Nitriles-buliding-blocks

Ghosh, Arun K’s team published research in Journal of Medicinal Chemistry in 2009-08-27 | 103261-68-3

Journal of Medicinal Chemistry published new progress about Antiviral agents. 103261-68-3 belongs to class nitriles-buliding-blocks, and the molecular formula is C10H9NO2, Quality Control of 103261-68-3.

Ghosh, Arun K.; Takayama, Jun; Aubin, Yoann; Ratia, Kiira; Chaudhuri, Rima; Baez, Yahira; Sleeman, Katrina; Coughlin, Melissa; Nichols, Daniel B.; Mulhearn, Debbie C.; Prabhakar, Bellur S.; Baker, Susan C.; Johnson, Michael E.; Mesecar, Andrew D. published the artcile< Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Protease>, Quality Control of 103261-68-3, the main research area is SARS CoV Coronavirus severe acute respiratory syndrome; naphthalene derivative SAR preparation antiviral agent.

We describe here the design, synthesis, mol. modeling, and biol. evaluation of a series of small mol., nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chem. library. We subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells. Upon the basis of the X-ray crystal structure of inhibitor (III)-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, (I) (enzyme IC50 = 0.46 μM; antiviral EC50 = 6 μM). Interestingly, its methylamine derivative, (II), displayed good enzyme inhibitory potency (IC50 = 1.3 μM) and the most potent SARS antiviral activity (EC50 = 5.2 μM) in the series. We have carried out computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Liu, Hui’s team published research in Organic & Biomolecular Chemistry in 2021 | 21667-62-9

Organic & Biomolecular Chemistry published new progress about Enantioselective synthesis. 21667-62-9 belongs to class nitriles-buliding-blocks, and the molecular formula is C9H6ClNO, Formula: C9H6ClNO.

Liu, Hui; Yan, Yingkun; Li, Min; Zhang, Xiaomei published the artcile< An enantioselective aza-Friedel-Crafts reaction of 5-aminoisoxazoles with isatin-derived N-Boc ketimines>, Formula: C9H6ClNO, the main research area is isoxazole amino oxindole preparation enantioselective chiral phosphoric acid catalyst; aminoisoxazole isatin boc ketimine aza Friedel Crafts.

By employing a chiral phosphoric acid as a catalyst, an enantioselective aza-Friedel-Crafts reaction of 5-aminoisoxazoles with isatin-derived N-Boc ketimines was realized. The reaction provided a wide variety of novel 3-isoxazole 3-amino-oxindoles I (R1 = C6H5, 4-OMeC6H4, 4-FC6H4, etc.; R2 = Me, Et, Bn, Allyl; R3 = H, 5-Me, 5-Cl, etc.; R4 = H, Me, Et, Bn, Boc) with good yields (up to 99%) and moderate to good enantioselectivities (up to 99%). The absolute configuration of one product was assigned by X-ray crystal structural anal. and a plausible reaction mechanism was proposed. In addition, a scale-up reaction was performed successfully. Finally, one product was subjected to Suzuki-Miyaura coupling with phenylboronic acid to afford the product in a moderate yield without erosion of the enantioselectivity.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Sanchez-Viesca, F’s team published research in Organic Preparations and Procedures International in 2004-04-30 | 6136-93-2

Organic Preparations and Procedures International published new progress about Hoesch reaction. 6136-93-2 belongs to class nitriles-buliding-blocks, and the molecular formula is C6H11NO2, Recommanded Product: 2,2-Diethoxyacetonitrile.

Sanchez-Viesca, F.; Gomez, Maria R.; Berros, Martha published the artcile< An anomalous Houben-Hoesch reaction and some applications in arylation reactions>, Recommanded Product: 2,2-Diethoxyacetonitrile, the main research area is anomalous Houben Hoesch reaction methoxybenzene arylation application.

α,α-Dichloro-2,4,5-trimethoxyacetophenone (1a), prepared via a Houben-Hoesch reaction between 1,2,4-trimethoxybenzene and dichloroacetonitrile, was very unreactive, failing to react with NaOAc, methoxide and ethoxide. Attempted preparation of α,α-diethoxy-2,4,5-trimethoxyacetophenone by Houben-Hoesch reaction of 1,2,4-trimethoxybenzene with diethoxyacetonitrile gave tris(2,4,5-trimethoxyphenyl)methane instead. Reaction of 1,2,4-trimethoxybenzene with diethoxyacetonitrile under Houben-Hoesch conditions gave 2,2-bis(2,4,5-trimethoxyphenyl)acetamide. 2,2-Dichloro-1-methoxy-1-(2,4,5-trimethoxyphenyl)ethane (preparation described) could be arylated by 1,2,4-trimethoxybenzene and 2,4-dimethoxychlorobenzene to give 2,2-dichloro-1,1-bis(2,4,5-trimethoxyphenyl)ethane and 2,2-dichloro-1-(5-chloro-2,4-dimethoxyphenyl)-1-(2,4,5-trimethoxyphenyl)ethane. Reactions of 1,2,4-trimethoxybenzene with RCH2CN (R = EtO, MeO) under Houben-Hoesch conditions gave 2,4,5-trimethoxyphenacyl chloride (unexpectedly) and α-methoxy-2,4,5-trimethoxyacetophenone, resp.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Meerwein, Hans’s team published research in Annalen der Chemie, Justus Liebigs in 1960 | 6136-93-2

Annalen der Chemie, Justus Liebigs published new progress about Anions. 6136-93-2 belongs to class nitriles-buliding-blocks, and the molecular formula is C6H11NO2, Formula: C6H11NO2.

Meerwein, Hans; Hederich, Volker; Morschel, Hans; Wunderlich, Klaus published the artcile< Intermolecular anion transfer during organic reactions>, Formula: C6H11NO2, the main research area is .

A class of reaction mechanisms, RA + R’+ → R’A + R+, is considered, where R+ is the more stable carbonium ion, A = hydride, cyanide, or alkoxide; isolation of the R+ salts is attempted. Ph3C+ is chosen as R’+ and prepared by stirring 44.5 g. BF3-EtOAc, b13 49-51°, into 61 g. Ph3COEt in 170 cc. EtOAc with exclusion of H2O and alc., separation of Ph3CBF3 (I) by filtering after 24 hrs., and washing with low-boiling petroleum; total yield after recovery of 2nd crop 90%, m. 197-8°. Addition of 7.4 g. 1,3-dioxolane to 16.5 g. I in 60 cc. liquid SO2 under reflux (dry ice condenser) results in hydride transfer and, after evaporation and treatment with CH2Cl2 and Et2O, isolation of 88.5% 1,3-dioxolenium fluoborate, m. 83°; β-iodoethyl formate b15 65-70°, prepared with NaI in MeCN. From the CH2Cl2 washings, 58% Ph3CH, m. 90.5-1.5°, is isolated. Similarly, 2-methyl-1,3-dioxolane, the 2-Ph compound (II), and the 2,4,4,5,5-Me5 compound yield, resp., 84, 83, and 77% Ph3CH, and 69, 100, and 76% (m. 150-2°) dioxolenium fluoborates. In order to substitute for I the nonexistent Et +, 9.5 g. (Et3O) (BF4) and 9 g. II is heated to 40°, 81% Et2O distilled, and 50% II-BF4 salt and C2H6 isolated. Another H- donor is (PhCH2)3N, reacting with I in MeCN at 40-50° to yield 84% Ph3CH and 94% benzylidenedibenzylimonium fluoborate, m. 132-4°, hydrolyzed in hot 30% NaOH to (PhCH2)2NH. Cyanide transfer occurs by cooling 5 g. 2-cyano-2-methyl-1,3-dioxolane (III) in 25 cc. MeCN with 14.5 g. I, filtering off after 1 hr. 6.5 g. Ph3CCN, m. 128.6-29° (total yield 82%), and adding Et2O to isolate 59% 2-methyldioxolenium fluoborate (IV), m. 162-4°, and recover more Ph3CCN from the filtrate. III reacts with (EtO)2CHBF4, m. 20°, in CH2Cl2 to yield 88% IV and 81% (EtO)2CHCN, b760 163-4°, b15 58-9.5°, n20D 1.3978. Alkoxide transfer is reversible and usually more rapid than hydride transfer. Camphor diethyl acetal, b10 99.5-101°, (18 g.) added to 16.5 g. I in 25 cc. MeCN precipitates 95% O-ethylcamphoroxonium fluoborate, decomposed at 104-5%, isolated by washing with Et2O; 90% Ph3COEt (V), m. 82°, is obtained by evaporation of the filtrate. Similar high-yield reactions of ROEt with I or HC(OEt)2BF4 (VI) give the R salt and V or HC(OEt)3 for R = O.CH2.CH2.O.CMe (both I and VI), C(OEt)3 (both I and VI), O.CMe2.CMe2.O.CH (I only), O.CHMe.CHMe.O.CH (I only), HC(OEt)2 (Ph3CSbCl6), Me2NCHOEt [Ph3CSbCl6, VI, and HC(OEt)2SbCl6]. V is cleaved by R’BF4 (R’ = 2-methyl-, 4,5-dimethyl-, or 2,4,4,5,5-pentamethyldioxolenium) with isolation of Ph3CH and AcH. With ROEt (R = O.CH2.CH2.CH), I in CH2Cl2 yields 88% RBF4 and 95% Ph3CH, but in MeCN the same reaction produces 91% Ph3COCH2CH2COCPh3 (VII), m. 188-9° (MeCOEt), and by attack on O and ring cleavage, some RBF4, and VI. When not isolated, VII decompose to Ph3CH. RBF4 in turn reacts with V in MeCN to yield 33% VII, and VII with VI in CH2Cl2 to yield 75% RBF4. From 13.2 g. I in 20-25 cc. dry CH2Cl2, treated with 8.5 g. RNMe2 (R = O.CH2.CH2.O.CMe), b. 142°, with cooling and stirring 30 min. after slow addition, Et2O precipitates [RN(CPh3)Me2]BF4, stable, m. 170°; the iodide, obtained by treatment with NaI in MeCN, decompose at 110° to 88.5% AcNMe2, b30 76-7°, recovered by distillation, and 78.6% ICH2CH2OCPh3, m. 136-7°, obtained by crystallization of the residue from alc. or MeCN. The ether is obtained independently for comparison from Ph3CH and HO(CH2)2Br in C5H5N via the Br compound, m. 126-7%, and refluxing the latter with NaI in MeCN. The mechanisms are discussed. The new (OCMe2CMe2OCH)BF4 m. 110-12° and (Me2NCHOEt)SbCl6 m. 156-8°.

Annalen der Chemie, Justus Liebigs published new progress about Anions. 6136-93-2 belongs to class nitriles-buliding-blocks, and the molecular formula is C6H11NO2, Formula: C6H11NO2.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Gore, Babasaheb Sopan’s team published research in Organic Letters in 2020-08-07 | 21667-62-9

Organic Letters published new progress about Crystal structure. 21667-62-9 belongs to class nitriles-buliding-blocks, and the molecular formula is C9H6ClNO, Formula: C9H6ClNO.

Gore, Babasaheb Sopan; Kuo, Chiao-Ying; Garkhedkar, Amol Milind; Chang, Yu-Lun; Wang, Jeh-Jeng published the artcile< Metal-Free Solvent/Base-Switchable Divergent Synthesis of Multisubstituted Dihydrofurans>, Formula: C9H6ClNO, the main research area is ketonitrile cyclization; dihydropyran preparation.

A general protocol for the synthesis of multisubstituted 2,3-dihydrofuran-2-carbonitriles and 4,5-dihydrofuran-3-carbonitriles was demonstrated under a metal-free regime with the same oxidant, TBHP. By simply switching the reaction solvent and base, the reaction proceeds via two pathways. An unexpected -CN group migration rearrangement and hydroxylation have occurred in nonpolar and polar solvents, resp., under the reported conditions. Furthermore, the source of the hydroxyl group and hydrogen in the reaction is indirectly confirmed with isotope labeling studies.

Organic Letters published new progress about Crystal structure. 21667-62-9 belongs to class nitriles-buliding-blocks, and the molecular formula is C9H6ClNO, Formula: C9H6ClNO.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Bawden, Joseph C.’s team published research in Journal of the American Chemical Society in 2022 | CAS: 105942-08-3

4-Bromo-2-fluorobenzonitrile(cas:105942-08-3) is used as a reagent in the synthesis of picolinamide derivatives as a novel class of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors.Electric Literature of C7H3BrFN 4-Bromo-2-fluorobenzonitrile is also used in the preparation of fluorinated CB2 receptor agonists for PET imaging.

In 2022,Bawden, Joseph C.; Francis, Paul S.; DiLuzio, Stephen; Hayne, David J.; Doeven, Egan H.; Truong, Johnny; Alexander, Richard; Henderson, Luke C.; Gomez, Daniel E.; Massi, Massimiliano; Armstrong, Blake I.; Draper, Felicity A.; Bernhard, Stefan; Connell, Timothy U. published an article in Journal of the American Chemical Society. The title of the article was 《Reinterpreting the Fate of Iridium(III) Photocatalysts-Screening a Combinatorial Library to Explore Light-Driven Side-Reactions》.Electric Literature of C7H3BrFN The author mentioned the following in the article:

Photoredox catalysts are primarily selected based on ground and excited state properties, but their activity is also intrinsically tied to the nature of their reduced (or oxidized) intermediates. Catalyst reactivity often necessitates an inherent instability, thus these intermediates represent a mechanistic turning point that affords either product formation or side-reactions. In this work, we explore the scope of a previously demonstrated side-reaction that partially saturates one pyridine ring of the ancillary ligand in heteroleptic iridium(III) complexes. Using high-throughput synthesis and screening under photochem. conditions, we identified different chem. pathways, ultimately governed by ligand composition The ancillary ligand was the key factor that determined photochem. stability. Following photoinitiated electron transfer from a sacrificial tertiary amine, the reduced intermediate of complexes containing 1,10-phenanthroline derivatives exhibited long-term stability. In contrast, complexes containing 2,2′-bipyridines were highly susceptible to hydrogen atom transfer and ancillary ligand modification. Detailed characterization of selected complexes before and after transformation showed differing effects on the ground and excited state reduction potentials dependent on the nature of the cyclometalating ligands and excited states. The implications of catalyst stability and reactivity in chem. synthesis was demonstrated in a model photoredox reaction. The results came from multiple reactions, including the reaction of 4-Bromo-2-fluorobenzonitrile(cas: 105942-08-3Electric Literature of C7H3BrFN)

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Askey, Hannah E.’s team published research in Journal of the American Chemical Society in 2021 | CAS: 1403850-00-9

2,4,6-Tris(diphenylamino)-3,5-difluorobenzonitrile(cas: 1403850-00-9) is cyanoarene-based donor-acceptor photocatalyst developed by the Zeitler group. While this catalyst has a balanced redox profile, allowing for its use in a variety of transformations, it stands out as the most reducing catalyst of the family.Reference of 2,4,6-Tris(diphenylamino)-3,5-difluorobenzonitrile

Reference of 2,4,6-Tris(diphenylamino)-3,5-difluorobenzonitrileOn October 6, 2021 ,《Photocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines》 was published in Journal of the American Chemical Society. The article was written by Askey, Hannah E.; Grayson, James D.; Tibbetts, Joshua D.; Turner-Dore, Jacob C.; Holmes, Jake M.; Kociok-Kohn, Gabriele; Wrigley, Gail L.; Cresswell, Alexander J.. The article contains the following contents:

A solution to these problems using organophotoredox catalysis, enabling a direct, modular and sustainable preparation of α-(di)substituted γ-arylamines, including challenging electron-neutral and moderately electron-rich aryl groups was reported. A broad range of functionalities were tolerated, and the reactions was run on multigram scale in continuous flow. The method was applied to a concise, protecting-group-free synthesis of the blockbuster drug Fingolimod, as well as a phosphonate mimic of its in-vivo active form (by iterative α-C-H functionalization of ethanolamine). The reaction was sequenced with an intramol. N-arylation to provided a general and modular access to valuable (spirocyclic) 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydronaphthyridines. Mechanistic and kinetic studies supportes an irreversible hydrogen atom transfer activation of the alkylamine by the azidyl radical and some contribution from a radical chain. The reaction was photon-limited and exhibits a zero-order dependence on amine, azide, and photocatalyst, with a first-order dependence on styrene. In the experimental materials used by the author, we found 2,4,6-Tris(diphenylamino)-3,5-difluorobenzonitrile(cas: 1403850-00-9Reference of 2,4,6-Tris(diphenylamino)-3,5-difluorobenzonitrile)

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Martin, Stephen F.’s team published research in Journal of the American Chemical Society in 1993 | CAS: 89245-35-2

2-(4-Bromo-3-indolyl)acetonitrile(cas: 89245-35-2) is a member of nitriles. Nitriles have been reduced to amines by many methods, especially by catalytic hydrogenation and by metal hydrides. Aliphatic and aromatic nitriles have also been reduced to nitro derivatives using hydrazinium monoformate in the presence of Raney-nickel.COA of Formula: C10H7BrN2

COA of Formula: C10H7BrN2On November 3, 1993 ,《Novel applications of vinylogous Mannich reactions. Total synthesis of rugulovasines A and B》 appeared in Journal of the American Chemical Society. The author of the article were Martin, Stephen F.; Liras, Spiros. The article conveys some information:

The total syntheses of the Ergot alkaloids rugulovasines A (I, R = MeNH, R1 = H) and B (R = H, R1 = MeNH) were completed in a concise sequence requiring only eight reactions from com. available 4-bromoindole. The two key steps of the synthesis were the vinylogous Mannich reaction of the iminium salt of II with the furan III and the cyclization of IV by a SRN1 reaction. Thus, 4-bromoindole was converted in a straightforward manner to the 3-acetaldehyde derivative, which after treatment with benzylmethylamine provided the intermediate enamine II. Treatment of II with silyloxyfuran III in the presence of acid produced IV via a vinylogous Mannich reaction. A photostimulated SRN1 reaction of IV was employed to construct the spirocyclic lactone moiety followed by hydrogenolysis gave rugulovasines A and B. The experimental process involved the reaction of 2-(4-Bromo-3-indolyl)acetonitrile(cas: 89245-35-2COA of Formula: C10H7BrN2)

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Garcia-Monroy, Ricardo’s team published research in Journal of the Mexican Chemical Society in 2021 | CAS: 614-16-4

3-Oxo-3-phenylpropanenitrile(cas: 614-16-4) has been used to produce 2-benzoyl-3-furan-2-yl-acrylonitrile. It is an active methylene compound, useful in heterocyclic synthesis, e.g. polyfunctional pyridines and pyrimidines.Formula: C9H7NO

Garcia-Monroy, Ricardo; Gonzalez-Calderon, Davir; Ramirez-Villalva, Alejandra; Mastachi-Loza, Salvador; Aguirre-de Paz, Jose G.; Fuentes-Benites, Aydee; Gonzalez-Romero, Carlos published their research in Journal of the Mexican Chemical Society in 2021. The article was titled 《Synthesis of novel benzylic 1,2,3-triazole-4-carboxamides and their in vitro activity against clinically common fungal species》.Formula: C9H7NO The article contains the following contents:

A library of novel benzylic 1,2,3-triazole-4-carboxamides I (R = Ph, 4-methylphenyl, 4-phenylphenyl; R1 = 4-methoxyphenyl, 2,6-dichlorophenyl, 2H-1,3-benzodioxol-5-yl, etc.) were obtained with acceptable yields via a one-pot procedure. The series of compounds I was screened for fungicidal activity and evaluated in vitro against four filamentous fungi and four Candida species. The former consisted of Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae and Mucor hiemalis, and the latter consisted of C. krusei, C. albicans, C. utilis and C. glabrata. According to the in vitro assays, I (R = Ph, R1 = 2,6-dichlorophenyl; R = Ph, R1 = 2H-1,3-benzodioxol-5-yl) were the most efficient fungicidal agents (of all the test compounds) against R. oryzae, even better than the reference drug (itraconazole). Thus, I (R = Ph, R1 = 2,6-dichlorophenyl; R = Ph, R1 = 2H-1,3-benzodioxol-5-yl) represent important scaffolds that can be modified to increase antifungal activity. Addnl., they are candidates for complementary studies on the inhibition of clin. infections produced by Rhizopus spp. strains.3-Oxo-3-phenylpropanenitrile(cas: 614-16-4Formula: C9H7NO) was used in this study.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Murugesan, Kathiravan’s team published research in Angewandte Chemie, International Edition in 2021 | CAS: 623-00-7

4-Bromobenzonitrile(cas: 623-00-7) has been used in the synthesis of 4-iodobenzonitrile via photo-induced aromatic Finkelstein iodination reaction.Quality Control of 4-Bromobenzonitrile It can also be used as an aryl halide test compound in developing greener reaction conditions for Suzuki cross-coupling between aryl halides and phenyl boronic acid.

Murugesan, Kathiravan; Donabauer, Karsten; Koenig, Burkhard published an article in 2021. The article was titled 《Visible-Light-Promoted Metal-Free Synthesis of (Hetero)Aromatic Nitriles from C(sp3)-H Bonds》, and you may find the article in Angewandte Chemie, International Edition.Quality Control of 4-Bromobenzonitrile The information in the text is summarized as follows:

The metal-free activation of C(sp3)-H bonds to value-added products is of paramount importance in organic synthesis. We report the use of the com. available organic dye 2,4,6-triphenylpyrylium tetrafluoroborate (TPP) for the conversion of methylarenes to the corresponding aryl nitriles via a photocatalytic process. Applying this methodol., a variety of cyanobenzenes have been synthesized in good to excellent yield under metal- and cyanide-free conditions. We demonstrate the scope of the method with over 50 examples including late-stage functionalization of drug mols. (celecoxib) and complex structures such as L-menthol, amino acids, and cholesterol derivatives Furthermore, the presented synthetic protocol is applicable for gram-scale reactions. In addition to methylarenes, selected examples for the cyanation of aldehydes, alcs. and oximes are demonstrated as well. Detailed mechanistic investigations have been carried out using time-resolved luminescence quenching studies, control experiments, and NMR spectroscopy as well as kinetic studies, all supporting the proposed catalytic cycle.4-Bromobenzonitrile(cas: 623-00-7Quality Control of 4-Bromobenzonitrile) was used in this study.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts