Fluorimetric determination of aromatic aldehydes with 2,2'-dithiobis(1-aminonaphthalene)

A sensitive fluorimetric method for the determination of aromatic aldehydes is based on their reaction in dilute sulfuric acid with a new reagent, 2,2'-dithiobis(l-amino-naphthalene) in the presence of tri-n-butylphosphine, sodium sulfite and sodium phosphite at ambient temperature. The fluorescences produced are fairly characteristic of individual aldehydes. The method is extremely selective for aromatic aldehydes and very sensitive, especially for p-hydroxybenzaldehyde, o-methoxybenzaldehyde, p-methoxybenzaldehyde and p-tolualdehyde which can be determined at concentrations of as little as 3–5 ng ml^-1.     

Direct α‐Vinylidenation of Aldehydes and Subsequent Cascade: Gold and Amine Catalysts Work Synergistically

Carbonyl‐substituted allenes are highly important synthetic intermediates for a number of heterocycles and strained‐ring systems. However, chemistry of allenyl aldehydes has not been explored as extensively as their ketone, ester, or amide analogues because of a lack of general synthetic methods. Described herein is the first direct α‐vinylidenation of aldehydes and an α‐vinylidenation/γ‐functionalization cascade to access tri‐ and tetrasubstituted allenyl aldehydes using a combination of a gold catalyst and an secondary amine. The reactive enamine intermediate of an aldehyde reacts with the gold‐activated hypervalent silylethynyl benziodoxolone to selectively generate the corresponding trisubstituted allenyl aldehyde. The allenyl aldehyde can further react with another equivalent of the alkynylation reagent or other electrophiles to afford tetrasubstituted allenes bearing an aldehyde group, an acetylene, and a halogen functionality. This method enables rapid access to polysubstituted furans from aldehydes.     

Synthesis of bis-α-amino acids through proline catalyzed asymmetric α-amination of higher homologs of Garner's aldehyde

A very convenient synthesis of bis-α-amino acids from the higher homologs of Garner's aldehyde is reported. The key step is proline catalyzed asymmetric amination of the aldehydes using dibenzylazodicarboxylate. The aldehydes used are either commercially available or can easily be prepared from aspartic or glutamic acid. One of the two chiral centers in the bis-amino acids comes from the aldehyde and the other one is generated through the proline catalyzed reaction, which were high yielding and proceeded with very high diastereoselectivity (93–99%). The reported route offers a general method for the synthesis of the title compounds with desired stereochemical outcome.     

Triflylpyridinium Enables Rapid and Scalable Controlled Reduction of Carboxylic Acids to Aldehydes using Pinacolborane

Building up new and efficient methods for the controlled conversion of carboxylic acids to aldehydes is important. Herein, we report a rapid, modular and scalable method for the conversion of carboxylic acids to aldehydes using pinacolborane at ambient temperature, in which a triflylpyridinium reagent is used. The conversion of carboxylic acid to intermediate acylpyridinium by triflylpyridinium is new. A binary pyridine-coordinated boronium complex is generated after reduction. The unprecedented reduction of the acylpyridinium by HBpin opens up a practically direct synthesis of aldehydes from carboxylic acids. Theoretical studies indicate that the reduction of acylpyridinium requires a lower activation free energy than that of the product aldehyde. The synthetic advantage of this protocol is further highlighted by the scalable synthesis of aldehyde via continuous flow process. Configuration retention for chiral acids are presented in those syntheses.     

Transition metal-catalyzed conversion of aldehydes to ketones

Ketones are one of the most important classes of organic compounds, and widely present in various pharmacological compounds, biologically active molecules and functional materials. Over the past few decades, transition metal-catalyzed conversion of aldehydes has been found to be a powerful method. With the continuous development in recent years, it has become an efficient and uncomplicated strategy for constructing ketones. There are four major mechanisms for transition metal-catalyzed ketone synthesis from aldehyde: (1) carbonyl-Heck reaction, that is 1,2-insertion of organometal species to aldehydic C=O double bond, (2) direct insertion of transition metal catalysts to aldehydic C-H bond, (3) aldehyde as acyl radical, (4) aldehyde as carbon radical acceptor. This article summarizes related reports on the transformations of aldehydes to generate corresponding ketones under different reaction conditions.     

Determination of nanomole quantities of lower aldehydes by cold-vapour atomic absorption spectrometry

A method is described for the determination of 10–100 nmole of methanal and 20–150 nmole of ethanal and propanal. The method is based on the oxidation of aldehydes to the corresponding acids by mercuric ion which in turn is reduced to elemental mercury, followed by cold-vapour atomic absorption spectrometry. Calibration plots were constructed between the concentration of each aldehyde and absorbance, while the calibration from the conventional cold vapour procedure was used for total aldehydes determination. The method is selective and can be used for aldehyde determination in the presence of ketones, acetals, alcohols, acids, esters, ethers, organic chlorides and epoxides. This simple method is characterised by 98–102% recoveries and standard deviations of 3%.     

Analysis of the compounds in the synthesis mixtures of hydroxy acids by a gradient programmed RP-HPLC with UV/vis and RI detectors

Summary A gradient programmed reversed phase high-performance liquid chromatographic (RP-HPLC) method is described for the quantitative determination of some aldehydes, hydroxy aldehydes, unsaturated aldehydes, hydroxy carboxylic acids, carboxylic acids, alcohols and polyols using an ultraviolet and a refractive index detector in series. The sample matrices are synthesis mixtures of hydroxy carboxylic acids. The structures of the hydroxy aldehyde intermediates are determined by¹³C NMR and the influence of sample preparation on analysis results is discussed. The limits of detection and the precision of the method are evaluated.     

1,3,5,7-Tetramethyl-8-aminozide-difluoroboradiaza-s-indacene as a new fluorescent labeling reagent for the determination of aliphatic aldehydes in serum with high performance liquid chromatography

A BODIPY-based fluorescent derivatization reagent with a hydrazine moiety, 1,3,5,7-tetramethyl-8-aminozide-difluoroboradiaza-s-indacene (BODIPY-aminozide), has been designed for aldehyde labeling. An increased fluorescence quantum yield was observed from 0.38 to 0.94 in acetonitrile when it reacted with aldehydes. Twelve aliphatic aldehydes from formaldehyde to lauraldehyde were used to evaluate the analytical potential of this reagent by high performance liquid chromatography (HPLC) on C₁₈ column with fluorescence detection. The derivatization reaction of BODIPY-aminozide with aldehydes proceeded at 60 °C for 30 min to form stable corresponding BODIPY hydrazone derivatives in the presence of phosphoric acid as a catalyst. The maximum excitation (495 nm) and emission (505 nm) wavelengths were almost the same for all the aldehyde derivatives. A baseline separation of all the 12 aliphatic aldehydes (except formaldehyde and acetaldehyde) is achieved in 20 min with acetonitrile–tetrahydrofuran (THF)–water as mobile phase. The detection limits were obtained in the range from 0.43 to 0.69 nM (signal-to-noise = 3), which are better than or comparable with those obtained by the existing methods based on aldehyde labeling. This reagent has been applied to the precolumn derivatization followed with HPLC determination of trace aliphatic aldehydes in human serum samples without complex pretreatment or enrichment method.     

A versatile preparation of alpha,beta-unsaturated lactones from homoallylic alcohols

[formula: see text] A new method for the synthesis of alpha,beta-unsaturated lactones from beta-acetoxy aldehydes by reaction with the lithium enolate of methyl acetate was developed. The reaction is relatively insensitive to structural changes in the aldehyde substrates. The process was extended to the synthesis of five-ring lactones from alpha-acetoxy aldehydes. Experimental evidence regarding the mechanism of this one-pot transformation was obtained. The observations are consistent with a pathway involving an initial aldol condensation with subsequent acyl migration, lactonization, and beta-elimination and not an enolate equilibration-aldol mechanism.     

Development of a novel colorimetric indicator pad for detecting aldehydes

A colorimetric indicator was developed and a colorimetric indicator pad was fabricated for the rapid detection of aldehydes. The detection pad has two sides: an observation side on top and a barrier on the bottom. The top side contains a reagent which reacts directly with aldehydes to produce a color change, while the bottom side is coated with a double-sided plastic tape barrier to prevent the escape of chemicals. Sensitivity of the indicator pads was determined using the vapor sensitive ASTM F739 technique with the presence of the indicator. A significant indicator color change (yellow to red) occurred about 5 min before the infrared analyzer response of the ASTM method. The chemical principle and reaction characterization of the test are described. The stability and potential interferences of the indicator pad were also examined by directly spiking aldehydes and compounds with other functional groups, respectively, onto the indicator pads. The newly developed aldehyde indicator pad should find utility in detecting aldehydes in both liquid and vapor phases and in collecting aldehyde permeation through PPE for further study.     

Aerobic oxidation of aldehydes by visible light photocatalysis

An efficient and environmentally benign method for the oxidation of aldehydes to carboxylic acids has been developed. Singlet oxygen, generated by visible light in the presence of a Ru or Ir photocatalyst, reacted with aldehydes to give the corresponding carboxylic acids in excellent yields. The reaction is highly chemo-selective, in which only an aldehyde moiety is reactive even in the presence of other photo-oxidation active sites. This method is an example of an ideal green chemical reaction in the sense that molecular oxygen and visible light are key sources for the transformation.     

Diarylprolinol as an Effective Organocatalyst in Asymmetric Cross-Aldol Reactions of Two Different Aldehydes

The aldol reaction is one of the most important carbon-carbon bond-forming reactions in organic chemistry. Asymmetric direct cross-aldol reaction of two different aldehydes has been regarded as a difficult reaction because of the side reactions such as self-aldol reaction and over reaction. We found that trifluoromethyl-substituted diarylprolinol, α,α-bis[3,5-bis(trifluoromethyl)phenyl]-2-pyrrolidinemethanol ( 1 ), is an effective organocatalyst that promotes several cross-aldol reactions of aldehydes with excellent diastereo- and enantioselectivities. Acetaldehyde can be employed as a suitable nucleophilic aldehyde. Successful electrophilic aldehydes are ethyl glyoxylate, chloroacetaldehyde, dichloroacetaldehyde, chloral, α-alkyl-α-oxo aldehyde, trifluoroacetaldehyde, glyoxal, alkenyl aldehyde, alkynyl aldehyde, and formaldehyde. Some of the aldehydes are commercially available as a polymer solution, an aqueous solution, or in the hydrated form. They can be used directly in the asymmetric aldol reaction as a commercially available form, which is a synthetic advantage. Given that the obtained aldol products possess several functional groups along with a formyl moiety, they are synthetically useful chiral building blocks.     

Colorimetric monitoring of solid-phase aldehydes using 2,4-dinitrophenylhydrazine

A simple and rapid method to achieve colorimetric monitoring of resin-bound aldehydes, based on ambient temperature reaction with 2,4-dinitrophenylhydrazine (DNPH) in the presence of dilute acid, has been developed as an adjunct to solid-phase organic synthesis and combinatorial chemistry. By this test, the presence of aldehydes is indicated by a red to dark-orange appearance, within a minute. Alternatively, resins that are free of aldehydes or in which aldehyde functions have reacted completely retain their original color. The DNPH test was demonstrated for poly(ethylene glycol)-polystyrene (PEG-PS), aminomethyl polystyrene (AMP), cross-linked ethoxylate acrylate resin (CLEAR), and acryloylated O,O'-bis(2-aminopropyl)poly(ethylene glycol) (PEGA) supports and gave results visible to the naked eye at levels as low as 18 micromol of aldehyde per gram of resin.     

Synthesis of tert-butyl peresters from aldehydes by Bu4NI-catalyzed metal-free oxidation and its combination with the Kharasch-Sosnovsky reaction

A new tert-butyl peresters synthesis directly from aldehydes and TBHP was developed via Bu(4)NI-catalyzed aldehyde C-H oxidation. Mechanistic studies suggest that the protocol proceeds via a radical process. Combining the method with the Kharasch-Sosnovsky reaction offers a practical approach for the synthesis of allylic esters from simple aldehydes and alkenes via a two-step one-pot procedure.     

Unsaturated aldehydes as alkene equivalents in the Diels-Alder reaction

A one-pot procedure is described for using alpha,beta-unsaturated aldehydes as olefin equivalents in the Diels-Alder reaction. The method combines the normal electron demand cycloaddition with aldehyde dienophiles and the rhodium-catalyzed decarbonylation of aldehydes to afford cyclohexenes with no electron-withdrawing substituents. In this way, the aldehyde group serves as a traceless control element to direct the cycloaddition reaction. The Diels-Alder reactions are performed in a diglyme solution in the presence of a catalytic amount of boron trifluoride etherate. Subsequent quenching of the Lewis acid, addition of 0.3% of [Rh(dppp)2Cl] and heating to reflux achieves the ensuing decarbonylation to afford the product cyclohexenes. Under these conditions, acrolein, crotonaldehyde and cinnamaldehyde have been reacted with a variety of 1,3-dienes to afford cyclohexenes in overall yields between 53 and 88%. In these transformations, the three aldehydes serve as equivalents of ethylene, propylene and styrene, respectively.     

An improved synthesis of 5,15-diaryloctaalkylporphyrins

The title compounds were prepared from an aromatic aldehyde and bis(3-ethyl-4-methyl-2-pyrrolyl)-methane in acetonitrile in the presence of catalytic amount of trichloroacetic acid, followed by p-chloranil oxidation. The reaction conditions employed here are milder than those previously reported, allowing efficient preparation of porphyrins with acid-labile groups such as cyclic acetals, for which the previous method provided no direct synthetic access. Using the new method, aromatic aldehydes with acid-labile groups, as well as sterically hindered aldehydes, gave the corresponding porphyrins in satisfactory yields (50–90%). This method therefore can be widely utilized for synthesis of 5,15-diaryloctaalkylporphyrins.     

Aldehyde separation by polymer-supported oligo(ethyleneimines)

Chlorosulfonated styrene (10%) divinylbenzene resin beads reacted with an excess of ethylenediamine (EDA), diethylenetriamine (DETA), and triethylenetetramine (TETA) to give the corresponding sulfonamides with pendant oligo(ethyleneimines). The resulting modified resins are useful in the separation of aldehydes from hydrocarbon mixtures. Sorption of aldehydes occurs through formation of both Schiff base and five-membered (imidazoline) rings. Sorbed aldehydes can readily be stripped from the resins by treating with dilute acid solutions. Since the sulfamide bond has a reasonable stability toward acid-base hydrolysis, the loaded resins can be regenerated and recycled by simple acid-base washings, without losing their activity. In the present study, sorption and desorption kinetics of acetaldehyde, benzaldehyde, and salicylaldehyde have been investigated under different conditions. The aldehyde sorption obeys second-order kinetics. The method presented is applicable for all aromatic aldehydes. However, in the case of aliphatic aldehydes carrying an α-hydrogen, aldol condensation products form in solution. So aliphatic aldehydes and their aldol products are sorbed together by the resins. This limits the recovery of aliphatic aldehydes. Consequently, the resins described are cost effective sorbents for the removal and recovery of aromatic aldehydes from various mixtures. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 2857–2864, 1997     

Two-carbon homologation of aldehydes and ketones to α,β-unsaturated aldehydes

Phosphonate reagents were developed for the two-carbon homologation of aldehydes or ketones to unbranched- or methyl-branched α,β-unsaturated aldehydes. The phosphonate reagents, diethyl methylformyl-2-phosphonate dimethylhydrazone and diethyl ethylformyl-2-phosphonate dimethylhydrazone, contained a protected aldehyde group instead of the usual ester group. A homologation cycle entailed condensation of the reagent with the starting aldehyde, followed by removal of the dimethylhydrazone protective group with a biphasic mixture of 1 M HCl and petroleum ether. This robust two-step process worked with a variety of aldehydes and ketones. Overall isolated yields of unsaturated aldehyde products ranged from 71% to 86% after the condensation and deprotection steps.     

Analysis of aldehydes via headspace SPME with on-fiber derivatization to their O-(2,3,4,5,6-pentafluorobenzyl)oxime derivatives and comprehensive 2D-GC-MS

A method for the analysis of the homologous series of alkanals, (E)-2-alkenals, and (E,E)-2,4-alkadienals is described utilizing a headspace solid-phase microextraction (HS-SPME) step and on-fiber derivatization with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) hydrochloride. Oxime derivatives formed on the fiber are desorbed in the gas chromatographic injector and analyzed by comprehensive 2-D GC coupled to quadrupole MS (GC x GC-qMS). Selecting specific fragment ions within the electron impact mass spectra of the oxime derivatives provides a suitable method for the target analysis of these aldehyde classes, which furthermore benefits from the increased separation efficiency by GC x GC. The analysis of higher molecular weight aldehydes is described in wine and grape seed oil as examples. Quantification of the aldehydes utilizes a stable isotope dilution analysis (SIDA) assay with octan-d(16)-al as isotopomeric internal standard. Besides the selectivity and sensitivity of aldehyde analysis using PFBHA derivatives, critical aspects on background level contamination and repeatability of the sample preparation method are discussed. Optimization of GC x GC-qMS parameters allowed a considerable saving of the cryogenic medium, involving additional (unmodulated) conditioning runs, rendering the method more amenable to routine analysis.     

Protonation of Homoenolate Equivalents Generated by N-Heterocyclic Carbenes

Homoenolate equivalents are generated by Lewis basic N-heterocyclic carbene catalysts and then protonated to generate efficiently saturated esters from unsaturated aldehydes. This reactivity is extended to the generation of β-acylvinyl anions from alkynyl aldehydes. The asymmetric protonation of a homoenolate equivalent generated from a β,β-disubstituted aldehyde can be accomplished with a chiral N-heterocyclic carbene.