An efficient synthesis of N-substituted 3-nitrothiophen-2-amines

• Sundaravel Vivek Kumar,
• Shanmugam Muthusubramanian,
• J. Carlos Menéndez and
• Subbu Perumal

Beilstein J. Org. Chem. 2015, 11, 1707–1712, doi:10.3762/bjoc.11.185

• associated with the lack of regioselectivity and difficult isomer separation [23]. Other methods for the synthesis of 2,3-disubsituted thiophenes include the reactions of (i) 1,4-dithiane-2,5-diol with nitroalkenes [24], activated nitriles [25] and cyanoacetamide [26]; (ii) 3-nitrothiophene with Grignard

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• electron-deficient alkenes; including maleic anhydride, maleic acid and related nitriles, in good yields (Scheme 10). Excess alkene was required to act as a trap for the conduction band electrons. In one instance a multigram reaction was successfully carried out with sunlight as the irradiation source

One-pot odourless synthesis of thioesters via in situ generation of thiobenzoic acids using benzoic anhydrides and thiourea

• Mohammad Abbasi and
• Reza Khalifeh

Beilstein J. Org. Chem. 2015, 11, 1265–1273, doi:10.3762/bjoc.11.141

• the reaction of benzoic anhydrides, thiourea and various organic halides (primary, allylic, and benzylic) or structurally diverse, electron-deficient alkenes (ketones, esters, and nitriles) in the presence of Et3N has been developed. In this method, thiobenzoic acids were in situ generated from the

• . In this protocol, a mixture of a benzoic anhydride, thiourea and an alkyl halide (primary, allylic or benzylic), or a conjugated olefin (ketones, esters, nitriles), Et3N and H2O produced the related thioesters in good to excellent yields. Experimental S-3-Oxobutyl benzothioate (1) Colorless oil; 1H

Development of variously functionalized nitrile oxides

• Haruyasu Asahara,
• Keita Arikiyo and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2015, 11, 1241–1245, doi:10.3762/bjoc.11.138

• ], nitriles [6], and 1,3-dicarbonyl compounds [7] to afford the corresponding polyfunctionalized heterocyclic compounds, which are not easily obtained by other approaches. Although this protocol is expected to be useful for synthesizing polyfunctionalized compounds, it is limited by the need of a N

Thiazole formation through a modified Gewald reaction

• Carl J. Mallia,
• Lukas Englert,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 875–883, doi:10.3762/bjoc.11.98

• The synthesis of thiazoles and thiophenes starting from nitriles, via a modified Gewald reaction has been studied for a number of different substrates. 1,4-Dithiane-2,5-diol was used as the aldehyde precursor to give either 2-substituted thiazoles or 2-substituted aminothiophenes depending on the

• , readily available 1,4-dithian-2,5-diol (10) has been previously reported as a coupling partner with various nitriles to give 2-aminothiophenes through a Gewald mechanism [21][22]. However, we have noticed that α-substituted benzylacetonitriles, alternatively yield 2-substituted thiazoles, when coupled

• with the aldehyde derived from 10. Although the thiazole formation from nitriles has already been shown to occur with ketones [23][24][25][26] and carboxylic acid [27][28] derivatives to give 2,5-disubstituted thiazoles, to our knowledge aldehydes have only been shown to form 2-aminothiophenes [29

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• ] and biological chemistry [249][250][251][252]. In the past, the Jacobsen group has used chiral (salen)Al complexes [253] as catalysts for the asymmetric 1,4-addition of azide [254], cyanide [219], substituted nitriles [255] and oximes [256] to α,β-unsaturated imides. The authors used these previous

Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

• Nikolai V. Rostovskii,
• Mikhail S. Novikov,
• Alexander F. Khlebnikov,
• Galina L. Starova and
• Margarita S. Avdontseva

Beilstein J. Org. Chem. 2015, 11, 302–312, doi:10.3762/bjoc.11.35

• ], amides [17][18][19], and nitriles [20][21], to give N–H insertion products or N- or N,O-heterocyclic systems. The reactivity of acyl- or diacyl-substituted Rh(II) carbenoids toward an sp2-hybridized nitrogen [22][23][24] is much less studied, while examples of their reactions with 2H-azirines are unknown

Novel biphenyl-substituted 1,2,4-oxadiazole ferroelectric liquid crystals: synthesis and characterization

• Mahabaleshwara Subrao,
• Dakshina Murthy Potukuchi,
• Girish Sharada Ramachandra,
• Poornima Bhagavath,
• Sangeetha G. Bhat and
• Srinivasulu Maddasani

Beilstein J. Org. Chem. 2015, 11, 233–241, doi:10.3762/bjoc.11.26

• -oxides to azomethines, nitriles and iminoesters. In the present study, we synthesized 1,2,4-oxadiazoles through amidoxime intermediates with substitutions at C-3 and C-5 positions. A moiety with a chiral center is attached to the phenyl ring (at C-5 position) of oxadiazole in the molecular structure. The

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• reaction proceeds in analogy to the one for benzenic starting materials by in situ generation of the diene and reaction with surface π-bonds on the nanodiamond acting as dienophiles. The successful grafting can be monitored by the appearance of the distinct signal of nitriles in the IR spectrum at ~2225 cm

• combustion analysis is not suitable for this type of nanodiamond derivatives. The dicyanopyrazine conjugate 4 can be submitted to a reduction of the nitrile groups using borane solution in THF. This mild yet efficient reaction leads to the complete transformation of the nitriles to amino groups as evidenced

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

• [1][2][3][4][5]. Simple amidines are generally synthesized from their corresponding nitriles either by the Pinner reaction [6] or by the thioimidate route [7]. Recently, much attention was given to the development of new routes for the synthesis of substituted amidines [8][9][10][11]. Even if these

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• -OTs). Furthermore, we have used Bt-OTs for conversion of aldoximes to nitriles and this reagent was generally comparable to BOP in those reactions. This factor additionally favored the selection of these two tosylate derivatives. As can be seen from Table 2, Bt-OTs is superior to BOP, and a wide range

A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H)-furanones

• Jubi John,
• Eliza Târcoveanu,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 1462–1470, doi:10.3762/bjoc.10.150

• analogue. The synthesized molecules are currently being screened for biological activities. We have also extended the reaction to triple-bonded electrophiles such as acetylenes, benzyne and nitriles; the results will be reported in due course. Studies are in progress to develop a stereoselective version of

Rasta resin–triphenylphosphine oxides and their use as recyclable heterogeneous reagent precursors in halogenation reactions

• Xuanshu Xia and
• Patrick H. Toy

Beilstein J. Org. Chem. 2014, 10, 1397–1405, doi:10.3762/bjoc.10.143

• the dehydration of oximes 12 to form nitriles 13. Capitalizing on the fact that 1 is formed as a byproduct from 3a,b in each of these reactions, Denton and co-workers have recently combined the Masaki–Fukui reaction with many of the functional group transformation outlined in Scheme 2, in one-pot

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• hydrophosphination of vinyl nitriles catalyzed by a dicationic nickel complex (Table 3). The method is based on the activation of the electrophile. It was suggested that complexation of the nitrile 50 to the chiral nickel Lewis acid activates the double bond towards 1,4-addition of the phosphine 25b. A final proton

• triarylphosphines 105a as phosphinating agents. This aryl–aryl exchange reaction was compatible with several functional groups such as ketones, aldehydes, esters, nitriles, ethers (Table 11) [192][193][194][195]. Products 106a were isolated in only moderate yields. Several P,N-biaryl ligands were prepared from the

Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

• Richard J. Ingham,
• Claudio Battilocchio,
• Joel M. Hawkins and
• Steven V. Ley

Beilstein J. Org. Chem. 2014, 10, 641–652, doi:10.3762/bjoc.10.56

• via a number of different approaches but the most environmentally friendly procedure is the hydration of nitriles [19]. Although this is generally considered to be a simple transformation, there are some inherent problems with the standard techniques of hydrolysis [20]. Further to our previous work

• which demonstrated the hydration of broad classes of nitriles by passing aqueous–organic solutions through a packed bed of manganese dioxide [21], we have found that heteroaromatic nitriles possessing a β-heteroatom can also be hydrolysed using hydrous zirconia [22][23] in a similar fashion (Figure 3

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• reaction involving nitriles 52 as pro-nucleophiles (Scheme 28) [71]. Wu and co-workers successfully employed the isoquinolinium-2-ylamides 43 as an ylidic species in two-component tandem [3 + 2]-cycloaddition reactions with a series of substrates including dimethyl acetylenedicarboxylate [72

Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones

• Murat Kucukdisli,
• Dorota Ferenc,
• Marcel Heinz,
• Christine Wiebe and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 466–470, doi:10.3762/bjoc.10.44

• )nitriles can be used as versatile and readily accessible pronucleophiles, e.g. for the construction of γ-amino acids [32], pyrrolidines [33], as well as pyrroles [34][35]. If an additional conjugated double bond is present, the anions of α-(alkylideneamino)nitriles 3 can undergo an electrocyclic ring

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• extension of the substrate scope of the Flögel-three-component reaction of lithiated alkoxyallenes, nitriles and carboxylic acids is presented. The use of dicarboxylic acids allowed the preparation of symmetrical bis(β-ketoenamides) from simple starting materials in moderate yields. Cyclocondensations of

• – discovered and mechanistically elucidated by Oliver Flögel – features a three-component reaction that employs alkoxyallenes, nitriles and carboxylic acids: upon treatment with n-butyllithium the allene is lithiated in α-position to the alkoxy moiety; the addition of a nitrile as electrophile to this highly

• investigations revealed that this method tolerates a broad variety of differently substituted starting materials – inter alia (het-)aromatic and (branched) aliphatic nitriles and carboxylic acids. It is also noteworthy to mention that the configurational integrity of enantiopure α-chiral carboxylic acids and/or

Organobase-catalyzed three-component reactions for the synthesis of 4H-2-aminopyrans, condensed pyrans and polysubstituted benzenes

• Moustafa Sherief Moustafa,
• Saleh Mohammed Al-Mousawi,
• Maghraby Ali Selim,
• Ahmed Mohamed Mosallam and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2014, 10, 141–149, doi:10.3762/bjoc.10.11

• -3,5-dicyanophthalic acid ester derivatives 37a–c were developed. The synthetic methods utilize one-pot reactions of acetylene carboxylic acid esters, α,β-unsaturated nitriles and/or active methylenenitriles in the presence of L-proline or DABCO. Plausible mechanisms are suggested for the formation of

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• aminooxygenation of alkenes, intercepting the hydroamination intermediate with various nucleophiles (i.e. alcohols, ethers and esters, Scheme 32a) [75]. A remarkable variety of products could be accessed with minimal variation of the reaction conditions. For instance, by using nitriles as solvents and only 2

A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime

• Raoni S. B. Gonçalves,
• Michael Dos Santos,
• Guillaume Bernadat,
• Danièle Bonnet-Delpon and
• Benoit Crousse

Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275

• supply a variety of organic functionalities including γ-amino alcohols [12], β-amino acids [13], β-hydroxy ketones [14][15] and β-hydroxy nitriles [14][15]. Fluorinated compounds play a central role in different branches of chemistry [16]. The incorporation of a fluorine atom into bioactive molecules

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

• pyridine structural class. Pyridine itself is produced industrially by either the traditional Chichibabin pyridine synthesis (Scheme 1, A), the Bönnemann reaction, a cobalt-catalysed cyclotrimerisation of alkynes and nitriles (Scheme 1, B) or the aerobic gas-phase condensation of croton aldehyde

• methods utilising cycloadditions of electron-rich oxazoles and acrylates [17][18] tri- and tetrazines with alkenes/alkynes [19] or pyrones with nitriles [20] have been used successfully to access specifically functionalised pyridines which are difficult to prepare by the more direct condensation routes. A

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• reviewed the synthesis of 1,2,4-oxadiazoles [33]. He pointed out that two general methods dominate the practical preparation (≈95%): (a) The condensation of amidoximes with carboxylic acid derivatives. (b) The dipolar cycloaddition of nitrile oxides to nitriles. The general approach for the synthesis of

• )–ZnCl2 as a catalyst for the synthesis of aniline 1 from amidoximes and organic nitriles [37]. tert-Butylamidoxime and 4-aminobenzonitrile were mixed in DMF with catalytic amounts of PTSA–ZnCl2. First, tert-butylamidoxime is activated by PTSA–ZnCl2; resulting in the formation of a Lewis acid–ammonia

[3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

• Stephan Cludius-Brandt,
• Lukas Kupracz and
• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1745–1750, doi:10.3762/bjoc.9.201

• cycloaddition reactions. They are commonly formed through three routes which are a) the addition of electrophilic carbenes to nitriles, b) the dehydrochlorination of imidoyl chlorides, and c) the photochemical ring opening of strained 2H-azirines 2 [2][3][4][5]. The latter route can be initiated by the