Effect of the π-conjugation length on the properties and photovoltaic performance of A–π–D–π–A type oligothiophenes with a 4,8-bis(thienyl)benzo[1,2-b:4,5-b′]dithiophene core

• Ni Yin,
• Lilei Wang,
• Yi Lin,
• Jinduo Yi,
• Lingpeng Yan,
• Junyan Dou,
• Hai-Bo Yang,
• Xin Zhao and
• Chang-Qi Ma

Beilstein J. Org. Chem. 2016, 12, 1788–1797, doi:10.3762/bjoc.12.169

• (reaction iv), and the final compounds, COOP-nHT-TBDTs 1–4, were obtained by Knoevenagel condensations of CHO-nHT-TBDTs 17–20 with octylcyanoacetate (reaction v). Since all these compounds have multiple alkyl chains, they are soluble in common organic solvents, so that the final compounds can be processed

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• units, reductive PKS release and Knoevenagel condensation yield the benzaldehyde intermediate 88. Oxidative dearomatisation of 88 catalysed by the salicylate monooxygenase AteafoD gives 89, which is hydroxylated at C8 by the oxygenase AteafoF. The positioning of this newly formed hydroxy group forces

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• . Some of these post-MCR transformations are: intramolecular cycloaddition reactions, Knoevenagel condensations, metathesis reactions, aza-Wittig reactions, Mitsunobu reactions, etc. [21]. Up to now, two review articles have been reported on azaheterocyclic phosphonates [22][23], but no overview article

• , carbamate 138, hexahydrobenzothiophene 140 and benzothiophene 142 were converted to the corresponding bisphosphonates 139, 141 and 143, respectively (Scheme 30). The synthesized heterocyclic bisphosphonates showed anti-inflammatory properties. 3 Knoevenagel-induced domino reactions An efficient method into

• phosphorylated heterocycles is the condensation of an activated methylene component with a carbonyl compound followed by subsequent transformations such as intramolecular cyclization, Michael-type addition and hetero-Diels–Alder cycloaddition. 3.1 Domino Knoevenagel/phospha-Michael process A convenient one-pot

Creating molecular macrocycles for anion recognition

• Amar H. Flood

Beilstein J. Org. Chem. 2016, 12, 611–627, doi:10.3762/bjoc.12.60

• a difunctional building block for the Knoevenagel condensation that forms cyanostilbenes. Treating the material to carbonate base-catalyzed conditions, he acquired the product in high yields, now optimized to 80% and scaling nicely up to 10 g quantities. The effectiveness of the central binding

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• ) pathway of a Michael–retro-Michael–Michael–Michael reaction. The same year Zhao and co-workers reported a novel domino Michael–Knoevenagel reaction between 2-mercaptobenzaldehydes 163 and easily accessible Michael acceptors 169 catalyzed by 9-epi-aminoquinine thiourea 57 (Scheme 55) [76]. Various adducts

• good yield and stereoselectivity, given the high molecular complexity that is being achieved in one step (Scheme 64). The researchers suggested that diketone 204 and benzaldehyde 205 reacts through Knoevenagel condensation, to produce 2-arylidene-1,3-indanediones, which is subsequently attacked by the

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• synthesis [65]. This preparation started with a Knoevenagel condensation of 2-fluoroacetophenone with malononitrile. The product of the condensation reacted with an excess of N,N-dimethylformamide dimethyl acetal to afford an enamine. This latter was treated with hydrochloric acid in acetic acid gave 4-aryl

Reactions of nitroxides 15. Cinnamates bearing a nitroxyl moiety synthesized using a Mizoroki–Heck cross-coupling reaction

• Jerzy Zakrzewski and
• Bogumiła Huras

Beilstein J. Org. Chem. 2015, 11, 1155–1162, doi:10.3762/bjoc.11.130

• Toxicology (in the 70s). The most recent reviews in this series were published in 2011 [10][11]. Cinnamic acid derivatives can be synthesized using Perkin, Knoevenagel, Claisen [7], and Wittig [12] condensation reactions. Since the discovery of catalytic coupling reactions, cinnamic derivatives have also

A hybrid electron donor comprising cyclopentadithiophene and dithiafulvenyl for dye-sensitized solar cells

• Gleb Sorohhov,
• Chenyi Yi,
• Michael Grätzel,
• Silvio Decurtins and
• Shi-Xia Liu

Beilstein J. Org. Chem. 2015, 11, 1052–1059, doi:10.3762/bjoc.11.118

• unit. Keywords: donor–acceptor systems; dye-sensitized solar cells; electrochemistry; intramolecular charge transfer; Knoevenagel reaction; tetrathiafulvalene; Introduction Dye-sensitized solar cells (DSSCs) have been intensively investigated as an alternative to silicon-based solar cells [1][2][3][4

• Discussion Synthesis Under Knoevenagel condensation reaction conditions, the corresponding aldehydes 4 and 7 can readily react with cyanoacetic acid leading to the target sensitizers 1 and 2, as depicted in Scheme 1. For the synthesis of the aldehyde precursor 4, the Horner–Wadsworth–Emmons (HWE) reaction

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• Knoevenagel/reduction/hydrolysis/decarboxylation pathway (steps a–d in Scheme 4) to carboxylic acid 10 suffered from low yields of the last two steps (total yield 33%). The attempt to obtain 5a directly from 9 by means of Krapcho decarboxylation [33] failed, as the product was contaminated with inseparable

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• 48 h the reaction proceeded to form mainly two compounds – Knoevenagel adduct 7 and Schiff base 8 (Scheme 3). Trace amounts of 2-hydroxy-N-(2-methoxyphenyl)-2-methyl-4-(3-methylisoxazol-5-ylamino)chroman-3-carboxamide (4a) were detected in the reaction mixture as well. Furthermore, both conventional

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• Knoevenagel–[1,5]-hydride shift cyclization reaction of a 4-aryl-2-phenyl-1,4-benzoxazepine derivative obtained from flavanone. The relative configuration of products were determined by the correlation of 3JH,H coupling data with the geometry of major conformers accessed by DFT conformational analysis

• cellular injuries in human neuroblastoma SH-SY5Y cells in the range of those of positive controls. Keywords: 1,4-benzoxazepine; diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization; neuroprotective; tert-amino effect; TDDFT-ECD calculation; Introduction The 1,4-benzoxazepine structural

• neuroprotective condensed 2-phenyl-1,4-benzoxazepines rac-7a,b through the diastereoselective domino Knoevenagel–1,5-hydride shift cyclization reaction rac-5→rac-7a,b from the readily available 4-aryl-2-phenyl-1,4-benzoxazepine derivative, rac-5 (Scheme 1). Ring-closure transformations involving C(sp3)–H bond

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• considerable number of pacidamycin analogues. 4. The multicomponent domino reactions initiated by the Knoevenagel condensation The Knoevenagel condensation can be considered as one of the most useful tools for the formation of C=C double bonds. The condensation products, i.e., electron-deficient alkenes

• , readily act in subsequent reactions as Michael acceptors, Diels–Alder (hetero)dienes or dienophiles, or dipolarophiles. Multicomponent domino reactions initiated by the Knoevenagel condensation are a valuable tool for the construction of many compounds with complex molecular structures [90]. The syntheses

• shown in Scheme 23 and Scheme 24 represent examples of the Knoevenagel condensation-initiated domino reactions where the nucleoside aldehyde (i.e., 5-formyl-3',5'-di-O-acetyl-2'-deoxyuridine (14) or 5-formyl-2'-deoxyuridine (27)) acted as the Knoevenagel acceptor. Compounds 61 to 65 were prepared by the

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• out a Knoevenagel-type condensation with benzaldehyde and 3,4-dichlorobenzaldehyde in acetic acid at 118 °C in the presence of triethylamine. Thus, the 5-arylmethylidenethiazolidin-4-ones 22–26 were obtained in 68–94% yield. The presence of only one signal for the benzylidene proton at 7.83–7.98 ppm

• thiazolidinone atropisomers, due to hindered rotation between the trichlorovinyl and the arylamino groups. X-ray analysis proved the Z-configuration of the nitrovinylidene group of 11. Subsequent reactions of the thiazolidinones, such as the SNVin thiolation in 2-position of the allylidene backbone, Knoevenagel

Primary-tertiary diamine-catalyzed Michael addition of ketones to isatylidenemalononitrile derivatives

• Akshay Kumar and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2014, 10, 929–935, doi:10.3762/bjoc.10.91

• -component version of the reaction by a domino Knoevenagel–Michael sequence. The Michael adduct 4a was transformed into spirooxindole 6 by a reduction with sodium borohydride in a highly enantioselective manner. Keywords: 3,3'-disubstituted oxindoles; Michael reaction; organocatalysis; primary-tertiary

• involves the initial formation of isatylidenemalononitrile by Knoevenagel condensation of isatin with malononitrile followed by the addition of acetone to provide Michael adduct 4a. Thus, catalyst 1a also finds its successful application in the multicomponet version of this reaction without compromising

• component process involving a domino Knoevenagel–Michael sequence was developed. 3,3'-Disubstituted oxindole could be transformed into spirooxindoles by reduction with NaBH4. Oxindole based Michael acceptors. Primary-tertiary diamine organocatalysts. Diamine catalyzed Michael addition of acetone to

One-pot three-component synthesis and photophysical characteristics of novel triene merocyanines

• Christian Muschelknautz,
• Robin Visse,
• Jan Nordmann and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 599–612, doi:10.3762/bjoc.10.51

• been accessed by Knoevenagel condensations [12][13][14] or substitution reactions [15][16][17][18]. Still the quest for new synthetic strategies, novel substitution patterns, and eventually unusual properties and effects has become an ongoing challenge for organic synthesis, physical organic chemistry

Substrate dependent reaction channels of the Wolff–Kishner reduction reaction: A theoretical study

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 259–270, doi:10.3762/bjoc.10.21

• (C=O → C=C, alkene) conversion reaction, the Knoevenagel condensation [12] was utilized. While the condensation is traditionally base-catalyzed, it was found to proceed readily in water even without any catalyst [13][14]. Not only can this synthesis be considered as clean (green chemistry), but also

• conversion? An investigation about the role of the proton transfers along the hydrogen bonds may be of interest. Is a base-free W-K reduction comparable to the Knoevenagel condensation possible? Which path (a) or (b) in Scheme 2 is more favorable? Is the carbanion R1(R2)HC− a probable intermediate? Is the

• uncatalyzed (without base) Knoevenagel condensation in water. Experimental conditions and yields are taken from a) ref. [13] and b) ref. [14], respectively. Reaction models of neutral (a) and anionic (b) systems. Water molecules are linked to oxygen lone-pair orbitals and to H–N bonds of hydrazine. In the

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• ozonolysis to give aldehyde 136 [123]. Knoevenagel condensation with 4-iodooxindole was achieved in the next step. Pfitzner–Moffatt oxidation [124] followed by elimination furnished trans-divinylcycloproane 137. Submission of this compound to elevated temperature initiated a very smooth DVCPR yielding

Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

• Ashley R. Longstreet,
• Suzanne M. Opalka,
• Brian S. Campbell,
• B. Frank Gupton and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2013, 9, 2570–2578, doi:10.3762/bjoc.9.292

• other value added structures that contain complex pyridines. The route terminates in a batch crystallization yielding high purity CAPIC. This outcome is expected to facilitate regulatory implementation of the overall process. Keywords: continuous; flow chemistry; HIV; Knoevenagel; nevirapine

• acetone and malononitrile (Scheme 3) using the Vapourtec R series reactor system [38]. The batch synthesis commences with a Knoevenagel reaction condensing malononitrile and acetone catalyzed by aluminum oxide producing isopropylidenemalononitrile (4) [39][40]. The penultimate enamine 5 results by

• complicate downstream operations. We immediately recognized the water formed in the Knoevenagel condensation would quench the DMF-DMA in the second step. In addition, our batch Knoevenagel condensation was base catalyzed and we discovered that base increased dimer byproducts in the enamine step. Therefore

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• readily prepared by chlorination of 2-pyridone (1.42) with phosphorous oxychloride (Scheme 8) [31][32]. The resulting primary alcohol 1.45 is then subjected to a second SNAr reaction with 4-fluorobenzaldehyde [33]. A Knoevenagel condensation of the aldehyde functionality in compound 1.47 with

• chromium(VI) oxide yielded the aldehyde 1.67 required for the previously described Knoevenagel condensation. The five membered heterocycle 2,4-thiazolidinedione (1.68) is readily available commercially, but can be easily prepared at scale via a simple cyclocondensation between thiourea and chloroacetic

• crude material in the subsequent Knoevenagel condensation with thiazolidinedione 1.68. In order to reduce the intermediate benzylidene double bond in this example sodium borohydride is used in the presence of cobalt chloride efficiently delivering pioglitazone in high purity. Other syntheses of

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• is assessed by studying four reactions, all involving formation of products bearing α,β-unsaturated carbonyl moieties; synthesis of 3-acetylcoumarin, Knoevenagel and Claisen–Schmidt condensations, and a Biginelli reaction. In each case it is possible to monitor the reactions and also in one case, by

• conversion using NMR spectroscopy. Comparison of the values shows a good correlation (Table 1). Expanding the technique to other reactions The Knovenagel condensation We turned our attention next to the Knoevenagel condensation of ethyl acetoacetate with a range of aromatic aldehydes (Scheme 2). Our

• procedure for monitoring the Knoevenagel reaction An analogous approach was used to prepare the Knoevenagel product as for the case of 1, benzaldehyde (5.306 g, 50 mmol, 1 equiv) being used in place of salicylaldehyde and there being no need for acetone interception of the product mixture. The Raman

Enhancement of efficiency in organic photovoltaic devices containing self-complementary hydrogen-bonding domains

• Rohan J. Kumar,
• Jegadesan Subbiah and
• Andrew B. Holmes

Beilstein J. Org. Chem. 2013, 9, 1102–1110, doi:10.3762/bjoc.9.122

• ] followed by a Knoevenagel condensation provided the target compound 2 in excellent yield. The solubilizing strategy of incorporating alkyl groups on the thiophene unit provided the compound with excellent solubility in a wide range of common solvents. Optoelectronic properties In chloroform solution the UV

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• imaging, particularly [18F]FDDNP (152), although this scaffold is also represented by only a few examples in the literature. Compound 152 was prepared starting from 1-(6-hydroxy-2-naphthyl)-1-ethanone (153) via a Bucherer reaction with 2-(methylamino)ethanol (154) followed by Knoevenagel reaction of 155

Synthesis of functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] via one-pot four-component reactions

• Li-Juan Zhang,
• Qun Wu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 846–851, doi:10.3762/bjoc.9.97

• ester A from the addition of arylamine to methyl propiolate. The second reaction is a Knoevenagel condensation of isatin with malononitrile or ethyl cyanoacetate under the catalysis of triethylamine to give the isatylidene deriatives B. The third reaction is a Michael addition of β-enamino ester

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• a C-2 phenyl substituent. The synthesis of flavans and flavones generally involves treatment of acetophenone (7) with a base to give enolate 8, which undergoes a Knoevenagel condensation with salicylaldehyde (5) to yield a chalcone 9. These chalcone derivatives are then cyclized by using various

• cleavage of the MOM protected hydroxy group delivered the desired flavan 16 in good yield. On the basis of the above precedent by Xue and co-workers, our group accomplished the synthesis of an array of flavans of type 10 [19]. The synthesis begins with a Knoevenagel reaction of salicylaldehyde (5) and

• and co-workers achieved the synthesis of flavone 11 relying on the reaction of salicylaldehyde (5) and an enolate derived from acetophenone (7, Scheme 5) [20]. To begin, chalcone 9 was prepared in 85% yield by the Knoevenagel reaction of salicylaldehyde (5) and acetophenone (7) in the presence of KOH

Total synthesis and biological evaluation of fluorinated cryptophycins

• Christine Weiß,
• Tobias Bogner,
• Benedikt Sammet and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231

• synthesis of the para-trifluoromethyl substituted unit A started with a modified Knoevenagel condensation [23][31]. The required aldehyde 9 was obtained by DIBAL-H reduction of the corresponding methyl ester 8 and was found to decompose upon chromatographic purification (Scheme 1). However, it can usually

• be employed in the Knoevenagel condensation without purification. Reaction of 9 with malonic acid in the presence of piperidine/acetic acid gave the β,γ-unsaturated carboxylic acid 10. The latter compound was transformed into the methyl ester by treatment with SOCl2 in methanol. The resulting ester