Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• tetrafluoroborates with various alkenes afforded isochromanones in good yields, according to a mechanism that was investigated. The advantage of using highly soluble esters rather than carboxylic acids as starting compounds became evident when the reactions were performed under flow conditions. On the other hand

• intercepted by other nucleophiles (such as isocyanides, carboxylates, etc.), in the case the attack by the solvent could be prevented. Unfortunately, reactions performed in inert solvents with isocyanides, carboxylic acids, and mixtures of both, alcohols or amines never succeeded in affording the desired

• the 3,4-disubstituted isochromanone was isolated in only 19% yield. Noteworthy, compounds 4c, 4d and 4f, whose synthesis was previously reported starting from carboxylic acids [5], were obtained with comparable yields. As no other detectable products were isolated from the reaction mixtures, we were

Mechanochemistry-assisted synthesis of hierarchical porous carbons applied as supercapacitors

• Desirée Leistenschneider,
• Nicolas Jäckel,
• Felix Hippauf,
• Volker Presser and
• Lars Borchardt

Beilstein J. Org. Chem. 2017, 13, 1332–1341, doi:10.3762/bjoc.13.130

• was expected since the porogens have not been removed during this step in the synthesis. The low specific surface area of 298 m2 g−1 for the composite arises from chemical activation processes of volatile functional groups such as carboxylic acids, which form micropores during pyrolysis. After

α-Acetoxyarone synthesis via iodine-catalyzed and tert-butyl hydroperoxide-mediateded self-intermolecular oxidative coupling of aryl ketones

• Liquan Tan,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2017, 13, 1079–1084, doi:10.3762/bjoc.13.107

• products and pharmaceuticals, and α-acetoxyaryl ketones are widely used as synthetic intermediates [1][2][3][4][5]. Traditional methods for the preparation of α-acyloxy ketones focus on the substitution reactions of α-halo carbonyl compounds with alkaline carboxylates or carboxylic acids [6][7], and

• transition-metal-catalyzed direct oxidative coupling reactions of carbonyl compounds with carboxylic acids (or their surrogates) [8][9]. Recently, robust approaches using organohypervalent iodine reagents and peroxide-mediated oxidative coupling have been developed [10][11]. Although impressive progress has

• ketones from aryl ketones using I2 and tert-butyl hydroperoxide (TBHP) [16][17][18] (Scheme 1). Several oxidative cross-coupling methods have been developed for the synthesis of α-acetoxy ketones from ketone derivatives and carboxylic acids [10], benzylic alcohols [19], toluene derivatives [20][21] and

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• exocyclic NH2 group and an endocyclic nucleophilic center, they can act both as primary amines and as 1,3-binucleophiles, therefore, their treatments with isocyanides, aldehydes and carboxylic acids may proceed either as Ugi-4CR (aminoazole – primary amine, acid – reagent) or as GBB-3CR (aminoazole – 1,3

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• -exo isomer). Hydrolysis of this mixture was achieved with LiOH giving carboxylic acids 18 and 19 and running the reaction at a 0.01–0.02 molar scale was important for it to go to completion overnight. Higher concentrations of the starting material seemed to slow down the reaction, which also caused

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• , in CDCl3). 4-Iodopyrazoles 3a–d are characterized by a marked upfield shift of the signal due to pyrazole C-4 compared the corresponding precursors 2a–d as a result of the heavy-atom α-effect of the iodine atom. The different hydrogen bonding situation in carboxylic acids 4a–d and the resultant

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• -containing functionalities, e.g., alcohols, ethers and carboxylic acids on the CD surface, which are likely the reason for the high water solubility exhibited by the nanomaterial. This type of chemical profile is typical of standard bottom-up synthesised CDs [15][28]. Interestingly, the team was also able to

• incorporation onto CDs occurred via amide formation, from the reaction between surface carboxylic acids and the corresponding amine SPA. This was further supported by the change in zeta-potential (ZP) values which shifted from −37.3 mV (non-passivated CD) to 3.46 mV (TTDDA passivated CD). Similar carbonaceous

• carboxylic acids that could be functionalised. Surface conjugation with PEG-diamine afforded a steric blocking, enhanced permeation and retention (EPR) shell, whilst providing an amine functionality for further surface conjugation. The anticancer drug methotrexate (MTX), which is a well-studied drug used to

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• hydrolysis transition states as well as having many other interesting properties. They are found in nature as pyrrolidines, piperidines, indolizidines, pyrrolizidines or nortropane alkaloids with a variety of ring substituents, typically hydroxy groups, carboxylic acids and amides [1]. The ability of

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• went on to a 3,6-di(pyrazol-1-yl)-1,2,4,5-tetrazine [11], and with 1,1,1-trifluoro-2,4-pentanedione two branches of TAG-Cl were converted into pyrazoline moieties and the third one into an enaminone [12]. Not much is known about the acylation of triaminoguanidines. Reactions with carboxylic acids have

• been addressed only rarely, reactions with acid chlorides appear to be unknown. We have recently reported on the threefold carbamoylation of N,N’,N’’-tris(benzylamino)guanidinium salts with aryl isocyanates [3]. Concerning the reaction with carboxylic acids, it is known that TAG-Cl and formic acid on

• , N4H···N11 2.061(1) Å; <(N4–H···N11) 168.7(2)°. UV–vis spectra of 7a–d in chloroform (c = 0.04 mmol L−1); λmax [nm] (ε [L mol−1 cm−1]): 7a: 350 (4710); 7b: 350 (5080); 7c: 430 (3510); 7d: 300 (2670). Reactions of aminoguanidines with carboxylic acids and acid chlorides. The structural formulae shown

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

• this case, activation of the Csp–COOH occurs via decarboxylation followed by the coupling with an iminium electrophile to produce the propargylamine. Although the strategy is interesting, functionalized acetylene carboxylic acids are difficultly accessible and the reaction is less 'atom economic

• only metal-catalyst-free approach from acetylene carboxylic acids that are difficultly accessible and with low atom economy. Thus the present reaction from easily available A3 components leading to the formation of propargylamine under metal-catalyst-free and solvent-free conditions could attract the

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• .13.48 Abstract This comprehensive review describes methods for the preparation of 1-indanones published in original and patent literature from 1926 to 2017. More than 100 synthetic methods utilizing carboxylic acids, esters, diesters, acid chlorides, ketones, alkynes, alcohols etc. as starting materials

• 5- (section 1), 6- (section 2) and simultaneous formation of 5- and 6-membered rings of 1-indanones (section 3) as well as functionalization of 1-indanones or related compounds (section 4). Review 1 Construction of the 5-membered ring 1.1 From carbonyl compounds 1.1.1 From carboxylic acids: The

• carboxylic acids 45 (85–95%) accompanied by 6-methyl-1-indanone (46) which was formed as a byproduct in 5–15% yields [35]. Irradiation of esters 44 in methanol gave 6-methyl-1-indanone (46) along with 2-(methoxymethyl)-5-methylacetophenone (47) and the corresponding free carboxylic acid 45 (Scheme 16). The

Solid-phase enrichment and analysis of electrophilic natural products

• Frank Wesche,
• Yue He and
• Helge B. Bode

Beilstein J. Org. Chem. 2017, 13, 405–409, doi:10.3762/bjoc.13.43

• dehydroalanine [6][7], ketones, aldehydes [8][9], carboxylic acids [8][9], amines [8][9][10], thiols [8][9], alcohols [11], epoxides [12], terminal alkynes [13][14] and azides [15] can be targeted to introduce a label. Such labels might increase the visibility in UV or MS detection in liquid chromatography

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• biosynthesis, full reduction to the fatty acyl group occurs systematically), and polyketides are most typically released in cyclic form, whereas fatty acids are liberated as carboxylic acids. The much more complicated biosynthetic control in PKSs is achieved by successive action of multiple FAS-like modules

Synthesis and optical properties of new 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles

• Anastasia S. Kostyuchenko,
• Tatyana Yu. Zheleznova,
• Anton J. Stasyuk,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2017, 13, 313–322, doi:10.3762/bjoc.13.34

• semiconducting and photoluminescent properties. First, alkaline hydrolysis of the esters 7b–g led to the corresponding carboxylic acids 12b–g in good yields (70–87%, Scheme 3). The corresponding hydrazide derivatives 13b,c were obtained in 67–73% yields by refluxing the esters 7b,c with hydrazine monohydrate in

• alcohol. The diacyl hydrazines 14b,c were obtained through the coupling of the hydrazide derivatives 13b,c with carboxylic acids 12b,c in the presence of N,N'-dicyclohexylcarbodiimide (DCC) as reported earlier [18]. A modified procedure, which avoids the preparation of hydrazides 13, was used for the

• synthesis of 14d–g. These intermediates were synthesized by the reaction of the acid chlorides with hydrazine dihydrochloride in the presence of pyridine. The required acid chlorides were prepared in situ through the reaction of the corresponding carboxylic acids 12b–g with oxalyl chloride. The yields of

A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

• Arno Verlee,
• Thomas Heugebaert,
• Tom van der Meer,
• Pavel I. Kerchev,
• Frank Van Breusegem and
• Christian V. Stevens

Beilstein J. Org. Chem. 2017, 13, 303–312, doi:10.3762/bjoc.13.33

• dichloromethane was used as solvent. The coupling of carboxylic acids with amines in flow through a benzotriazole activation [19], or with immobilized reagents as for the synthesis of grossamide [20] is already known. However, we wanted to use m-(chlorosulfonyl)benzoyl chloride since this can be synthesized in

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• second flow reactor the Grignard was reacted with CO2 to obtain carboxylic acids (Figure 5). The whole process was monitored by on-line 1H NMR spectroscopy using a low field NMR instrument (Spinsolve-60 from Magritek). The reaction was analysed by in-line NMR and off-line with a standard NMR tube. In the

Continuous-flow synthesis of highly functionalized imidazo-oxadiazoles facilitated by microfluidic extraction

• Ananda Herath and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2017, 13, 239–246, doi:10.3762/bjoc.13.26

• -oxadiazoles starting from carboxylic acids is reported. This process was applied to the multistep synthesis of imidazo[1,2-a]pyridin-2-yl-1,2,4-oxadiazoles, using a three reactor, multistep continuous-flow system without isolation of intermediates. This continuous-flow method was successfully combined with a

• developed methodology, our next goal was to incorporate a carboxylic acid synthesis step into the flow process. As noted above, we previously reported the continuous-flow synthesis of imidazo[1,2-a]pyridine-2-carboxylic acids in a single, uninterrupted process directly from readily available starting

• point solvent removal step. Conclusion In summary, we have developed a telescoped continuous-flow method for the synthesis of diversely substituted imidazo[1,2-a]pyridine-2-yl-1,2,4-oxadiazole derivatives directly from commercial nitriles, aminopyridine carboxylic acids and hydroxylamine. Moreover, we

Diels–Alder reactions of myrcene using intensified continuous-flow reactors

• Christian H. Hornung,
• Miguel Á. Álvarez-Diéguez,
• Thomas M. Kohl and
• John Tsanaktsidis

Beilstein J. Org. Chem. 2017, 13, 120–126, doi:10.3762/bjoc.13.15

• of the most important. In many cases increased control over the process and improvements in product quality are the result. Herein, we describe the synthesis of several Diels–Alder adducts made from myrcene (1) and a series of dienophiles, which contain carboxylic acids, esters or acid anhydrides. In

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• ], and in intermolecular coupling of radicals generated by anodic decarboxylation of carboxylic acids [15][16]. At the anode radicals can be generated by anodic decarboxylation of carboxylic acids in molar quantities, in a simple procedure, unaffected by cage effects and in large diversity. For that

• reason, we were interested in exploring the structural influence of chiral auxiliaries (Figure 1) and the carboxylic acid on the diastereoselectivity in the anodic coupling of carboxylic acids. We report here on the diastereoselectivity found in the anodic hetero- and homo-coupling of menthol- (1)-, 8

• -methylmenthol- (2)-, 8-phenylmenthol- (3)-, and 8-p-anisylmenthol- (4)-2-alkylmalonates (Figure 1). Results and Discussion Anodic hetero- and homo-coupling of carboxylates The carboxylic acids 13a/b–18a/b for the Kolbe electrolyses were synthesized according to Scheme 1. The chiral auxiliary 1–4 is acylated

Supramolecular frameworks based on [60]fullerene hexakisadducts

• Andreas Kraft,
• Johannes Stangl,
• Ana-Maria Krause,
• Klaus Müller-Buschbaum and
• Florian Beuerle

Beilstein J. Org. Chem. 2017, 13, 1–9, doi:10.3762/bjoc.13.1

• are cross-linked by hydrogen bonding. Thereby, six of the twelve side arms form linear COOH dimers (four intralayer and two interlayer) and two carboxylic acids are bound to malonate ester groups from adjacent layers (see Figure S10 in Supporting Information File 1). The remaining four carboxylic acid

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• ] since they are considered as important surrogates for α-amino carboxylic acids, peptide mimics as well as versatile intermediates for the design of potential anticancer agents. β-Aminophosphonates present also an important place among the various compounds containing both a P–C bond and an amino group

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• isobutyraldehyde 8a/acetone 8b, carboxylic acids 10a–c (formic, acetic or propionic acid) and ethyl isocyanoacetate 9 (Scheme 3). The reactions were conducted at room temperature in trifluoroethanol (TFE) for 1–2 days to yield the acylhydrazino-peptomers 11a–f in moderate to good yields (59–90%). Aliphatic

• aldehydes, ketones and carboxylic acids succeeded in the hydrazino-Ugi reaction, except for paraformaldehyde, fatty acids and aromatic substrates, which led to formation of a complex mixture. These results limited the obtention of a greater variety of acylhydrazino-peptomers by this method. The choice of

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• modelling and chemical lead optimization. Examples of successful inhibitors are represented by the scaffolds of various 2-benzamidobenzoic acids [11][25][26], 2-nitrophenyl derivatives [27][28][29], ureidothiophene-2-carboxylic acids [24][30], and catechol-based compounds [31]. Many promising in vitro

Catalytic Wittig and aza-Wittig reactions

• Zhiqi Lao and
• Patrick H. Toy

Beilstein J. Org. Chem. 2016, 12, 2577–2587, doi:10.3762/bjoc.12.253

• catalytic aza-Wittig reactions (Scheme 16) [33]. It was reported that mixing 2-aminobenzoyl azides 55, carboxylic acids 56, isocyanides 57 with aldehydes 6 in methanol generated intermediates 58, which underwent rearrangement to isocyanates 59 in refluxing toluene. Finally, catalytic aza-Wittig reactions

• materials (Scheme 19) [37]. For example, reactions of carboxylic acids 71 with acid chlorides 72 to generate the corresponding carboxylic acid anhydride in situ afforded 4H-benzo[d][1,3]-oxazin-4-ones 73. In these reactions, 1 was used as the catalyst for the aza-Wittig reaction and copper triflate was used

• as the catalyst for phosphine oxide reduction. Using similar conditions the corresponding reactions of carboxylic acids 74 with aromatic acid chlorides 72 produced 4-benzylidene-2-aryloxazol-5(4H)-ones 75. Lastly, the research group of Piet Herdewijn extended this general concept and reported

Selective and eco-friendly procedures for the synthesis of benzimidazole derivatives. The role of the Er(OTf)₃ catalyst in the reaction selectivity

• Natividad Herrera Cano,
• Jorge G. Uranga,
• Mónica Nardi,
• Antonio Procopio,
• Daniel A. Wunderlin and
• Ana N. Santiago

Beilstein J. Org. Chem. 2016, 12, 2410–2419, doi:10.3762/bjoc.12.235

• ][12]. One frequently used protocol for the synthesis of benzimidazole derivatives is the coupling of o-phenylenediamines with carboxylic acids [13][14]. Another widely used procedure for the same synthesis represents the condensation of o-phenylenediamine with aldehydes. The latter approach has become