Extending mechanochemical porphyrin synthesis to bulkier aromatics: tetramesitylporphyrin

• Qiwen Su and
• Tamara D. Hamilton

Beilstein J. Org. Chem. 2019, 15, 1149–1153, doi:10.3762/bjoc.15.111

• reaction medium [18]. This widened the variety of substituted aldehydes successfully converted to porphyrins, but employment of a caustic solvent at high temperature is a drawback. These conditions also proved inappropriate for several substituted benzaldehydes, and the best yields have been in the order

• yield similar to that obtained from the Lindsey synthesis. Additionally, several monosubstituted benzaldehydes, as well as two isomers of naphthaldehyde, were shown to undergo successful mechanochemical reaction in reasonable yields. Mesitaldehyde has been considered a representative “sterically

• groups become oriented above and below the plane of the porphyrin ring, forming a protective shroud around the reactive center, much like some protein systems (Figure 1B) [12][20][21][22]. The corresponding substituted benzaldehydes, however, have not easily yielded results upon reaction with pyrrole

Unexpected polymorphism during a catalyzed mechanochemical Knoevenagel condensation

• Sebastian Haferkamp,
• Andrea Paul,
• Adam A. L. Michalchuk and
• Franziska Emmerling

Beilstein J. Org. Chem. 2019, 15, 1141–1148, doi:10.3762/bjoc.15.110

• condensation in detail. Results and Discussion The catalyzed Knoevenagel condensations of mono-fluorinated benzaldehydes 1a–c with malonodinitrile (2) are depicted in Scheme 1. In contrast to previous work, which reported the uncatalyzed reaction [19], piperidine was used as a basic catalyst. This was done as

• the fluorinated benzaldehydes 1a–c no XRPD pattern could be recorded. For the reaction of 1a with 2, the amount of catalyst was varied and the reaction monitored in each case. XRPD analysis confirmed that, independent of the amount of catalyst, the same bulk product was formed. The intensity of the

• led directly to formation of m3b [23] and m3c [28], respectively, at both 30 Hz and 50 Hz milling frequency (Figures S4 and S5 in Supporting Information File 1). Conclusion The mechano-assisted catalyzed Knoevenagel condensation of mono-fluorinated benzaldehydes and malonodinitrile was explored in

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• Knoevenagel–Michael adducts (Figure 2) [24]. By analogy with our results obtained with the use of other aminoazoles in the reactions with benzaldehydes and Meldrum’s acid [25] we expected the formation of one or several isomers of tetrahydroimidazopyrimidinone derivatives (Figure 2). However, a short time (3

• –5 min) and reflux of the equimolar amounts of amines 1, para-substituted benzaldehydes 2, and Meldrum’s acid 3 in 2-propanol led to Knoevenagel–Michael adducts 4a–h (Table 1). Beside the short reaction times and mild conditions, this catalyst-free three-component condensation is characterized by a

• active compounds, that can lead to cyclic products, has a high potential for diversity-oriented synthesis. In the three-component condensations of equimolar amounts of 2-amino-4-arylimidazoles 1, para-substituted benzaldehydes 2 and malononitrile (12) in 2-propanol the Knoevenagel–Michael adduct was not

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• achieved from benzyl alcohol using a Br+ source as the catalyst (Figure 16). In the reaction pot subcomponents such as benzaldehydes and H+ were formed which further participated in a cascade transformation to give dihydropyrimidones 29. Dynamic combinatorial chemistry and mechano-milling Dynamic

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• Geniculosporium sp. [18] and on a series of structurally related phenols, benzaldehydes and anisole derivatives from Hypoxylon invadens [19] that could only be identified with certainty following this approach of extensive compound comparisons. Members of the family Hypoxylaceae are regarded to be extremely rich

The mechanochemical synthesis of quinazolin-4(3H)-ones by controlling the reactivity of IBX

• Md Toufique Alam,
• Saikat Maiti and
• Prasenjit Mal

Beilstein J. Org. Chem. 2018, 14, 2396–2403, doi:10.3762/bjoc.14.216

• benzaldehydes, aniline and IBX under ball-milling conditions an explosion was observed (Figure 1a; Caution! see experimental section) [30][31] and similar observations were made with Dess–Martin periodinane (DMP). On the other hand, benzamide was found to be unreactive with IBX and no reaction was observed

• when monoalkyl-substituted benzaldehydes (3a,b and 3d–f) were used compared to the reaction with unsubstituted benzaldehyde (3c). However, sterically congested aromatic aldehydes afforded the desired quinazolin-4(3H)-ones 3g and 3u in relatively poor yields. The reactions were found to proceed smoothly

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• -substituted benzaldehydes gave the best enantioselectivity, and the desired aldol products were obtained with anti diastereoselectivity (Scheme 26). In addition, when DMF was used as solvent, a positive effect on the enantioselectivity but negative effect on the diastereoselectivity were observed. The

• aldol reaction between 21 and 70 and offered superior diastereo- and enantioselectivities in the presence of chloroacetic acid (96% conversion, 86:14 anti diastereoselectivity and 73% ee) (Scheme 25). Under the optimum reaction media, a series of diverse benzaldehydes bearing electron withdrawing groups

An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• benzaldehydes bearing electron-withdrawing or electron-donating substituents on the phenyl ring reacted smoothly via condensation–cycloaddition–oxidation in the one-pot process, delivering the corresponding pyrrolo[3,4-c]pyrrole-1,3-diones in moderate to good yields (53–77%). Heteroaromatic aldehydes 7i and 7j

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• . The selectivity of these reactions depends on the geometry of the intermediate enolates. Here, we have reacted octyl pentafluoro-λ6-sulfanylacetate with substituted benzaldehydes and acetaldehyde under the conditions of the silicon-mediated Mukaiyama aldol reaction. The transformations proceeded with

• high diastereoselectivity. In case of benzaldehydes with electron-withdrawing substituents in the para-position, syn-α-SF5-β-hydroxyalkanoic acid esters were produced. The reaction was also successful with meta-substituted benzaldehydes and o-fluorobenzaldehyde. In contrast, p-methyl-, p-methoxy-, and

• (Table 2, entries 1–6). In contrast, from the reactions of 1 with benzaldehydes bearing electron-donating substituents (methyl-, methoxy-, ethoxy-) no aldol addition products could be isolated (Table 2, entries 7–9), but the aldol condensation products 4g–i were isolated in fair yields (see below). On

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -aminopyrazole 16 with aldehydes 47 and ethyl cyanoacetate (94) in ethanol in presence of p-toluenesulfonic acid which resulted in a diastereomeric mixture of cis- and trans-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridines 95. Benzaldehydes 47 with electron withdrawing groups provided better yields of the cis

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• bond synthesis under ball-milling conditions. Cross dehydrogenative coupling reactions between benzaldehydes and benzylamines were performed in presence of phenyliodine diacetate (PIDA) using the acid salt NaHSO4 [81]. The highly exergonic reaction (contact explosive) of acidic iodine(III) and basic

• -donating and -withdrawing substitutions on benzaldehydes or in benzoic acids have worked well under the mechano-chemical conditions [116]. In a multicomponent Strecker reaction the syntheses of α-aminonitriles are generally done by condensation of aldehydes, ammonia and hydrogen cyanide [117][118]. The

• give benzaldehydes and H+ under solvent-free mechanochemical conditions within 30 min. Further, addition of 1,3-dicarbonyl compounds and urea derivatives within the same milling jar led to the desired products in 78–95% yield at 3 h (Scheme 32). Benzaldehydes with electron-donating or -withdrawing

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• 5,6,7-trimethoxyisoquinoline (7b) with 1.5 equivalents of the Knochel–Hauser base (TMPMgCl∙LiCl) exclusively occurs at C-1. Trapping with appropriate benzaldehydes opened an access to benzylisoquinoline and oxoaporphine-type alkaloids [13]. Here we describe the extension of this approach to the

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• efficiency while ester showed the lowest efficiency in directing the C–H hydroxylation. Moreover, this protocol could be easily applied in the hydroxylation of anisoles. They further successfully applied this catalytic system to the hydroxylation of benzaldehydes, affording 2-hydroxylbenzaldehydes in

• moderate yields (Scheme 48) [78]. In terms of substrate scope, both electron-rich and electron-deficient benzaldehydes provided comparable yields. Intermolecular competition experiments showed that weakly coordinating aldehydes gave lower yields under the same conditions when compared with amides and

• and carbamates. [RuCl2(p-cymene)]2 catalyzed hydroxylation of benzaldehydes. [RuCl2(p-cymene)]2 catalyzed hydroxylation of ethyl benzoates, benzamides and carbamates. Different regioselective ortho-hydroxylation. Ruthenium-complex-catalyzed hydroxylation of flavones. Vanadium-catalyzed hydroxylation

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• the hydroxy group in the ortho position of salicylaldehyde in A3 coupling. A search in the literature revealed vast examples of A3 coupling with different benzaldehydes. However, only few research groups [12][19][20][21][22][23][24] reported their experiments with salicylaldehyde only in the presence

(Z)-Selective Takai olefination of salicylaldehydes

• Stephen M. Geddis,
• Caroline E. Hagerman,
• Warren R. J. D. Galloway,
• Hannah F. Sore,
• Jonathan M. Goodman and
• David R. Spring

Beilstein J. Org. Chem. 2017, 13, 323–328, doi:10.3762/bjoc.13.35

• )-selectivity of 6, a number of ortho-substituted benzaldehydes were subjected to Takai olefination conditions; the results are summarised in Table 1 [11]. Unsubstituted benzaldehyde (Table 1, entry 1) gave the usual high (E)-selectivity expected of the Takai olefination (Takai et al. reported an (E):(Z)-ratio

• (Table 2, entries 5 and 6). As expected, the electron-donating methoxy group caused a drop in the amount of (Z)-product, and conversely for the electron-withdrawing CO2Me group. Our results highlight two key points: a) generation of the (Z)-product during Takai olefination of benzaldehydes is favoured by

• mechanism for (Z)-selective Takai olefination, whereby coordination of the ortho-OH to the neighbouring Cr centre causes the aldehyde substituent to adopt a pseudo-axial orientation. (E):(Z) product ratios for Takai olefination of ortho-substituted benzaldehydes. (E):(Z)-product ratios for Takai olefination

Superelectrophilic activation of 5-hydroxymethylfurfural and 2,5-diformylfuran: organic synthesis based on biomass-derived products

• Dmitry S. Ryabukhin,
• Dmitry N. Zakusilo,
• Mikhail O. Kompanets,
• Anton A.Tarakanov,
• Irina A. Boyarskaya,
• Tatiana O. Artamonova,
• Mikhail A. Khohodorkovskiy,
• Iosyp O. Opeida and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 2125–2135, doi:10.3762/bjoc.12.202

• and Lewis superacids. Previously superelectrophilic activation of aldehyde groups was achieved for heteroaromatic aldehydes [34][35][36][37], substituted benzaldehydes and o-phthalic dicarboxaldehyde [38]. Based on these findings, one would expect the activation of an aldehyde group of 5-HMF and 2,5

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• studies on this topic [196][239][240][241][242][243][244][245][246]. Hydroxylated and methoxylated benzaldehydes 69 (Scheme 21) and acetophenones 72 (Scheme 22) can be oxidized to the corresponding phenols 70a–d, and 73 in good yields in the presence of the H2O2/MeReO3 system in ionic liquids [bmim]BF4 or

Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

• Lucian G. Bahrin,
• Henning Hopf,
• Peter G. Jones,
• Laura G. Sarbu,
• Cornelia Babii,
• Alina C. Mihai,
• Marius Stefan and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2016, 12, 1065–1071, doi:10.3762/bjoc.12.100

• , synthesized by reacting morpholine with halogenated benzaldehydes [21][22], are collected in Table 1. The individual substitution patterns and yields for flavonoids 4a–m and 5a–m are presented in Table 2. The reaction between brominated and iodinated phenacyl carbodithioates 2a–f and halogenated aminals 3a–e

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

• M. Emin Cinar,
• Bernward Engelen,
• Martin Panthöfer,
• Hans-Jörg Deiseroth,
• Jens Schlirf and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 813–824, doi:10.3762/bjoc.12.80

• substituents at the aldehyde and/or ketone moiety was more systematically analyzed using series of benzaldehydes (3a, 3c and 3d) and propiophenones (1a–c) both substituted by H, OMe and F at the para-phenyl position. Yields increased with time as expected. The introduction of two F or MeO substituents leads to

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• Experimental study The starting acetal-fulvenes 3 were prepared by the condensation of substituted 2-(1,3-dioxolan-2-yl)benzaldehydes 4 with cyclopentadiene following a well-established synthetic methodology [33]. With the aim of promoting the desired hydride transfer by thermal activation, we first heated the

• the experiments or in the course of the processing of the crude reaction mixtures and the purification steps. Besides, we also explored the thermally induced transformations of related fulvenes bearing non-cyclic acetalic units (Scheme 8 and Table 2). To this end, benzaldehydes 23 were transformed

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• imine substrates. In 2002, Li and co-workers reported enantioselective alkynylations of N-aryl aldimines formed in situ from benzaldehydes and anilines (Scheme 1) [16][17]. This reaction employs a CuOTf/Ph-Pybox catalyst system to achieve generally high yields and ee’s of propargylic amines 2. Notably

Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes via intramolecular [1,5]-hydride shift/isomerization reaction

• Chun-Huan Jiang,
• Xiantao Lei,
• Le Zhen,
• Hong-Jin Du,
• Xiaoan Wen,
• Qing-Long Xu and
• Hongbin Sun

Beilstein J. Org. Chem. 2014, 10, 2892–2896, doi:10.3762/bjoc.10.306

• Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes via intramolcular [1,5]-hydride shift/isomerization reaction has been realized, using the inherent reducing power of 3-pyrrolines. A series of N-arylpyrrole containing amines are obtained in high yields. Keywords

• part of our interest in expanding the inherent reducing power of 3-pyrrolines, we report herein the Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes using the iminium group as the H-shift acceptor (Scheme 1, reaction 3). Notably, this reaction should meet the

• established the optimized reaction conditions using ZnCl2 (5 mol %) as the catalyst and CH2Cl2 as the solvent, and running the reaction at room temperature or under reflux. Under the optimized conditions, the results of the amination reaction of 2a with various 2-(3-pyrroline-1-yl)benzaldehydes 1 are shown in

Synthesis of α-amino amidines through molecular iodine-catalyzed three-component coupling of isocyanides, aldehydes and amines

• Praveen Reddy Adiyala,
• D. Chandrasekhar,
• Jeevak Sopanrao Kapure,
• Chada Narsimha Reddy and
• Ram Awatar Maurya

Beilstein J. Org. Chem. 2014, 10, 2065–2070, doi:10.3762/bjoc.10.214

• amides [13][14] and α-amino amidines [15][16][17][18][19] through Ugi and related MCRs. Synthesis of imidazolopyridines 7a–d through a three-component coupling reaction of substituted benzaldehydes, 2-aminopyridine, and tert-butyl isocyanide using 1 mol % iodine as catalyst. A plausible reaction

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

• J. Alexander Willms,
• Rita Beel,
• Martin L. Schmidt,
• Christian Mundt and
• Marianne Engeser

Beilstein J. Org. Chem. 2014, 10, 2027–2037, doi:10.3762/bjoc.10.211

• detection of a similar intermediate for the aldol reaction beween acetone and selected benzaldehydes using rather unusual and presumably extremely soft ESI conditions, and their results indeed confirm its facile fragmentation [20]. Interestingly, the signal at m/z 290.12 can be assigned to a further

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• protocol and the results are summarized in Table 2. Different azides 1a–j with electron-donating groups (Table 2, entries 2–8, 12–17, 20–23), electron-withdrawing groups (Table 2, entries 9, 10, 18 and 19), two different 4-(prop-2-yn-1-yloxy)benzaldehydes 2a,b, and two different 1,2-diaminobenzenes 3a,b

• )-1H-benzo[d]imidazole. Optimization of the solvent system.a Scope and limitations of the protocol employing different 4-(prop-2-yn-1-yloxy)benzaldehydes (2), phenylazides (1) and 1,2-diaminobenzenes (3)a. Supporting Information Supporting Information File 66: Experimental procedures and analytical