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Search for "benzoic acid" in Full Text gives 160 result(s) in Beilstein Journal of Organic Chemistry.
Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives
- Zhi-Cong Geng,
- Jian Chen,
- Ning Li,
- Xiao-Fei Huang,
- Yong Zhang,
- Ya-Wen Zhang and
- Xing-Wang Wang
Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195
- ). Soluble organic bases were also tested and failed to increase the yields (Table 1, entries 11 and 12). When benzoic acid (5a) was used as an additive, the yield was slightly improved to 77% (Table 1, entry 13). With the increase of the acidity, the yield was noticeably decreased (Table 1, entry 13 versus
Graphical Abstract
Figure 1: Important heterocycles containing pyrazolidine or pyrazoline structures.
Figure 2: X-ray crystal structure of racemic 4a (25% thermal ellipsoids).
Figure 3: X-ray crystal structure of racemic 4n (25% thermal ellipsoids).
Figure 4: The X-ray crystal structure of chiral compound 4s (40% thermal ellipsoids).
Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines
- Chittaranjan Bhanja,
- Satyaban Jena,
- Sabita Nayak and
- Seetaram Mohapatra
Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191
- sieves (4 Å) in the reaction (Scheme 2). Wang et al. [44] investigated the same tandem reaction of salicylaldehydes 1 and α,β-unsaturated aldehydes 2 employing TES-protected diphenylprolinol Ie as organocatalyst with high catalyst loading (30 mol %). With benzoic acid as cocatalyst and dichloroethane as
- )-diphenylpyrrolinol silyl ether (Ia) as organocatalyst and benzoic acid as cocatalyst in toluene at room temperature (Scheme 18). The protocol provides good yield and high enantioselectivity of the desired products. The yield of the reactions does not reduce appreciably when substituents are present on the aromatic
- of diphenylprolinol trimethylsilyl ether Ib as catalyst and benzoic acid as additive, provides 1,2-dihyroquinolines 53 with high yields (90%) and high ee (>99%) (Scheme 27). Various enal substituents, such as aryl, alkyl and ester groups, are readily tolerated in the reaction. However, with β-alkyl α
Graphical Abstract
Figure 1: Some representative molecules having chromene, thiochromene or 1,2-dihydroquinolin structural motif...
Figure 2: Screened chiral proline and its derivatives as organocatalysts. Rb = rubidium.
Figure 3: Screened chiral bifunctional thiourea, its derivatives, cinchona alkaloids and other organocatalyst...
Scheme 1: Diarylprolinolether-catalyzed tandem oxa-Michael–aldol reaction reported by Arvidsson.
Scheme 2: Tandem oxa-Michael–aldol reaction developed by Córdova.
Scheme 3: Domino oxa-Michael-aldol reaction developed by Wei and Wang.
Scheme 4: Chiral amine/chiral acid catalyzed tandem oxa-Michael–aldol reaction developed by Xu et al.
Scheme 5: Modified diarylproline ether as amino catalyst in oxa-Michael–aldol reaction as reported by Xu and ...
Scheme 6: Chiral secondary amine promoted oxa-Michael–aldol cascade reactions as reported by Wang and co-work...
Scheme 7: Reaction of salicyl-N-tosylimine with aldehydes by domino oxa-Michael/aza-Baylis–Hillman reaction, ...
Scheme 8: Silyl prolinol ether-catalyzed oxa-Michael–aldol tandem reaction of alkynals with salicylaldehydes ...
Scheme 9: Oxa-Michael–aldol sequence for the synthesis of tetrahydroxanthones developed by Córdova.
Scheme 10: Synthesis of tetrahydroxanthones developed by Xu.
Scheme 11: Diphenylpyrrolinol trimethylsilyl ether catalyzed oxa-Michael–Michael–Michael–aldol reaction for th...
Scheme 12: Enantioselective cascade oxa-Michael–Michael reaction of alkynals with 2-(E)-(2-nitrovinyl)-phenols...
Scheme 13: Domino oxa-Michael–Michael–Michael–aldol reaction of 2-(2-nitrovinyl)-benzene-1,4-diol with α,β-uns...
Scheme 14: Tandem oxa-Michael–Henry reaction catalyzed by organocatalyst and salicylic acid, as reported by Xu....
Scheme 15: Asymmetric synthesis of nitrochromenes from salicylaldehydes and β-nitrostyrene, as reported by San...
Scheme 16: Domino Michael–aldol reaction between salicyaldehydes with β-nitrostyrene, as reported by Das and c...
Scheme 17: Enantioselective synthesis of 2-aryl-3-nitro-2H-chromenes, as reported by Schreiner.
Scheme 18: (S)-diphenylpyrrolinol silyl ether-promoted cascade thio-Michael–aldol reactions, as reported by Wa...
Scheme 19: Organocatalytic asymmetric domino Michael–aldol condensation of mercaptobenzaldehyde and α,β-unsatu...
Scheme 20: Organocatalytic asymmetric domino Michael–aldol condensation between mercaptobenzaldehyde and α,β-u...
Scheme 21: Hydrogen-bond-mediated Michael–aldol reaction of 2-mercaptobenzaldehyde with α,β-unsaturated oxazol...
Scheme 22: Domino Michael–aldol reaction of 2-mercaptobenzaldehydes with maleimides catalyzed by cinchona alka...
Scheme 23: Domino thio-Michael–aldol reaction between 2-mercaptoacetophenone and enals developed by Córdova an...
Scheme 24: Enantioselective tandem Michael–Henry reaction of 2-mercaptobenzaldehyde with β-nitrostyrenes repor...
Scheme 25: Enantioselective tandem Michael–Knoevenagel reaction between 2-mercaptobenzaldehydes and benzyliden...
Scheme 26: Cinchona alkaloid thiourea catalyzed Michael–Michael cascade reaction, as reported by Wang and co-w...
Scheme 27: Domino aza-Michael–aldol reaction between 2-aminobenzaldehydes and α,β-unsaturated aldehydes, as re...
Scheme 28: (S)-Diphenylprolinol TES ether-promoted aza-Michael–aldol cascade reaction, as developed by Wang’s ...
Scheme 29: Domino aza-Michael–aldol reaction reported by Hamada.
Scheme 30: Organocatalytic asymmetric synthesis of 3-nitro-1,2-dihydroquinolines by a dual activation protocol...
Scheme 31: Asymmetric synthesis of 3-nitro-1,2-dihydroquinolines by cascade aza-Michael–Henry–dehydration reac...
Organocatalytic C–H activation reactions
- Subhas Chandra Pan
Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159
- Brønsted acids as catalysts was screened for this reaction, and the best reaction efficiency in terms of yield and reaction time was achieved with benzoic acid (10 mol %). The scope of the reaction was investigated and was found to tolerate a wide variety of functional groups including nitro, nitriles
- -membered lactols, δ-hydroxypyrroles 8 were achieved as the products in good yields (Scheme 6). Later, Pan and Seidel independently extended this methodology to indolines using benzoic acid as the catalyst, conducting the reaction under reflux and microwave irradiation conditions, respectively, to generate
- explanation is the formation of azomethine ylide intermediate 11 (Scheme 8) [19][20]. The carbanion of ylide 11 is then protonated by benzoic acid, and the resulting benzoate anion supports the aromatization process. In fact, Seidel and co-workers provided the experimental evidence for the existence of
Graphical Abstract
Scheme 1: Triflic acid-catalysed synthesis of cyclic aminals.
Scheme 2: PTSA-catalysed synthesis of cyclic aminals.
Scheme 3: Plausible mechanism for cyclic aminal synthesis.
Scheme 4: Annulation cascade reaction with double nucleophiles.
Scheme 5: Mechanism for the indole-annulation cascade reaction.
Scheme 6: Synthesis of N-alkylpyrroles and δ-hydroxypyrroles.
Scheme 7: Synthesis of N-alkylindoles 9 and N-alkylindolines 10.
Scheme 8: Mechanistic study for the N-alkylpyrrole formation.
Scheme 9: Benzoic acid catalysed decarboxylative redox amination.
Scheme 10: Organocatalytic redox reaction of ortho-(dialkylamino)cinnamaldehydes.
Scheme 11: Mechanism for aminocatalytic redox reaction of ortho-(dialkylamino)cinnamaldehydes.
Scheme 12: Asymmetric synthesis of tetrahydroquinolines having gem-methyl ester groups.
Scheme 13: Asymmetric synthesis of tetrahydroquinolines from chiral substrates 18.
Scheme 14: Organocatalytic biaryl synthesis by Kwong, Lei and co-workers.
Scheme 15: Organocatalytic biaryl synthesis by Shi and co-workers.
Scheme 16: Organocatalytic biaryl synthesis by Hayashi and co-workers.
Scheme 17: Proposed mechanism for organocatalytic biaryl synthesis.
Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of β-ketoesters
- Wen-Bin Yi,
- Xin Huang,
- Zijuan Zhang,
- Dian-Rong Zhu,
- Chun Cai and
- Wei Zhang
Beilstein J. Org. Chem. 2012, 8, 1233–1240, doi:10.3762/bjoc.8.138
- determined by chiral phase HPLC analysis on an SHIMADZU LC-20AD system. Synthesis of fluorous quinine ester C-1 Thionyl chloride (1.19 g, 10 mmol) was added to a mixture of (1H,1H,2H,2H-perfluorooctyl)benzoic acid (0.468 g, 1 mmol) and pyridine (75 mg, 1 mmol). After stirring of the mixture for 4 h at 50 °C
- , 101.4, 114.5, 118.9, 121.8, 127.0, 131.8, 141.7, 143.5, 144.8, 147.4, 149.6, 157.9, 170.0, 199.5, 200.2; ACPIMS m/z: 367.2 (M+ + 1). Synthesis of fluorous pyrrolidine ester C-6 N,N'-Dicyclohexylcarbodiimide (DCC) (0.206 g, 1 mmol) was added to a mixture of (1H,1H,2H,2H-perfluorooctyl)benzoic acid (0.468
Graphical Abstract
Figure 1: Biologically interesting α-fluorinated β-ketoesters.
Scheme 1: Preparation of quinine ester C-1.
Figure 2: Promoters for asymmetric fluorination.
Scheme 2: Preparation of 2a by using recycled quinine ester C-1.
Figure 3: The asymmetric fluorination of various β-ketoesters.
Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports
- Kerstin Knepper,
- Sylvia Vanderheiden and
- Stefan Bräse
Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132
- benzoic acids on Merrifield resin: In a three-necked round-bottom flask equipped with a mechanical stirrer, 5 equiv of cesium carbonate are suspended in DMF (mL/mmol) and are stirred for 30 min at 50 °C. Next, 5 equiv of benzoic acid are added and the mixture is stirred for another 30 min. Afterwards, one
Graphical Abstract
Scheme 1: Diverse synthesis of indoles using Bartoli reactions. aSee [24].
Figure 1: Nitroarenes on solid supports. In red: Nitroarenes failed to give indoles. aResin has been reported...
Figure 2: Temperature optimization with Grignard reagent 2{b}.
Figure 3: Temperature optimization with Grignard reagent 2{a}. Isolated yield.
Figure 4: Optimization studies of ester 1{h} with a Grignard reagent 2{d} to give indole 3{h,d} and methyl 3-...
Scheme 2: Stille reaction on solid supports.
Scheme 3: Suzuki reaction on solid supports.
Scheme 4: Sonogashira–Hagihara reaction on solid supports.
Parallel solid-phase synthesis of diaryltriazoles
- Matthias Wrobel,
- Jeffrey Aubé and
- Burkhard König
Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115
- potential inhibitors of protein–protein interactions. Results and Discussion Synthesis of azide-functionalized Wang resins Two azide-functionalized resins were prepared for the solid-phase synthesis of diaryl-triazoles. The commercially available 4-(bromomethyl)benzoic acid (5) was converted into azide 6 in
- phenyl ring of the benzoic acid as constant structural elements and the third ring consisting either of substituted benzenes, heteroarenes or a polycyclic aromatic compound. Lower product yields were obtained in this series of compounds, ranging from 21 to 63%. The lower reactivity of the aromatic azide
- of regioisomers in reaction 3. Instead of the 1,4-disubstituted triazoles obtained from copper(I) catalysis, the complex pentamethylcyclopentadienylbis(triphenylphosphine)ruthenium(II) chloride leads to 1,5-disubstituted triazole compounds [19]. 4-(Azidomethyl)benzoic acid functionalized Wang resin 7
Graphical Abstract
Scheme 1: Terphenyl scaffold 1 [13,14]; oxazole-pyridazine-piperazine 2 [14,15] and aryl-triazoles 3 and 4 [15,16] as α-helix mime...
Scheme 2: Synthesis of azido-functionalized resins 7 and 9.
Building photoswitchable 3,4'-AMPB peptides: Probing chemical ligation methods with reducible azobenzene thioesters
- Gehad Zeyat and
- Karola Rück-Braun
Beilstein J. Org. Chem. 2012, 8, 890–896, doi:10.3762/bjoc.8.101
- for the application in ligation studies. AMPB = (aminomethylphenylazo)benzoic acid. Structure of the glycine-linked auxiliary conjugates 7 and 8. Structural differences between the trans- and the cis-state of azopeptides with a SKV PDZ binding motif. Solid-phase synthesis of the ligation-mediating
Graphical Abstract
Figure 1: Structures of azobenzene thioesters, Nα-ligation auxiliaries and peptides for the application in li...
Scheme 1: Structural differences between the trans- and the cis-state of azopeptides with a SKV PDZ binding m...
Figure 2: Structure of the glycine-linked auxiliary conjugates 7 and 8.
Scheme 2: Solid-phase synthesis of the ligation-mediating peptides 3–5.
Scheme 3: Reduction of the diazene unit of 4,4'-AMPB thioesters and peptides during aliphatic thiol-based Nα-...
Scheme 4: Synthesis of the azopeptides 16/17 by final TFA cleavage of the Boc-protecting groups, and of the a...
meta-Oligoazobiphenyls – synthesis via site-selective Mills reaction and photochemical properties
- Raphael Reuter and
- Hermann A. Wegner
Beilstein J. Org. Chem. 2012, 8, 877–883, doi:10.3762/bjoc.8.99
- ) was oxidized with potassium permanganate in a 1:1 solvent mixture of pyridine/H2O, to the corresponding benzoic acid 5. The reaction proceeded with an acceptable yield of 66%. However, the resulting highly deactivated aromatic system 5 did not react even under harsh bromination conditions with NBS in
Graphical Abstract
Figure 1: para-Substituted bisazobiphenyls 1 investigated by Hecht (R1, R2 = H, Me, R3 = t-Bu) and by Woolley...
Figure 2: Synthetic strategy for the assembly of meta-substituted oligo-azobiphenyls 2.
Scheme 1: Synthesis of 2-nitro-4-tert-butyl-6-bromobenzoic acid (6).
Scheme 2: Preparation of nitroso derivative 10.
Scheme 3: Assembly of oligomer 2 by Suzuki cross-coupling and site-selective Mills reaction.
Figure 3: Isomerization studies of compound 13 (a), 15 (b), 16 (c) and 2 (d) (Irradiation at 356 nm in CHCl3)....
Figure 4: Comparison of the absorption as well as the photostationary state of compounds 13, 15, 16, 2.
Figure 5: Four different isomers of 2.
Regio- and stereoselective oxidation of unactivated C–H bonds with Rhodococcus rhodochrous
- Elaine O’Reilly,
- Suzanne J. Aitken,
- Gideon Grogan,
- Paul P. Kelly,
- Nicholas J. Turner and
- Sabine L. Flitsch
Beilstein J. Org. Chem. 2012, 8, 496–500, doi:10.3762/bjoc.8.56
- 29% of p-chlorobenzoic acid. The isolation of the benzoic acid derivative suggests that benzylic hydroxylation takes place, leading to cleavage of the unstable acetal [19][20]; however, this was not investigated further and the oxidation products were not characterised. The most interesting
Graphical Abstract
Scheme 1: Regioselective hydroxylation of Cbz-piperidine by Rhodococcus rhodochrous resting cells.
Scheme 2: Results from the incubation of THP ether derivatives with Rhodococcus rhodochrous showing the isola...
Scheme 3: Influence of substrate structure and linker length on the regioselectivity of hydroxylation.
Scheme 4: Regioselective hydroxylation following incubation of THF ether derivatives with Rhodococcus rhodoch...
Derivatives of phenyl tribromomethyl sulfone as novel compounds with potential pesticidal activity
- Krzysztof M. Borys,
- Maciej D. Korzyński and
- Zbigniew Ochal
Beilstein J. Org. Chem. 2012, 8, 259–265, doi:10.3762/bjoc.8.27
- yields. It is worth noting that we encountered significant difficulties while applying the Philips method for the cyclization of diamine 9 with benzoic acid and 4-chlorobenzoic acid. The expected benzimidazole was not formed, and only the substrates were isolated from the reaction mixture. Therefore we
Graphical Abstract
Scheme 1: Retrosynthetic analysis of the designed target molecules.
Scheme 2: Synthetic routes for 4-chlorophenyl tribromomethyl sulfone (1).
Scheme 3: Halogenation/nitration sequence for 4-halogenphenyl methyl sulfones 4 and 4'.
Scheme 4: SNAr transformations of sulfone 6.
Scheme 5: Preparation of phenylhydrazones 8a–8l.
Scheme 6: Products of the nitro group reduction of sulfone 7a.
Scheme 7: Synthesis of benzimidazole derivatives 11a–11g.
Scheme 8: Preparation and further transformation of 2-mercaptobenzimidazole 11h.
Efficient, highly diastereoselective MS 4 Å-promoted one-pot, three-component synthesis of 2,6-disubstituted-4-tosyloxytetrahydropyrans via Prins cyclization
- Naseem Ahmed and
- Naveen Kumar Konduru
Beilstein J. Org. Chem. 2012, 8, 177–185, doi:10.3762/bjoc.8.19
- the solvent of choice at reflux temperature (Table 1, entries 5, 6, 8–10). Similarly, various acids like trifluoroacetic acid (TFA), benzoic acid, acetic acid, benzylphosphonic acid, and O,O’-diethyl dithiophosphate were tried as catalysts but all of them failed to give the desired product. We
Graphical Abstract
Figure 1: Tetrahydropyran ring containing natural products.
Scheme 1: Plausible side products mechanism.
Scheme 2: Plausible reaction mechanism via Prins cyclization.
Figure 2: Schematic NOE diagram of compound 3b.
Scheme 3: Deprotection of the hydroxy group.
Laterally substituted symmetric and nonsymmetric salicylideneimine-based bent-core mesogens
- Sonja Findeisen-Tandel,
- Wolfgang Weissflog,
- Ute Baumeister,
- Gerhard Pelzl,
- H. N. Shreenivasa Murthy and
- Channabasaveshwar V. Yelamaggad
Beilstein J. Org. Chem. 2012, 8, 129–154, doi:10.3762/bjoc.8.15
- benzoic acids 2 and hydrogenolytic deprotection of the hydroxy group according to [47]. The final products OH 1a–c were obtained by esterification of the phenols 3 with 4-(4-dodecyloxy-2-hydroxybenzylideneamino)benzoic acid (4), which exhibits a liquid-crystalline phase itself (Cr 204 N 269 I) [42]. It
Graphical Abstract
Scheme 1: Examples for bent mesogens containing salicylideneimine moieties.
Scheme 2: Synthetic pathway to prepare compounds OH 1.
Figure 1: Polarising optical microscopy images. a) Compound OH 1a: Grainy texture with smectic Schlieren area...
Figure 2: X-ray diffraction pattern of a powderlike sample of OH 1b at 131 °C (inset: Small angle region; low...
Figure 3: Electro-optical behaviour of compound OH 1a: a) current response curve (U = 182 Vpp, f = 30 Hz, T =...
Figure 4: Switching behaviour of compound H 1a, which depends on how quickly the electric field is switched o...
Scheme 3: Reaction pathways to prepare the monosalicylideneaniline compounds OH 2a–j.
Figure 5: Compound OH 2a: Texture of the SmCP phase at 126 °C.
Figure 6: a) 2D X-ray pattern of a surface-aligned sample of compound OH 2a at 128 °C (lower part of the patt...
Figure 7: Electro-optical switching behaviour of compound OH 2a: a) current response (U = 230 Vpp, f = 25 Hz, ...
Scheme 4: Synthetic steps followed to prepare the compounds OH 3 and OH 4.
Figure 8: Optical photomicrographs of compound OH 3a: a) On cooling of the isotropic liquid; c) U = 0 V; b) U...
Figure 9: Electro-optical behaviour of compound OH 3a: a) Current response curve (U = 308 Vpp, f = 35 Hz, T =...
Figure 10: Growth of a fan-shaped texture from lancetlike filaments upon cooling of the isotropic liquid of co...
Figure 11: a) 2D X-ray pattern of a surface-aligned sample of compound OH 3b at 160 °C (lower part of the patt...
Figure 12: Compound OH 3b: Texture of the SmCPA phase in dependence on the polarity of the applied D.C. field.
Figure 13: Compound OH 4b, exhibiting a fan-shaped texture together with a Schlieren texture upon cooling of t...
Figure 14: 2D X-ray diffraction pattern of a partially surface-aligned sample of OH 4b at 115 °C (inset: Small...
Figure 15: Switching behaviour of compound OH 4b at 120 °C: a) Current response curve (U = 116 Vpp, f = 40 Hz, ...
Figure 16: Compound OH 4d: a) Microphotograph of a growing fringe pattern of a SmCP phase upon cooling of the ...
Figure 17: Electro-optical behaviour observed on the fan-shaped texture of compound OH 4d; UD.C. = 47 V; T = 1...
Figure 18: a) 2D X-ray diffraction pattern for a surface-aligned sample of OH 4d at 122 °C on cooling; b) χ-sc...
Scheme 5: Reaction steps employed for the preparation of the compounds OH 5 and OH 6.
Figure 19: Compound OH 5d: Optical photomicrographs of chiral domains at 122 °C; polariser and analyser are un...
Figure 20: Compound OH 5b: a), b) Chiral domains at 175 °C, 0 V, polarisers uncrossed by about ±8° from the 90...
Figure 21: X-ray diffraction patterns of compounds OH 5: a) Pattern of a powderlike sample of compound OH 5g a...
Figure 22: Photomicrographs of compound OH 5f: a) Appearance of spiral filaments on slow cooling of the isotro...
Figure 23: Current response of compound OH 6b exhibiting two repolarisation peaks proving an antiferroelectric...
Figure 24: On cooling the isotropic liquid phase of compound OH 6c; a Schlieren texture together with fringe p...
Figure 25: Electro-optical behaviour of compound OH 6c: a) Current response (UA.C. = 17 V/µm, f = 39 Hz, T = 1...
Synthesis and characterization of new diiodocoumarin derivatives with promising antimicrobial activities
- Hany M. Mohamed,
- Ashraf H. F. Abd EL-Wahab,
- Ahmed M. EL-Agrody,
- Ahmed H. Bedair,
- Fathy A. Eid,
- Mostafa M. Khafagy and
- Kamal A. Abd-EL-Rehem
Beilstein J. Org. Chem. 2011, 7, 1688–1696, doi:10.3762/bjoc.7.199
- ), 170 (COOH); MS m/z (% relative intensity): 533 (M+, 45), 425 (M+ – NH-C6H4-OH, 100), 341 (16), 214 (10), 171 (17), 87 (63). 2-(6,8-Diiodocoumarin-3-carboxamido)benzoic acid (10). Yellow crystals: Yield 91%; mp 315 °C; Anal. calcd for C17H9I2NO5: C, 36.37; H, 1.60; N, 2.50; found: C, 36.39; H, 36.39; N
Graphical Abstract
Scheme 1: Synthesis of 6,8-diiodocoumarin derivatives 1–7.
Scheme 2: Proposed fragmentation pathways for the EI ions of the substituted 6,8-diiodocoumarins 3 and 7.
Scheme 3: Synthesis of 6,8-diiodocoumarin-3-N-carboxamide derivatives 8–11.
Scheme 4: Synthesis of ethyl cyanoacetate and pyridine derivatives 12 and 13.
Scheme 5: Synthesis of 1,3-oxazocine derivatives 14a,b.
Figure 1: Graphical representation of the antibacterial activity of tested compounds compared to ampicillin.
Figure 2: Graphical representation of antifungal activity of tested compounds, compared to calforan.
A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions
- Ameer F. Zahoor,
- Sarah Thies and
- Uli Kazmaier
Beilstein J. Org. Chem. 2011, 7, 1299–1303, doi:10.3762/bjoc.7.151
- aldehyde group. Therefore, we decided to run the reaction also under neat conditions as reported for the γ-oxo-amino acids. With acetic acid as the acidic component the yield of 6a was comparable to the previous examples. In principle, other acids such as benzoic acid or Cbz-protected glycine can be used
Graphical Abstract
Scheme 1: Passerini reactions of α,β-unsaturated aldehyde 5.
Scheme 2: Passerini and Ugi reaction of saturated aldehyde 7.
Use of mixed Li/K metal TMP amide (LiNK chemistry) for the synthesis of [2.2]metacyclophanes
- Marco Blangetti,
- Patricia Fleming and
- Donal F. O'Shea
Beilstein J. Org. Chem. 2011, 7, 1249–1254, doi:10.3762/bjoc.7.145
- 4a and 4e, giving purified 4-methyl-2-(3-methylphenethyl)benzoic acid (6f) (Table 1, entry 6). This product is the result of oxidative hetero coupling of benzylic metalated xylene and 2-(methyl-metalated)-4-methylbenzoate. To more clearly illustrate a site selective metalation of 4e for the methyl
Graphical Abstract
Scheme 1: Selective benzylic metalation with LiNK conditions. DG = directing group.
Scheme 2: Iterative LiNK/oxidative coupling synthesis of [2.2]metacyclophanes.
Figure 1: Xylene substrates.
Figure 2: Metalation selectivity for 4e (arrows indicate potential metalation sites). 2H NMR spectrum in CH2Cl...
Figure 3: Di-metalation selectivity for 6f. 2H NMR spectrum in CH2Cl2. *CD2Cl2.
Figure 4: X-Ray structure of 8c with thermal ellipsoids drawn at 50% probability level.
A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction
- Christian Eidamshaus,
- Roopender Kumar,
- Mrinal K. Bera and
- Hans-Ulrich Reissig
Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108
- -protected lactic acid, the corresponding ketoenamides 61 and 62 were isolated in 58% yield. Reaction of lithiated methoxyallene with O-TBS-protected lactic nitrile and benzoic acid furnished 64 in high yield. Heterocyclic moieties were also well tolerated as demonstrated by the efficient reaction of 2
- and (S)-TBS-lactic nitrile (200 mg, 1.14 mmol) in anhydrous diethyl ether (5 mL) was added to the mixture. After stirring for 4 h, a solution of benzoic acid (0.84 g, 6.88 mmol) in anhydrous DMF (10 mL) was added. The mixture was stirred overnight and slowly allowed to reach r.t. The reaction was
Graphical Abstract
Scheme 1: Preparation of β-ketoenamides and subsequent cyclocondensation to 4-hydroxypyridines. a) Et2O, −40 ...
Scheme 2: Mechanistic rational for the formation of β-ketoenamides 16.
Scheme 3: Reaction of proline derivative 45 and formation of β-ketoenamide 47 and enolester 48.
Figure 1: 1H NMR spectra of 49 and the mixture of diastereoisomers 49 and 49’.
Scheme 4: Synthesis of pyrid-4-yl nonaflate 52.
Scheme 5: O-Methylation of pyridine derivatives 22 and 30 followed by desilylation.
Scheme 6: Formation of 5-alkoxypyrimidines from β-alkoxy-β-ketoenamides.
Isotopic labelling studies for a gold-catalysed skeletal rearrangement of alkynyl aziridines
- Paul W. Davies,
- Nicolas Martin and
- Neil Spencer
Beilstein J. Org. Chem. 2011, 7, 839–846, doi:10.3762/bjoc.7.96
- proposed mechanism does not account for the formation of 2,4-disubstituted pyrrole without deuterium incorporation at the C-5 position. More information on whether a 1,2-aryl shift occurs was therefore sought using a non-labile 13C label at the aziridine carbon. 13C labelling studies 13C-Enriched benzoic
- acid was converted into imine 10 and subsequently coupled with 7 to give the aziridine 11, in four steps, as a 1:5 13C:12C mixture (Scheme 6). Two further 13C-enriched alkynyl aziridines, 14 and 15, with different substituents on the alkyne, were later prepared using the sulfonium salts 12 and 13. On
Graphical Abstract
Scheme 1: Gold-catalysed cycloisomerisations of aryl–alkynyl aziridine to pyrroles.
Scheme 2: Working mechanism to rationalise the formation of two regiosomeric pyrroles in the gold catalysed c...
Scheme 3: Bond fissions featured in the proposed mechanistic hypothesis and the initial mechanism probe.
Scheme 4: Preparation of D-labelled alkynyl aziridine 4. DMP = Dess–Martin periodinane.
Scheme 5: Reaction of deuterated alkynyl aziridine 4 in the skeletal rearrangement reaction.
Scheme 6: Preparation of 13C-enriched alkynyl aziridines.
Scheme 7: Cycloisomerisation of 11 in the skeletal rearrangement reaction.
Scheme 8: Cycloisomerisation of 11 to give 2,5-disubstituted pyrrole.
Scheme 9: Cycloisomerisation of 14 in the skeletal rearrangement reaction.
Scheme 10: Cycloisomerisation of 15 in the skeletal rearrangement reaction.
Scheme 11: Revised mechanism for the formation of 2,4-isomers by skeletal rearrangement.
Scheme 12: Synthesis of alkynyl aziridines 30 and 31.
Scheme 13: Electronic effects on the outcome of the skeletal rearrangement processes.
Scheme 14: Mechanistic rationale for the deuterium labelling study using Ph3PAuCl/AgOTf.
Continuous flow hydrogenation using polysilane-supported palladium/alumina hybrid catalysts
- Hidekazu Oyamada,
- Takeshi Naito and
- Shū Kobayashi
Beilstein J. Org. Chem. 2011, 7, 735–739, doi:10.3762/bjoc.7.83
- could also be carried out successfully in water (Scheme 4). The reduction of aqueous maleic acid proceeded quantitatively. Dehalogenation of p-chlorobenzoic acid in basic aqueous solution also proceeded smoothly and benzoic acid was obtained after acid treatment. In the case of p-chlorophenol, the
Graphical Abstract
Figure 1: Schematic diagram of the continuous flow reactor (left) and the column top (right).
Scheme 1: Hydrogenation of ethyl cinnamate.
Scheme 2: Hydrogenation of trans-stilbene and trans-chalcone.
Scheme 3: Hydrogenation of nitrobenzene and deprotection of the Cbz group.
Scheme 4: Hydrogenation in water.
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
- of solvents and the influence of additives was undertaken [40]. It was identified that the use of a specific 23 mol % of benzoic acid significantly increased the cis/trans ratio from a base level of 55:45 to 92:8 (16 h reaction time at ambient temperature) in an overall yield of 86%. It was also
Graphical Abstract
Figure 1: Structures of atorvastatin and other commercial statins.
Figure 2: Structure of compactin.
Scheme 1: Synthesis of pentasubstituted pyrroles.
Scheme 2: [3 + 2] Cycloaddition to prepare 5-isopropylpyrroles.
Scheme 3: Regiospecific [3 + 2] cycloaddition to prepare the pyrrole scaffold.
Scheme 4: Formation of the pyrrole core of atorvastatin via [3 + 2] cycloaddition.
Scheme 5: Formation of pyrrole 33 via the Paal–Knorr reaction.
Scheme 6: Convergent synthesis towards atorvastatin.
Figure 3: Binding pocket of sunitinib in the TRK KIT.
Scheme 7: Synthesis of sunitinib.
Scheme 8: Alternative synthesis of sunitinib.
Scheme 9: Key steps in the syntheses of sumatriptan and zolmitriptan.
Scheme 10: Introduction of the N,N-dimethylaminoethyl side chain.
Scheme 11: Japp–Klingemann reaction in the synthesis of sumatriptan.
Scheme 12: Synthesis of the intermediate sulfonyl chlorides 62 and 63.
Scheme 13: Alternative introduction of the sulfonamide.
Scheme 14: Negishi-type coupling to benzylic sulfonamides.
Scheme 15: Heck reaction used to introduce the sulfonamide side chain of naratriptan.
Scheme 16: Synthesis of the oxazolinone appendage of zolmitriptan.
Scheme 17: Grandberg indole synthesis used in the preparation of rizatriptan.
Scheme 18: Improved synthesis of rizatriptan.
Scheme 19: Larock-type synthesis of rizatriptan.
Scheme 20: Synthesis of eletriptan.
Scheme 21: Heck coupling for the indole system in eletriptan.
Scheme 22: Attempted Fischer indole synthesis of elatriptan.
Scheme 23: Successful Fischer indole synthesis for eletriptan.
Scheme 24: Mechanistic rationale for the Bischler–Möhlau reaction.
Scheme 25: Bischler-type indole synthesis used in the fluvastatin sodium synthesis.
Scheme 26: Palladium-mediated synthesis of ondansetron.
Scheme 27: Fischer indole synthesis of ondansetron.
Scheme 28: Optimised Pictet–Spengler reaction towards tadalafil.
Figure 4: Structures of carvedilol 136 and propranolol 137.
Scheme 29: Synthesis of the carbazole core of carvedilol.
Scheme 30: Alternative syntheses of 4-hydroxy-9H-carbazole.
Scheme 31: Convergent synthesis of etodolac.
Scheme 32: Alternative synthesis of etodolac.
Figure 5: Structures of imidazole-containing drugs.
Scheme 33: Synthesis of functionalised imidazoles towards losartan.
Scheme 34: Direct synthesis of the chlorinated imidazole in losartan.
Scheme 35: Synthesis of trisubstituted imidazoles.
Scheme 36: Preparation of the imidazole ring in olmesartan.
Scheme 37: Synthesis of ondansetron.
Scheme 38: Alternative route to ondansetron and its analogues.
Scheme 39: Proton pump inhibitors and synthesis of esomeprazole.
Scheme 40: Synthesis of benzimidazole core pantoprazole.
Figure 6: Structure of rabeprazole 194.
Scheme 41: Synthesis of candesartan.
Scheme 42: Alternative access to the candesartan key intermediate 216.
Scheme 43: .Medicinal chemistry route to telmisartan.
Scheme 44: Improved synthesis of telmisartan.
Scheme 45: Synthesis of zolpidem.
Scheme 46: Copper-catalysed 3-component coupling towards zolpidem.
Figure 7: Structure of celecoxib.
Scheme 47: Preparation of celecoxib.
Scheme 48: Alternative synthesis of celecoxib.
Scheme 49: Regioselective access to celecoxib.
Scheme 50: Synthesis of pazopanib.
Scheme 51: Syntheses of anastrozole, rizatriptan and letrozole.
Scheme 52: Regioselective synthesis of anastrozole.
Scheme 53: Triazine-mediated triazole formation towards anastrozole.
Scheme 54: Alternative routes to 1,2,4-triazoles.
Scheme 55: Initial synthetic route to sitagliptin.
Figure 8: Binding of sitagliptin within DPP-IV.
Scheme 56: The process route to sitagliptin key intermediate 280.
Scheme 57: Synthesis of maraviroc.
Scheme 58: Synthesis of alprazolam.
Scheme 59: The use of N-nitrosoamidine derivatives in the preparation of fused benzodiazepines.
Figure 9: Structures of itraconazole, ravuconazole and voriconazole.
Scheme 60: Synthesis of itraconazole.
Scheme 61: Synthesis of rufinamide.
Scheme 62: Representative tetrazole formation in valsartan.
Figure 10: Structure of tetrazole containing olmesartan, candesartan and irbesartan.
Scheme 63: Early stage introduction of the tetrazole in losartan.
Scheme 64: Synthesis of cilostazol.
Figure 11: Structure of cefdinir.
Scheme 65: Semi-synthesis of cefdinir.
Scheme 66: Thiazole syntheses towards ritonavir.
Scheme 67: Synthesis towards pramipexole.
Scheme 68: Alternative route to pramipexole.
Scheme 69: Synthesis of famotidine.
Scheme 70: Efficient synthesis of the hyperuricemic febuxostat.
Scheme 71: Synthesis of ziprasidone.
Figure 12: Structure of mometasone.
Scheme 72: Industrial access to 2-furoic acid present in mometasone.
Scheme 73: Synthesis of ranitidine from furfuryl alcohol.
Scheme 74: Synthesis of nitrofurantoin.
Scheme 75: Synthesis of benzofuran.
Scheme 76: Synthesis of amiodarone.
Scheme 77: Synthesis of raloxifene.
Scheme 78: Alternative access to the benzo[b]thiophene core of raloxifene.
Scheme 79: Gewald reaction in the synthesis of olanzapine.
Scheme 80: Alternative synthesis of olanzapine.
Figure 13: Access to simple thiophene-containing drugs.
Scheme 81: Synthesis of clopidogrel.
Scheme 82: Pictet–Spengler reaction in the preparation of tetrahydrothieno[3,2-c]pyridine (422).
Scheme 83: Alternative synthesis of key intermediate 422.
Figure 14: Co-crystal structures of timolol (left) and carazolol (right) in the β-adrenergic receptor.
Scheme 84: Synthesis of timolol.
Scheme 85: Synthesis of tizanidine 440.
Scheme 86: Synthesis of leflunomide.
Scheme 87: Synthesis of sulfamethoxazole.
Scheme 88: Synthesis of risperidone.
Figure 15: Relative abundance of selected transformations.
Figure 16: The abundance of heterocycles within top 200 drugs (5-membered rings).
Regioselective ester cleavage during the preparation of bisphosphonate methacrylate monomers
- Kamel Chougrani,
- Gilles Niel,
- Bernard Boutevin and
- Ghislain David
Beilstein J. Org. Chem. 2011, 7, 364–368, doi:10.3762/bjoc.7.46
- 4c and 5c. The two aromatic targets 6c and 7c were prepared from p-(aminomethyl)benzoic acid (17) which was converted into the bisphosphonate 18 in 92% yield under Kabachnik–Fields conditions. This common intermediate 18 was either reduced by diborane to the alcohol 19 followed by esterification by
Graphical Abstract
Scheme 1: Novel bisphosphonate methacrylate monomers.
Scheme 2: Synthesis of novel bisphosphonate methacrylate monomers 1c–7c, by use of the following reagents and...
Scheme 3: Schematic procedure for phosphonate methacrylate monomer deprotection.
Approaches towards the synthesis of 5-aminopyrazoles
- Ranjana Aggarwal,
- Vinod Kumar,
- Rajiv Kumar and
- Shiv P. Singh
Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25
- -ketonitriles 16 with a substituted hydrazine in the presence of Et3N in ethanol under reflux conditions. The intermediate 16 was obtained from β-ketoester 15 on treatment with TFA, which in turn was synthesized by condensing 4-(phenylsulfonamidomethyl)cyclohexane carboxylic acid or benzoic acid 13
Graphical Abstract
Figure 1: Pharmacologically active 5-aminopyrazoles.
Scheme 1: General equation for the condensation of β-ketonitriles with hydrazines.
Scheme 2: Reaction of hydrazinoheterocycles with α-phenyl-β-cyanoketones (4).
Scheme 3: Condensation of cyanoacetaldehyde (7) with hydrazines.
Scheme 4: Synthesis of 5-aminopyrazoles and their sulfonamide derivatives.
Scheme 5: Synthesis of 5-aminopyrazoles, containing a cyclohexylmethyl- or phenylmethyl- sulfonamido group at...
Scheme 6: Regioselective synthesis of 3-amino-2-alkyl (or aryl) thieno[3,4-c]pyrazoles 19.
Scheme 7: Solid supported synthesis of 5-aminopyrazoles.
Scheme 8: Synthesis of 5-aminopyrazoles from resin supported enamine nitrile 25 as the starting material.
Scheme 9: Two-step “catch and release” solid-phase synthesis of 3,4,5-trisubstituted pyrazoles.
Scheme 10: Synthesis of pyrazolo[5,1-d][1,2,3,5]tetrazine-4(3H)-ones.
Scheme 11: Synthesis of the 5,5-ring system, imidazo[1,2-b]pyrazol-2-ones.
Scheme 12: Synthesis of 5-amino-3-(pyrrol-2-yl)pyrazole-4-carbonitrile.
Scheme 13: Synthesis of N-(1,3-diaryl-1H-pyrazol-5-yl)benzamide.
Scheme 14: Synthesis of 3,7-bis(arylazo)-6-methyl-2-phenyl-1H-imidazo[1,2-b]pyrazoles.
Scheme 15: Synthesis of 3,5-diaminopyrazole.
Scheme 16: Synthesis of 5-amino-4-cyanopyrazole and 5-amino-3-hydrazinopyrazole.
Scheme 17: Synthesis of 3,5-diaminopyrazoles with substituted malononitriles.
Scheme 18: Synthesis of 3,5-diamino-4-oximinopyrazole.
Scheme 19: Synthesis of 4-arylazo-3,5-diaminopyrazoles.
Scheme 20: Synthesis of 3- or 5-amino-4-cyanopyrazoles.
Scheme 21: Synthesis of triazenopyrazoles.
Scheme 22: Synthesis of 5(3)-aminopyrazoles.
Scheme 23: Synthesis of 3-substituted 5-amino-4-cyanopyrazoles.
Scheme 24: Synthesis of 2-{[(1-acetyl-4-cyano-1H-pyrazol-5-yl)amino]methylene}malononitrile.
Scheme 25: Synthesis of 5-aminopyrazole carbodithioates and 5-amino-3-arylamino-1-phenylpyrazole-4-carboxamide...
Scheme 26: Synthesis of 5-amino-4-cyanopyrazoles.
Scheme 27: Synthesis of thiazolylpyrazoles.
Scheme 28: Synthesis of 5-amino-1-heteroaryl-3-methyl/aryl-4-cyanopyrazoles.
Scheme 29: Synthesis of 5-amino-3-methylpyrazole-4-carboxamide.
Scheme 30: Synthesis of 4-acylamino-3(5)-amino-5(3)-arylsulfanylpyrazoles.
Scheme 31: Synthesis of 5-amino-1-aryl-4-diethoxyphosphoryl-3-halomethylpyrazoles.
Scheme 32: Synthesis of substituted 5-amino-3-trifluoromethylpyrazoles 114 and 118.
Scheme 33: Solid-support synthesis of 5-N-alkylamino and 5-N-arylaminopyrazoles.
Scheme 34: Synthesis of 5-amino-1-cyanoacetyl-3-phenyl-1H-pyrazole.
Scheme 35: Synthesis of 3-substituted 5-amino-1-aryl-4-(benzothiazol-2-yl)pyrazoles.
Scheme 36: Synthesis of 5-amino-4-carbethoxy-3-methyl-1-(4-sulfamoylphenyl)pyrazole.
Scheme 37: Synthesis of inhibitors of hsp27-phosphorylation and TNFa-release.
Scheme 38: Synthesis of the diglycylpyrazole 142.
Scheme 39: Synthesis of 5-amino-1-aryl-4-benzoylpyrazole derivatives.
Scheme 40: Synthesis of 4-benzoyl-3,5-diamino-1-(2-cyanoethyl)pyrazole.
Scheme 41: Synthesis of the 5-aminopyrazole derivative 150.
Scheme 42: Synthesis of 3,5-diaminopyrazoles 153.
Scheme 43: Synthesis of 5-aminopyrazoles derivatives 155 via lithiated intermediates.
Scheme 44: Synthesis of 5-amino-4-(1,2,4-oxadiazol-5-yl)-pyrazoles 157.
Scheme 45: Synthesis of a 5-aminopyrazole with anticonvulsant activity.
Scheme 46: Synthesis of tetrasubstituted 5-aminopyrazole derivatives.
Scheme 47: Synthesis of substituted 5-aminopyrazoles from hydrazonoyl halides.
Scheme 48: Synthesis of 3-amino-5-phenylpyrazoles from isothiazoles.
Scheme 49: Synthesis of 5-aminopyrazoles via ring transformation.
Novel 2-(ω-phosphonooxy-2-oxaalkyl)acrylate monomers for self-etching self-priming one part adhesive
- Joachim E. Klee and
- Uwe Lehmann
Beilstein J. Org. Chem. 2010, 6, 766–772, doi:10.3762/bjoc.6.95
- -trimethylbenzoyl)phenyl phosphine oxide and 0.0392 g 4-(N,N-dimethylamino)benzoic acid ethyl ester were dissolved in a solvent mixture of 3.5201 g ethanol and 1.7484 g water. Adhesive compositions 4c–i were prepared from 3c–i in the same manner as described above. The following procedure was applied prior to
- conditions. The subtraction of these runs from one another removed the effect of different baselines for the dark and the illumination periods. In the monomers were dissolved 0.3 mol % camphorquinone and 0.35 mol % 4-(N,N-dimethylamino)benzoic acid ethyl ester. Adhesion of an adhesive composition 4
Graphical Abstract
Scheme 1: Synthesis of novel ethyl 2-(ω-phosphonooxy-2-oxaalkyl)acrylates 3.
Figure 1: Adhesion of an adhesive composition 4, comprising of polymerizable acids 3, on enamel and dentin.
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
- and form 1,3-bis(SCF3) benzene [38][39][40] and 4-SCF3-benzoic acid fluoride, respectively [55]. The use of hydrogen fluoride has some advantages. Due to its low boiling point (+19.4 °C) and good solubility in water, excess HF is easily removed from the reaction mixture. Unlike HF, reactions with SbF3
Graphical Abstract
Figure 1: Examples of industrial fluorine-containing bio-active molecules.
Figure 2: CF3(S)- and CF3(O)-containing pharmacologically active compounds.
Figure 3: Hypotensive candidates with SRF and SO2RF groups – analogues of Losartan and Nifedipin.
Figure 4: The variety of the pharmacological activity of RFS-substituted compounds.
Figure 5: Recent examples of compounds containing RFS(O)n-groups [12-18].
Scheme 1: Fluorination of ArSCCl3 to corresponding ArSCF3 derivatives. For references see: a[38-43]; b[41,42]; c[43]; d[44]; e[38-43,45-47]; f[38-43,48,49]; g...
Scheme 2: Preparation of aryl pentafluoroethyl sulfides.
Scheme 3: Mild fluorination of the aryl SCF2Br derivatives.
Scheme 4: HF fluorinations of aryl α,α,β-trichloroisobutyl sulfide at various conditions.
Scheme 5: Monofluorination of α,α-dichloromethylene group.
Scheme 6: Electrophilic substitution of phenols with CF3SCl [69].
Scheme 7: Introduction of SCF3 groups into activated phenols [71-74].
Scheme 8: Preparation of tetrakis(SCF3)-4-methoxyphenol [72].
Scheme 9: The interactions of resorcinol and phloroglucinol derivatives with RFSCl.
Scheme 10: Reactions of anilines with CF3SCl.
Scheme 11: Trifluoromethylsulfanylation of anilines with electron-donating groups in the meta position [74].
Scheme 12: Reaction of benzene with CF3SCl/CF3SO3H [77].
Scheme 13: Reactions of trifluoromethyl sulfenyl chloride with aryl magnesium and -mercury substrates.
Scheme 14: Reactions of pyrroles with CF3SCl.
Scheme 15: Trifluoromethylsulfanylation of indole and indolizines.
Scheme 16: Reactions of N-methylpyrrole with CF3SCl [80,82].
Scheme 17: Reactions of furan, thiophene and selenophene with CF3SCl.
Scheme 18: Trifluoromethylsulfanylation of imidazole and thiazole derivatives [83].
Scheme 19: Trifluoromethylsulfanylation of pyridine requires initial hydride reduction.
Scheme 20: Introduction of additional RFS-groups into heterocyclic compounds in the presence of CF3SO3H.
Scheme 21: Introduction of additional RFS-groups into pyrroles [82,87].
Scheme 22: By-products in reactions of pyrroles with CF3SCl [82].
Scheme 23: Reaction of aromatic iodides with CuSCF3 [93,95].
Scheme 24: Reaction of aromatic iodides with RFZCu (Z = S, Se), RF = CF3, C6F5 [93,95,96].
Scheme 25: Side reactions during trifluoromethylsulfanylation of aromatic iodides with CF3SCu [98].
Scheme 26: Reactions with in situ generated CuSCF3.
Scheme 27: Perfluoroalkylthiolation of aryl iodides with bulky RFSCu [105].
Scheme 28: In situ formation and reaction of RFZCu with aryl iodides.
Figure 6: Examples of compounds obtained using in situ generated RFZCu methodology [94].
Scheme 29: Introduction of SCF3 group into aromatics via difluorocarbene.
Scheme 30: Tetrakis(dimethylamino)ethylene dication trifluoromethyl thiolate as a stable reagent for substitut...
Scheme 31: The use of CF2=S/CsF or (CF3S)2C=S/CsF for the introduction of CF3S groups into fluorinated heteroc...
Scheme 32: One-pot synthesis of ArSCF3 from ArX, CCl2=S and KF.
Scheme 33: Reaction of aromatics with CF3S− Kat+ [115].
Scheme 34: Reactions of activated aromatic chlorides with AgSCF3/KI.
Scheme 35: Comparative CuSCF3/KI and Hg(SCF3)2/KI reactions.
Scheme 36: Me3SnTeCF3 – a reagent for the introduction of the TeCF3 group.
Scheme 37: Sandmeyer reactions with CuSCF3.
Scheme 38: Reactions of perfluoroalkyl iodides with alkali and organolithium reagents.
Scheme 39: Perfluoroalkylation with preliminary breaking of the disulfide bond.
Scheme 40: Preparation of RFS-substituted anilines from dinitrodiphenyl disulfides.
Scheme 41: Photochemical trifluoromethylation of 2,4,6-trimercaptochlorobenzene [163].
Scheme 42: Putative process for the formation of B, C and D.
Scheme 43: Trifluoromethylation of 2-mercapto-4-hydroxy-6-trifluoromethylyrimidine [145].
Scheme 44: Deactivation of 2-mercapto-4-hydroxypyrimidines S-centered radicals.
Scheme 45: Perfluoroalkylation of thiolates with CF3Br under UV irradiation.
Scheme 46: Catalytic effect of methylviologen for RF• generation.
Scheme 47: SO2−• catalyzed trifluoromethylation.
Scheme 48: Electrochemical reduction of CF3Br in the presence of SO2 [199,200].
Scheme 49: Participation of SO2 in the oxidation of ArSCF3−•.
Scheme 50: Electron transfer cascade involving SO2 and MV.
Scheme 51: Four stages of the SRN1 mechanism for thiol perfluoroalkylation.
Scheme 52: A double role of MV in the catalysis of RFI reactions with aryl thiols.
Scheme 53: Photochemical reaction of pentafluoroiodobenzene with trifluoromethyl disulfide.
Scheme 54: N- Trifluoromethyl-N-nitrosobenzene sulfonamide – a source of CF3• radicals [212,213].
Scheme 55: Radical trifluoromethylation of organic disulfides with ArSO2N=NCF3.
Scheme 56: Barton’s S-perfluoroalkylation reactions [216].
Scheme 57: Decarboxylation of thiohydroxamic esters in the presence of C6F13I.
Scheme 58: Reactions of thioesters of trifluoroacetic and trifluoromethanesulfonic acids in the presence of ar...
Scheme 59: Perfluoroalkylation of polychloropyridine thiols with xenon perfluorocarboxylates or XeF2 [222,223].
Scheme 60: Interaction of Xe(OCORF)2 with nitroaryl disulfide [227].
Scheme 61: Bi(CF3)3/Cu(OCOCH3)2 trifluoromethylation of thiophenolate [230].
Scheme 62: Reaction of fluorinated carbanions with aryl sulfenyl chlorides.
Scheme 63: Reaction of methyl perfluoromethacrylate with PhSCl in the presence of fluoride.
Scheme 64: Reactions of ArSCN with potassium and magnesium perfluorocarbanions [237].
Scheme 65: Reactions of RFI with TDAE and organic disulfides [239,240].
Scheme 66: Decarboxylation of perfluorocarboxylates in the presence of disulfides [245].
Scheme 67: Organization of a stable form of “CF3−” anion in the DMF.
Scheme 68: Silylated amines in the presence of fluoride can deprotonate fluoroform for reaction with disulfide...
Figure 7: Other examples of aminomethanols [264].
Scheme 69: Trifluoromethylation of diphenyl disulfide with PhSO2CF3/t-BuOK.
Scheme 70: Amides of trifluoromethane sulfinic acid are sources of CF3− anion.
Scheme 71: Trifluoromethylation of various thiols using “hyper-valent” iodine (III) reagent [279].
Scheme 72: Trifluoromethylation of p-nitrothiophenolate with diaryl CF3 sulfonium salts [280].
Scheme 73: Trifluoromethyl transfer from dibenzo (CF3)S-, (CF3)Se- and (CF3)Te-phenium salts to thiolates [283].
Scheme 74: Multi-stage paths for synthesis of dibenzo-CF3-thiophenium salts [61].
Pd-catalyzed decarboxylative Heck vinylation of 2-nitrobenzoates in the presence of CuF2
- Lukas J. Gooßen,
- Bettina Zimmermann and
- Thomas Knauber
Beilstein J. Org. Chem. 2010, 6, No. 43, doi:10.3762/bjoc.6.43
- yield 2-nitro-stilbene (3aa) as a model reaction, and investigated the catalytic activity of various combinations of palladium precursors, additives and oxidants (Table 1). The choice of an electron-deficient benzoic acid was motivated by our intention to overcome substrate limitations observed in Myers
Graphical Abstract
Scheme 1: Proposed mechanism for the decarboxylative Heck reaction.
Molecular recognition of organic ammonium ions in solution using synthetic receptors
- Andreas Späth and
- Burkhard König
Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32
Graphical Abstract
Figure 1: Biologically important amines and quaternary ammonium salts: histamine (1), dopamine (2) and acetyl...
Figure 2: Crown ether 18-crown-6.
Figure 3: Conformations of 18-crown-6 (4) in solvents of different polarity.
Figure 4: Binding topologies of the ammonium ion depending on the crown ring size.
Figure 5: A “pseudorotaxane” structure consisting of 24-crown-8 and a secondary ammonium ion (5); R = Ph.
Figure 6: Typical examples of azacrown ethers, cryptands and related aza macrocycles.
Figure 7: Binding of ammonium to azacrown ethers and cryptands [111-113].
Figure 8: A 19-crown-6-ether with decalino blocking groups (11) and a thiazole-dibenzo-18-crown-6-ether (12).
Figure 9: 1,3-Bis(6-oxopyridazin-1-yl)propane derivatives 13 and 14 by Campayo et al.
Figure 10: Fluorescent azacrown-PET-sensors based on coumarin.
Figure 11: Two different pyridino-cryptands (17 and 18) compared to a pyridino-crown (19); chiral ammonium ion...
Figure 12: Pyridino-18-crown-6 ligand (21), a similar acridino-18-crown-6 ligand (22) and a structurally relat...
Figure 13: Ciral pyridine-azacrown ether receptors 24.
Figure 14: Chiral 15-crown-5 receptors 26 and an analogue 18-crown-6 ligand 27 derived from amino alcohols.
Figure 15: C2-symmetric chiral 18-crown-6 amino alcohol derivatives 28 and related macrocycles.
Figure 16: Macrocycles with diamide-diester groups (30).
Figure 17: C2-symmetric chiral aza-18-crown-6 ethers (31) with phenethylamine residues.
Figure 18: Chiral C-pivot p-methoxy-phenoxy-lariat ethers.
Figure 19: Chiral lariat crown ether 34.
Figure 20: Sucrose-based chiral crown ether receptors 36.
Figure 21: Permethylated fructooligosaccharide 37 showing induced-fit chiral recognition.
Figure 22: Biphenanthryl-18-crown-6 derivative 38.
Figure 23: Chiral lariat crown ethers derived from binol by Fuji et al.
Figure 24: Chiral phenolic crown ether 41 with “aryl chiral barriers” and guest amines.
Figure 25: Chiral bis-crown receptor 43 with a meso-ternaphthalene backbone.
Figure 26: Chromogenic pH-dependent bis-crown chemosensor 44 for diamines.
Figure 27: Triamine guests for binding to receptor 44.
Figure 28: Chiral bis-crown phenolphthalein chemosensors 46.
Figure 29: Crown ether amino acid 47.
Figure 30: Luminescent receptor 48 for bis-alkylammonium guests.
Figure 31: Luminescent CEAA (49a), a bis-CEAA receptor for amino acids (49b) and the structure of lysine bindi...
Figure 32: Luminescent CEAA tripeptide for binding small peptides.
Figure 33: Bis crown ether 51a self assembles co-operatively with C60-ammonium ion 51b.
Figure 34: Triptycene-based macrotricyclic dibenzo-[24]-crown-8 ether host 52 and guests.
Figure 35: Copper imido diacetic acid azacrown receptor 53a and the suggested His-Lys binding motif; a copper ...
Figure 36: Urea (54) and thiourea (55) benzo crown receptor for transport and extraction of amino acids.
Figure 37: Crown pyryliums ion receptors 56 for amino acids.
Figure 38: Ditopic sulfonamide bridged crown ether receptor 57.
Figure 39: Luminescent peptide receptor 58.
Figure 40: Luminescent receptor 59 for the detection of D-glucosamine hydrochloride in water/ethanol and lumin...
Figure 41: Guanidinium azacrown receptor 61 for simple amino acids and ditopic receptor 62 with crown ether an...
Figure 42: Chiral bicyclic guanidinium azacrown receptor 63 and similar receptor 64 for the enantioselective t...
Figure 43: Receptors for zwitterionic species based on luminescent CEAAs.
Figure 44: 1,10-Azacrown ethers with sugar podand arms and the anticancer agent busulfan.
Figure 45: Benzo-18-crown-6 modified β-cyclodextrin 69 and β-cyclodextrin functionalized with diaza-18-crown-6...
Figure 46: Receptors for colorimetric detection of primary and secondary ammonium ions.
Figure 47: Porphyrine-crown-receptors 72.
Figure 48: Porphyrin-crown ether conjugate 73 and fullerene-ammonium ion guest 74.
Figure 49: Calix[4]arene (75a), homooxocalix[4]arene (75b) and resorcin[4]arene (75c) compared (R = H, alkyl c...
Figure 50: Calix[4]arene and ammonium ion guest (R = H, alkyl, OAcyl etc.), possible binding sites; A: co-ordi...
Figure 51: Typical guests for studies with calixarenes and related molecules.
Figure 52: Lower rim modified p-tert-butylcalix[5]arenes 82.
Figure 53: The first example of a water soluble calixarene.
Figure 54: Sulfonated water soluble calix[n]arenes that bind ammonium ions.
Figure 55: Displacement assay for acetylcholine (3) with a sulfonato-calix[6]arene (84b).
Figure 56: Amino acid inclusion in p-sulfonatocalix[4]arene (84a).
Figure 57: Calixarene receptor family 86 with upper and lower rim functionalization.
Figure 58: Calix[6]arenes 87 with one carboxylic acid functionality.
Figure 59: Sulfonated calix[n]arenes with mono-substitution at the lower rim systematically studied on their r...
Figure 60: Cyclotetrachromotropylene host (91) and its binding to lysine (81c).
Figure 61: Calixarenes 92 and 93 with phosphonic acids groups.
Figure 62: Calix[4]arene tetraphosphonic acid (94a) and a double bridged analogue (94b).
Figure 63: Calix[4]arene tetraphosphonic acid ester (92c) for surface recognition experiments.
Figure 64: Calixarene receptors 95 with α-aminophosphonate groups.
Figure 65: A bridged homocalix[3]arene 95 and a distally bridged homocalix[4]crown 96.
Figure 66: Homocalix[3]arene ammonium ion receptor 97a and the Reichardt’s dye (97b) for colorimetric assays.
Figure 67: Chromogenic diazo-bridged calix[4]arene 98.
Figure 68: Calixarene receptor 99 by Huang et al.
Figure 69: Calixarenes 100 reported by Parisi et al.
Figure 70: Guest molecules for inclusion in calixarenes 100: DAP × 2 HCl (101a), APA (101b) and Lys-OMe × 2 HC...
Figure 71: Different N-linked peptido-calixarenes open and with glycol chain bridges.
Figure 72: (S)-1,1′-Bi-2-naphthol calixarene derivative 104 published by Kubo et al.
Figure 73: A chiral ammonium-ion receptor 105 based on the calix[4]arene skeleton.
Figure 74: R-/S-phenylalaninol functionalized calix[6]arenes 106a and 106b.
Figure 75: Capped homocalix[3]arene ammonium ion receptor 107.
Figure 76: Two C3 symmetric capped calix[6]arenes 108 and 109.
Figure 77: Phosphorous-containing rigidified calix[6]arene 110.
Figure 78: Calix[6]azacryptand 111.
Figure 79: Further substituted calix[6]azacryptands 112.
Figure 80: Resorcin[4]arene (75c) and the cavitands (113).
Figure 81: Tetrasulfonatomethylcalix[4]resorcinarene (114).
Figure 82: Resorcin[4]arenes (115a/b) and pyrogallo[4]arenes (115c, 116).
Figure 83: Displacement assay for acetylcholine (3) with tetracyanoresorcin[4]arene (117).
Figure 84: Tetramethoxy resorcinarene mono-crown-5 (118).
Figure 85: Components of a resorcinarene based displacement assay for ammonium ions.
Figure 86: Chiral basket resorcin[4]arenas 121.
Figure 87: Resorcinarenes with deeper cavitand structure (122).
Figure 88: Resorcinarene with partially open deeper cavitand structure (123).
Figure 89: Water-stabilized deep cavitands with partially structure (124, 125).
Figure 90: Charged cavitands 126 for tetralkylammonium ions.
Figure 91: Ditopic calix[4]arene receptor 127 capped with glycol chains.
Figure 92: A calix[5]arene dimer for diammonium salt recognition.
Figure 93: Calixarene parts 92c and 129 for the formation molecular capsules.
Figure 94: Encapsulation of a quaternary ammonium cation by two resorcin[4]arene molecules (NMe4+@[75c]2 × Cl−...
Figure 95: Encapsulation of a quaternary ammonium cation by six resorcin[4]arene molecules (NMe3D+@[130]6 × Cl−...
Figure 96: Structure and schematic of cucurbit[6]uril (CB[6], 131a).
Figure 97: Cyclohexanocucurbit[6]uril (CB′[6], 132) and the guest molecule spermine (133).
Figure 98: α,α,δ,δ-Tetramethylcucurbit[6]uril (134).
Figure 99: Structure of the cucurbituril-phthalhydrazide analogue 135.
Figure 100: Organic cavities for the displacement assay for amine differentiation.
Figure 101: Displacement assay methodology for diammonium- and related guests involving cucurbiturils and some ...
Figure 102: Nor-seco-Cucurbituril (±)-bis-ns-CB[6] (140) and guest molecules.
Figure 103: The cucurbit[6]uril based complexes 141 for chiral discrimination.
Figure 104: Cucurbit[7]uril (131c) and its ferrocene guests (142) opposed.
Figure 105: Cucurbit[7]uril (131c) guest inclusion and representative guests.
Figure 106: Cucurbit[7]uril (131c) binding to succinylcholine (145) and different bis-ammonium and bis-phosphon...
Figure 107: Paraquat-cucurbit[8]uril complex 149.
Figure 108: Gluconuril-based ammonium receptors 150.
Figure 109: Examples of clefts (151a), tweezers (151b, 151c, 151d) and clips (151e).
Figure 110: Kemp’s triacid (152a), on example of Rebek’s receptors (152b) and guests.
Figure 111: Amino acid receptor (154) by Rebek et al.
Figure 112: Hexagonal lattice designed hosts by Bell et al.
Figure 113: Bell’s amidinium receptor (156) and the amidinium ion (157).
Figure 114: Aromatic phosphonic acids.
Figure 115: Xylene phosphonates 159 and 160a/b for recognition of amines and amino alcohols.
Figure 116: Bisphosphonate recognition motif 161 for a colorimetric assay with alizarin complexone (163) for ca...
Figure 117: Bisphosphonate/phosphate clip 164 and bisphosphonate cleft 165.
Figure 118: N-Methylpyrazine 166a, N-methylnicotinamide iodide (166b) and NAD+ (166c).
Figure 119: Bisphosphate cavitands.
Figure 120: Bisphosphonate 167 of Schrader and Finocchiaro.
Figure 121: Tweezer 168 for noradrenaline (80b).
Figure 122: Different tripods and heparin (170).
Figure 123: Squaramide based receptors 172.
Figure 124: Cage like NH4+ receptor 173 of Kim et al.
Figure 125: Ammonium receptors 174 of Chin et al.
Figure 126: 2-Oxazolin-based ammonium receptors 175a–d and 176 by Ahn et al.
Figure 127: Racemic guest molecules 177.
Figure 128: Tripods based on a imidazole containing macrocycle (178) and the guest molecules employed in the st...
Figure 129: Ammonium ion receptor 180.
Figure 130: Tetraoxa[3.3.3.3]paracyclophanes 181 and a cyclophanic tetraester (182).
Figure 131: Peptidic bridged paraquat-cyclophane.
Figure 132: Shape-selective noradrenaline host.
Figure 133: Receptor 185 for binding of noradrenaline on surface layers from Schrader et al.
Figure 134: Tetraphosphonate receptor for binding of noradrenaline.
Figure 135: Tetraphosphonate 187 of Schrader and Finocchiaro.
Figure 136: Zinc-Porphyrin ammonium-ion receptors 188 and 189 of Mizutani et al.
Figure 137: Zinc porphyrin receptor 190.
Figure 138: Zinc porphyrin receptors 191 capable of amino acid binding.
Figure 139: Zinc-porphyrins with amino acid side chains for stereoinduction.
Figure 140: Bis-zinc-bis-porphyrin based on Tröger’s base 193.
Figure 141: BINAP-zinc-prophyrin derivative 194 and it’s guests.
Figure 142: Bisaryl-linked-zinc-porphyrin receptors.
Figure 143: Bis-zinc-porphyrin 199 for diamine recognition and guests.
Figure 144: Bis-zinc-porphyrin crown ether 201.
Figure 145: Bis-zinc-porphyrin 202 for stereodiscrimination (L = large substituent; S = small substituent).
Figure 146: Bis-zinc-porphyrin[3]rotaxane and its copper complex and guests.
Figure 147: Dien-bipyridyl ligand 206 for co-ordination of two metal atoms.
Figure 148: The ligand and corresponding tetradentate co-complex 207 serving as enantioselective receptor for a...
Figure 149: Bis(oxazoline)–copper(II) complex 208 for the recognition of amino acids in aqueous solution.
Figure 150: Zinc-salen-complexes 209 for the recognition tertiary amines.
Figure 151: Bis(oxazoline)–copper(II) 211 for the recognition of amino acids in aqueous solution.
Figure 152: Zn(II)-complex of a C2 terpyridine crown ether.
Figure 153: Displacement assay and receptor for aspartate over glutamate.
Figure 154: Chiral complex 214 for a colorimetric displacement assay for amino acids.
Figure 155: Metal complex receptor 215 with tripeptide side arms.
Figure 156: A sandwich complex 216 and its displaceable dye 217.
Figure 157: Lanthanide complexes 218–220 for amino acid recognition.
Figure 158: Nonactin (221), valinomycin (222) and vancomycin (223).
Figure 159: Monesin (224a) and a chiral analogue for enantiodiscrimination of ammonium guests (224b).
Figure 160: Chiral podands (226) compared to pentaglyme-dimethylether (225) and 18-crown-6 (4).
Figure 161: Lasalocid A (228).
Figure 162: Lasalocid derivatives (230) of Sessler et al.
Figure 163: The Coporphyrin I tetraanion (231).
Figure 164: Linear and cyclic peptides for ammonium ion recognition.
Figure 165: Cyclic and bicyclic depsipeptides for ammonium ion recognition.
Figure 166: α-Cyclodextrin (136a) and novocaine (236).
Figure 167: Helical diol receptor 237 by Reetz and Sostmann.
Figure 168: Ammonium binding spherand by Cram et al. (238a) and the cyclic[6]metaphenylacetylene 238b in compar...
Figure 169: Receptor for peptide backbone and ammonium binding (239).
Figure 170: Anion sensor principle with 3-hydroxy-2-naphthanilide of Jiang et al.
Figure 171: 7-bromo-3-hydroxy-N-(2-hydroxyphenyl)naphthalene 2-carboxamide (241) and its amine binding.
Figure 172: Naturally occurring catechins with affinity to quaternary ammonium ions.
Figure 173: Spiropyran (244) and merocyanine form (244a) of the amino acid receptors of Fuji et al.
Figure 174: Coumarin aldehyde (245) and its iminium species with amino acid bound (245a) by Glass et al.
Figure 175: Coumarin aldehyde appended with boronic acid.
Figure 176: Quinolone aldehyde dimers by Glass et al.
Figure 177: Chromogenic ammonium ion receptors with trifluoroacetophenone recognition motifs.
Figure 178: Chromogenic ammonium ion receptor with trifluoroacetophenone recognition motif bound on different m...
