensitizer. The reaction occurs with fragmentation of the C2−C3 and C4−O bonds either in the presence of electron‐releasing substituents in the 3‐aryl groups, or when chloranil is used as photosensitizer. Thus, CR of the methoxy‐substituted derivative trans,trans‐3‐(4‐methoxyphenyl)‐4‐methyl‐2‐phenyloxetane (1b) results in the production of trans‐anethole and benzaldehyde. In this case, the trans‐anethole radical cation has been detected as transient intermediate by means of laser flash photolysis. Likewise, CR of 1a, photosensitized by chloranil, results in the formation of products arising from the trapping of the trans‐β‐methylstyrene radical cation by chloranil‐derived intermediates. The reverse regioselectivity has been previously found in the ET cycloreversion of 4‐methyl‐2,3‐diphenyloxetane (1a) using (thio)pyrylium salts as photosensitizers. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Improved Synthesis of Pyrylium Salts Leading to 2,4‐Disubstituted Diarylfurans via Novel Mechanism.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Mercuration of Salts of 2- and 4-Methyl-substituted Heterocyclic Cations: A Quantum-Chemical Study

The deprotonation energies (ΔH r) of salts of 2- and 4-methyl-substituted pyridinium, pyrylium, quinolinium, and indolinium salts were evaluated by AM1 calculations. These data allow prediction of the mercuration pathway in reactions of these compounds with mercury salts. The structural factors affecting ΔH r and the main trends in variation of the geometric and electronic structures of the compounds upon their deprotonation in the course of mercuration were analyzed.

Conversion of phenyl-substituted cyclopentadienes to pyrylium cations.

Phenyl-substituted cyclopentadienes are proved to form phenylated pyrylium cations in the presence of silver(I) perchlorate by insertion of an oxygen atom into the cyclopentadiene-ring. Three phenylated pyrylium compounds, [(Ph(5)C(5)O(+))(ClO(4)(-))](2)(CH(2)Cl(2)) (1), Ag(ClO(4))(H(2)O)(Ph(4)HC(5)O(+)) (ClO(4)(-)) (2), and (Ph(3)H(2)C(5)O(+))(ClO(4)(-)) (3) have been synthesized and characterized. A possible reaction pathway and formation mechanism of the pyrylium cation are proposed and discussed.

Reaction of 2-Benzotelluropyrylium Salts with Organocopper Reagents: Introduction of a Carbon Functional Group at the C-1 Position of the Telluropyrylium Cation Ring

3-tert-Butyl-2-benzotelluropyrylium salt (13A) react with lithium dialkyl(phenyl)copper to give in good yield the corresponding isotellurochromenes (15A) having a carbon functional group at the C-1 position. Similarly, the 1-substituted isoselenochromenes (15B) and the 4-substituted tellurochromene (19) were also prepared from the corresponding pyrylium salts (13B, 18). The obtained isotellurochromenes (15A) were easily converted into the corresponding 2,4-disubstituted 2-benzotelluropyrylium salts (20) by the treatment with triphenylcarbenium tetrafluoroborate (Ph 3 C + BF 4 -).

Simple synthesis of a weak nucleophilic base (4-ethyl-2,6-diisopropyl-3,5-dimethylpyridine) evidencing a double Janus group effect.

By analogy with 2,6-di-tert-butylpyridine and its 4-methyl-substituted derivatives, which are nonnucleophilic bases, 4-ethyl-2,6-diisopropyl-3,5-dimethylpyridine (4) is also such a base. The isopropyl groups (Janus-like groups) are forced by the neighboring methyl groups to turn their "tert-butyl-analogue face" toward the heteroatom, thereby protecting it sterically against electrophilic attack. The synthesis proceeds in two stages via the corresponding pyrylium salt 3 that is obtained by alkene diacylation. X-ray data for 4, its picrate, and the hexafluorophosphate of 3 confirm that the ground-state conformation agrees with the Janus effect prediction. The chemical behavior of 4 indicates that it is indeed a weak nucleophilic base, which is able to substitute the nonnucleophilic bases in organic syntheses. The compound 3 reacts at normal pressure with methylamine or ethylamine, forming N-alkylpyridinium salts. The cationic polymerization of isobutene in the presence of 4 was also investigated.

Improved synthesis of pyrylium salts leading to 2,4-disubstituted diarylfurans via novel mechanism

Improved synthesis of pyrylium salts from either substituted benzoic acids or their methyl esters, and substituted acetophenone is reported en route to the synthesis of 2,4-diarylfurans. The mechanism involved in the formation of the pyrylium salt using these starting materials is proposed.

On triazoles XLIX. Synthesis of 5,6‐dihydrothiazolo[3,2‐b]‐[1,2,4]triazol‐2‐yl‐, 6,7‐dihydro‐5H‐[1,2,4]triazolo[5,1‐b][1,3]thiazin‐2‐yl‐, and 5,6,7,8‐tetrahydro[1,2,4]triazolo[5,1‐b] [1,3]thiazepin‐2‐yl‐isoquinolinium salts

Abstract5′‐Mercapto‐1′H‐1,2,4‐triazol‐3′‐yl‐isoquinolinium salts (6) were synthesised by the reaction of ortho‐acyl phenylacetones (2) or the corresponding pyrylium salts (3) and 5‐amino‐2,3‐dihydro‐1H‐1,2,4‐triazole‐3‐thione (5). Treatment of thioles 6 withα,ω‐dibromoalkanes led to type 15, 16 and 17 isoquinolinium salts condensed with thiazole, thiazine and thiazepine rings. When 6 are reacted with dibromomethane (10) 11 type dimeric structures are obtained.

Lewis acid-catalyzed benzannulation via unprecedented [4+2] cycloaddition of o-alkynyl(oxo)benzenes and enynals with alkynes.

The reaction of o-alkynyl(oxo)benzenes 1 with alkynes 2 in the presence of a catalytic amount of AuCl(3) in (CH(2)Cl)(2) at 80 degrees C gave the [4+2] benzannulation products, naphthyl ketone derivatives 3 and 4, in high yields. When the reaction was carried out using AuBr(3) instead of AuCl(3), the reaction speed was enhanced and the chemical yield was increased. On the other hand, when the reaction was carried out in the presence of a catalytic amount of Cu(OTf)(2) and 1 equiv of a Brønsted acid, such as CF(2)HCO(2)H, in (CH(2)Cl)(2) at 100 degrees C, the decarbonylated naphthalene products 5 were obtained in high yields. Similarly, the Cu(OTf)(2)-H(2)O-promoted reaction of the enynals 7 with an alkyne 2 afforded the corresponding [4+2] benzannulation products, decarbonylated benzene derivatives 8, in good yields. Both AuX(3)- and Cu(OTf)(2)-catalyzed benzannulations proceed most probably through the formation of the benzo[c]pyrylium ate complex 10, the Diels-Alder addition of alkynes 2 to the ate complex, and the resulting bicyclic pyrylium ion intermediate 12. The mechanistic difference between the AuX(3) and Cu(OTf)(2)-HA system is discussed.

Unexpected Formation of 2,3,7‐Triphenylcyclopenta[c]pyran from the Reaction of 1,2‐Diphenylethanedione (Benzil) with Cyclopentadiene.

The reaction of 1,2-diphenylethanedione (benzil) with cyclopentadiene in the presence of sodium methoxide unexpectedly afforded the novel fully conjugated 2,3,7-triphenyl derivative of cyclopenta[c]pyran, a pyranic pseudoazulene. The structure was proved by physical methods (IR, UV/VIS; 'H-NMR, 1 3 C-NMR; MS), and confirmed by X-ray crystallography. Protonation affords a pyrylium salt with a structure that agrees with the results of semiempirical and ab-initio methods, which also agree fairly well with experimentally-determined bond lengths.

Photosensitiser-controlled regioselectivity in the electron-transfer cycloreversion of 2,3-diphenyloxetanes.

The regioselectivity of the oxidative electron-transfer cycloreversion of trans,trans-2,3-diphenyl-4-methyloxetane is photosensitiser dependent. With chloranil the reaction proceeds through the trans-beta-methylstyrene radical cation; however, in the case of pyrylium salts, the trans-stilbene radical cation is formed.

Pyridinium‐Based Cationic Lipids as Gene‐Transfer Agents

AbstractCationic lipids are a promising alternative to viral vectors for gene therapy, allowing the delivery of larger plasmids without immunogenicity, despite their lower transfection efficiency. Among them, heterocyclic systems with imidazolium or pyridinium polar head groups have definite advantages such as the excellent transfection profiles and low cytotoxicity. Our approach for synthesizing heterocyclic cationic lipids differs from those previously described because we synthesize a pyridinium ring from simple starting materials. First a pyrylium salt is formed via diacylation of alkenes. The pyrylium salt is then converted by primary amines into pyridinium salts. Appropriate choice of the primary amine allows the attachment of two hydrophobic chains yielding compounds 21A and 25A (with various chain lengths derived from palmitic, stearic and oleic acids). The same strategy allowed the preparation of lipophilic derivatives 21B, 25B useful as strongly fluorescent markers for the study of the properties of biological membranes. Preliminary tests with some of the compounds 21A and 25A, on several cell lines, showed comparable transfection efficiencies and lower cytotoxicity than those obtained with standard commercial transfection agents. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Facile Synthesis and X-ray Structure of Alkoxy-Functionalized Dibenzo[fg,op]naphthacenes

[structure: see text] 1,3-Bis(2-bromophenyl)-2,5-diphenylbenzenes are readily available by the condensation of phenylacetates with the corresponding pyrylium salts and undergo a palladium-catalyzed dehydrohalogenation to give functionalized dibenzo[fg,op]naphthacenes.

Stereocontrolled Catalytic Synthesis of Substituted Hydroxyethylpiperidines from Pyrylium Salts.

Stereocontrolled Catalytic Synthesis of Substituted Hydroxyethylpiperidines from Pyrylium Salts.

Synthesis by the Gilch Method of Blue-Light-Emitting Poly(p-phenylenevinylene) Derivatives Bearing Highly Phenylated Pendants

Two novel poly(p-phenylenevinylene) (PPV) derivatives bearing highly phenylated side groups with different chemical structures were prepared by Gilch dehydrohalogenation polyaddition. The intermediate substituted 1,4-bis(bromomethyl)benzenes (monomers 6 and 11) were synthesized by a convenient synthetic route utilizing pyrylium salts. The polymers were amorphous and showed limited solubility in THF, chloroform, 1,2-dichloroethane, 1,1,2,2-tetrachloroethane, and 1,2-dichlorobenzene. They displayed relatively high Tg values (158−176 °C) and good thermal stability, being stable up to approximately 270−350 °C in N2 or air and affording anaerobic char yields of 53−56% at 800 °C. The bulky side groups caused a significant steric effect on the PPV backbone and reduced the chromophore length. The solutions of polymers in THF emitted blue light with a maximum around 455 nm. This emission maximum is blue-shifted in comparison with that of other previously synthesized PPVs that emit green to red light. At low temper...

Direct Photophysical Evidence for Quenching of the Triplet Excited State of 2,4,6-Triphenyl(thia)pyrylium Salts by 2,3-Diaryloxetanes

The thiapyrylium salt 1b is an efficient electron-transfer photosensitizer in the preparative irradiation of trans,trans-2,3-diphenyl-4-methyloxetane (2a). Previously, the reaction has been assumed to occur through the triplet excited state of 1b, which has a very high intersystem crossing yield (φISC = 0.97). In the present report, direct evidence for triplet quenching in the oxidative cycloreversion of the 2,3-diaryloxetanes is provided. The rate constants kq(T1) and the free energy changes of the electron transfer ΔGET(T1) have been determined for the reaction between 1b and oxetanes 2a−d and 2a‘. The process has been found to be exergonic in all cases except for 2d; this agrees with the fact that no photoproduct was obtained in the preparative irradiation of 1b in the presence of 2d. Good correlation between kq(T1) and ΔGET(T1) was observed, confirming the involvement of the excited triplet state in the reaction mechanism.