Syntheses of 2-substituted 1-amino-4-bromoanthraquinones (bromaminic acid analogues) – precursors for dyes and drugs

• Enas M. Malik,
• Younis Baqi and
• Christa E. Müller

Beilstein J. Org. Chem. 2015, 11, 2326–2333, doi:10.3762/bjoc.11.253

• -substituted derivative which, under different reaction conditions, yielded the corresponding carbaldehyde, carboxylic acid, and nitrile derivatives. The latter was further reacted to obtain 1-amino-2-tetrazolylanthraquinone. Subsequent bromination using bromine in DMF led to the corresponding bromaminic acid

• Shie et al., compound 9 was treated with sodium azide and zinc bromide under MW irradiation [62], however, the desired product 1-amino-4-bromo-2-tetrazolylanthraquinone (10, Scheme 2) could not be obtained. Following an alternative procedure, nitrile 9 was reacted with sodium azide in a mixture of N

• ) using the same oxidative amination procedure as described above. A total of six equivalents of iodine was needed to produce the desired product 12 in high yield (Scheme 3, Table 1). The method of Gutmann et al. was subsequently applied to the conversion of nitrile 12 to the corresponding 1-amino-2

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• oxacarbenium-ion intermediate by a nitrile and subsequent intramolecular nucleophilic attack of the vicinal C2 ether or a free hydroxy group [32][33][34]. Such glycooxazolines are exploited for the generation of N-glycan structures [35]. In O-glycosylation reactions, an oxacarbenium-ion intermediate interacts

• with nitrile solvents, providing a transient α,β-glycosyl nitrilium species that could produce an oxazolinium intermediate through the participation of the vicinal oxygen atom. In 1981, Pavia and co-workers proposed the formation of uncharacterized oxazolinium from glycosyl hemiacetal in acetonitrile

• were eventually found to be unstable. Later in 2004, García Fernández and co-workers elegantly showed the formation of fused and spiroglycooxazolines from D-fructose [37]. More recently, Mong and co-workers synthesized fused glucopyranose oxazolines in nitrile solvents from thioglycoside donors and

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• chloride/anhydrides [6][7][8][9][10][11], nitrile hydrolysis [12][13][14][15][16], Goldberg C–N cross coupling reaction [17], aldehyde/ketone amidation [18][19][20][21][22][23], the transamidation [24][25][26][27][28][29], and oxime rearrangement [30][31][32][33], to name only a few. It is obvious that the

Chiral Cu(II)-catalyzed enantioselective β-borylation of α,β-unsaturated nitriles in water

• Lei Zhu,
• Taku Kitanosono,
• Pengyu Xu and
• Shū Kobayashi

Beilstein J. Org. Chem. 2015, 11, 2007–2011, doi:10.3762/bjoc.11.217

• the synthesis of biologically interesting compounds and of other materials. In particular, compounds with a nitrile group in the β-position with respect to the boron moiety represent an important subset of organoboron intermediates because these compounds contain two functional groups. Their C–B

• linkage can be transformed into C–O, C–N, as well as into C–C bonds, while retaining stereogenic centers [1][2][3][4]. The nitrile group can be transformed into a range of functional groups, such as amides [5], carboxylic acids [6], aldehydes [7], esters [8], alcohols [9], and amines [10

• catalysis, which has been reported recently for asymmetric boron conjugate addition, is characterized by the effective and thermodynamically stable catalysis in water. Furthermore, a broad range of α,β-unsaturated acceptors, including one example of an α,β-unsaturated nitrile, are applicable, and the

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• having a strained cyclobutane ring did not form the desired oxaspirocyclohexadienone (Scheme 6). Instead, γ-bromoketone 8e was isolated in 44% yield along with nitrile 5a in 80% yield. The formation of γ-bromoketone 8e is most likely caused by radical ring opening from the transient cyclobutoxy radical I

Stereochemistry of ring-opening/cross metathesis reactions of exo- and endo-7-oxabicyclo[2.2.1]hept-5-ene-2-carbonitriles with allyl alcohol and allyl acetate

• Piotr Wałejko,
• Michał Dąbrowski,
• Lech Szczepaniak,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 1893–1901, doi:10.3762/bjoc.11.204

• geometry Z/E was reported. It should be emphasized that in the presence of a nitrile group an efficient metathetic transformation is difficult to carry out due to a competitive complexation of Ru by the nitrile group [22]. The influence of the reaction conditions on the distribution of the type A products

• products (1-2 and 1-3). While the reaction of endo-nitrile 2 with alcohol 4 proceeded with lower Z/E selectivity (1.5:1) (Table 1, entries 13–15), the exo-isomer 1 reacted without any stereoselectivity (Table 1, entries 7–9). It is worth to note that the reactions of nitriles 1 and 2 promoted by the Grubbs

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• electron- deficient olefin cross metathesis partner has received attention for the synthesis of polymer precursors. For instance, we have reported the reduction of the nitrile functional group into primary amine [22] and the reduction of the formyl group into alcohol [23][24]. Herein, we focused on the

• by intramolecular trans-esterification from 6, 7 and 8, as well as cyclic amines by intramolecular cyclization involving primary amine resulting from hydrogenation of the nitrile functionality in 5. All these aspects will be further developed in our group. Cross metathesis of 1 with methyl acrylate

Influence of bulky yet flexible N-heterocyclic carbene ligands in gold catalysis

• Alba Collado,
• Scott R. Patrick,
• Danila Gasperini,
• Sebastien Meiries and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 1809–1814, doi:10.3762/bjoc.11.196

• selected: alkyne hydration, nitrile hydration, and the synthesis of homoallylic ketones. To place these results into context, [Au(IPr)(NTf2)] (10) [46] was also tested under the same conditions. Alkyne hydration Alkyne hydration is an attractive transformation to generate ketones from alkynes with high

• obtained in all cases (Table 1, entries 5–8). However, the best conversion was observed when complex 10 bearing the IPr ligand was used (Table 1, entry 5). Complexes 7–9 afforded lower conversions, with [Au(IHept)(NTf2)] (8) being the most efficient amongst them (Table 1, entries 6–9). Nitrile hydration

• characterised. The impact of varying the length of the alkyl chain of the ligands in gold-promoted transformations has been explored. All gold complexes were shown to be active in water inclusive reactions (alkyne and nitrile hydration) and in the synthesis of homoallylic ketones from allylic alcohols and

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• function by first hydrolyzing the amide function to the corresponding amine following by the preparation of the diazonium and substitution of the diazonium function with a nitrile group. The latter was then converted to a carboxylic group under strongly acidic conditions. The acid derivative was treated

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

• -functionalized isoxazole derivatives. Since the amide was prepared by the cycloaddition reaction of ethynylbenzene and N-methylcarbamoylnitrile oxide, the nitrile oxide served as the equivalent of the nitrile oxides bearing a variety of functional groups such as carboxy, alkoxycarbonyl, carbamoyl, acyl and

• formyl moieties. Keywords: acylnitrile oxide; amide; formylnitrile oxide; functionalized nitrile oxide; Weinreb amide; Introduction Nitrile oxides are valuable synthetic synthons for the construction of heterocyclic compounds by cycloaddition reactions, which lead to the formation of two bonds in a

• single experimental step [1][2]. In addition, cycloadducts serve as precursors of polyfunctionalized compounds by ring opening reaction followed by N–O bond fission [2][3]. Hence, functionalized nitrile oxides are clearly useful for the preparation of more complex systems. However, because the precursors

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

• and chloroacetyl chloride. The crude nitrile product 81 was then collected in a batch vessel and isolated in pure form after crystallisation and washing with n-heptane. Alkylation of 81 with the corresponding amino-adamantane derivate in the presence of excess K2CO3 following an existing batch

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

• general, substrates which have an α-methylene adjacent to the nitrile group gave 2-aminothiophene (Scheme 1) whilst those that possessed an α-methine yielded the corresponding 2-substituted thiazole. Originally, reactions were performed using conventional heating, however, to allow for a wider temperature

• conversion and isolated yield (58%) with tetramethylethylenediamine (TMEDA) also giving a respectable yield of 50% (Table 1, entries 1 and 10). The stronger guanidine bases 1,1,3,3-tetramethylguanidine (TMG) and 1,8-diazabicycloundec-7-ene (DBU) both gave full consumption of the nitrile starting material

• its condensation with the aldehyde component (generated from 10), which inhibits the transformation. In addition, a sulfonic acid bound resin (QP-SA) was also trialled as an additive but showed no conversion allowing full recovery of the starting nitrile (see later discussion on mechanism). These

Trifluoromethyl-substituted tetrathiafulvalenes

• Olivier Jeannin,
• Frédéric Barrière and
• Marc Fourmigué

Beilstein J. Org. Chem. 2015, 11, 647–658, doi:10.3762/bjoc.11.73

• the deformation of the unsymmetrically substituted dithiole rings, when bearing one, or two different EWG, and attributed to the mesomeric effect of ester or nitrile groups, is not notably modified or counter-balanced by the introduction of a neighboring trifluoromethyl group. DFT calculations confirm

• these observations and also show that the low energy HOMO–LUMO absorption band found in nitrile or ester-substituted TTFs is not found in TTF-CF3, where, as in TTF itself, the low energy absorption band is essentially attributable to a HOMO→LUMO + 1 transition. Despite relatively high oxidation

• tetrathiafulvalenes functionalized by electron-withdrawing groups (EWG) are less documented, essentially because the presence of such substituents as halogen, acyl, ester, amide or nitrile on the TTF redox core dramatically increases its oxidation potential and destabilizes the radical cation form. This strong anodic

TTFs nonsymmetrically fused with alkylthiophenic moieties

• Rafaela A. L. Silva,
• Bruno J. C. Vieira,
• Marta M. Andrade,
• Isabel C. Santos,
• Sandra Rabaça,
• Dulce Belo and
• Manuel Almeida

Beilstein J. Org. Chem. 2015, 11, 628–637, doi:10.3762/bjoc.11.71

• cyanoethyl groups, by C–H…N hydrogen bonds and S…N short contacts. There are no interactions between A and D molecules and the stacks are out-of-registry; 2) on the other side the stacking interaction is between the nitrile groups of A and the methyl groups of D, and is mediated by a weak C–H…N hydrogen bond

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts

• Bin Yin,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2015, 11, 85–91, doi:10.3762/bjoc.11.12

• Bin Yin Shinsuke Inagi Toshio Fuchigami Department of Electronic Chemistry, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8502, Japan 10.3762/bjoc.11.12 Abstract Anodic fluorination of dithioacetals bearing electron-withdrawing ester, acetyl, amide, and nitrile groups at their

• having a strongly electron-withdrawing nitrile group gave the α-fluorination product predominantly regardless of the poly(HF) salts used. Keywords: anodic fluorination; anodic fluorodesulfurization; electrosynthesis; fluorination product selectivity; poly(HF) salt; Introduction The introduction of

A carbohydrate approach for the formal total synthesis of (−)-aspergillide C

• Pabbaraja Srihari,
• Namballa Hari Krishna,
• Ydhyam Sridhar and
• Ahmed Kamal

Beilstein J. Org. Chem. 2014, 10, 3122–3126, doi:10.3762/bjoc.10.329

• deprotecting the acetyl groups (without affecting the benzoate functionality) by employing acetyl chloride in anhydrous methanol to afford diol 13 [33]. A two-fold silylation and selective mono desilylation afforded primary alcohol 14 which was converted to its corresponding nitrile via the triflate. The

• nitrile functionality was hydrolysed with 8 N NaOH in ethanol to yield the seco acid 4. The seco acid 4 was already utilized for the total synthesis of (−)-aspergillide C through macrolactonization and TBS deprotection as reported earlier by Kuwahara (Table 1) [23]. Thus, by synthesizing 4, we have

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• α-amino nitrile, reinstalled the N-acyliminium ion. Reduction of the N-acyliminium afforded the major diastereoisomer as shown in Scheme 14 in 79% after column chromatography. Further synthetic modification of this key intermediate afforded the total synthesis of (+)-myrtine (66) in a further 5

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

• 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

• (0.60 mmol g−1) is corroborated by the value obtained in the modified Kaiser test (see below). The reduction of the nitrile groups has an important influence on the colloidal stability of the ND conjugate. Whereas the nitrile derivate 4 is soluble in rather nonpolar organic solvents, the amino derivate

• mmol g−1 (calculated from corrected TGA); zetapotential: +12.2 mV (measured in aqueous dispersion). FTIR-spectra of annealed nanodiamond 2 (a), nitrile 4 (b) and amine 5 (c). As can be seen from the disappearance of the CN signal after the reduction of 4 the nitrile is fully converted into the

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• chemistry as tracers for tumor detection, myocardial ischemia or infarct diagnostics [10]. The group of Perez et al has taken a particular interest in the chemistry of 2-aminoheptoses [11][12][13][14] which they prepared via an amino-nitrile synthesis [15]. This method, first described by Kuhn and

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• addition of trimethylsilylcyanide to the formed Schiff-base provided aminonitrile 168 as the major diastereomer (dr 95:5). Oxidative cleavage of the phenylglycinol moiety with Pb(OAc)4 liberated the amino-functionality and hydrolysis of the amide and nitrile under acidic conditions finally gave DCG-IV (162

• )4 liberated the amino functionality and hydrolysis of both the phosphonamide and nitrile groups under acidic conditions finally provided phosphonocyclopropylamino acid 21. This compound showed to be a group III mGluRs selective ligand with moderate potency as mGluR4 and mGluR6 agonist (EC50 59 µM

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• reaction have not been elucidated. As shown in Scheme 1, the Strecker reaction includes two reaction stages. The first reaction stage is the condensation of aldehydes with ammonia and hydrogen cyanide leading to α-aminonitriles . The second reaction stage is the hydrolysis of the nitrile group. In these

• )-CNH+ R-CH(NH2)-CNH+ + OH2 → R-CH(NH2)-C(OH)=NH + H+ However, the proton affinity (PA) of the nitrile is much smaller than that of the amino group, for example, the PAs of the cyano and amino groups of 2-amino-propanonitrile (Me-CH(NH2)-CN) are 190.7 and 199.6 kcal/mol, respectively. Thus, in the

• -aminopropanonitrile 8. Starting from 4, a concerted SN2-type pathway was also examined, which directly leads to the nitrile compound 8; see Scheme 6. In this pathway, the proton is transferred from the NH3+ group to the hydroxy group via a two-water-molecule bridge. At the same time, the H2O elimination and the

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• and purification on silica gel finally afforded the β-alkynyl-enolphosphate in 61–75% yield [58]. Azide, nitrile and thiocyanate were three other nucleophilic species used to produce pseudohalogenated phosphorus species by the AT reaction. Among them, the commercially available diphenyl

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

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• into pyrazines, even when stored in a fridge. Different mechanisms of dimerization were assumed, such as formation and dimerization of nitrile ylides [37][40], hydrolysis to α-aminoketenes followed by condensation [37][41], intermediate formation of metal complexes in the reaction mediated by metals

• [41][43][46]. It was found that water [37], Brønsted [44][48] and Lewis acids [40][41][43] facilitate the formation of pyrazine derivatives. 2H-Azirines undergo ring opening on electronic excitation to give nitrile ylides [50]. Nitrile ylide formation under thermal conditions even from such strained

• compounds as 2H-azirines needs to overcome a quite high energy barrier. According to calculations at the DFT B3LYP/6-31G(d) level the free energy barriers to formation of nitrile ylides 13a–c from azirines 2a–c are 48.4, 47.6, 47.9 kcal·mol−1 (353 K, benzene (PCM)), respectively. Therefore the process of