The Forgotten Carbonyl Reaction: Chloroacetylation and Bromoacetylation of Carbonyl Compounds

Halomethyl acetates ( 3 ) could be prepared from aliphatic, α,β‐unsaturated and aromatic aldehydes, as well as from alicyclic ketones with high yields in simple one‐pot reactions. Very often, the products didn't have to be purified and could directly be used for synthetic purposes after evaporation of the solvent. Obviously, the ‘bad reputation’ of the reaction in the literature stemed from the fact that the reactions didn't take place under the best conditions. Carbonyl compounds ( 1 ) and acyl halides ( 2 ) form equilibria which are completely on the side of the halomethyl acetates ( 3 ) at room temperature (starting with aliphatic and most aromatic aldehydes) and which can be strongly influenced by the reaction parameters. It is crucial to work at low temperature in apolar solvents and to remove (or deactivate) the catalyst before workup. Reactions may be realized with or without solvents. Side reactions were observed with formaldehyde and acetaldehyde but, with exception of formaldehyde, could be reduced close to zero (see Fig. 5). By‐products were essentially avoided if the reaction took place in apolar solvents and with a local excess of acetyl chloride. In many cases clean products were available which could directly be used for synthetic purposes. Halomethyl acetates ( 3 ) are bifunctional carbonyl derivatives with two different leaving groups, whose preparative advantages have been useful for the synthesis of various pentafulvenes, but were especially important for preparing unstable parent fulvenes and fulvalenes.     

A three-component Mannich-type reaction for selective tyrosine bioconjugation

A new selective bioconjugation reaction is described for the modification of tyrosine residues on protein substrates. The reaction uses imines formed in situ from aldehydes and electron-rich anilines to modify phenolic side chains through a Mannich-type electrophilic aromatic substitution pathway. The reaction takes place under mild pH and temperature conditions and can modify protein substrates at concentrations as low as 20 muM. Using an efficient fluorescence-based assay, we demonstrated the reaction using a number of aldehydes and protein targets. Importantly, proteins lacking surface-accessible tyrosines remained unmodified. It was also demonstrated that enzymatic activity is preserved under the mild reaction conditions. This strategy represents one of the first carbon-carbon bond-forming reactions for protein modification and provides an important complement to more commonly used lysine- and cysteine-based methods.     

一个新的Cu(II)-二胺配合物催化的Henry反应

研究了L-脯氨酸制得的C2-对称二胺,与醋酸铜形成新的配合物,催化各种醛与硝基烷烃间的Henry反应。 考察了反应温度、溶剂和催化剂用量对收率和反应速率的影响。 研究结果表明,在室温下,以乙醇作为反应溶剂时,摩尔分数10%的二胺醋酸铜配合物能够有效地催化醛与硝基甲烷反应,生成相应的β-硝基醇,收率为60%~92%。 醛与硝基乙烷的Henry反应产物具有非对映立体选择性。 芳香醛参与Henry反应产物的非对映选择性高达24∶1,但脂肪醛为底物时,此催化剂对Henry反应的非对映选择性不明显。     

Aldehyde detection by chromogenic/fluorogenic oxime bond fragmentation

Amination of 4-nitrophenol, umbelliferone and 4-methylumbelliferone gave the corresponding oxyamines 1-3. These oxyamines react with aldehydes and ketones to form oximes. In the case of aliphatic aldehydes and electron-poor aromatic aldehydes, the oximes undergo base-catalyzed fragmentation in aqueous buffer in the presence of bovine serum albumin to give the parent phenols, which is the acyclic analog of Kemp's elimination reaction of 5-nitrobenzisoxazole 28. The process can be used as a spectrophotometric assay for formaldehyde under aqueous neutral conditions.     

House bulb light-induced photochemical acetalization of carbonyl compounds catalyzed by Eosin Y

We have systematically studied the reactions of acetalization and found that high reaction efficiency can be achieved using cheap and readily available organic Eosin Y as catalyst. The reaction proceeds smoothly under house bulbs and shows excellent functional group tolerance. The substrates of the reaction system are compatible with aromatic aldehydes, aliphatic aldehydes, aromatic ketones, and cyclic ketones with high yields.     

A mild titanium-based system for the reduction of amides to aldehydes

A mild method for the reduction of amides to aldehydes using 1,1,3,3-tetramethyldisiloxane/titanium(IV) isopropoxide reducing system is described. The reaction occurs under mild conditions and allows the reduction of aromatic as well as aliphatic, tertiary amides to the corresponding aldehydes, in good yields. This methodology was extended to the reduction of aromatic secondary and primary amides to the corresponding aldehydes.     

Synthesis of various acylating agents directly from carboxylic acids

Abstract

A straightforward synthesis of acylating reagents such as Weinreb and MAP amides from aromatic, aliphatic carboxylic acids, and amino acids using PPh₃/NBS combination is described. A chemo-selective modification of the carboxylic acid group into Weinreb amide in the presence of more reactive aldehydes and ketones is presented. All reactions were performed at ambient temperature under air using undried commercial grade solvent. Furthermore, the present methodology could be performed at a gram scale under inert-free reaction conditions. In addition, 7-azaindoline amide auxiliary (used for catalytic asymmetric aldol- and Mannich-type reactions), which behaves like Weinreb amide is also synthesized under similar reaction conditions.     

Radical mediated-direct conversion of aldehydes into acid bromides

A method of preparing acid bromides directly from aldehydes with Br₃CCO₂Et under radical conditions was developed. Aromatic aldehydes with electron-donating group were found to be more reactive than aromatic aldehydes with electron-withdrawing group and aliphatic aldehydes under reaction conditions.     

Asymmetric aza-Henry reactions from N-p-tolylsulfinylimines

[reaction: see text] N-Sulfinylimines derived from aromatic or aliphatic aldehydes and ketones react with nitromethane and NaOH in a highly diastereoselective manner under mild conditions. In the presence of TBAF, the reaction rates are strongly increased and the stereoselectivity is inverted. This method provides enantiomerically pure beta-nitroamines derived from enolizable aldimines and ketimines, which so far are hardly accessible by aza-Henry reactions.     

醛类自氧化振荡反应动力学的研究

研究了醛类在乙酸和水混合溶剂中以Ｃｏ＾２＋和Ｂｒ＾－为催化剂的自氧化振荡反应。得知某些取代苯甲醛和脂肪醛在适当条件下能发生振荡，并研究了苯甲醛、正丁醛和乙醛的周期受动力学制约的影响，提出了相关的机理模型。依此模型以Ｇｅａｒ方法计算其振荡周期基本与实验结果相符。     

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     

Sulfamidation of 2-arylaldehydes and ketones with chloramine-T

[reaction: see text] A series of aliphatic and aromatic carbonyl compounds has been transformed into the corresponding sulfamidated products by means of amine-catalyzed nitrene transfer of chloramine-T. Depending on the residues R, either alpha-sulfamidation in the case of aromatic aldehydes and acetone derivatives or direct sulfamidation at the carbonyl functionality of aliphatic aldehydes has been observed. Applying microwave conditions, good to excellent yields under significantly reduced reaction times could be obtained, thus providing a facile access to alpha,alpha-disubstituted amino acids.     

Microwave-assisted Cannizzaro reaction—Optimisation of reaction conditions

The microwave-assisted Cannizzaro reaction was studied in order to develop fully reproducible synthetic protocols for transformation of aldehydes to carboxylic acid and alcohols. Optimised were the following process parameters: power, temperature, and time. Aromatic, heteroaromatic and aliphatic aldehydes were used in the studies. It was found that furfural, thiophene-2-carbaldehyde, pyridinecarboxaldehyde and aromatic aldehydes react under mild conditions, while 1-methyl-pyrrole-2-carboxaldehyde derivatives and aliphatic aldehydes require more drastic reaction conditions and a longer exposure time to microwave radiation.     

Z- and E-selective Horner–Wadsworth–Emmons reactions

In the present work, we determined and evaluated the stereochemical outcome of the Horner–Wadsworth–Emmons (HWE) reaction of 2-oxoalkylphosphonates with different ester functions (bis(2,2,2-trifluoroethyl), 2,2,2-trifluoroethyl methyl, dimethyl) and side chains (aliphatic, aromatic) with three different aldehydes (benzaldehyde, THP- and PPB-protected Corey aldehydes) under two reaction conditions. The “trans” protocol is generally used in the E-selective HWE reactions, while “cis” protocol promotes the Z-selectivity.     

Green Synthetic Method for 1,5‐Disubstituted Carbohydrazones

A green synthetic method for 1,5‐disubstituted carbohydrazones is described. The reaction of dimethyl carbonate with hydrazine hydrate first gave carbohydrazide, which further reacted with various aromatic aldehydes or aliphatic ketones under solvent‐free conditions to efficiently afford 1,5‐disubstituted carbohydrazone. This protocol has the advantages of using nontoxic dimethyl carbonate as starting material, no use of organic solvents, short reaction time, high yield, and simple workup procedure.     

Solventless DBU-promoted Mannich-type reactions of α-amido p-tolylsulfones with diethyl fluoromalonates and diethyl malonates

Mannich-type reactions of α-amido p-tolylsulfones with diethyl fluoromalonates and diethyl malonates, respectively in presence of catalytic amount of DBU have been developed. A variety of α-amido p-tolylsulfones prepared from aromatic and aliphatic aldehydes reacts with diethyl fluoromalonates and diethyl malonates, respectively under mild reaction conditions to afford α-fluoro β-amino esters and β-amino esters in moderate to good yield.     

The chemistry of acylals. 3. Cyanohydrin esters from acylals with cyanide reagents

[reaction: see text] When treated with KCN in DMSO at room temperature, acylals from aliphatic aldehydes gave the corresponding cyanohydrin esters in good to excellent yields. Acylals from aromatic aldehydes were less reactive and gave several byproducts in addition to fair yields of cyanohydrin under the same conditions. Trimethylsilyl cyanide mixed with titanium(IV) chloride afforded cyanohydrin esters in good to excellent yields from both aliphatic and aromatic aldehydes.     

Amino acid catalyzed direct asymmetric aldol reactions: a bioorganic approach to catalytic asymmetric carbon-carbon bond-forming reactions.

Direct asymmetric catalytic aldol reactions have been successfully performed using aldehydes and unmodified ketones together with commercially available chiral cyclic secondary amines as catalysts. Structure-based catalyst screening identified L-proline and 5,5-dimethyl thiazolidinium-4-carboxylate (DMTC) as the most powerful amino acid catalysts for the reaction of both acyclic and cyclic ketones as aldol donors with aromatic and aliphatic aldehydes to afford the corresponding aldol products with high regio-, diastereo-, and enantioselectivities. Reactions employing hydroxyacetone as an aldol donor provide anti-1,2-diols as the major product with ee values up to >99%. The reactions are assumed to proceed via a metal-free Zimmerman-Traxler-type transition state and involve an enamine intermediate. The observed stereochemistry of the products is in accordance with the proposed transition state. Further supporting evidence is provided by the lack of nonlinear effects. The reactions tolerate a small amount of water (<4 vol %), do not require inert reaction conditions and preformed enolate equivalents, and can be conveniently performed at room temperature in various solvents. In addition, reaction conditions that facilitate catalyst recovery as well as immobilization are described. Finally, mechanistically related addition reactions such as ketone additions to imines (Mannich-type reactions) and to nitro-olefins and alpha,beta-unsaturated diesters (Michael-type reactions) have also been developed.     

Asymmetric nitroaldol reaction catalyzed by a C2-symmetric bisoxazolidine ligand

A C2-symmetric bisoxazolidine was found to effectively catalyze the asymmetric Henry reaction of aliphatic and aromatic aldehydes. Beta-hydroxy nitroalkanes were produced in up to 99% yield and 95% ee. The bisoxazolidine-catalyzed nitroaldol formation requires relatively short reaction times, proceeds under mild conditions and is applicable to a wide range of substrates including sterically hindered aldehydes.     

A convenient and highly efficient method for the protection of aldehydes using very low loading hydrous ruthenium(III) trichloride as catalyst

A convenient method for the chemoselective protections of both aliphatic and aromatic aldehydes has been developed. Ruthenium(III) trichloride (0.1 mol %) has found to be an highly efficient catalyst in the acetalizations of aldehydes with various simple alcohols such as methanol, ethanol, or diols such as 1,2-ethylanediol and 1,3-propanediol under mild reaction conditions.