Knoevenagel Products Research Articles

ChemInform Abstract: N‐Heterocyclic Carbene Catalyzed Three‐Component Domino Reaction of Alkynyl Aldehydes with Oxindoles.

AbstractThe reaction leads to the stereoselective formation of highly functionalized spirooxindole 4H‐pyran‐2‐ones with three contiguous stereocenters, generally accompanied by small amounts of Knoevenagel products.

L-Proline-Catalyzed Knoevenagel Condensation: A Facile, Green Synthesis of (E)-Ethyl 2-Cyano-3-(1H-indol-3-yl)acrylates and (E)-3-(1H-Indol-3-yl)acrylonitriles

L-Proline has been utilized as a novel and ecofriendly catalyst in ethanol medium for the Knoevenagel condensation of indole-3-carboxyaldehydes and their N-methyl derivatives 1(a–e) and 4(a–e) with the active methylene compound, ethyl cyanoacetate (2) to afford substituted (E)-ethyl 2-cyano-3-(1H-indol-3-yl)acrylates 3(a–e) and 5(a–e) respectively. These products were reacted with dimethyl sulfate in the presence of PEG-600 as an efficient and green solvent to afford the corresponding N-mthylated derivatives 5(a–e). These Knoevenagel products react with 5% NaOH, yielding (E)-3-(1H-indol-3-yl)acrylonitriles 6(a–e) and 7(a–e).

Models for incomplete nucleophilic attack on a protonated carbonyl group and electron-deficient alkenes: salts and zwitterions from 1-dimethylamino-naphthalene-8-carbaldehyde

The X-ray crystal structures of salts and zwitterionic Knoevenagel products from 1-dimethylamino-naphthalene-8-carbaldehyde show long N-C bonds between peri-groups which provide models for incomplete nucleophilic attack on a protonated carbonyl group and electron-deficient alkenes respectively. For the salts the N-C bonds lie in the range 1.625-1.638 Å with C-OH bonds intermediate in length between single and double bonds, while for the zwitterions the N-C bonds lie in the range 1.612-1.660 Å. The structural assignment of the former is supported by solid state (13)C and (15)N NMR studies on doubly isotopically-labelled material. Several zwitterions were converted to naphtha[1,8-bc]azepines by a mechanism involving the tertiary amino effect.

Synthesis of highly stable CoFe 2O 4 nanoparticles and their use as magnetically separable catalyst for Knoevenagel reaction in aqueous medium

Synthesis of spinel cobalt ferrite magnetic nanoparticles (MNPs) with average sizes in the range 40–50 nm has been achieved using a combined sonochemical and co-precipitation technique in aqueous medium without any surfactant or organic capping agent. The nanoparticules form stable dispersions in aqueous or alcoholic medium. The uncapped nanoparticles were utilized directly as a reusable catalyst for Knoevenagel reaction in aqueous ethanol (1:3). Compartmentation and recovery of the catalyst from reaction medium was done with the aid of an external magnet. High yield of corresponding Knoevenagel products were obtained within a very short time in presence of just 5 mol% of the catalyst at 50 °C.

Diastereoselective synthesis of 1-alkyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3′-(1′,2′,3′,4′-tetrahydroquinolines)

Knoevenagel products formed by the condensation of N-monoalkyl barbituric acids with o- tert-amino benzaldehydes undergo tert-amino effect reactions (T-reactions) yielding 1-alkyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3′-(1′,2′,3′,4′-tetrahydroquinoline) derivatives as a mixture of ( S ∗, S ∗)- and ( S ∗, R ∗)-diastereomers. Mostly, the major diastereomer has the S ∗, S ∗-configuration. According to X-ray diffraction data in the solid form and NOE data in solution, diastereoselectivity of the T-reactions can be associated with the structure of the Knoevenagel products whose conformation is fixed by the strong intramolecular C–H⋯π interaction.

Knoevenagel reaction: alum-mediated efficient green condensation of active methylene compounds with arylaldehydes

A solvent-free stirred mixture of active methylene compounds, arylaldehyde and 10 mol% alum at 80°C afforded Knoevenagel products in excellent yields. The use of a green catalyst, the solvent-free conditions, and shorter reaction times are the main features of this efficient protocol.

A Highly Stereoselective Knoevenagel Reaction of N-Tosylimines with Active Methylene Compounds in DMSO

Abstract In the presence of molecular sieves (MS) 4A in dimethyl sulfoxide (DMSO), a highly stereoselective Knoevenagel reaction of various N-tosylimines with active methylene compounds proceeded smoothly, producing the corresponding Knoevenagel products in high to excellent yields.

Construction of Chiral Quaternary Carbon Centers via Palladium-Catalyzed Asymmetric Deconjugative Allylation

A Pd(0)-catalyzed asymmetric deconjugative allylation of various Knoevenagel products and allylic compounds was investigated. It was found that various compounds, having a quaternary carbon center directly attached to sp 2 -carbon centers including a 1,3-diene moiety, could be synthesized through this methodology, although the yield and enantiomeric excess varied from low to modest depending on the structure of substrates and the reaction conditions.

Rearrangement of Propargylic Esters: Metal-Based Stereospecific Synthesis of (E)- and (Z)-Knoevenagel Derivatives

Alkoxy-substituted propargylic esters undergo regioselective 1,3-acyloxy migration in the presence of Pt(II) and Cu(I) catalysts, allowing the preparation of α-ylidene-β-keto and -malonate esters. The reaction proved to also be stereodivergent as the Pt(II) and the Cu(I) catalysts perform the isomerization with complementary Z/E selectivity. Moreover, alkynyl-conjugated Knoevenagel products are produced from (bisalkynyl)methyl acetates. In such a case, the reaction is chemoselective as the 1,3-acetyl migration takes place through the alkoxyalkyne group in preference over the phenylalkyne group. The resulting (E)-alkynylenone unit suffers metal-catalyzed cyclization into the furyl ring, generating a copper(I) carbene species.

E- orZ-Selective Knoevenagel Condensation of Acetoacetic Derivatives: Effect of Acylated Substituent, that is, TEMPO and Amines, as an Auxiliary, and New Accesses to TrisubstitutedE- andZ-2-Alkenals and Furans

Knoevenagel condensation of O-acetoacetylTEMPOs (2,2,6,6-tetramethylpiperidine-1-oxyl) with aldehydes substituted with an electron-withdrawing group such as aromatic and heteroaromatic ones leads preferentially to E-adducts, while acylacetoamides including Weinreb amides produce Z-adducts, exclusively. These E- and Z-adducts are selectively converted to the corresponding (2E)- and (2Z)-2-hyroxyalkyl-2-alkenals, respectively, by stepwise reductions of the acyl group with DIBALH and then the carboxylic functions after protection of the hydroxy group. Transformation of the Knoevenagel products by taking advantage of the E-geometry to trisubstituted furans is also developed.

Wadsworth–Emmons reactions catalyzed by nanocrystalline MgO

Wadsworth–Emmons reactions between different aldehydes including aliphatic, aromatic, cyclic and heterocyclic with various phosphonates affords α,β-unsaturated nitriles and esters under mild conditions without the formation of by-products such as Michael or Knoevenagel products using a nanocrystalline MgO catalyst.

Solid-Phase Three-Component Domino Reactions: Combinatorial Approach to Substituted 3,4-Dihydro-2H-pyrans

Resin-linked acetoacetate 1 reacts with aldehydes 2 to give the Knoevenagel products 3, which undergo hetero-Diels-Alder-reactions with the enol ethers 4 to afford the polymer-bound cycloadducts 5/6. Cleavage from the support is achieved by base-induced transesterification to give the 3,4-dihydropyrans 7/8 in high purity. The suitability of these transformations for generating combinatorial libraries is demonstrated.

Reactions of 1,3-diethyl-2-thiobarbituric acid with aldehydes: formation of arylbis(1,3-diethyl-2-thiobarbitur-5-yl)methanes † and crystallographic evidence for ground state polarisation in 1,3-diethyl-5-[4-(dimethylamino)benzylidene]-2-thiobarbituric acid

The reactions of 1,3-diethyl-2-thiobarbituric acid (detba) in ethanol at room temperature with 4-(dimethylamino)benzaldehyde (dmabza) or cinnamaldehyde afford the Knoevenagel products 3 and 4, respectively. Under identical conditions, pyridine-4-carbaldehyde, 4-methoxybenzaldehyde, benzaldehyde, 4-cyanobenzaldehyde, 4-nitrobenzaldehyde and 4-ferrocenylbenzaldehyde yield exclusively the arylbis(1,3-diethyl-2-thiobarbitur-5-yl)methane Michael adducts 2, 5, 6, 7, 8 and 9, respectively. Although 3 can be forced to react further by treatment with excess detba in refluxing ethanol, the product 10 is unstable in solution and readily reverts to 3. The stability of 4 is attributed to extended conjugation, and it is likely that the pronounced difference in reactivity between dmabza and the other arylaldehydes arises primarily from electronic factors, i.e. the strongly electron donating effect of the -NMe2 substituent. Single crystal X-ray structures have been determined for the products 3 and 6. The structure of 6 confirms the formation of the Michael adduct and shows that both of the detba rings are present in mixed keto–enol forms, although the oxygens differ slightly in their degree of enolic character. The bond distances in 3 provide clear evidence for extensive ground state polarisation, in accord with the marked molecular nonlinear optical properties of the analogous -N(nBu)2 compound.

Stereoselective Intramolecular Hetero Diels–Alder Reactions of Cyclic Benzylidenesulfoxides and DFT Calculations on the Transition Structures

The 4-benzylidene-3-oxo[1,3]oxathiolan-5-ones 13–15, which were derived from the 3-oxo[1,3]oxathiolan-5-ones 9–11 by Knoevenagel condensation with the aldehydes 12, cyclize in an intramolecular hetero Diels–Alder reaction with high yield and excellent endo/exo as well as induced diastereoselectivity to give the hetero Diels–Alder adducts 16–18. The preferred formation of the Knoevenagel products 13–15 with a (Z) configuration was predicted with DFT calculations (B3LYP-6-311+G*) using the model systems 28 and 29. In addition B3LYP-6-31G*/sB3LYP/3-21G(*) calculations on transition structures for the hetero Diels–Alder reaction of 29 and 30 allowed a good correlation with the experimental results, which show that an endo attack of the dienophile syn to the S–O group in 13–15 leads to the main products.

A Convenient Synthesis of Benzopyranacetylenes

Knoevenagel products 3 of 3-formylchromone (1) with isoxazol- 5-one 2, after reduction with NaBH4 and exposure to aqueous sodium nitrite/acetic acid and ferrous sulphate gave various benzopyranacetylenes 4 in good yield. IICT Communication No. 3850

Minute Synthesis of Electrophilic Alkenes under Microwave Irradiation

Condensation of carbonyl derivatives 2 with active methylene compounds 1 is efficiently achieved, within 3 to 15 minutes under microwave irradiation by a solvent free reaction in the presence of carefully adjusted amounts of piperidine leading to Knoevenagel products 3 in good to excellent yields.

Bismuth(III)chloride as a New Catalyst for Knoevenagel Condensation in the Absence of Solvent

Abstract The Knoevenagel condensation of various aldehydes was carried out under heterogenous catalysts conditions using bismuth(III)chloride in absence of solvent. The method gives high yields of Knoevenagel products.

Catalysis of the knoevenagel condensation

Xonotlite alone or made more basic by doping of potassium t -butoxide catalyses the title reaction between aromatic aldehydes and malononitrile or alkyl cyanoacetates. At ambient temperatures, this procedure specifically gives high yields of E olefinic Knoevenagel products.