Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• screen of alternative solvents, tertiary amines and bases showed that NMM and NaOH in CH2Cl2 was the optimum reagent combination for the aziridination. Having optimised our aziridination protocol for tert-butyl cinnamate, our attention then turned to examining the scope for aromatic substitution in the

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• studied for this class of transformation. In 2010, three research groups independently reported organocatalytic biaryl synthesis from unactivated arenes and aryl halides [33][34][35]. Since these reactions follow a homolytic radical aromatic substitution mechanism (HAS) as pointed out by Studer and Curran

• LUMO and thus accepts an electron to generate a radical anion, and then passes the electron to aryl halide [35]. A general mechanism for the organocatalytic cross-coupling reactions was proposed by Studer and Curran [36], which suggests a “base-promoted homolytic aromatic substitution” mechanism. In

Exploring chemical diversity via a modular reaction pairing strategy

• Joanna K. Loh,
• Sun Young Yoon,
• Thiwanka B. Samarakoon,
• Alan Rolfe,
• Patrick Porubsky,
• Benjamin Neuenswander,
• Gerald H. Lushington and
• Paul R. Hanson

Beilstein J. Org. Chem. 2012, 8, 1293–1302, doi:10.3762/bjoc.8.147

• nucleophilic aromatic substitution (SNAr) diversification pathway is reported. Eight benzofused sultam cores were generated by means of a sulfonylation/SNAr/Mitsunobu reaction pairing protocol, and subsequently diversified by intermolecular SNAr with ten chiral, non-racemic amine/amino alcohol building blocks

• . Computational analyses were employed to explore and evaluate the chemical diversity of the library. Keywords: benzoxathiazocine 1,1-dioxides; chemical diversity; informatics; nucleophilic aromatic substitution (SNAr); sultams; Introduction The demand for functionally diverse chemical libraries has emerged, as

Highly selective synthesis of (E)-alkenyl-(pentafluorosulfanyl)benzenes through Horner–Wadsworth–Emmons reaction

• George Iakobson and
• Petr Beier

Beilstein J. Org. Chem. 2012, 8, 1185–1190, doi:10.3762/bjoc.8.131

• cyclized product 10d resulting from electrophilic aromatic substitution of the substituted phenyl cation intermediate (formed by the decomposition of the diazonium salt), to the electron-rich anisole ring in an unusual meta-position relative to the methoxy group. The more activated para-position is

• 11d in good yield (Scheme 4). To avoid problems with alkene reduction and electrophilic aromatic substitution during nitro group removal, we decided to try a different approach to the general synthesis of SF5-containing stilbene derivatives, as demonstrated in the synthesis of 13d shown in Scheme 5

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

• Nicola Otto and
• Till Opatz

Beilstein J. Org. Chem. 2012, 8, 1105–1111, doi:10.3762/bjoc.8.122

• formation; diaryl ethers; nucleophilic aromatic substitution; Ullmann-type coupling; Introduction The diaryl ether linkage is a common structural motif encountered in numerous classes of natural products. Moreover, various diaryl ethers have been shown to possess antibacterial, anti-inflammatory

Multistep organic synthesis of modular photosystems

• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2012, 8, 897–904, doi:10.3762/bjoc.8.102

• crude dibromo cNDA 32. Microwave-assisted reaction [15] with amines 14 and 15 gave the mixed cNDI 44 together with the symmetric side products. The obtained mixture of 2,6- and 3,7-regioisomers was not separated throughout the entire synthesis of photosystem 1. Nucleophilic aromatic substitution with

Directed aromatic functionalization

• Victor Snieckus

Beilstein J. Org. Chem. 2011, 7, 1215–1218, doi:10.3762/bjoc.7.141

• extent, nucleophilic aromatic substitution (SNAr) [2][6][7] reactions as taught to many generations of students in their first organic chemistry courses [8] (Figure 1). Being less steeped in history, radical nucleophilic substitution (SRN1) [9] and vicarious nucleophilic substitution (VNS) [10][11][12

• -selective reactions [49][50]. The fleeting benzyne species, representing aromatic 1,2-dipole reactivity, is experiencing a renaissance due to milder and dependable methodologies for its generation [51][52]. Somewhat akin to SRN1 and, to a lesser extent VNS, the Minisci radical aromatic substitution

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• elucidation of the structure and the first synthesis of the azulene skeleton by Pfau and Plattner [21][22], its reactivity has been intensively studied [23][24][25][26]. The aromatic system is susceptible to nucleophilic addition in the 4-, 6- and 8-positions [23], whereas electrophilic aromatic substitution

One-pot gold-catalyzed synthesis of 3-silylethynyl indoles from unprotected o-alkynylanilines

• Jonathan P. Brand,
• Clara Chevalley and
• Jérôme Waser

Beilstein J. Org. Chem. 2011, 7, 565–569, doi:10.3762/bjoc.7.65

• functionalization have been extensively studied [3][4]. Among the numerous syntheses of indoles, the cyclization of 2-alkynylanilines has the advantage that the resulting products, 2-substituted indoles, are easily functionalized by electrophilic aromatic substitution at position 3. Traditionally, this

Unusual behavior in the reactivity of 5-substituted-1H-tetrazoles in a resistively heated microreactor

• Bernhard Gutmann,
• Toma N. Glasnov,
• Tahseen Razzaq,
• Walter Goessler,
• Dominique M. Roberge and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2011, 7, 503–517, doi:10.3762/bjoc.7.59

• in a 3 μL fused-silica capillary, albeit not under continuous flow conditions, is the nucleophilic aromatic substitution reaction of 4-fluoro-1-nitrobenzene (15) with pyrrolidine (16) in THF (ΔV≠ = −58 cm3/mol) (Scheme 5) [71]. In order to confirm that these pressure enhancements can also be

• , significant corrosion of the reactor material can result, leading to unwanted side reactions. In addition, in specific cases reaction pressure can influence reaction rates as evidenced by the nucleophilic aromatic substitution reaction of 1-fluoro-4-nitrobenzene with pyrrolidine in the 60–180 bar pressure

• fresh 100 mL portions of KCN/m-nitrobenzenesulfinic acid sodium salt in water mixture before the reactor was finally washed with distilled water for 30 min to remove any remaining residues of the KCN/m-nitrobenzenesulfinic acid sodium salt in water mixture. Pressure dependence of nucleophilic aromatic

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• group unmasks the aniline which undergoes nucleophilic aromatic substitution to introduce the pyrimidine system with the formation of 253. Methylation of the secondary amine function with methyl iodide prior to a second SNAr reaction with a sulfonamide-derived aniline affords pazopanib (Scheme 50) [76

Anion–π interactions influence pK_a values

• Christopher J. Cadman and
• Anna K. Croft

Beilstein J. Org. Chem. 2011, 7, 320–328, doi:10.3762/bjoc.7.42

• aromatic substitution. The pKa' values for these 1,8-disubstituted arene naphthols have been measured in acetonitrile/water (R = NO2, 8.42; R = Cl, 8.52; R = H, 8.56; R = Me 8.68; and R = OMe, 8.71) and indicate a correlation with the electronic nature of the arene substituent, as determined through LFER

SbCl₃-catalyzed one-pot synthesis of 4,4′-diaminotriarylmethanes under solvent-free conditions: Synthesis, characterization, and DFT studies

• Ghasem Rezanejade Bardajee

Beilstein J. Org. Chem. 2011, 7, 135–144, doi:10.3762/bjoc.7.19

• the reaction can be summarized as a tandem regioselective electrophilic aromatic substitution reaction of N,N-dimethylaniline and aldehydes, in which SbCl3 (as a Lewis acid catalyst) activates the carbonyl group of the aldehydes. If we accept this mechanism, one can expect a general influence of

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• that aniline (B) is not derived from either chloro- (A) and iodo- (C)-sulfides, and iodo-product (C) is not formed from chlorosulfide (A). It is known [164] that photochemical nucleophilic aromatic substitution is promoted by electron-donating groups. Therefore, it appears most likely that the sulfides

Chromo- and fluorophoric water-soluble polymers and silica particles by nucleophilic substitution reaction of poly(vinyl amine)

• Katja Hofmann,
• Ingolf Kahle,
• Frank Simon and
• Stefan Spange

Beilstein J. Org. Chem. 2010, 6, No. 79, doi:10.3762/bjoc.6.79

• chromophoric and fluorescent carbonitrile-functionalized poly(vinyl amine) (PVAm) and PVAm/silica particles were synthesized by means of nucleophilic aromatic substitution of 8-oxo-8H-acenaphtho[1,2-b]pyrrol-9-carbonitrile (1) with PVAm in water. The water solubility of 1 has been mediated by 2,6-O-β

• potential which can be used for versatile subsequent derivatization reactions [17][19][20][21]. In previous articles we reported the nucleophilic aromatic substitution of activated fluoroaromatic compounds with PVAm [22][23][24]. Reactions of PVAm with derivatization agents seem at first glance to be simple

• with nitrogen-, oxygen-, or sulfur-containing nucleophiles by nucleophilic aromatic substitution reactions (SNArH) [32][33][34][35][36]. The reaction of 1 with 3-thiopropionic acid has used to produce a fluorescent sensor for cys/Hcy with a 75-fold fluorescence enhancement [34]. The SNArH reaction of 1

9,10-Dioxa-1,2-diaza-anthracene derivatives from tetrafluoropyridazine

• Graham Pattison,
• Graham Sandford,
• Dmitrii S. Yufit,
• Judith A. K. Howard,
• John A. Christopher and
• David D. Miller

Beilstein J. Org. Chem. 2010, 6, No. 45, doi:10.3762/bjoc.6.45

• systems. Keywords: benzodioxinopyridazine; 9,10-dioxa-1,2-diaza-anthracene; heterocyclic synthesis; nucleophilic aromatic substitution; perfluoroheteroaromatic; tetrafluoropyrazine; Introduction Drug discovery programmes are continually searching for viable synthetic routes to highly novel classes of

• highly novel classes of polyfunctional heterocyclic compounds. Several dipyrido[1,2-a:3′,4′-d]imidazole analogues 2 were prepared by the displacement of the remaining ring fluorine atoms by nucleophilic aromatic substitution processes (Scheme 1). We were interested in further expanding the use of highly

• regioselectivity of the nucleophilic aromatic substitution processes (Scheme 2). Both 5 and 6 have ring fluorine atoms present that may, in principle, be displaced by nucleophiles which could lead to the synthesis of many analogues of these systems. The dioxa-1,2-diaza-anthracene (or 3,4-difluorobenzo[5,6][1,4

Preparation, structures and preliminary host–guest studies of fluorinated syn-bis-quinoxaline molecular tweezers

• Markus Etzkorn,
• Jacob C. Timmerman,
• Matthew D. Brooker,
• Xin Yu and
• Michael Gerken

Beilstein J. Org. Chem. 2010, 6, No. 39, doi:10.3762/bjoc.6.39

• reported procedures [29][30][31][32] did not significantly alter the outcome. It should be noted that all fluorinated bis-quinoxalines are stable compounds which do not show any decomposition over extended periods of time; loss of fluorine has only been observed under typical nucleophilic aromatic

• substitution conditions. Although the new compounds, in particular the cyclohexadiene-derived species 15b–c, were reasonably soluble in dipolar aprotic solvents (DMSO, DMF) or halogenated aromatic solvents (C6H5Cl), they only displayed poor solubility in several standard organic solvents (CHCl3, CH2Cl2, CH3OH

Perhalogenated pyrimidine scaffolds. Reactions of 5-chloro- 2,4,6-trifluoropyrimidine with nitrogen centred nucleophiles

• Emma L. Parks,
• Graham Sandford,
• John A. Christopher and
• David D. Miller

Beilstein J. Org. Chem. 2008, 4, No. 22, doi:10.3762/bjoc.4.22

• in parallel synthesis. 5-Chloro-2,4,6-trifluoropyrimidine may be used as a scaffold for the synthesis of polyfunctional pyrimidine systems if sequential nucleophilic aromatic substitution processes are regioselective. Results Use of 5-chloro-2,4,6-trifluoropyrimidine as a core scaffold for the

• synthesis of functionalised pyrimidine systems is assessed in reactions with a small range of nitrogen centred nucleophiles. Mixtures of products arising from nucleophilic aromatic substitution processes are formed, reflecting the activating effect of ring nitrogen and the steric influences of the chlorine

• derivatives can be isolated in acceptable yields using this methodology. Keywords: pyrimidine; rapid analogue synthesis; perfluoroheteroaromatic; nucleophilic aromatic substitution; Introduction Highly functionalised pyrimidine derivatives are of great importance to the life-science industries and, indeed

Trifluoromethyl ethers – synthesis and properties of an unusual substituent

• Frédéric R. Leroux,
• Baptiste Manteau,
• Jean-Pierre Vors and
• Sergiy Pazenok

Beilstein J. Org. Chem. 2008, 4, No. 13, doi:10.3762/bjoc.4.13

• electron withdrawing behavior to the alkoxy group but also acts to deactivate the aromatic ring system [53]. Electrophilic Aromatic Substitution Trifluoromethoxybenzene, for example, undergoes nitration considerably (up to 5 times) more slowly than benzene. The electrophilic substitution occurs selectively

Expedient syntheses of the N-heterocyclic carbene precursor imidazolium salts IPr·HCl, IMes·HCl and IXy·HCl

• Lukas Hintermann

Beilstein J. Org. Chem. 2007, 3, No. 22, doi:10.1186/1860-5397-3-22

• them from participating as electrophiles in aromatic substitution reactions. Conclusion The useful imidazolium salts IPr·HCl (1), IMes·HCl (2) and IXy·HCl (3) have previously been synthesized by a range of methods giving the products in variable purity and yields. We now present a protocol for the