Pyrrole β-amides: Synthesis and characterization of a dipyrrinone carboxylic acid and an N-Confused fluorescent dipyrrinone

Pyrrole β-amides are useful building blocks for the preparation of novel molecular architectures that can be used in supramolecular chemistry and sensor development. Under basic conditions, pyrrole β-amides with an α-aldehyde produce different condensation products when reacted with pyrrolinones depending on the amide substitution. Secondary amides form the expected dipyrrinones, but unexpectedly undergo a subsequent trans-amidation with the pyrrolinone nitrogen to produce an unsymmetrical imide (an N-confused fluorescent dipyrrinone). Under the same conditions, tertiary amides produce the expected dipyrrinone carboxylic acids, which have been shown to have strong self-association properties as determined by vapor pressure osmometry measurements, NMR studies, and X-ray crystal structure determination. Furthermore, an N-confused fluorescent dipyrrinone was produced from the same trans-amidation reaction during attempts to decarboxylate a dipyrrinone amide with a 9-carboxylic moiety.     

Intramolecular Hydrogen-Bonding in a C(10)-Exploded Bilirubinoid

Summary. A new linear tetrapyrrole, with two dipyrrinones connected by a string of 5 carbons, was synthesized from two equivalents of a 9H-dipyrrinone and one of glutaryl dichloride. Unlike typical dipyrrinones, which are intermolecularly hydrogen bonded in the crystal and in CHCl₃ solution, 1,3-bis-[2,3,7,8-tetraethyl-(10H)-dipyrrin-9-carbonyl]propane is a monomer in CHCl₃, as determined by vapor phase osmometry (VPO) measurements. Its crystal structure determination revealed a folded conformation with a novel type of dipyrrinone to dipyrrinone intramolecular hydrogen bonding. Unexpectedly, the same conformation apparently persists in CHCl₃ solution, as shown by ¹H NMR spectroscopy.     

Synthesis and Hepatic Metabolism of Xanthobilirubinic Acid Regioisomers

Summary.  A set of four regioisomeric dipyrrinone propionic acids has been synthesized and their hepatic metabolism examined in rats: xanthobilirubinic acid and pseudo-xanthobilirubinic acid each with a propionic acid on a pyrrole ring; exo-ψ-xanthobilirubinic acid and endo-ψ-xanthobilirubinic acid, each with a propionic acid transposed to a lactam ring. After intravenous injection all four isomers were excreted to some degree in unchanged form in bile in normal rats. Xanthobilirubinic acid, the structurally closest dipyrrinone to bilirubin, and exo-ψ-xanthobilirubinic acid were excreted almost entirely in unchanged form. However, a small fraction of xanthobilirubinic acid acyl glucuronide was also detected. More extensive acyl glucuronidation was observed for pseudo-xanthobilirubinic acid, and endo-ψ-xanthobilirubinic acid underwent slow metabolism to unidentified more polar products that did not seem to be glucuronides.     

Molecular recognition studies with a simple dipyrrinone

We present our investigations of 2-ethyl-3-methyl-(10H)-dipyrrin-1-one, its self-association, and anion binding properties. This receptor is easily accessible in a facile single step synthesis with a straightforward workup. An examination of the concentration dependence of the dipyrrinone NH chemical shifts in CDCl₃ and (CDCl₂)₂ over the temperature range from −20 °C to 100 °C determined the self-association constant to be 3850 M⁻¹. Molecular recognition studies have shown that it has a preference for guests with an OH moiety, such as hydrogen sulfate (HSO₄⁻) and carboxylic acids (RCO₂H).     

Strongly fluorescent dipyrrinones. Internal quenching

Yellow N,N′-carbonyl-bridged dipyrrinones can generally be prepared from dipyrrinones simply by reaction with N,N′-carbonyldiimidazole in the presence of a strong, non-nucleophilic base. They are typically intensely fluorescent, with fluorescent quantum yields approaching 1.0. In an effort to shift the excitation wavelength, and thus the fluorescence emissions, strongly to the red, we prepared bridged dipyrrinones conjugated with thiobarbituric acid and Meldrum’s acid substituents at C-9. Such conjugation causes the dipyrrinones to have a magenta color (absorption wavelength shifted from ∼400 nm of a typical dipyrrinone to ∼550 nm of the dipyrrinone conjugate). For comparison, we also prepared analogs with formyl, carboxyl, acrylate, and acetyl substituents at C-9. Unexpectedly and uniquely, the 9-CHO substituent caused the fluorescence quantum yield to drop to ∼10⁻³ while carboethoxy substituent exerted only a minor influence.     

Beiträge zur Chemie der Pyrrolpigmente, 85. Mitt.: Darstellung und Lumineszenz hetero-bichromophorer Oligopyrrol-Systeme

Summary Systems consisting of a bilindione or dipyrrinone chromophore and a covalently attached, but nonconjugated, fluorescing naphthyl, anthranyl, and indolyl residue were prepared and their luminescence properties measured. Excitation energy is very effectively quenched by the dipyrrin radiationless deexcitation channel of bilins as well as by the photodiastereomerization mode of dipyrrinone fragments. A Förster type energy transfer mechanism is inferred from intermolecular Stern-Volmer kinetics in solvents of different viscosity.

     

Strongly fluorescent dipyrrinones—substituent effects

Bright yellow N,N'‐carbonyl‐bridged dipyrrinones (substituted 3H,5H‐dipyrrolo[1,2‐c:2′,1′‐f]pyrimidine‐3,5‐diones) were synthesized by reaction of the parent dipyrrinone with carbonyldiimidazole. Their solutions in organic solvents fluoresced strongly, with fluorescent quantum yields (?_F)0.32‐0.92.     

Strongly fluorescent dipyrrinones. Internal quenching

Yellow N,N′-carbonyl-bridged dipyrrinones can generally be prepared from dipyrrinones simply by reaction with N,N′-carbonyldiimidazole in the presence of a strong, non-nucleophilic base. They are typically intensely fluorescent, with fluorescent quantum yields approaching 1.0. In an effort to shift the excitation wavelength, and thus the fluorescence emissions, strongly to the red, we prepared bridged dipyrrinones conjugated with thiobarbituric acid and Meldrum’s acid substituents at C-9. Such conjugation causes the dipyrrinones to have a magenta color (absorption wavelength shifted from ∼400 nm of a typical dipyrrinone to ∼550 nm of the dipyrrinone conjugate). For comparison, we also prepared analogs with formyl, carboxyl, acrylate, and acetyl substituents at C-9. Unexpectedly and uniquely, the 9-CHO substituent caused the fluorescence quantum yield to drop to ∼10⁻³ while carboethoxy substituent exerted only a minor influence. Correspondence: David A. Lightner, Department of Chemistry, University of Nevada, Reno, 89557 Nevada, USA.     

Beiträge zur Chemie der Pyrrolpigmente, 79. Mitt. Zum strukturellen Einfluß stark raumerfüllender Reste bei 10-substituierten 1,19-Bilindionen

Summary 1,19-Bilindiones bearing a phenanthryl, mesityl,tert-butyl, and isopropyl substituent at the C-10 position were synthesized. Conformational analysis using¹³C- and¹H-NMR spectroscopic techniques and absorption spectroscopy together with semiempirical calculations revealed that the aryl derivatives adopt the common circular helical geometry, whereas thetert-butyl derivative is heavily distorted. The mean planes of the two dipyrrinone moieties are orthogonally positioned to each other. The 10-isopropyl-bilindione tautomerizes to the 10-isopropyliden-biladiene-ac.

     

Glycine Imine—The Elusive α-Imino Acid Intermediate in the Reductive Amination of Glyoxylic Acid

Simple unhindered aldimines tend to hydrolyze or oligomerize and are therefore spectroscopically not well characterized. Herein we report the formation and spectroscopic characterization of the simplest imino acid, namely glycine imine, by cryogenic matrix isolation IR and UV/Vis spectroscopy. Glycine imine forms after UV irradiation of 2-azidoacetic acid by N₂ extrusion in anti-(E,E)- and anti-(Z,Z)-conformation that can be photochemically interconverted. In matrix isolation pyrolysis experiments with 2-azidoacetic acid, glycine imine cannot be trapped as it further decarboxylates to aminomethylene. In aqueous solution glycine imine is hydrolyzed to hydroxy glycine and hydrated glyoxylic acid. At higher concentrations or in the presence of Fe^IISO₄ as a reducing agent glycine imine undergoes self-reduction by oxidative decarboxylation chemistry. Glycine imine may be seen as one of the key reaction intermediates connecting prebiotic amino acid and sugar formation chemistry.     

Fluorescence detected circular dichroism of a red-shifted exciton-coupling chromophore N,N′-carbonyl-bridged dipyrrinone derivative using an ellipsoidal device

A fluorescent red-shifted exciton-coupling chromophore, N,N′-carbonyl-bridged dipyrrinone, was subjected to fluorescence-detected CD (FDCD) measurements as a primitive structure-elucidating probe with trans-1,2-cyclohexanediol template in several solvents under various instrumental conditions. With the help of a JASCO ellipsoidal mirror device FDCD465, a chloroform solution achieved the sensitivity enhancement by 50 times of the transmission CD and 5 times of the conventional FDCD. All FDCD spectra were completely free from the polarization artifacts.     

Competitive electron impact induced methylene imine elimination from methyl- and dimethylamino N-heterocycles. 1—substituted melamines

Competitive intramolecular expulsion of methylene imine is evaluated for heterocyclic methylamino and dimethylamino substituents using selectively labelled N²,N²,N⁴-trimethylmelamine. In this compound methylene imine expulsion from the dimethylamino group is favored by more than 2:1 over loss from the methylamino group. The effects of other fragmentations and hydrogen randomisation are estimated independently using methylmelamines with each of the groups as the sole source of methylene imine loss.     

On the chemistry of pyrrole pigments,LXXXIX: Vinylogous linear di- and tetrapyrroles

Summary A vinylogous dipyrrinone, its Ehrlich aldehyde condensate, and the vinylogous bilindione derived from the vinylogous dipyrrinone were prepared. Their structural aspects of tautomerism, configuration and conformation were derived by analysis of their¹H-NMR data. Selected physical properties were determined and are discussed.

---

Zur Chemie von Pyrrolpigmenten, 89. Mitt.: Vinyloge Lineare Di- und Tetrapyrrole

Zusammenfassung Ein vinyloges Dipyrrinon, sein Ehrlich-Aldehyd-Kondensat und ein vom vinylogen Dipyrrin abgeleitetes vinyloges Bilindion wurden dargestellt. Ihre strukturellen Aspekte der Tautomerie, Konfiguration und Konformation wurden durch Analyse ihrer¹H-NMR-Daten abgeleitet. Ausgewählte physikalische Eigenschaften wurden gemessen und diskutiert.

     

The mutual influence of the imine substituents of terephthal-bis-imines concerning their reactivity towards Fe2(CO)9

The reaction of terephthal-bis-imines with Fe₂(CO)₉ proceeds via a C---H activation reaction in the ortho position with respect to one of the imine functions. The corresponding hydrogen atom is shifted towards the former imine carbon atom producing a methylene group instead. The dinuclear iron complexes formed by this reaction sequence and showing no coordination of the second imine group were isolated from reactions of bis-imines with both phenyl and cyclohexyl substituents at the imine nitrogen atoms. In addition, we observed three different reaction pathways of the second imine substituent of the starting material which is obviously thus influenced by the fact that the first one is coordinating an Fe₂(CO)₆ moiety. If the organic substituent at the imine nitrogen atoms is a phenyl group the formation of a trinuclear complex is achieved in which an additional Fe(CO)₃ group is coordinating the CN double bond and one of the carbon---carbon bonds of the central phenyl ring in an η⁴-fashion. The same reaction leads to the isolation of a tetranuclear iron---carbonyl compound in which both imine substituents were transformed via the pathway described above, each building up dinuclear subunits. In contrast to this the reaction of a bis-imine with cyclohexyl groups at the imine nitrogen and thus an enhanced nucleophilicity leads to the formation of a tetranuclear complex in which only one imine group reacts under C---H activation with subsequent hydrogen migration towards the former imine carbon atom. The second imine substituent also shows a C---H activation reaction in the ortho position with respect to the imine group but the corresponding hydrogen atom is transferred to one of the aromatic carbon atom of the central phenyl ring of the ligand. The C=N double bond remains unreacted and only coordinates the second Fe₂(CO)₆ moiety via the nitrogen lone pair.     

Light-Fueled Transformations of a Dynamic Cage-Based Molecular System

In a chemical equilibrium, the formation of high-energy species—in a closed system—is inefficient due to microscopic reversibility. Here, we demonstrate how this restriction can be circumvented by coupling a dynamic equilibrium to a light-induced E/Z isomerization of an azobenzene imine cage. The stable E-cage resists intermolecular imine exchange reactions that would “open” it. Upon switching, the strained Z-cage isomers undergo imine exchange spontaneously, thus opening the cage. Subsequent isomerization of the Z-open compounds yields a high-energy, kinetically trapped E-open species, which cannot be efficiently obtained from the initial E-cage, thus shifting an imine equilibrium energetically uphill in a closed system. Upon heating, the nucleophile is displaced back into solution and an opening/closing cycle is completed by regenerating the stable all-E-cage. Using this principle, a light-induced cage-to-cage transformation is performed by the addition of a ditopic aldehyde.     

Syntheses and properties of benzodipyrrinones

2,3‐Benzannelated dipyrrinone analogs ( 1 and 2 ) of xanthobilirubic acid ( 3 ) are prepared by base‐catalyzed condensation of isoindolinone ( 5 ) and indolin‐2‐one ( 6 ) respectively, with methyl 3‐(2‐formyl‐3,5‐dimethyl‐1H‐pyrrol‐4‐yl)propanoate ( 4 ). Nuclear Overhauser effect H‐nmr studies indicate that both 1 and 2 adopt preferentially a syn‐Z configuration. The former forms a hydrogen‐bonded homodimer in nonpolar solvents; the latter is intramolecularly hydrogen bonded.     

Inducing anti-Conformers of Biliverdin Chromophores by Reducing Sterical Hindrance

Summary. Two different types of conformational changes of the biliverdin chromophore were accomplished by the concept of reducing sterical hindrance. On one hand, model compounds unsubstituted at position 7 and/or 13 adopt the semi-extended geometry with anti-conformation of the dipyrrinone moiety. On the other hand, stretching of the chromophore with anti-conformation of the dipyrrin substructure was achieved with a model compound unsubstituted at position 12. Both kinds of anti-conformations have been proved by 2D NMR and UV-Vis spectroscopy.Current address: Voestalpine Stahl GmbH, Voest-Alpine-Straße 1, A-4020 Linz, Austria     

Highly Enantioselective Extraction of Underivatized Amino Acids by the Uryl‐Pendant Hydroxyphenyl‐Binol Ketone

The hydroxyphenyl chiral ketone, (S)‐ 3 , reacts with D ‐amino acids bearing hydrophobic side chains exclusively over the L ‐amino acids in a two‐phase liquid–liquid extraction, and thus acts as a highly stereoselective extractant. Calculations for the energy‐minimized structures for the imine diastereomers and the comparison of the selectivities with other phenyl ketones, (S)‐ 4 and (S)‐ 5 , demonstrate that the hydrogen bond between the carboxylate group and the phenolic hydroxyl group contributes to the remarkable enantioselectivities. The multiple hydrogen bonds present in the imine of (S)‐ 3 reinforce the rigidity, and results in the difference between the stabilities of the imine diastereomers. The imine could be hydrolyzed in methanolic HCl solution, and the extraction of the evaporated residues revived the organic layer of (S)‐ 3 , which could enter into a new extractive cycle and leaves the D ‐amino acid with enantiomeric excess (ee) values of over 97 % in the aqueous layer.     

Iridium(iii)-(hydrido)cyclometallated-imine complexes and metal-promoted hydrolytic cleavage of imines

The room temperature reaction of the complex cis,trans,cis-[Ir(H)₂(PPh₃)₂(Solv)₂]PF₆ (Solv is a solvent) with the imine PhCH₂N=CHPh in acetone generates (with loss of H₂) the orthometallated complex [Ir(H){PhCH₂N=CH(o-C₆H₄)}(PPh₃)₂(Me₂CO)]PF₆ (3) containing a five-membered cyclometallated imine moiety. In MeOH, the reaction at an imine : Ir ratio = 1 leads to the corresponding MeOH analog of 3, while with excess imine, the mixed orthometallated imine/bezylamine complex [Ir(H){PhCH₂N=CH(o-C₆H₄)}(PPh₃)₂(PhCH₂NH₂)]PF₂ (4) is formed; the source of the coordinated amine is an Ir-promoted hydrolysis of the imine, the water likely coming from imine. Complexes 3 and 4 are fully characterized by elemental analysis, ¹H and ³¹P{¹H} NMR spectroscopy, and X-ray crystal structure analysis.     

Catalytic Asymmetric Synthesis of Alkynyl Aziridines: Both Enantiomers of cis‐Aziridines from One Enantiomer of the Catalyst

Alkynyl aziridines can be obtained from the catalytic asymmetric aziridination (AZ reaction) of alkynyl imines with diazo compounds in high yields and high asymmetric inductions mediated by a chiral boroxinate or BOROX catalyst. In contrast to the AZ reaction with aryl‐ and alkyl‐substituted imines, alkynyl imines react to give cis‐substituted aziridines with both diazo esters and diazo acetamides. Remarkably, however, the two diazo compounds give different enantiomers of the cis‐aziridine from the same enantiomer of the catalyst. Theoretical considerations of the possible transition states for the enantiogenic step reveal that the switch in enantiomers results from a switch from Si‐face to Re‐face addition to the imine, which in turn is related to a switch from reaction with an E‐imine in the former and a Z‐isomer of the imine in the latter.