The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• this challenging compound was reported in 2013 and aims to evaluate the benefits of flow chemistry in order to avoid shortcomings of previous batch synthesis efforts particularly in regard to scale up [93]. The investigation first involved the preparation of the key acetophenone starting material 112

A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

• Roman A. Irgashev,
• Arseny A. Karmatsky,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2015, 11, 1000–1007, doi:10.3762/bjoc.11.112

• significant preparative interest, since the target compounds are formed from isatins 7 and ketones 8 in four steps in low yields. The formation of model thieno[2,3-b]indole 12a from 1-ethylisatin (7a) and acetophenone (8a) has been studied in details, as the first step of our research (Scheme 3). The

• phosphorane derivative 13 which is formed by pre-functionalization of acetophenone (8a), and this approach can be regarded as an alternative synthetic route just in some specific cases. Thus, the two-step approach to convert isatins 7 into thieno[2,3-b]indoles 12 via intermediacy of 10 (Path B) has been

• acetophenone (8a) according to the synthetic procedure described above. Isatin 7c containing an n-hexyl substituent at the nitrogen atom has been applied to ensure a good solubility of the target product 12o, as well as of the intermediate 10o. It should be noted that bromination of 2-phenyl-substituted thieno

DBU-promoted carboxylative cyclization of o-hydroxy- and o-acetamidoacetophenone

• Wen-Zhen Zhang,
• Si Liu and
• Xiao-Bing Lu

Beilstein J. Org. Chem. 2015, 11, 906–912, doi:10.3762/bjoc.11.102

• corresponding products (Table 3, entries 2 and 3). The reactions using benzamido- (3d) and p-toluenesulfonamido- (3e) acetophenone gave complex mixtures and no carboxylative cyclization product was observed (Table 3, entries 4 and 5). A likely mechanism for the carboxylative cyclization of o

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

• the starting substrates A simple retrosynthesis of enaminones 3 leads to the corresponding β-diketones 4 accessible through Claisen condensation of 3-phenylpropionic ester 5 with the appropriate acetophenone 6 (Scheme 3). The synthesis of ester 5 was accomplished according to Scheme 4. The classic

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• hydride-catalyzed reductive aldolization of acetophenone [19]. Therefore, tert-butyl acrylate (1d) was used to replace methyl acrylate, and several biphosphorous ligands were screened for improving the diastereoselectivity (Table 3). Diastereomers of 3da were separated, which were subjected to further

• vs entry 1), and an effect of ligands on the diastereoselectivity of lactone was observed too. Xantphos was superior to other ligands. Overall, the diastereoselectivities were much lower than those in the reactions of tert-butyl acrylate with acetophenone and silane. The diastereoselectivity varied

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• acetophenone in only four steps in an overall yield of 30%. A similar protocol for the synthesis of 3-alkylphenylalanines was independently developed by Soloshonok et al. [56]. These authors used sodium hydroxide for the deprotonation of 10 and 1-phenylalkyl bromides for the alkylation of the enolate. Once

Superoxide chemistry revisited: synthesis of tetrachloro-substituted methylenenortricyclenes

• Basavaraj M. Budanur and
• Faiz Ahmed Khan

Beilstein J. Org. Chem. 2014, 10, 2531–2538, doi:10.3762/bjoc.10.264

• norcamphor using o-amino acetophenone hydrochloride. Ladenberger and co-worker [27] observed the rearrangement of a lithiated-tetrachloronorbornyl intermediate to a tricyclene derivative in a study about stability of vinyl carbanions. Li and co-workers [28][29] have synthesized aryl/benzyl substituted

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• was first described by Wawzonek, converting benzophenone and acetophenone to benzylic acid and 2-hydroxy-2-phenylpropionic acid, respectively [79]. This offers an electrochemical route for several commercially relevant α-aryl propionic acids, used as non-steroidal anti-inflammatory drugs (NSAIDs) [80

• electrocarboxylated in an undivided cell with stable anode. CO2 fixation in acetophenone was done in good yields in an undivided cell using a quaternary ammonium oxalate as an electrolyte and a sacrificial reducing agent [52][94][95][112][113]. Benzalanilines were carboxylated electrochemically with 79% faradaic

(CF₃CO)₂O/CF₃SO₃H-mediated synthesis of 1,3-diketones from carboxylic acids and aromatic ketones

• JungKeun Kim,
• Elvira Shokova,
• Victor Tafeenko and
• Vladimir Kovalev

Beilstein J. Org. Chem. 2014, 10, 2270–2278, doi:10.3762/bjoc.10.236

• of acetophenone (2e) only modestly increase the yield of diketone 3d from 64 to 69% (Table 2, entry 11), and usually we added equimolecular quantities of an acid and a ketone. An excess of acetic acid in acylation reactions (Table 2, entries 4, 8 and 13) was employed considering that this acid was

• acylation of the ketones by several functionally substituted carboxylic acids. Whereas glycine did not react with the ketones, β-alanine (1i) reacting with 1-indanone, 1-tetralone and acetophenone formed the corresponding trifluoroacylated β-aminodiketones 3u–w (reaction 1 in Scheme 2). A fuller acylation

Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects

• Axel G. Griesbeck and
• Melissa Reckenthäler

Beilstein J. Org. Chem. 2014, 10, 1143–1150, doi:10.3762/bjoc.10.114

• -catalyzed photohydroxymethylation of ketones by methanol were investigated in order to evaluate the most active photocatalyst system. Dialkoxytitanium dichlorides are the most efficient species for chemoselective hydroxymethylation of acetophenone as well as other aromatic and aliphatic ketones. Pinacol

• photochemical homogenous titanium-catalyzed hydroxymethylation and to develop a truly catalytic process, we used a model reaction for catalyst screening (acetophenone/methanol) and applied the optimal homogenous reaction conditions involving titanium catalysis to other ketones and keto esters. Results Nature of

• different catalytic activities. In order to simulate the different complex stages, we applied different monomeric titanium complexes of the type TiCln(OiPr)4−n (n = 0, 1, 2, 3) [25][26][27] in the model process, the irradiation of a solution of acetophenone (3) in methanol (Scheme 2). In the absence of any

A convenient enantioselective decarboxylative aldol reaction to access chiral α-hydroxy esters using β-keto acids

• Zhiqiang Duan,
• Jianlin Han,
• Ping Qian,
• Zirui Zhang,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 969–974, doi:10.3762/bjoc.10.95

• ). Trace amount of side product acetophenone was formed through decarboxylative protonation of β-keto acid 1a, which was commonly observed in the case of chiral organic base catalysed decarboxylative additions. Further optimisation of the reaction conditions showed that CHCl3 was the best solvent choice in

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

• Fei Wang,
• Lingchun Li,
• Chuanfa Ni and
• Jinbo Hu

Beilstein J. Org. Chem. 2014, 10, 344–351, doi:10.3762/bjoc.10.32

• . Although a non-activated ketone such as acetophenone is unreactive under similar conditions, activated ketones could undergo this Wittig olefination reaction. Representative results for the olefination at a slightly elevated temperature (80 °C) are shown in Figure 2. A range of aryl trifluoromethyl (6a–d

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

• , H2N–NH2 and OH−(H2O)7. Here, ketones are acetone and acetophenone. While routes of the ketone → hydrazone → diimine are similar, those from the diimines are different. From the isopropyl diimine, the N2 extrusion and the C–H bond formation takes place concomitantly. The concomitance leads to the

• product. For both ketone substrates, the diimines undergoing E2 reactions were found to be key intermediates. Keywords: acetone; acetophenone; DFT calculations; diimine intermediate; reduction reaction; transition states; Wolff–Kishner; Introduction The Wolff–Kishner (W-K) reduction is an organic

• mechanism variant or invariant with respect to the substrate, ketone or aldehyde? We addressed these questions by DFT calculations, which were carried out for two substrates, acetone and acetophenone. Reaction paths including proton transfers [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• ; Chakravarty et al. [24] tested an ansa-bridged BINOL-based PV-cyclodiphosphazane in the asymmetric reduction of acetophenone with BH3 (5–8% ee), while Gade et al. [25] recently introduced BINOL-based PIII-cyclodiphosphazane ligands to transition-metal catalysis (up to 84% ee). We anticipated that by

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• reaction products were separated by column chromatography. 1-Hydroxy-1-phenylpentan-3-one (42) was isolated as a by-product in 16% yield [248]. The peroxidation of 1,4-dienes 43a,b with the Co(modp)2/Et3SiH/O2 system according to a similar reaction scheme gave dioxolanes 44a,b. Acetophenone (45) was

Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde

• Haijun Qu,
• Xuejian Li,
• Fan Mo and
• Xufeng Lin

Beilstein J. Org. Chem. 2013, 9, 2846–2851, doi:10.3762/bjoc.9.320

• chemistry [5][6][7][8]. Recently, many one-pot variants of Biginelli-type reactions for the preparation of novel DHPMs using various active methylene compounds [9][10][11][12][13][14][15], such as enaminone, cyclic β-diketones, acetophenone, benzocyclic ketones and β-oxodithioesters etc., have also been

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• materials; for instance, anisole and chloro- or iodobenzene gave an ortho > para ≈ meta preferential order of substitution, while toluene, acetophenone, N,N-dimethylaniline or nitrobenzene afforded the para-substituted compound as the major product. The reaction could be monitored by EPR, which showed an

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• )phenyllithium with geranyl bromide and 1n by two Wittig reactions from 2’-(phenylethynyl)acetophenone (see Supporting Information File 1). First, the hydroxycyclization of 1m, as a pure E isomer, under the previously established conditions afforded the dihydronaphthalene derivative 7m as a single isomer (Scheme

Regioselective carbon–carbon bond formation of 5,5,5-trifluoro-1-phenylpent-3-en-1-yne

• Motoki Naka,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2013, 9, 2182–2188, doi:10.3762/bjoc.9.256

• . Their proportion seemed to be affected by the bulky substituent and pivalaldehyde attained the higher ratio of 88%. Although 5 and 6 were obtained in 50 to 70% combined yields by the reaction with aldehydes, lower reactivity was displayed by the less electrophilic and more hindered acetophenone

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• hydrogenation catalyst or not), the cis/trans-imine ratios were found to be static in the aprotic reaction solvents we measured them in. Reduction of imines 2 The reported cis/trans ratio (5:95) for imine 2a [55][63][64], from acetophenone (1a), is very similar to our own measurement (6:94). (Regarding the

• ratio assessment is to compare the two down field quartets originating from the PEA auxiliary. See the 1H NMR data for imine 4a (Table 1) of ref [47]. Hogeveen reduced the (S)-N-phenylethylimine of acetophenone with Pd-C/H2 and recorded a 70% de. This is much lower than what we and others have observed

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

• effect on the outcome of the reaction (Table 2, entries 3 and 4). The Claisen–Schmidt condensation We moved next to study the Claisen–Schmidt condensation of benzaldehyde with acetophenone to yield chalcone (Scheme 3). Chalcones display interesting biological properties such as antioxidant, cytotoxic

• (CH), 129.74 (CH), 130.93 (CH), 133.17 (C), 134.88 (C), 141.48 (CH), 168.00 (C), 194.87 (C) [54]. Typical procedure for monitoring the Claisen–Schmidt reaction Into a 50 mL volumetric flask was added 4-fluorobenzaldehyde (1.551 g, 12.5 mmol, 1 equiv) and acetophenone (1.637 g, 12.5 mmol, 1 equiv

• = 10 s). Monitoring the conversion of benzaldehyde with acetophenone to chalcone, 3a, across a range of reaction conditions (scan time = 15 s, integration = 10 s). Monitoring the conversion of benzaldehyde, ethyl acetoacetate, and urea to 5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H

Total synthesis of ochnaflavone

• Monica M. Ndoile and
• Fanie R. van Heerden

Beilstein J. Org. Chem. 2013, 9, 1346–1351, doi:10.3762/bjoc.9.152

• formation of the chalcone by an aldol condensation reaction with a suitably substituted acetophenone. Selective methylation of 2,4,6-trihydroxyacetophenone with methyl iodide yielded 2'-hydroxy-4',6'-dimethoxyacetophenone (5) in moderate yield. The Claisen–Schmidt condensation of 5 with diaryl ether 4 under

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• acetophenone [33]. Among the different AQ derivatives that were tested, 1,4-diamino-2,3-dichloro-antraquinone (DADCAQ) was the most effective in terms of both conversion and selectivity of the ketone product. The potential of this catalytic system was proved by extending its application, in the absence of

• hydrocarbons, Xu and co-workers developed other redox initiators in addition to the NHPI/quinone systems previously described. In 2005 they reported the selective oxygenation of ethylbenzene to the corresponding acetophenone by means of a NHPI/o-phenanthroline-mediated organocatalytic system, in the presence

• described above led to the formation of acetophenone as the major product of ethylbenzene oxidation. A different result was achieved by Fierro et al. who, in the same year, reported the ethylbenzene oxidation to its hydroperoxide by operating in the presence of NHPI (or other NHIs, i.e., N

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

• and [11C]-labeled chalcones 19a and 19b were synthesized using similar methods, and a representative synthesis of 19a is shown (Scheme 2B). Aldol condensation between the appropriate acetophenone 22 and benzaldehyde 23 afforded the chalcone backbone, which was subsequently pegylated to give 24 and