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Search for "carboxylic acid amides" in Full Text gives 6 result(s) in Beilstein Journal of Organic Chemistry.
Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles
- Ivan Lyutin,
- Vasilisa Krivovicheva,
- Grigory Kantin and
- Dmitry Dar’in
Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164
- well as a wide range of nucleophiles provides access to a structural diversity of medically relevant 2-oxoazetidine-3-carboxylic acid amides and esters. Keywords: β-lactams; diazotetramic acids; nucleophiles; spirocycles; thermolysis; Wolff rearrangement; Introduction The importance of the β-lactam
Graphical Abstract
Scheme 1: Synthetic routes to 2-oxoazetidine-3-carboxylic acid derivatives.
Scheme 2: Scope of diazotetramic acids 1 thermolysis in the presence of various nucleophiles. PMP = p-methoxy...
Scheme 3: Negative results with several N-, O-, and C-nucleophiles and with diazo reagent 1m.
Scheme 4: Preparation of acids 4 by hydrogenolysis of benzyl esters and examples of acid 4a amidation.
Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations
- Paul Hommes and
- Hans-Ulrich Reissig
Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112
- efficacy. We also examined an alternative approach to β-ketoenamides by the addition of carboxylic acid amides to alkynones. This approach can potentially lead to products that are formally derived from unsymmetrically substituted 1,3-dicarbonyl compounds. The best result was obtained with picolinic acid
Graphical Abstract
Scheme 1: Synthesis of highly functionalized 2,2'-bipyridines 4a and 5b from symmetrical 1,3-diketones 1a and ...
Scheme 2: Synthesis of β-ketoenamines 2c–e and of β-ketoenamides 3c–h.
Scheme 3: Synthesis of α-methoxy-β-ketoenamine 2i, its N-acylation to 3i and the reaction of β-ketoenamide 3a...
Scheme 4: Cyclizations of β-ketoenamide 3i leading to 2,2´-bipyridine derivative 4i or to the related 2-(2-py...
Scheme 5: Suzuki-couplings of 2,2'-bipyrid-4-yl nonaflates 5a and 5b to compounds 9 and 10.
Scheme 6: Palladium-catalyzed couplings of chloro-substituted 2,2'-bipyrid-4-yl nonaflate 5g leading to compo...
Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors
- Joana Salta,
- Jens Dernedde and
- Hans-Ulrich Reissig
Beilstein J. Org. Chem. 2015, 11, 638–646, doi:10.3762/bjoc.11.72
- compounds could not be tested as L-selectin inhibitor by SPR due to their insolubility in water, nevertheless, a divalent and a trivalent amide showed surprisingly good activities with IC50 values in the low micromolar range. Keywords: aminopolyols; carbohydrate mimetics; carboxylic acid amides; inhibition
Graphical Abstract
Scheme 1: General approach to divalent or trivalent carbohydrate mimetics on the basis of aminopyran 1 or ser...
Scheme 2: Hydroxy group protection of aminopyran 1 to give compound 3, synthesis of amide 4 and subsequent de...
Scheme 3: Attempt to synthesize protected divalent compound 6. Conditions: a) succinic acid dichloride, Et3N,...
Scheme 4: HATU-mediated synthesis of divalent amide 25 and trivalent amides 27 and 29. Conditions: a) HATU, Et...
Scheme 5: Polysulfations of amides 5 and 13. Conditions: a) 1) SO3∙DMF, DMF-d7, 1 d, rt; 2) 1 M NaOH, 0 °C; 3...
Scheme 6: Polysulfation of divalent amides 21 and 22 leading to tetrasulfated amides 32 and 33. Conditions: a...
Scheme 7: Conversion of trivalent compound 27 into nonasulfated carbohydrate mimetic 34. Conditions: a) 1) SO3...
Figure 1: Structures of O-sulfated divalent amide 32 and trivalent amide 34 and their respective IC50 values ...
Recent advances in the electrochemical construction of heterocycles
- Robert Francke
Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303
- nucleophilic trapping of anodically formed iminium (23) or alkoxycarbenium species (24). The reactive intermediates can be generated directly from ethers or carboxylic acid amides (Scheme 9) [32]. However, aliphatic ethers and amides generally exhibit high oxidation potentials, and a large number of functional
Graphical Abstract
Figure 1: Common types of electrochemically induced cyclization reactions.
Scheme 1: Principle of indirect electrolysis.
Scheme 2: Anodic intramolecular cyclization of olefines in methanol.
Scheme 3: Anodic cyclization of olefines in CH2Cl2/DMSO.
Scheme 4: Intramolecular coupling of 1,6-dienes in CH2Cl2/DMSO.
Scheme 5: Cyclization of bromopropargyloxy ester 12.
Scheme 6: Proposed mechanism for the radical cyclization of bromopropargyloxy ester 12.
Scheme 7: Preparation of pyrrolidines and tetrahydrofurans via Kolbe-type electrolysis of unsaturated carboxy...
Scheme 8: Anodic cyclization of chalcone oximes 19.
Scheme 9: Generation of N-acyliminium (23) and alkoxycarbenium species (24) from amides and ethers with and w...
Scheme 10: Anodic cyclization of dipeptide 25.
Scheme 11: Anodic cyclization of a dipeptide using an electroauxiliary.
Scheme 12: Anodic cyclization of hydroxyamino compound 29.
Scheme 13: Cyclization of unsaturated thioacetals using the ArS(ArSSAr)+ mediator.
Scheme 14: Cyclization of biaryl 35 to carbazol 36 as key-step of the synthesis of glycozoline (37).
Scheme 15: Electrosynthesis of 39 as part of the total synthesis of alkaloids 40 and 41.
Scheme 16: Wacker-type cyclization of alkenyl phenols 42.
Scheme 17: Cathodic synthesis of indol derivatives.
Scheme 18: Fluoride mediated anodic cyclization of α-(phenylthio)acetamides.
Scheme 19: Synthesis of 2-substituted benzoxazoles from Schiff bases.
Scheme 20: Synthesis of euglobal model compounds via electrochemically induced Diels–Alder cycloaddition.
Scheme 21: Cycloaddition of anodically generated N-acyliminium species 58 with olefins and alkynes.
Scheme 22: Electrochemical aziridination of olefins.
Scheme 23: Proposed mechanism for the aziridination reaction.
Scheme 24: Electrochemical synthesis of benzofuran and indole derivatives.
Scheme 25: Anodic anellation of catechol derivatives 66 with different 1,3-dicarbonyl compounds.
Scheme 26: Electrosynthesis of 1,2-fused indoles from catechol and ketene N,O-acetals.
Scheme 27: Reaction of N-acyliminium pools with olefins having a nucleophilic substituent.
Scheme 28: Synthesis of thiochromans using the cation-pool method.
Scheme 29: Electrochemical synthesis and diversity-oriented modification of 73.
Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics
- Gijs Koopmanschap,
- Eelco Ruijter and
- Romano V.A. Orru
Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50
Graphical Abstract
Scheme 1: The proposed mechanism of the Passerini reaction.
Scheme 2: The PADAM-strategy to α-hydroxy-β-amino amide derivatives 7. An additional oxidation provides α-ket...
Scheme 3: The general accepted Ugi-mechanism.
Scheme 4: Three commonly applied Ugi/cyclization approaches. a) UDC-process, b) UAC-sequence, c) UDAC-combina...
Scheme 5: Ugi reaction that involves the condensation of Armstrong’s convertible isocyanide.
Scheme 6: Mechanism of the U-4C-3CR towards bicyclic β-lactams.
Scheme 7: The Ugi 4C-3CR towards oxabicyclo β-lactams.
Scheme 8: Ugi MCR between an enantiopure monoterpene based β-amino acid, aldehyde and isocyanide resulting in...
Scheme 9: General MCR for β-lactams in water.
Scheme 10: a) Ugi reaction for β-lactam-linked peptidomimetics. b) Varying the β-amino acid resulted in β-lact...
Scheme 11: Ugi-4CR followed by a Pd-catalyzed Sn2 cyclization.
Scheme 12: Ugi-3CR of dipeptide mimics from 2-substituted pyrrolines.
Scheme 13: Joullié–Ugi reaction towards 2,5-disubstituted pyrrolidines.
Scheme 14: Further elaboration of the Ugi-scaffold towards bicyclic systems.
Scheme 15: Dihydroxyproline derivatives from an Ugi reaction.
Scheme 16: Diastereoselective Ugi reaction described by Banfi and co-workers.
Scheme 17: Similar Ugi reaction as in Scheme 16 but with different acids and two chiral isocyanides.
Scheme 18: Highly diastereoselective synthesis of pyrrolidine-dipeptoids via a MAO-N/MCR-procedure.
Scheme 19: MAO-N/MCR-approach towards the hepatitis C drug telaprevir.
Scheme 20: Enantioselective MAO-U-3CR procedure starting from chiral pyrroline 64.
Scheme 21: Synthesis of γ-lactams via an UDC-sequence.
Scheme 22: Utilizing bifunctional groups to provide bicyclic γ-lactam-ketopiperazines.
Scheme 23: The Ugi reaction provided both γ- as δ-lactams depending on which inputs were used.
Scheme 24: The sequential Ugi/RCM with olefinic substrates provided bicyclic lactams.
Scheme 25: a) The structural and dipole similarities of the triazole unit with the amide bond. b) The copper-c...
Scheme 26: The Ugi/Click sequence provided triazole based peptidomimetics.
Scheme 27: The Ugi/Click reaction as described by Nanajdenko.
Scheme 28: The Ugi/Click-approach by Pramitha and Bahulayan.
Scheme 29: The Ugi/Click-combination by Niu et al.
Scheme 30: Triazole linked peptidomimetics obtained from two separate MCRs and a sequential Click reaction.
Scheme 31: Copper-free synthesis of triazoles via two MCRs in one-pot.
Scheme 32: The sequential Ugi/Paal–Knorr reaction to afford pyrazoles.
Scheme 33: An intramolecular Paal–Knorr condensation provided under basic conditions pyrazolones.
Scheme 34: Similar cyclization performed under acidic conditions provided pyrazolones without the trifluoroace...
Scheme 35: The Ugi-4CR towards 2,4-disubstituted thiazoles.
Scheme 36: Solid phase approach towards thiazoles.
Scheme 37: Reaction mechanism of formation of thiazole peptidomimetics containing an additional β-lactam moiet...
Scheme 38: The synthesis of the trisubstituted thiazoles could be either performed via an Ugi reaction with pr...
Scheme 39: Performing the Ugi reaction with DMB-protected isocyanide gave access to either oxazoles or thiazol...
Scheme 40: Ugi/cyclization-approach towards 2,5-disubstituted thiazoles. The Ugi reaction was performed with d...
Scheme 41: Further derivatization of the thiazole scaffold.
Scheme 42: Three-step procedure towards the natural product bacillamide C.
Scheme 43: Ugi-4CR to oxazoles reported by Zhu and co-workers.
Scheme 44: Ugi-based synthesis of oxazole-containing peptidomimetics.
Scheme 45: TMNS3 based Ugi reaction for peptidomimics containing a tetrazole.
Scheme 46: Catalytic cycle of the enantioselective Passerini reaction towards tetrazole-based peptidomimetics.
Scheme 47: Tetrazole-based peptidomimetics via an Ugi reaction and a subsequent sigmatropic rearrangement.
Scheme 48: Resin-bound Ugi-approach towards tetrazole-based peptidomimetics.
Scheme 49: Ugi/cyclization approach towards γ/δ/ε-lactam tetrazoles.
Scheme 50: Ugi-3CR to pipecolic acid-based peptidomimetics.
Scheme 51: Staudinger–Aza-Wittig/Ugi-approach towards pipecolic acid peptidomimetics.
Figure 1: The three structural isomers of diketopiperazines. The 2,5-DKP isomer is most common.
Scheme 52: UDC-approach to obtain 2,5-DKPs, either using Armstrong’s isocyanide or via ethylglyoxalate.
Scheme 53: a) Ugi reaction in water gave either 2,5-DKP structures or spiro compounds. b) The Ugi reaction in ...
Scheme 54: Solid-phase approach towards diketopiperazines.
Scheme 55: UDAC-approach towards DKPs.
Scheme 56: The intermediate amide is activated as leaving group by acid and microwave assisted organic synthes...
Scheme 57: UDC-procedure towards active oxytocin inhibitors.
Scheme 58: An improved stereoselective MCR-approach towards the oxytocin inhibitor.
Scheme 59: The less common Ugi reaction towards DKPs, involving a Sn2-substitution.
Figure 2: Spatial similarities between a natural β-turn conformation and a DKP based β-turn mimetic [158].
Scheme 60: Ugi-based syntheses of bicyclic DKPs. The amine component is derived from a coupling between (R)-N-...
Scheme 61: Ugi-based synthesis of β-turn and γ-turn mimetics.
Figure 3: Isocyanide substituted 3,4-dihydropyridin-2-ones, dihydropyridines and the Freidinger lactams. Bio-...
Scheme 62: The mechanism of the 4-CR towards 3,4-dihydropyridine-2-ones 212.
Scheme 63: a) Multiple MCR-approach to provide DHP-peptidomimetic in two-steps. b) A one-pot 6-CR providing th...
Scheme 64: The MCR–alkylation–MCR procedure to obtain either tetrapeptoids or depsipeptides.
Scheme 65: U-3CR/cyclization employing semicarbazone as imine component gave triazine based peptidomimetics.
Scheme 66: 4CR towards triazinane-diones.
Scheme 67: The MCR–alkylation–IMCR-sequence described by our group towards triazinane dione-based peptidomimet...
Scheme 68: Ugi-4CR approaches followed by a cyclization to thiomorpholin-ones (a) and pyrrolidines (b).
Scheme 69: UDC-approach for benzodiazepinones.
Scheme 70: Ugi/Mitsunobu sequence to BDPs.
Scheme 71: A UDAC-approach to BDPs with convertible isocyanides. The corresponding amide is cleaved by microwa...
Scheme 72: microwave assisted post condensation Ugi reaction.
Scheme 73: Benzodiazepinones synthesized via the post-condensation Ugi/ Staudinger–Aza-Wittig cyclization.
Scheme 74: Two Ugi/cyclization approaches utilizing chiral carboxylic acids. Reaction (a) provided the product...
Scheme 75: The mechanism of the Gewald-3CR includes three base-catalysed steps involving first a Knoevnagel–Co...
Scheme 76: Two structural 1,4-thienodiazepine-2,5-dione isomers by U-4CR/cyclization.
Scheme 77: Tetrazole-based diazepinones by UDC-procedure.
Scheme 78: Tetrazole-based BDPs via a sequential Ugi/hydrolysis/coupling.
Scheme 79: MCR synthesis of three different tricyclic BPDs.
Scheme 80: Two similar approaches both involving an Ugi reaction and a Mitsunobu cyclization.
Scheme 81: Mitsunobu–Ugi-approach towards dihydro-1,4-benzoxazepines.
Scheme 82: Ugi reaction towards hetero-aryl fused 5-oxo-1,4-oxazepines.
Scheme 83: a) Ugi/RCM-approach towards nine-membered peptidomimetics b) Sequential peptide-coupling, deprotect...
Scheme 84: Ugi-based synthesis towards cyclic RGD-pentapeptides.
Scheme 85: Ugi/MCR-approach towards 12–15 membered macrocycles.
Scheme 86: Stereoselective Ugi/RCM approach towards 16-membered macrocycles.
Scheme 87: Passerini/RCM-sequence to 22-membered macrocycles.
Scheme 88: UDAC-approach towards 12–18-membered depsipeptides.
Figure 4: Enopeptin A with its more active derivative ADEP-4.
Scheme 89: a) The Joullié–Ugi-approach towards ADEP-4 derivatives b) Ugi-approach for the α,α-dimethylated der...
Scheme 90: Ugi–Click-strategy for 15-membered macrocyclic glyco-peptidomimetics.
Scheme 91: Ugi/Click combinations provided macrocycles containing both a triazole and an oxazole moiety.
Scheme 92: a) A solution-phase procedure towards macrocycles. b) Alternative solid-phase synthesis as was repo...
Scheme 93: Ugi/cyclization towards cyclophane based macrocycles.
Scheme 94: PADAM-strategy towards eurystatin A.
Scheme 95: PADAM-approach for cyclotheanamide.
Scheme 96: A triple MCR-approach affording RGD-pentapeptoids.
Scheme 97: Ugi-MiBs-approach towards peptoid macrocycles.
Scheme 98: Passerini-based MiB approaches towards macrocycles 345 and 346.
Scheme 99: Macrocyclic peptide formation by the use of amphoteric aziridine-based aldehydes.
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
- )-arylsulfanylpyrazoles 107 by the reaction of 2-acylamino-3-arylsulfanyl-3-chloroacrylonitriles 106 with hydrazine hydrate has been described. Compounds 106 were readily obtained from 105, the addition products of carboxylic acid amides and trichloroacetaldehyde, by the reaction sequence shown in the Scheme 30 [72]. The
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.
