Mechanically induced oxidation of alcohols to aldehydes and ketones in ambient air: Revisiting TEMPO-assisted oxidations

• Andrea Porcheddu,
• Evelina Colacino,
• Giancarlo Cravotto,
• Francesco Delogu and
• Lidia De Luca

Beilstein J. Org. Chem. 2017, 13, 2049–2055, doi:10.3762/bjoc.13.202

• primary and secondary alcohols to the corresponding aldehydes and ketones by mechanical processing under air. Ball milling was shown to promote the quantitative conversion of a broad set of alcohols into carbonyl compounds with no trace of an over-oxidation to carboxylic acids. The mechanochemical

• over-oxidation to the carboxylic acids. The final products could be easily separated/purified from the crude reaction mixture without using toxic organic solvents. Under mechanical activation conditions, the reactions provided better yields and proceeded faster than classical, homogeneous phase TEMPO

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• -oxazolines, which are valuable heterocycles found in ligand scaffolds, natural products such as the leupyrrins [18][19], and potential pharmaceuticals (Figure 1) [20][21][22]. Traditional routes to this heterocycle include the dehydration of amino alcohols with carboxylic acids, however, this process

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• efficient for the enzyme-catalyzed selective esterification of the model compound erythro-1a, partly due to the non-reversibility of the reaction. However, isopropenyl esters of carboxylic acids are, in general, not readily available. Therefore, in order to find alternative acyl donors for the biocatalyst

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

• -substituted isoquinolines at C-1, followed by reaction with iodine. Subsequent Suzuki cross-coupling of the resulting 1-iodoisoquinolines to methyl 2-(isoquinolin-1-yl)benzoates and intramolecular acylation of the corresponding carboxylic acids with Eaton’s reagent afforded five alkaloids of the

• valuable intermediates for the further conversion to the target oxoisoaporphines, and in previous protocols [7][17] the esters were typically converted into the corresponding carboxylic acids, and then cyclized using polyphosphoric acid. Previously we found that esters can directly be subjected to this

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid

• Kohei Yamada,
• Naoto Kamimura and
• Munetaka Kunishima

Beilstein J. Org. Chem. 2017, 13, 1478–1485, doi:10.3762/bjoc.13.146

• one-pot oxazole synthesis/Suzuki–Miyaura coupling sequence has been developed. One-pot formation of 5-(triazinyloxy)oxazoles using carboxylic acids, amino acids and a dehydrative condensing reagent, DMT-MM, followed by Ni-catalyzed Suzuki–Miyaura coupling with boronic acids provided the corresponding

• synthesis of oxazolone from carboxylic acids and amino acids using a dehydrative condensing reagent, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM [19][20][21][22])[23]. Formation of 5-(triazinyloxy)oxazole is also reported to occur when an excess of DMT-MM was used. Recently

• )oxazole would provide trisubstituted oxazoles (Scheme 1b). Since many kinds of carboxylic acids, amino acids and boronic acids, which are corresponding to 2-, 4-, and 5-substituents of the oxazole, respectively, are commercially available, this method is suitable for the synthesis of a diverse variety of

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• heterocycles. Many methods use 2-aminobenzylamine (2-ABA) that reacts with amidines, carboxylic acids, orthoformates, or aldehydes in oxidative conditions to yield N-unsubstituted dihydroquinazolines [11][16][26][27][28][29][30][31][32][33][34][35]. A different approach is based on the heterocyclization of

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