Aldehyde Components Research Articles

Synthesis of Tumor Selective Indole and 8-Hydroxyquinoline Skeleton Containing Di-, or Triarylmethanes with Improved Cytotoxic Activity.

The reaction between glycine-type aminonaphthol derivatives substituted with 2- or 1-naphthol and indole or 7-azaindole has been tested. Starting from 2-naphthol as a precursor, the reaction led to the formation of ring-closed products, while in the case of a 1-naphthol-type precursor, the desired biaryl ester was isolated. The synthesis of a bifunctional precursor starting from 5-chloro-8-hydroxyquinoline, morpholine, and ethyl glyoxylate via modified Mannich reaction is reported. The formed Mannich base 10 was subjected to give bioconjugates with indole and 7-azaindole. The effect of the aldehyde component and the amine part of the Mannich base on the synthetic pathway was also investigated. In favor of having a preliminary overview of the structure-activity relationships, the derivatives have been tested on cancer and normal cell lines. In the case of bioconjugate 16, as the most powerful scaffold in the series bearing indole and a 5-chloro-8-hydroxyquinoline skeleton, a potent toxic activity against the resistant Colo320 colon adenocarcinoma cell line was observed. Furthermore, this derivative was selective towards cancer cell lines showing no toxicity on non-tumor fibroblast cells.

Strategies for the Development of Asymmetric and Non-Directed Petasis Reactions.

The Petasis reaction is a multicomponent reaction of aldehydes, amines and organoboron reagents and is a useful method for the construction of substituted amines. Despite the significant advancement of the Petasis reaction since its invention in 1993, strategies for asymmetric and non-directed Petasis reactions remain limited. To date, there are very few catalytic asymmetric Petasis reactions and almost all asymmetric reports employ a chiral auxiliary. Likewise, the aldehyde component often requires a directing group, ultimately limiting the reaction's scope. In this Concept, key methods for asymmetric and non-directed Petasis reactions are discussed, focusing on how these conceptual advances can be applied to solve long-standing gaps in the Petasis literature.

Thermo physical properties and IR spectral studies of some binary liquid mixtures and correlation with the Jouyban–Acree model

ABSTRACT Excess molar volume, excess isentropic compressibility, deviation in viscosity and excess Gibbs free energy for activation of viscous flow for binary mixtures of propargyl alcohol (J) with benzyl aldehyde (J1), benzylamine (J2) and benzyl alcohol (J3) components with selected compositions were determined from the measured values of densities (ρ), viscosities (η), and speeds of sound (u) of pure components and their mixtures from 303.15 K to 313.15 K. The effect of various functional groups on the excess properties has been discussed in terms of attractive forces between the components. The results of the Jouyban-Acree model are discussed in terms of the mean relative deviation and individual relative between the calculated and experimental densities, speed of sound, and viscosities as an accuracy criterion.FTIR studies have also been added to confirm the experimental findings of the investigated mixtures

Identification of Volatile Compounds Contributory to Mango and Tropical-Type Aroma in Whisky

There is an increasing drive across the global distilling industry for a greater understanding of the development of sensory properties in whisky. Origins of the fruity aroma descriptor have been reasonably well-explored in the current literature, but this umbrella term captures a wide range of quite varied sub-descriptors. One such fruit-type lexicon term that has received limited attention is that of mango. The present trial assessed the sensory profiles of 14 commercial whisky products and identified whiskies elevated in the target mango trait. Further analysis of product volatile compound composition allowed for the shortlisting of candidate compounds potentially contributory to this trait. Spiking of candidate compounds into a base whisky identified a potential role for several common whisky components in the development of mango aroma. In particular, aldehyde and acetal components (such as isobutyraldehyde, isovaleraldehyde, and isovaleraldehyde diethyl acetal) were found to positively impact the sensory reporting of mango aroma in whisky. These compounds are not atypical to whisky, and their production pathways and precursors are previously identified; this provides scope for their control without substantial process modification.

Formation and distribution of (E,E)‐2,4‐decadienal in deep‐fried dough sticks under different conditions

Abstract(E,E)‐2,4‐Decadienal is an important product of deep‐frying systems and is regarded as a health hazard. The present study investigated the formation of (E,E)‐2,4‐decadienal in deep‐fried dough sticks under different conditions, including types of deep‐frying oils, deep‐frying temperature, and dough composition. In addition, the correlation between (E,E)‐2,4‐decadienal formation and deep‐frying conditions was analyzed. The results showed that the (E,E)‐2,4‐decadienal content in the deep‐frying system was related to the linoleic acid level in the deep‐frying oils. Furthermore, adding 6% soy protein isolate to the dough considerably suppressed the formation of (E,E)‐2,4‐decadienal in the deep‐frying system, resulting in the lowest content at 43.52 mg kg–1. The highest (E,E)‐2,4‐decadienal content in the deep‐frying system (64.65 mg kg–1) was observed when a dough with a moisture content of 38% was used. The results of the correlation analysis revealed a strong association between the (E,E)‐2,4‐decadienal content in the deep‐fried dough sticks and their oil absorption capacity. The (E,E)‐2,4‐decadienal content increased with higher oil content in the deep‐fried dough sticks. Therefore, suppressing the oil absorption of deep‐fried dough sticks is an important approach for controlling (E,E)‐2,4‐decadienal content.Practical applications: As one kind of traditional deep‐fried foods in China, deep‐fried dough sticks attracted the attention of consumers because of its desirable flavor and texture. Thus, it is crucial to improve its safety and quality. As is known, (E,E)‐2,4‐decadienal is harmful to health, and it is the main aldehyde component in the deep‐frying system. Herein, it is important to improve the safety of deep‐fried dough sticks while suppressing the formation of (E,E)‐2,4‐decadienal in deep‐frying system and reducing the content of (E,E)‐2,4‐decadienal in deep‐fried dough sticks. On the one hand, the use of deep‐frying oils with lower level of linoleic acid could limit the formation of (E,E)‐2,4‐decadienal in deep‐frying system, which could also be achieved with the addition of protein into the dough. On the other hand, suppressing the oil uptake ability of deep‐fried dough sticks is an important approach to limit the level of (E,E)‐2,4‐decadienal in deep‐fried dough sticks.

Thermophysical properties of binary liquid mixtures at various temperatures, supported by FTIR spectral studies and correlation with the Jouyban–Acree model (allyl alcohol, benzyl aldehyde, benzylamine and benzyl alcohol)

ABSTRACT Excess molar volume, excess isentropic compressibility, deviation in viscosity and excess Gibbs free energy for activation of viscous flow for binary mixtures of allyl alcohol (C) with benzyl aldehyde (C1), benzylamine (C2) and benzyl alcohol (C3) components in selected compositions were determined from the measured values of densities (ρ), viscosities (η) and speeds of sound (u) of pure components and their mixtures at 303.15–313.15 K. These results were analysed by different theoretical models, such as PFP and Jouyban–Acree model. The effect of various functional groups on the excess properties was discussed in terms of disruption of H-bonding and dipole–dipole interaction between the components of the mixtures. The thermodynamic results of the present investigation have been correlated with FTIR spectral studies and have obtained a good agreement.

Impact of Smoking Technology on the Quality of Food Products: Absorption of Polycyclic Aromatic Hydrocarbons (PAHs) by Food Products during Smoking

The food industry is striving for a sustainable development of thermal food processing. Smoking is an example of a process that has grown in popularity in recent years. There is a lack of systematic knowledge in the literature regarding this undervalued process, so the purpose of this review is to analyze the state of knowledge about the methods and technologies of smoking food products and their impact on changing the quality of essential food products. Therefore, a comprehensive review of the literature on smoking processes from the past two decades was conducted. The most essential components absorbed from smoke during smoking are polycyclic aromatic hydrocarbons (PAHs). In the present work, 24 PAHs are summarized, and the capability of 12 food products to absorb them is described. Analysis of the principal components of absorbed PAHs showed that some products from different groups exhibit a similar ability to absorb these compounds, mainly influenced by their physical properties. The pre-treatment practices of raw materials before smoking, the smoking raw materials used, and their quality parameters were characterized (along with the effects of smoking methods on selected product groups: fish, meats, and cheeses). In addition, the gap in research concerning the absorption of other components of smoke, e.g., phenols, alcohols, ketones, and aldehydes, which directly impact food quality, is indicated.

Hydroxycinnamaldehyde-derived benzofuran components in lignins.

Lignin is an abundant polymer in plant secondary cell walls. Prototypical lignins derive from the polymerization of monolignols (hydroxycinnamyl alcohols), mainly coniferyl and sinapyl alcohol, via combinatorial radical coupling reactions and primarily via the endwise coupling of a monomer with the phenolic end of the growing polymer. Hydroxycinnamaldehyde units have long been recognized as minor components of lignins. In plants deficient in cinnamyl alcohol dehydrogenase, the last enzyme in the monolignol biosynthesis pathway that reduces hydroxycinnamaldehydes to monolignols, chain-incorporated aldehyde unit levels are elevated. The nature and relative levels of aldehyde components in lignins can be determined from their distinct and dispersed correlations in 2D 1H-13C-correlated nuclear magnetic resonance (NMR) spectra. We recently became aware of aldehyde NMR peaks, well resolved from others, that had been overlooked. NMR of isolated low-molecular-weight oligomers from biomimetic radical coupling reactions involving coniferaldehyde revealed that the correlation peaks belonged to hydroxycinnamaldehyde-derived benzofuran moieties. Coniferaldehyde 8-5-coupling initially produces the expected phenylcoumaran structures, but the derived phenolic radicals undergo preferential disproportionation rather than radical coupling to extend the growing polymer. As a result, the hydroxycinnamaldehyde-derived phenylcoumaran units are difficult to detect in lignins, but the benzofurans are now readily observed by their distinct and dispersed correlations in the aldehyde region of NMR spectra from any lignin or monolignol dehydrogenation polymer. Hydroxycinnamaldehydes that are coupled to coniferaldehyde can be distinguished from those coupled with a generic guaiacyl end-unit. These benzofuran peaks may now be annotated and reported and their structural ramifications further studied.

Zn,N co-doped 3D carbon frameworks constructed by in-situ polymerization-pyrolysis of fluid precursors and their applications in boosting atmospheric CO2 capture and fixation

Through the rational design of 1-butyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)imide ([Bmim][NTf2])-based multi-component fluid precursors, we present a novel and sustainable strategy for preparing Zn,N co-doped 3D carbon frameworks (Zn@CTDPOP-IL) via in-situ polymerization-pyrolysis of fluid precursors, and explore their applications in atmospheric CO2 capture and clean conversion into cyclic carbonates. The structure and performance of Zn@CTDPOP-IL frameworks were optimized by preparing them under different pyrolysis temperatures and fluid precursor compositions. It was found that the in-situ polymerization of aldehyde and amine components in fluid precursors was crucial for achieving a high specific surface area of carbon frameworks; [Bmim][NTf2] was used as both the solvent and catalyst for in-situ polymerization, as well as the soft template agent during subsequent pyrolysis process. The carbon frameworks also possess multiple Lewis acid/base active sites, exhibiting excellent CO2 adsorption (3340 μmol/g) and conversion performance under mild (40 °C, 0.1 MPa) and solvent-free conditions. The cyclic carbonate yield reaches up to 94 % with a selectivity of 99 %, which is attributed to the superior activation abilities of Lewis acid/base sites towards epoxide and CO2 respectively. The reusability and universality of the catalyst were further investigated, revealing its exceptional structural stability and satisfactory versatility. Finally, we elucidated a proposed cycloaddition mechanism catalyzed by multiple active sites in Zn@CTDPOP-IL. Compared to other reported porous carbon materials, the Zn@CTDPOP-IL frameworks developed herein are simple and environmentally friendly in preparation while exhibiting excellent dual functionality for CO2 adsorption and catalytic conversion, making them highly promising for cleaner treatment of low-pressure waste CO2 resource.

The nature and magnitude of heterosis for the economic traits of vetiver{Chrysopogon zizanioides (L.) Roberty}

A total of 65 F1 vetiver hybrids were developed using the L × T design by mating 13 males with 5 females. The goal of this endeavor is to increase the possibility of developing high-yielding, quality essential oil varieties by utilizing heterosis and genetic variability. The heritability (%) was high for the traits CH4, CH7 to CH11 (81.90–99.69%). A positive and highly significant association exists between the features of CH2 and CH3. The trait CH8 showed the highest direct contributions to CH4, followed by CH-3, CH-5, CH4, and CH1. Heritability, correlations, and heterosis components all have an impact on the nature and degree of heterosis. It recommends that when selecting superior hybrids, breeders should take into account the genetic correlation between key traits. Based on average performance and heterosis for the root yield/plot, the top two crosses were determined to be L13 × T1 and L10 × T3. While hybrids L10 × T5, L2 × T3, and L4 × T5 showed high essential oil yield, four hybrids, L1 × T2, L3 × T3, L9 × T4, and L2 × T5, had the highest essential oil (%). A nor-sesquiterpene aldehyde (khusilal), two cedrene family chemicals (α-cedrenal and α-cedrenol), and one sesquiterpene alcohol, or khusol constitute the oil composition. The inclusion of just alcoholic and aldehydic components makes the oil fingerprint distinct. Further research was conducted on these hybrids to take advantage of heterosis and employ them in further hybridization programs to create superior genotypes.

Chemo- and Diastereoselective Entries into All-Carbon α-Quaternary Aldehydes via C-C Insertion of 4-Diazoisoquinolin-3-ones into C-CHO Bonds.

Herein, we describe a chemo- and diastereoselective formal C-C insertion reaction of 1,2-disubstituted 4-diazo-3(2H)-isoquinolones and 4-diazoisochroman-3-one into C-CHO bonds of aldehydes, delivering all-carbon α-quaternary aldehydes bearing medicinally important 1,4-dihydro-3(2H)-isoquinolone scaffold. Our protocol is enabled by the preferential 1,2-carbon migration over more common 1,2-H shift. The corresponding reaction tolerates a wide range of functionalities in both aldehyde and diazo components, giving the target homologated aldehydes in generally high yields. The synthetic utility of this method has been further showcased by some transformations of the formyl moiety.

Functional differentiation of two general-odorant binding proteins in Hyphantria cunea (Drury) (Lepidoptera: Erebidae).

General odor-binding proteins (GOBPs) play critical roles in insect olfactory recognition of sex pheromones and plant volatiles. Therefore, the identification of GOBPs in Hyphantria cunea (Drury) based on their characterization to pheromone components and plant volatiles is remain unknown. In this study, two H. cunea (HcunGOBPs) genes were cloned, and their expression profiles and odorant binding characteristics were systematically analyzed. Firstly, the tissue expression study showed that both HcunGOBP1 and HcunGOBP2 were highly expressed in the antennae of both sexes, indicating their potential involvement in the perception of sex pheromones. Secondly, these two HcunGOBPs genes were expressed in Escherichia coli and ligand binding assays were used to assess the binding affinities to its sex pheromone components including two aldehydes and two epoxides, and some plant volatiles. HcunGOBP2 showed high binding affinities to two aldehyde components (Z9, Z12, Z15-18Ald and Z9, Z12-18Ald), and showed low binding affinities to two epoxide components (1, Z3, Z6-9S, 10R-epoxy-21Hy and Z3, Z6-9S, 10R-epoxy-21Hy), whereas HcunGOBP1 showed weak but significant binding to all four sex pheromone components. Furthermore, both HcunGOBPs demonstrated variable binding affinities to the plant volatiles tested. Thirdly, in silico studies of HcunGOBPs utilized homology, structure modeling, and molecular docking revealed critical hydrophobic residues might be involved in the binding of HcunGOBPs to their sex pheromone components and plant volatiles. Our study suggests that these two HcunGOBPs may serve as potential targets for future studies of HcunGOBPs ligand binding, providing insight in the mechanism of olfaction in H. cunea. © 2023 Society of Chemical Industry.

Synthesis of Bioactive Aminomethylated 8-Hydroxyquinolines via the Modified Mannich Reaction.

8-hydroxyquinoline (oxine) is a widely known and frequently used chelating agent, and the pharmacological effects of the core molecule and its derivatives have been studied since the 19th century. There are several synthetic methods to modify this core. The Mannich reaction is one of the most easily implementable examples, which requires mild reaction conditions and simple chemical reagents. The three components of the Mannich reaction are a primary or secondary amine, an aldehyde and a compound having a hydrogen with pronounced activity. In the modified Mannich reaction, naphthol or a nitrogen-containing naphthol analogue (e.g., 8-hydroxyquinoline) is utilised as the active hydrogen provider compound, thus affording the formation of aminoalkylated products. The amine component can be ammonia and primary or secondary amines. The aldehyde component is highly variable, including aliphatic and aromatic aldehydes. Based on the pharmacological relevance of aminomethylated 8-hydroxyquinolines, this review summarises their syntheses via the modified Mannich reaction starting from 8-hydroxyquinoline, formaldehyde and various amines.

Experimental investigation of salicylaldehydes in Groebke-Blackburn-Bienayme -3-component reaction

Salicylaldehyde with different substitutions as the aldehyde component in the Groebke-Blackburn-Bienayme-3-component reaction (GBB-3CR) was investigated in the absence of the any catalyst. The results showed that the type of salicylaldehyde substitution plays an effective role in the reaction process. Salicylaldehydes with Br and Cl substitution groups led to a pseudo four-components reaction, producing 4H-1,3-benzodioxine-4,4-dicarboxamides. In these cases, 2-aminopyridines did not participate in the reactions, but played a prominent role. Conversely, salicylaldehydes with NO2 substitution participated in the GBB-3CR and produced 2-(3-aminoimidazo[1,2-a]pyridin-2-yl)phenols (6a-l). Interestingly, regarding salicylaldehyde without substitution, both pseudo-four-component reaction and GBB-3CR were performed.

Solvent-Responsive Reversible and Controllable Conversion between a Polyimine Membrane and an Organic Molecule Cage.

Adaptive bionic self-correcting behavior offers an attractive property for chemical systems. Here, based on the dynamic feature of imine formation, we propose a solvent-responsive strategy for smart switching between an amorphous ionic polyimine membrane and a crystalline organic molecule cage without the addition of other building blocks. To adapt to solvent environmental constraints, the aldehyde and amine components undergo self-correction to form a polymer network or a molecular cage. Studies have shown that the amorphous film can be switched in acetonitrile to generate a discrete cage with bright birefringence under polarized light. Conversely, the membrane from the cage crystal conversion can be regained in ethanol. Such a membrane-cage interconversion can be cycled continuously at least 5 times by switching the two solvents. This work builds a bridge between the polymer network and crystalline molecules and offers prospects for smart dynamic materials.

Three-Component Betti Condensation for Synthesis of Aminomethylnaphthols Incorporating Deoxy-isoequilenine Scaffold-Absolute Configuration and Application

Chiral aminomethylnaphthols have been prepared highly diastereoselective by means of three-component “Betti condensation”, using steroidal 2-naphthol analogue, synthesized from estrone. The use of 2-methoxybenzaldehyde or 2-pyridinecarboxaldehyde as aldehyde component and (S)-(–)-1-phenylethan-1-amine or (S)-(–)-1-(naphthalen-2-yl)ethan-1-amine, as chiral non-racemic amine component providing the diastereoselectivity, allowed the synthesis of structurally diverse aminomethylnaphthols. The latter easily form 1,3-dihydronaphthoxazines through reaction with formaldehyde. The absolute configurations of the new aminomethylnaphthols synthesized have been determined through advanced nuclear magnetic resonance (NMR) experiments and confirmed by X-ray crystallography. The chiral steroidal aminomethylnaphthols obtained as pure diastereoisomers have been evaluated as pre-catalysts in the enantioselective addition of diethylzinc to aldehydes with enantioselectivities of up to 97% ee.

Switching the Mode of Drug Release from a Reaction-Coupled Low-Molecular-Weight Gelator System by Altering Its Reaction Pathway.

Low-molecular-weight hydrogels are attractive scaffolds for drug delivery applications because of their modular and facile preparation starting from inexpensive molecular components. The molecular design of the hydrogelator results in a commitment to a particular release strategy, where either noncovalent or covalent bonding of the drug molecule dictates its rate and mechanism. Herein, we demonstrate an alternative approach using a reaction-coupled gelator to tune drug release in a facile and user-defined manner by altering the reaction pathway of the low-molecular-weight gelator (LMWG) and drug components through an acylhydrazone-bond-forming reaction. We show that an off-the-shelf drug with a reactive handle, doxorubicin, can be covalently bound to the gelator through its ketone moiety when the addition of the aldehyde component is delayed from 0 to 24 h, or noncovalently bound with its addition at 0 h. We also examine the use of an l-histidine methyl ester catalyst to prepare the drug-loaded hydrogels under physiological conditions. Fitting of the drug release profiles with the Korsmeyer-Peppas model corroborates a switch in the mode of release consistent with the reaction pathway taken: increased covalent ligation drives a transition from a Fickian to a semi-Fickian mode in the second stage of release with a decreased rate. Sustained release of doxorubicin from the reaction-coupled hydrogel is further confirmed in an MTT toxicity assay with MCF-7 breast cancer cells. We demonstrate the modularity and ease of the reaction-coupled approach to prepare drug-loaded self-assembled hydrogels in situ with tunable mechanics and drug release profiles that may find eventual applications in macroscale drug delivery.

Boron Trifluoride‐Mediated Synthesis of Oxazole N‐oxides

AbstractA new synthetic protocol for the preparation of oxazole N‐oxides in the form of stable boron trifluoride complexes has been developed. It is based on the condensation of α‐diketone monooximes with an appropriate aldehyde component in the presence of an equimolar amount of boron trifluoride. The method opens access to a broad scope of derivatives including previously unknown 2‐unsubstituted oxazole N‐oxides. Its abilities were demonstrated via the synthesis of 25 diverse oxazole derivatives in 14–89 % yields.

The Synthesis of Novel 7-(Substituted benzyl)-4,5-dihydro[1,2,3]triazolo[1,5-a]pyrazin-6(7H)-ones via Tandem Ugi–Huisgen Reactions

AbstractA convenient method for the synthesis of 2-azido-3-arylpropanoic acids via the Meerwein halogenoarylation reaction of acrylic acid esters with diazonium salts, subsequent nucleophilic substitution of the halogen by an azide, and saponification is developed. The newly formed 2-azido-3-arylpropanoic acids react under the conditions of non-catalytic four-component Ugi reactions, leading to the formation of α-azidoamides in good yields. The use of propargylamine as the amine component allows the formation of Ugi adducts with azide and acetylene motifs ready for intramolecular 1,3-dipolar Huisgen cycloaddition to give the [1,2,3]triazolo[1,5-a]pyrazine annulated system. The Ugi reaction is found to give 2-azido-3-aryl-N-(2-oxo-1,2-disubstituted ethyl)-N-(prop-2-yn-1-yl)propanamides at room temperature without azide–alkyne cycloaddition. These dipeptides are converted into 4,5-dihydro[1,2,3]triazolo[1,5-a]pyrazin-6(7H)-ones in near quantitative yields by heating in toluene. However, when the Ugi reaction is carried out by heating, it results in a one-pot Ugi–Huisgen tandem reaction leading to 4,5-dihydro[1,2,3]triazolo[1,5-a]pyrazin-6(7H)-ones in excellent yields. Moreover, the possibility of the incorporation of a bromovinyl fragment (the synthetic equivalent of an acetylene fragment) via the aldehyde component of the Ugi reaction is demonstrated in an alternative preparation of the [1,2,3]triazolo[1,5-a]pyrazine system.

Fine-Tuned Reactivity of N-Containing Naphthol Analogues.

6-Hydroxyquinoline and 3-hydroxyisoquinoline as N-containing naphthol analogues were tested in modified Mannich reactions (mMr’s). In the case of 6-hydroxyquinoline, the outcomes of the attempted Mannich reactions were strongly influenced by the amine components. Aminoalkylation of this substrate with reagents 1-naphthaldehyde and N-benzylmethylamine led to the isolation of a diol regarded as a stabilised water adduct of an ortho-quinone methide (o-QM), of which formation can be ascribed to the presence of a hydroxide ion in a relatively higher concentration generated by the bulky and basic amine component with decreased nucleophilicity. The classical Mannich base was isolated as a single product when the amine component was replaced for morpholine, featuring nucleophilicity rather than basic character under the applied reaction conditions. Starting from the isomer substrate 3-hydroxyisoquinoline, independently on the nucleophile (methanol or morpholine) besides the formation of the classical Mannich base, the nucleophilic attack at position one of the heterocyclic substrate was also observed. The DFT analysis of the acceptor molecular orbitals of the potential electrophilic components and the thermodynamics of the assumed-possible transformations demonstrated that this regioselective addition is a feasible process on the investigated heterocyclic skeleton. DFT modelling studies also suggest that besides the steric bulk, the orbital-controlled electronic properties of the aryl group, originating from the aldehyde components, have a strong influence on the ratios and the NMR-monitored interconversions of the C-1-substituted 3-hydroxyisoquinolines and the classical Mannich bases formed in multistep reaction sequences. On the basis of the DFT analysis of the thermodynamics of alternative pathways, a reaction mechanism was proposed for the rationalization of these characteristic substrate-controlled interconversions.