Synthesis of heterocycle‐substituted pyropheophorbide derivatives

Methyl pyropheophorbide‐a (MPPa) ( 1 ) was converted to two aldehydes, methyl 2‐formylmethyl‐2‐devinylpyropheophorbide‐a ( 2 ) and methyl 2‐formyl‐2‐devinylpyropheophorbide‐a ( 3 ). The former 2 reacted with active methylene compounds having a cyano function in the presence of sulfur to afford thiophene‐substituted chlorins 5a‐c and reacted with arylhydrazines to yield indole‐substituted chlorins 6a‐d . From the latter 3 , a α‐diketo chlorin 7 was obtained via Wittig reaction and oxidation. Compound 7 reacted with o‐phenylenediamine to afford 2‐quinoxalyl‐substituted pyropheophorbide‐a 8. The reaction of MPPa ( 1 ) with anthranilamide to give a spiro‐substituted compound 9 .     

Synthesis of Chlorins Fused with Nitrogen‐Containing Heterocycle by the Modification along Their N21–N23 axis

Quinoxalinodeoxopyropheophorbide‐a and benzimidazolopurpurin‐18 imide were obtained from methyl pheophorbide‐a by one‐pot method. The synthesis of a series of chlorins fused with nitrogen‐containing heterocycle was fulfilled by chemical modifications along their N²¹–N²³ axis such as LiOH‐promoted allomerization of C12‐methyl group, electrophilic addition to C3‐vinyl group, substitution at 20‐meso‐position and 1, 3‐dipolar cycloaddition with diazomethane at 3‐position. The structures of new chlorins were characterized by UV–vis, MS, ¹H NMR spectra, and elemental analysis.     

Syntheses of C2-labelled 11Z-retinals

To enable solid-state NMR investigations of the rhodopsin chromophore and its photointermediates, a series of 11Z-retinal isotopomers have been synthesised containing pairs of adjacent ¹³C labels at C9/C10, C10/C11 or C11/C12, respectively. The C9 labelled carbon atom was introduced through the Heck reaction of a ¹³C-labelled Weinreb acrylamide derivative, and the label at the C12 position derived from a ¹³C-containing ethoxy Bestmann-Ohira reagent. The ¹³C labels at C10 and C11 were introduced through the reaction of β-ionone with labelled triethyl phosphonoacetate.     

Urea-formaldehyde resins. III. Constitutional characterization by 13C fourier transform NMR spectroscopy

¹³C Fourier transform NMR has been used to characterize a random chemical structure of ureaformaldehyde resins. By comparison of ¹³C chemical shifts with synthesized standard derivatives from urea and formaldehyde the analysis of reacted formaldehyde was completed. In a ¹³C spectrum of resin each signal due to reacted formaldehyde (e.g., methylol group, methylene group, and dimethylene ether group) was isolated. Measurement of a ¹³C spectrum of resin by the gated decoupling of proton without nuclear Overhauser effect made a quantitative analysis of reacted formaldehyde possible. In this quantitative analysis a ¹³C quantity of carbonyl groups in urea residue can be directly compared with that of each combined formaldehyde.     

Rapid and efficient synthesis of five- to eight-membered cyclic aminals under ultrasound irradiation

A simple, efficient, and green procedure has been developed for the synthesis of cyclic aminals from alkylenediamines and aqueous formaldehyde under ultrasound irradiation. Applying this methodology a series of five-to eight-membered 1,3-dibenzyl substituted aminals were synthesized in excellent yields after short reaction times. Results were compared to thermal conventional method. All novel compounds were identified and characterized by ¹H and ¹³C NMR spectra.     

Ab initio quantum-mechanical calculations of the propagation enthalpies for the radical and anionic polymerizations of formaldehyde and methanimine

The gas phase enthalpies of formation for oligomeric radicals and anions H(CH₂NH)_n^* and H(CH₂O)_n^* were theoretically determined by ab initio quantum-mechanical calculations with n in the range 1 to 6. From these results, the reaction enthalpies for each of the first five propagation steps of the polymerization were estimated for methanimine (H₂C = NH) and formaldehyde (H₂C = O). At the same step of oligomerization, enthalpies associated with anionic polymerizations are always more negative than enthalpies corresponding to radical polymerizations, but the difference between them decreases with increasing n. Both Delta;H (propagation) vs. n curves tend rapidly, particularly for radical polymerizations, towards an asymptotic value independent of the mode of polymerization and equal to - 12 kcal/mol for formaldehyde and - 14 kcal/mol for methanimine. Experimental data for the gas phase polymerization of formaldehyde are in good agreement with our theoretical value. These results demonstrate that heats of polymerization can be reasonably estimated by intensive calculation methods if a careful choice of the reaction mimicking the propagation step is done.     

Membrane permeation continuous‐flow isotope ratio mass spectrometry for on‐line carbon isotope ratio determination

Gaseous membrane permeation (MP) technologies have been combined with continuous‐flow isotope ratio mass spectrometry for on‐line δ¹³C measurements. The experimental setup of membrane permeation‐gas chromatography/combustion/isotope ratio mass spectrometry (MP‐GC/C/IRMS) quantitatively traps gas streams in membrane permeation experiments under steady‐state conditions and performs on‐line gas transfer into a GC/C/IRMS system. A commercial polydimethylsiloxane (PDMS) membrane sheet was used for the experiments. Laboratory tests using CO₂ demonstrate that the whole process does not fractionate the C isotopes of CO₂. Moreover, the δ¹³C values of CO₂ permeated on‐line give the same isotopic results as off‐line static dual‐inlet IRMS δ¹³C measurements. Formaldehyde generated from aqueous formaldehyde solutions has also been used as the feed gas for permeation experiments and on‐line δ¹³C determination. The feed‐formaldehyde δ¹³C value was pre‐determined by sampling the headspace of the thermostated aqueous formaldehyde solution. Comparison of the results obtained by headspace with those from direct aqueous formaldehyde injection confirms that the headspace sampling does not generate isotopic fractionation, but the permeated formaldehyde analyzed on‐line yields a ¹³C enrichment relative to the feed δ¹³C value, the isotopic fractionation being 1.0026 ± 0.0003. The δ¹³C values have been normalized using an adapted two‐point isotopic calibration for δ¹³C values ranging from ?42 to ?10‰. The MP‐GC/C/IRMS system allows the δ¹³C determination of formaldehyde without chemical derivatization or additional analytical imprecision. Copyright © 2009 John Wiley & Sons, Ltd.     

Microbial evolution of carbazonyloxy-based chalcones

The Claisen–Schmidt condensation reaction was carried out between a carbazol-based acetyl group and various aldehydes. Reaction was performed in metal alkoxide as a alkali homogenous catalyst. A series of 12 1-{4-[3-(9H-carbazol-4-yloxy)-2-hydroxy-propylamino]-phenyl}-3-(substituted aryl)-propenone were synthesized and characterized using FTIR, ¹H NMR, and ¹³C NMR spectroscopy analysis. Synthesized compounds were tested against bacteria and fungi strains.     

Synthesis and antimicrobial activity of novel quinazolinone–thiazolidine–quinoline compounds

A series of 2-(2-chloroquinolin-3-yl)-5-((aryl)benzylidene)-3-(4-oxo-2-phenylquinazolin-3(4H)-yl)thiazolidin-4-ones (V)_1–12 have been synthesized. In order to establish optimization of different parameters of chemical transformation, that is the reaction pathway for each step and reaction conditions in the each step, in the present paper, different solvents and catalysts were used. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, ¹H NMR and ¹³C NMR spectral data. All the newly synthesized compounds were screened against various strains of bacteria and fungi.     

Synthesis,Reactions, and Anticancer Activity of Some 1,3,4-Thiadiazole/Thiadiazine Derivatives of Carbazole

A novel method for the synthesis of 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives bearing a carbazole moiety is described. Carbazole was transformed into carbazole-9-thiocarbohydrazide in two steps. This compound was allowed to react with various electrophiles to yield 1,3,4-thiadiazole derivatives. The reaction with bifunctional electrophiles led to 1,3,4-thiadiazines. 2-(Carbazol-9-yl)-5,6-dihydro-4H-1,3,4-thiadiazin-5-one reacted with piperidine and formaldehyde to yield the 4-(piperidin-1-ylmethyl) derivative. The reaction with aromatic aldehydes led to the corresponding 6-arylidene derivatives, which were transformed into pyrimidino[4,5-e]-1,3,4-thiadiazines and pyrazolo[3,4-e]-1,3,4-thiadiazines by a reaction with guanidine, acetamidine, or phenylhydrazine, respectively. Structures of the products were confirmed by ¹H NMR, ¹³C NMR, IR, and mass spectrometric measurements. Selected examples of products were screened for anticancer activity.     

The synthesis of chlorophyll-a skeleton homologs bearing linear six-carbon chain from methyl pheophorbide-a

The synthesis of chlorins bearing 6C-straight chain was accomplished from methyl pheophorbide-a. A series of chemical modifications were employed for the construction of active functional groups, such as bromine atom or aldehyde group, on the periphery of chlorins. These functionalized chlorins further reacted with the reagent containing straight carbon-chain by common chemical reactions to produce target compounds. The structures of all new chlorins were characterized by elemental analysis, IR, UV-Vis and ¹H NMR spectra.     

Quantitative and qualitative 1H, 13C,and 15N NMR spectroscopic investigation of the urea–formaldehyde resin synthesis

Urea–formaldehyde resins are bulk products of the chemical industry. Their synthesis involves a complex reaction network. The present work contributes to its elucidation by presenting results from detailed NMR spectroscopic studies with different methods. Besides¹H NMR and¹³C NMR,¹⁵N NMR spectroscopy is also applied.¹⁵N‐enriched urea was used for the investigations. A detailed NMR signal assignment and a model of the reaction network of the hydroxymethylation step of the synthesis are presented. Because of its higher spectral dispersion and the fact that all key reactions directly involve the nitrogen centers,¹⁵N NMR provides a much larger amount of detail than do¹H and¹³C NMR spectroscopy. Symmetric and asymmetric dimethylol urea can be clearly distinguished and separated from monomethylol urea, trimethylol urea, and methylene‐bridged urea. The existence of hemiformals of methylol urea is confirmed. 1,3,5‐Oxadiazinan‐4‐on (uron) and its derivatives were not found in the reaction mixtures investigated here but were prepared via alternative routes. The molar ratios of formaldehyde to urea were 1, 2, and 4, the pH values 7.5 and 8.5, and the reaction temperature 60 °C. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis and optical properties of bacteriochlorophyll-a derivatives having various C3 substituents on the bacteriochlorin pi-system

Methyl bacteriopyropheophorbide-a derivatives having a series of substituents at the C3 position were prepared and their optical properties were compared with the corresponding chlorin analogues. Two kinds of oxidation reaction (C3-vinyl --> formyl --> carboxy group) were found to be applicable with a little alteration of the free-base bacteriochlorin macrocycles. The Qx and Qy electronic absorption peak positions of synthetic bacteriochlorins in CH2Cl2 were affected by the C3 substituents and found to be more sensitive than those of the chlorins. The observed Qx/Qy peaks in their monomeric states were shifted to a longer wavelength in the order of 1-hydroxyethyl < hydroxymethyl < acetoxymethyl < vinyl < acetyl < carboxy < formyl < 2,2-dicyanoethynyl group. Zinc complex with the C3-hydroxymethyl group formed self-aggregates in a nonpolar organic solvent, which showed the largest red-shift of the Qy band (2380 cm(-1), 726 nm in THF to 878 nm in 1% THF-cyclohexane) among those of the synthetic self-aggregative (bacterio)chlorins examined.     

Synthesis and Characterization of Some Novel Dichromophoric Cyanine Dyes

Here, the synthesis of two novel series of dichromophoric cyanine dyes were reported. The first series of novel bis-azacyanine dyes 3a–d was afforded by reaction of 2-(1,3,3-trimethyle indoline-2-ylidene)acetaldehyde with diaminoaromatics, and the second series of novel bis-diazacyanine dyes 4a–d was obtained using quaternization of an amine group in disazo compounds, which were produced by the reaction of disazoaromatics with 2-methylene-1,3,3-trimethyle indoline. The products were identified by ¹H NMR, ¹³C NMR, infrared, UV-vis, and mass spectroscopy.     

13C Kinetic Isotope Effect of the Pudovik Reaction

Abstract

¹³C kinetic isotope effect (KIE) was determined by means of ¹³C NMR for the carbonyl atom in 2-nitrobenzaldehyde in its reaction with 2H-2-oxo-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphorinane in acetonitrile at 25°C. The observed isotope effect k₁₂/k₁₃ = 1.0238 ± 0.0031 evidences that the formation of the P?C bond in the Pudovik reaction catalyzed by triethylamine is less advanced than the π-bond breakage of the aldehyde carbonyl group.     

Access to the 2,3-dihydropyridazin-3-one and as-triazino[3,4-a]phthalazine ring systems from 4-aryl-2-oxo-butanoic acids

A novel series of 2,3-dihydropyridazin-3-ones 15 were synthesized via condensation between hydrazines and 4-(p-chlorophenyl)-2-hydroxy-2-(2-oxo-2-substituted ethyl)butanoic acids 8 which in turn were prepared by the reaction of substituted benzylpyruvic acids 6 with methyl alkyl(aryl) ketones 7. Dehydration of 8b-d by a mixture of glacial acetic acid and hydrochloric acid afforded 4-(p-chorophenyl)-2-(substituted phenacyl)-2-butenoic acids 10. Condensation reaction of 10 with hydrazines gave type 15 compounds in good yields. Also, a new series of as-triazino[3,4-a]phthalazines 20 was obtained from the reaction of substituted benzylpyruvic acids 6 with hydralazine to give the hydralazones 19 which underwent dehydrative cyclization reaction with PPA to afford 20. Structure assignments are based on ¹H, ¹³C nmr and ir spectra.     

The development of nuclear microprobe techniques for the spatial determination of13C and13C/12C ratios

Sensitive and selective nuclear reaction methods have been sought for the nuclear microprobe measurement of the spatial distributions of¹³C and¹³C/¹²C ratios. The¹³C(α, n)¹⁶O reaction, with neutron detection, is the most selective for¹³C, and has a sensitivity of ca. 100 ppm. The reactions¹³C(d, p)¹⁴C and¹²C(d, p)¹³C, with proton detection, are the most sensitive for the simultaneous measurement of¹³C and¹²C, with detection limits of 30 and 2 ppm respectively. Less sensitive alternative reaction pairs are;¹³C(³He, p)¹⁵N and¹²C(³He, p)¹⁴N;¹³C(d, nγ)¹⁴N and¹²C(d, pγ)¹³C;¹³C(³He, pγ)¹⁵N and¹²C(³He, pγ)¹⁴N. The conditions governing their use, particularly light element interferences, are detailed.     

Chemical behaviour of N-(2-hydroxybenzyl)anthranilic acids in the presence of acyclic anhydrides

The synthesis of 11-acyl-11,12-dihydrodibenz[bf][1,5]oxazocin-6-ones 9-13 is reported by reaction of N-(2-hydroxybenzyl)anthranilic acids 1 with acetic, isobutyric, 2-ethylbutyric anhydrides. The structures of the obtained 6,8,6 products are proved with the use of ir, mass spectrometry, ¹H and ¹³C nmr spectra, homo-and heteronuclear two-dimensional nmr experiments. The formation of 9-13 is discussed in relation to the obtainment of 12H-quino[2,1-b][1,3]benzoxazin-5-ones 2-8 and 6a,12-dihydro[3,1]benzoxazino[2,1-b][1,3]-benzoxazin-5-ones 14-19 from the same starting products 1 with suitable anhydrides under controlled reaction conditions.     

Chemical shifts of phenolic monomers in solution and implications for addition and self‐condensation

Alkali metal counter‐cations alter the electron density of phenolates in solution by electrostatic interactions. This change in electron density affects their reactivity toward formaldehyde, hydroxymethylphenols, and isocyanates during polymerization. The electronic perturbation of phenolic model compounds in the presence of alkali metal hydroxides was investigated with ¹³C and ¹H nuclear magnetic resonance in polar solvents relative to non‐ionic controls, altering the chemical shifts of the model compounds, thus indicating changes in electron density using the chemical shift as a proxy. These shifts were attributed to Coulombic electrostatic interactions of the counter‐cation with the phenolate anion that correlated to hydrated ionic radius and solvent dielectric constants. The predicted relative reaction rates for formaldehyde addition based on electron density ranking from ¹³C nuclear magnetic resonance of the phenolic models was compared with the literature values. Predictions for condensation reactions of 2‐ and 4‐hydroxymethylphenol from chemical shifts were consistent with published results. The results permit predictions for the reaction of phenolic compounds for the formation of thermosetting polymeric materials. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis of chlorophyll‐a skeleton homologs using grignard reaction with methyl pyropheophorbide‐a

From methyl pyropheophorbide‐a (MPPa) (1), methyl 2‐formylmethyl‐2‐devinyl‐9‐ethylenedioxy‐9‐deoxopyropheophorbide‐a (2) and methyl 3‐acetyl‐9‐ethylenedioxy‐2‐devinyl‐9‐deoxopyropheophorbide‐a (3) were prepared. The Grignard reactions of 2 and 3 were performed using cycloalkyl magnesium bromides to afford cycloalkyl‐substituted sec‐alcohol 4 and tert‐alcohols 9a‐c, respectively. By the deprotection of the ethylenedioxy group, these alcohols were respectively converted to exocyclic ketones 5 and 10a‐c, which were dehydrated to give chlorins 6 and 11a‐c having an alkenyl function at the 2‐position. On the other hand, the oxidation and deprotection of the alcohol 4 gave a diketo chlorin 8.