Home Cart 0 Sign in  
X

[ CAS No. 1204-44-0 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 1204-44-0
Chemical Structure| 1204-44-0
Chemical Structure| 1204-44-0
Structure of 1204-44-0 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 1204-44-0 ]

Related Doc. of [ 1204-44-0 ]

Alternatived Products of [ 1204-44-0 ]

Product Details of [ 1204-44-0 ]

CAS No. :1204-44-0 MDL No. :MFCD03424659
Formula : C12H10ClN Boiling Point : -
Linear Structure Formula :- InChI Key :JPBWZIPCMDZOPM-UHFFFAOYSA-N
M.W : 203.67 Pubchem ID :262261
Synonyms :

Calculated chemistry of [ 1204-44-0 ]

Physicochemical Properties

Num. heavy atoms : 14
Num. arom. heavy atoms : 12
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 0.0
Num. H-bond donors : 1.0
Molar Refractivity : 61.29
TPSA : 26.02 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.08 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.18
Log Po/w (XLOGP3) : 3.47
Log Po/w (WLOGP) : 3.6
Log Po/w (MLOGP) : 3.61
Log Po/w (SILICOS-IT) : 3.44
Consensus Log Po/w : 3.26

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.86
Solubility : 0.0283 mg/ml ; 0.000139 mol/l
Class : Soluble
Log S (Ali) : -3.7
Solubility : 0.0408 mg/ml ; 0.0002 mol/l
Class : Soluble
Log S (SILICOS-IT) : -5.18
Solubility : 0.00135 mg/ml ; 0.00000665 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.48

Safety of [ 1204-44-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1204-44-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1204-44-0 ]

[ 1204-44-0 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 75-15-0 ]
  • [ 1204-44-0 ]
  • <i>N</i>,<i>N</i>'-bis-(4'-chloro-biphenyl-2-yl)-thiourea [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; iodine
With ethanol; sulfur
With potassium hydroxide
  • 2
  • [ 6271-80-3 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
99% With iron(III) chloride; hydrazine hydrate; potassium carbonate; pyrographite In methanol; water at 85℃; for 2h; Preparation of compound (4). A mixture of 4'-chloro-2-nitro-1,1'-biphenyl 3aa (2.34g, 10 mmol), FeCl3 (0.0811g, 0.5 mmol), 0.2g activated charcoal and K2CO3 (0.1381g 1mmol) was heated at reflux in MeOH (20 mL). Then, 80% N2H4.H2O (1.1mL 18mmol) was added dropwise to the solution. The resulting mixture was stirred for 2 h under reflux, then, cooled to room temperature, extracted with CH2Cl2 (3×10 mL) and dried over MgSO4. Filtration and concentration under reduced pressure gave 4'-chloro-[1,1'-biphenyl]-2-amine 4 as a pale solid 4.03g (99%).
98% With iron(III)-acetylacetonate; hydrazine hydrate In methanol at 150℃; Microwave irradiation; Green chemistry;
98% With trichlorosilane; N-ethyl-N,N-diisopropylamine In dichloromethane at 25℃; for 0.833333h; Flow reactor; General procedure for the continuous-flow reaction using a0.5 mL PTFE reactor General procedure: Syringe A was filled with a solution ofHSiCl3 (2.4 mmol) in dry CH2Cl2 (1.5 mL). Syringe B wasloaded with a solution of the nitro compound (0.6 mmol) andHünig’s base (3.6 mmol) in dry CH2Cl2 (1.5 mL). Syringes Aand B were connected to a syringe pump and the reagents werepumped into the microreactor at the indicated flow rate(mL/min) at room temperature. The outcome of the reactor wascollected in a flask containing a 10% NaOH solution. Fivereactor volumes were collected. CH2Cl2 was removed in vacuoand the aqueous layer was extracted three times with ethylacetate. The combined organic layers were washed with brine,dried with Na2SO4 and concentrated in vacuo. 1H NMR spectroscopy of the crude was used to calculate the reaction conversion; in case of a full conversion of the starting material nofurther purification was required
98% With hydrogenchloride; acetic acid; zinc In water; ethyl acetate at 70℃; for 4h; Inert atmosphere; Synthesis of the 2-(4-chlorophenyl)aniline (2) 2-(4-Chorophenyl)nitrobenzene (9.35 g, 40 mmol) and ethyl acetate (100 mL) wereadded to a 250 mL three-necked flask and stirred to dissolve completely. Then zinc powder(15.70 g, 240 mmol) was added to the reaction mixture and the reactants were heated to therequired temperature of 70 °C, and a mixed solution of 40 mL of concentrated hydrochloricacid and 20 mL of AcOH was added dropwise over a period of 1 h under a protection of N2atmosphere. After the reaction was finished (about 3 h), the reaction mixture was cooled toroom temperature, ammonia water was added slowly to adjust pH 10. The mixture wasallowed to stir for another 1 h at room temperature, and then 100 mL ethyl acetate was addedfor extraction. The aqueous phase was further extracted by 50 mL of ethyl acetate, and theorganic phases were combined, dried over anhydrous Na2SO4 and filtered. Finally, the filtratewas concentrated to give a pale yellow oily liquid. The oily liquid 2-(4-chlorophenyl)aniline(8.00 g) was purified by column chromatography, yield 98%.
97.9% With hydrogen; potassium iodide In ethanol; water at 35 - 87℃; for 1.5h; 1 Example 1: Preparation of 4 '- chloro - 2 - aminobiphenyl by Potassium Iodide as Catalyst The content of 40 g was 99.7% of 4 '- chloro - 2 - nitro - biphenyl is melted into liquid 280 g of 5% ethanol in water,Heated to complete dissolution,And the solution was heated into a 500 mL hydrogenation vessel while hot,When the mixture was cooled to 35 ° C, 0.12 g of potassium iodide was addedAnd 1.2 g of Renny nickel in turn into the hydrogenation kettle,Close the hydrogenation kettle, nitrogen replacement 3 times, began to heat up,When the temperature rises to 75 ° C,Open the hydrogen valve, hydrogen through the hydrogenation tank to the pressure of 1.0MPa,Close the hydrogen valve,After hydrogen is added to the hydrogenation tankThe temperature rises to 83 to 87 ° C,And control the reaction between 83 and 87 ° C throughout the hydrogenation process,And whenever the hydrogenation tank pressureDown to 0.85MPa,Open the hydrogen valve to add hydrogen to the kettle pressure of 1.0 MPa,Until the pressure inside the kettle no longer decline,At this time continue to heat 1.5h, sampling for GC detection,The results showed that there was no 4 '- chloro - 2 - nitrobiphenyl remaining 4' - chloro - 2 -The area of biphenyl is 99.4%, and the area of 2-aminobiphenyl is 0.41%.At this point the reaction solution is filtered, the filtrate is de-dissolved,And then distilled under the negative pressure to get the product 4 '- chloro - 2 - aminobiphenyl, then HPLC quantitative content of 99.2%The content of dechlorinated benzidine was 0.48%, the reaction yield was 97.9%
97% With hydrogenchloride; zinc
95% With sodium tetrahydroborate; cobalt(II) sulphate heptahydrate In ethanol; water at 0 - 21℃; for 0.05h;
93.4% With iron; ammonium chloride; acetic acid In methanol; water at 40℃; for 5h; 1.2 (2) A mixture of 7.0 (0.03 mol) of g4'-chloro-2-nitrobiphenyl, 8.4 g (0.15 mol) of reduced iron powder,(0.045 mol) of ammonium chloride, 50 mL of methanol and 10 mL of water were charged into a 100 mL three-necked flask, and the temperature was raised to 40 ° C.(0.06 mol) of glacial acetic acid, and the mixture was heated to reflux for 5 h. After cooling to room temperature,Concentrated and washed with ethyl acetate, washed with water to neutral and dried, and concentrated to give 5.7 g of 4'-chloro-2-aminobiphenyl,Yield 93.4%
91% With hydrogen In xylene at 100℃; Autoclave; 3 In a 20 ml autoclave were placed 1 g of xylene, 6 mg of a Pt/C catalyst (containing 1 % by weight of Pt with respect to the weight of carbon) and 0.25 g (1 mmol) of 4'-chloro-2- nitrobiphenyl obtained in example 1.4. The mixture was stirred under hydrogen pressure (7-8 bar) at 100 0C until the starting material had disappeared (monitoring via HPLC). After completion of the reaction the mixture was cooled to ambient temperature and diluted with 15 ml of acetone. The catalyst was filtered off and the filtrate was evaporated in vacuo yielding 0.2 g (91 % of theory) of the title compound in a purity of 93 % (HPLC % by weight).1H-NMR (500 MHz, CD2CI2): δ = 7.42-7.37 (m, 4H), 7.15-7.09 (m, 1 H), 7.08-7.03 (m, 1 H), 6.80-6.70 (m, 2H), 3.73 (br s, 2H) ppm.13C-NMR (125 MHz, CD2CI2): δ = 144.1 , 138.6, 133.3, 130.9, 130.6, 129.3, 129.2, 126.3, 1 18.9, 116.0 ppm.
88% With hydrogenchloride; tin(ll) chloride In tetrahydrofuran; ethanol for 16h;
88% With indium; ammonium chloride In ethanol; water at 120℃; for 3h; Sealed tube; General procedure: General procedure: 2-Nitrobiphenyl (1 mmol, 0.2 g) was dissolved in EtOH(4 mL) and transferred to a tube reactor. Then, a mixture of NH4Cl (2 mmol,0.107 g) in H2O (1.2 mL) and indium powder (3 mmol, 0.344 g, 99.99%100 mesh, use preferably a freshly opened bottle or stored under Ar) were added where upon a magnetic stirrer bar was transferred to the tube. The tube was then sealed and the reaction mixture was stirred and heated at 120°C for3 h. The reaction mixture was cooled to room temperature and diluted withethyl acetate (30 mL). The resulting mixture was filtered through a pad of celiteto remove the catalyst. Another portion (20 mL) of ethyl acetate was used to wash through the filter pad. The resulting transparent organic phase was driedover Na2SO4 , filtered and the solvent was removed under reduced pressureusing a rotary evaporator to obtain the target compound.
87% With water; iron; ammonium chloride In ethanol at 95℃; for 5h; 1.2 (2) In a 1 L round bottom flask,4'-chloro-2-nitro-biphenyl (50.06g, 214.25mmol),Dissolved in 500ml of anhydrous ethanol,After fully dissolving, add 125 ml of water,Ammonium chloride (25.91 g, 484.39 mmol) was added,With full agitation,The iron powder (40.62 g, 727.31 mmol) was added slowly,95 oil bath under reflux mechanical stirring 5h.TLC (petroleum ether: ethyl acetate = 10: 1) After the reaction was complete, the mixture was heated and stirred, and then suction was carried out with diatomaceous earth. The filter was washed with ethanol and then with ethanol. The resulting filtrate was distilled at 55 ° C under reduced pressure to remove ethanol and extracted three times with dichloromethane. The organic phases were combined and dried over anhydrous sodium sulfate.The column was concentrated to give 37.96 g of 4'-chloro-2-aminobiphenyl,Was orange-yellow liquid, the yield was 87%.
85% With iron; ammonium chloride In water at 45℃; for 12h;
84% With iron(III)-acetylacetonate; hydrazine hydrate In ethanol for 1h; Reflux; chemoselective reaction;
81% With 10 % platinum on carbon; cyclohexene In water; <i>tert</i>-butyl alcohol at 150℃; for 0.5h; Microwave irradiation;
55% With hydrogen at 40℃;
With iron Eisen ist mit wss. Salzsaeure vorbehandelt;
With nickel Hydrogenation;
With hydrogenchloride; tin(ll) chloride In tetrahydrofuran; ethanol; water at 20℃; for 14h;
176 mg With iron; ammonium chloride In ethanol; water at 85℃; for 1h;
With hydrogenchloride; tin(ll) chloride In water at 50℃; for 0.0666667h; Microwave irradiation;
With tin(II) chloride dihdyrate In ethanol at 75℃; for 5h;
With iron; ammonium chloride In water; isopropyl alcohol Reflux; Inert atmosphere;
With indium; ammonium chloride In ethanol; water at 120℃; for 3h; Sealed tube;
Stage #1: 4'-chloro-2-nitrobiphenyl With iron(III) chloride hexahydrate; potassium carbonate; pyrographite In methanol at 20℃; Stage #2: With hydrazine hydrate In methanol for 1h; Reflux; 1.3 Step three 100 mL of methanol was added to the reaction kettle, and 0.01 mol of activated carbon was stirred under stirring.Ferric chloride hexahydrate 0.01 mol,0.02 mol of potassium carbonate and 0.2 mol of 2-(4-chlorophenyl)nitrobenzene obtained in the second step were added to the reaction vessel, stirred at room temperature for 5-6 hours, heated to reflux, and 20 mL of hydrazine hydrate was added dropwise.The mixture was kept for 1 hour, filtered, and the filtrate was decomposed to recover methanol under reduced pressure.Add 150 mL of toluene and 50 mL of water to wash, and separate the water layer.After the oil layer is desolved to recover toluene, 2-(4-chlorophenyl)aniline is obtained.
With iron; ammonium chloride In ethanol; water at 85℃; for 1h; Inert atmosphere; Sealed tube;
With iron; ammonium chloride In tetrahydrofuran; water at 45℃; for 12h;

Reference: [1]Wang, Fengze; Wang, Chen; Sun, Guoping; Zou, Gang [Tetrahedron Letters, 2020, vol. 61, # 7]
[2]Cantillo, David; Baghbanzadeh, Mostafa; Kappe, C. Oliver [Angewandte Chemie - International Edition, 2012, vol. 51, # 40, p. 10190 - 10193]
[3]Porta, Riccardo; Puglisi, Alessandra; Colombo, Giacomo; Rossi, Sergio; Benaglia, Maurizio [Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 2614 - 2619]
[4]Xu, Jian; Lan, Xiao-Bing; Xia, Lin-Jian; Yang, Yi; Cao, Gao [Journal of the Serbian Chemical Society, 2021, vol. 86, # 3, p. 247 - 256]
[5]Current Patent Assignee: TAIZHOU BAILLY CHEMICAL CO. LTD - CN106883130, 2017, A Location in patent: Paragraph 0013-0021
[6]Li, Dong-Hui; He, Xu-Xian; Xu, Chang; Huang, Fei-Dong; Liu, Ning; Shen, Dong-Sheng; Liu, Feng-Shou [Organometallics, 2019, vol. 38, # 12, p. 2539 - 2552]
[7]Lundevall, Frida Johanne; Elumalai, Vijayaragavan; Drageset, Audun; Totland, Christian; Bjørsvik, Hans-René [European Journal of Organic Chemistry, 2018, vol. 2018, # 26, p. 3416 - 3425]
[8]Current Patent Assignee: CHINA NORTH INDUSTRIES GROUP CORPORATION - CN104725303, 2017, B Location in patent: Paragraph 0009; 0026; 0028; 0033; 0038; 0041; 0044; 0047
[9]Current Patent Assignee: BASF SE - WO2010/102980, 2010, A1 Location in patent: Page/Page column 43
[10]Spivey, Alan C.; Tseng, Chih-Chung; Hannah, Joseph P.; Gripton, Christopher J. G.; De Fraine, Paul; Parr, Nigel J.; Scicinski, Jan J. [Chemical Communications, 2007, # 28, p. 2926 - 2928]
[11]Elumalai, Vijayaragavan; Bjørsvik, Hans-René [Tetrahedron Letters, 2016, vol. 57, # 11, p. 1224 - 1226]
[12]Current Patent Assignee: CHINA AGRICULTURAL UNIVERSITY - CN106518793, 2017, A Location in patent: Paragraph 0041; 0043
[13]Takale, Balaram S.; Thakore, Ruchita R.; Mallarapu, Rushil; Gallou, Fabrice; Lipshutz, Bruce H. [Organic Process Research and Development, 2020, vol. 24, # 1, p. 101 - 105]
[14]Cantillo, David; Moghaddam, Mojtaba Mirhosseini; Kappe, C. Oliver [Journal of Organic Chemistry, 2013, vol. 78, # 9, p. 4530 - 4542]
[15]Location in patent: experimental part Glasnov, Toma N.; Kappe, C. Oliver [Advanced Synthesis and Catalysis, 2010, vol. 352, # 17, p. 3089 - 3097]
[16]Oger, Nicolas; Le Grognec, Erwan; Felpin, François-Xavier [ChemCatChem, 2015, vol. 7, # 14, p. 2085 - 2094]
[17]Current Patent Assignee: PFIZER INC - US2079450, 1935, A
[18]Bradsher; Wissow [Journal of the American Chemical Society, 1946, vol. 68, p. 404]
[19]Caron, Laurence; Campeau, Louis-Charles; Fagnou, Keith [Organic Letters, 2008, vol. 10, # 20, p. 4533 - 4536]
[20]Location in patent: experimental part Felpin, Francois-Xavier; Fouquet, Eric; Zakri, Cecile [Advanced Synthesis and Catalysis, 2009, vol. 351, # 4, p. 649 - 655]
[21]Tan, Xin; Zhou, Zi Jie; Zhang, Jia Xin; Duan, Xin Hong [European Journal of Organic Chemistry, 2014, vol. 2014, # 24, p. 5153 - 5157]
[22]Yuan, Ming; Chen, Li; Wang, Junwei; Chen, Shenjie; Wang, Kongchao; Xue, Yongbo; Yao, Guangmin; Luo, Zengwei; Zhang, Yonghui [Organic Letters, 2015, vol. 17, # 2, p. 346 - 349]
[23]Lai, Mei-Jung; Lee, Hsueh-Yun; Chuang, Hsun-Yueh; Chang, Li-Hsun; Tsai, An-Chi; Chen, Mei-Chuan; Huang, Han-Lin; Wu, Yi-Wen; Teng, Che-Ming; Pan, Shiow-Lin; Liu, Yi-Min; Mehndiratta, Samir; Liou, Jing-Ping [Journal of Medicinal Chemistry, 2015, vol. 58, # 16, p. 6549 - 6558]
[24]Bjørsvik, Hans-René; Elumalai, Vijayaragavan [European Journal of Organic Chemistry, 2016, vol. 2016, # 33, p. 5474 - 5479]
[25]Current Patent Assignee: JIANGSU CHENGYANG CROP SCIENCE - CN108997210, 2018, A Location in patent: Paragraph 0012
[26]Lee, Juyoung; Hong, Boseok; Lee, Anna [Journal of Organic Chemistry, 2019, vol. 84, # 14, p. 9297 - 9306]
[27]Takale, Balaram S.; Thakore, Ruchita R.; Handa, Sachin; Gallou, Fabrice; Reilly, John; Lipshutz, Bruce H. [Chemical Science, 2019, vol. 10, # 38, p. 8825 - 8831]
  • 3
  • [ 1204-44-0 ]
  • [ 343945-64-2 ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: 4′-chloro-[1,1′-biphenyl]-2-amine With hydrogenchloride; NaNO2 In lithium hydroxide monohydrate at 5℃; for 1.16667h; Stage #2: With potassium iodide In lithium hydroxide monohydrate at 20℃;
67% Stage #1: 4′-chloro-[1,1′-biphenyl]-2-amine With hydrogenchloride; NaNO2 In lithium hydroxide monohydrate at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: With potassium iodide In lithium hydroxide monohydrate at 20℃; for 12h; Inert atmosphere; 1.1-A-1 1-A-1) Synthesis of Intermediate 1-A-2 Under nitrogen flow, add 4'-chloro-[1,1'-biphenyl]-2-amine, 85 g, 417.4 mmol) and water (H2O, 400ml), NaNO2 (43.19g, 626.0mmol) was dissolved in water (H2O, 450ml), and it was slowly added to the reaction solution at a temperature between 0 and 5°C. After the addition, the mixture was stirred at room temperature for 1 hour, then KI (138.55 g, 834.6.0 mmol) was dissolved in water (H 2 O, 700 ml) and added slowly, and the reaction was carried out with stirring at room temperature for 12 hours. After the completion of the reaction, the reaction solution was added with NaHSO3 aqueous solution and the organic layer was separated with ethyl acetate, and purified by silicagel column chromatography and recrystallization to prepare 88.2 g of Intermediate 1-A-2 (yield 1-A-2). : 67%).
With sulfuric acid Diazotization.Behandlung der Diazoniumsalz-Loesung mit KI und Kupfer unter Erwaermen;
With hydrogenchloride; potassium iodide; NaNO2 In lithium hydroxide monohydrate at 0 - 20℃;
1.29 g Stage #1: 4′-chloro-[1,1′-biphenyl]-2-amine With hydrogenchloride; NaNO2 In lithium hydroxide monohydrate for 1h; Cooling; Stage #2: With potassium iodide In lithium hydroxide monohydrate at 20℃;
With toluene-4-sulfonic acid; potassium iodide; NaNO2 In lithium hydroxide monohydrate; acetonitrile at 0 - 20℃; for 2h;
Stage #1: 4′-chloro-[1,1′-biphenyl]-2-amine With hydrogenchloride; NaNO2 In tetrahydrofuran; lithium hydroxide monohydrate at 0 - 5℃; for 1h; Stage #2: With potassium iodide In tetrahydrofuran; lithium hydroxide monohydrate at 20℃;
Stage #1: 4′-chloro-[1,1′-biphenyl]-2-amine With hydrogenchloride; NaNO2 In tetrahydrofuran; lithium hydroxide monohydrate at 0℃; for 0.333333h; Stage #2: With potassium iodide In tetrahydrofuran; lithium hydroxide monohydrate at 0 - 20℃; for 1h; General method B: Synthesis of cyclic diphenyleniodoniumtrifluoromethanesulfonate derivatives 5a-5aa General procedure: The preparation was performed according to the literatureprocedure [24]. To a stirred solution of biphenylamine 3a-3aa (1.0eq.) in THF (0.1 M) was added 4 M HCl (3 mL), and the solution wascooled in an ice water bath. A solution of NaNO2 (1.2 eq.) in H2O(3 mL) was added dropwise. After 20 min, a solution of KI (2.5 eq.)in H2O (3 mL) was added, and stirred for 10 min in an ice waterbath. Then the solution was slowly warmed to room temperatureand stirred for 1 h before an aqueous solution of 20% Na2S2O3 wasadded until the colour of the mixture didn't change. The phaseswere separated, and the aqueous phase extracted with EtOAc(15 mL x 3). Then the combined organic layers were washed withH2O and brine, dried over MgSO4, and concentrated. The residuewas purified by flash column chromatography using 0e5% EtOAc/petroleum benzine to give the biphenyliodide 4. These compoundswere used directly in the next step.
Stage #1: 4′-chloro-[1,1′-biphenyl]-2-amine With hydrogenchloride In lithium hydroxide monohydrate at 0℃; for 1h; Stage #2: With NaNO2 In lithium hydroxide monohydrate at 5℃; for 1.16667h; Stage #3: With potassium iodide In lithium hydroxide monohydrate at 20℃;
Stage #1: 4′-chloro-[1,1′-biphenyl]-2-amine With hydrogenchloride In tetrahydrofuran; lithium hydroxide monohydrate at 0℃; Inert atmosphere; Stage #2: With NaNO2 In tetrahydrofuran; lithium hydroxide monohydrate at 0℃; for 0.333333h; Inert atmosphere; Stage #3: With potassium iodide In tetrahydrofuran; lithium hydroxide monohydrate at 0 - 20℃; for 1.16667h; Inert atmosphere;
Stage #1: 4′-chloro-[1,1′-biphenyl]-2-amine With hydrogenchloride; NaNO2 In lithium hydroxide monohydrate at 0 - 5℃; for 2h; Stage #2: With potassium iodide In lithium hydroxide monohydrate at 0 - 20℃;
Stage #1: 4′-chloro-[1,1′-biphenyl]-2-amine With hydrogenchloride In lithium hydroxide monohydrate at 0℃; for 1h; Stage #2: With NaNO2 In lithium hydroxide monohydrate at 0 - 5℃; for 1.16667h; Stage #3: With potassium iodide In lithium hydroxide monohydrate at 5 - 20℃;

Reference: [1]Jiang, Hang; Zhang, Yu; Chen, Dushen; Zhou, Bo; Zhang, Yanghui [Organic Letters, 2016, vol. 18, # 9, p. 2032 - 2035]
[2]Current Patent Assignee: MAT SCIENCE CO LTD - CN114573546, 2022, A Location in patent: Paragraph 0161; 0165-0167
[3]Bradsher; Wissow [Journal of the American Chemical Society, 1946, vol. 68, p. 404]
[4]Li, Jian; Wang, Hongni; Sun, Jiangtao; Yang, Yang; Liu, Li [Organic and Biomolecular Chemistry, 2014, vol. 12, # 40, p. 7904 - 7908]
[5]Shi, Guangfa; Chen, Dushen; Jiang, Hang; Zhang, Yu; Zhang, Yanghui [Organic Letters, 2016, vol. 18, # 12, p. 2958 - 2961]
[6]Naveen, Kanagaraj; Nikson, Savariyappan Albert; Perumal, Paramasivan Thirumalai [Advanced Synthesis and Catalysis, 2017, vol. 359, # 14, p. 2407 - 2413]
[7]Wang, Ming; Fan, Qiaoling; Jiang, Xuefeng [Organic Letters, 2018, vol. 20, # 1, p. 216 - 219]
[8]Nguyen, Nghi; Wilson, Danny W.; Nagalingam, Gayathri; Triccas, James A.; Schneider, Elena K.; Li, Jian; Velkov, Tony; Baell, Jonathan [European Journal of Medicinal Chemistry, 2018, vol. 148, p. 507 - 518]
[9]Xu, Yankun; Liu, Xiaodong; Chen, Wenqi; Deng, Guobo; Liang, Yun; Yang, Yuan [Journal of Organic Chemistry, 2018, vol. 83, # 22, p. 13930 - 13939]
[10]Wang, Gang; Xiong, Biquan; Zhou, Congshan; Liu, Yu; Xu, Weifeng; Yang, Chang-An; Tang, Ke-Wen; Wong, Wai-Yeung [Chemistry - An Asian Journal, 2019, vol. 14, # 23, p. 4365 - 4374]
[11]Elsherbini, Mohamed; Moran, Wesley J. [Organic and Biomolecular Chemistry, 2021, vol. 19, # 21, p. 4706 - 4711]
[12]Zhang, Minghao; Deng, Wenbo; Sun, Mingjie; Zhou, Liwei; Deng, Guobo; Liang, Yun; Yang, Yuan [Organic Letters, 2021, vol. 23, # 15, p. 5744 - 5749]
  • 4
  • [ 1204-44-0 ]
  • [ 98-09-9 ]
  • N-(4'-chloro-[1,1'-biphenyl]-2-yl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere;
With pyridine
With pyridine In dichloromethane at 20℃; for 16h; Inert atmosphere;
YieldReaction ConditionsOperation in experiment
With sodium hypobromide
  • 6
  • [ 100-65-2 ]
  • [ 108-90-7 ]
  • [ 1205-71-6 ]
  • [ 1204-44-0 ]
  • [ 1203-43-6 ]
  • [ 1204-42-8 ]
  • 7
  • [ 108-90-7 ]
  • [ 100-63-0 ]
  • [ 1205-71-6 ]
  • [ 1204-44-0 ]
  • [ 1203-43-6 ]
  • 9
  • 2-methyl-5-difluoromethyl-2H-1,2,3-triazole-4-carboxylic acid methyl ester [ No CAS ]
  • [ 1204-44-0 ]
  • 5-difluoromethyl-2-methyl-2H-1,2,3-triazole-4-carboxylic acid (4'-chloro-biphenyl-2-yl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With sodium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 22.275h; 4 EXAMPLE 4; This Example illustrates the preparation of Compound No. 3.017 [5-difluoromethyl-2-methyl-2H-1, 2,3-triazole-4-carboxylic acid (4'-chloro-biphenyl-2- yl)-amide]. To a solution [OF 2-METHYL-5-DIFLUOROMETHYL-2H-1,] 2,3-triazole-5-carboxylic acid methyl ester (300mg; 1.57mmol) and [4'-CHLORO-BIPHENYL-2-YLAMINE] (320mg; 1. [57MMOL)] in THF [(3ML)] was added sodium bis [(TRIMETHYLSILYL)-AMIDE] (0. 88ml 2M in THF; 1.76mmol ; 1. [12EQ.)] by syringe at [0°C] over 1. 5minutes. The reaction mixture was stirred at [0°C] for 15minutes and then at ambient temperature for 22 hours. It was then poured on cold saturated [NH4CL] solution and extracted with ethyl acetate. After washing with brine it was dried (anhydrous [MGSO4)] and evaporated to dryness to give a solid, which was triturated with hexane. The colourless crystalline product was filtered and dried: 300mg (53%) [m. p. [155-156°C] ; 1H-NMR [(300MHZ,] CDCl3), [6] (ppm): 8.5 (br, exchangeable with [D20,] 1H), 8.4 (d, 1H), 7.5-7. 2 (m, 7H), 7.38 (t, [JHF] = 52.5 Hz, 1H, [CHF2),] 4.2 (s, 3H), LC-MS: 363 [(M+H)].]
  • 10
  • [ 203448-82-2 ]
  • [ 1204-44-0 ]
  • [ 577955-06-7 ]
YieldReaction ConditionsOperation in experiment
44.5% With triethylamine In tetrahydrofuran at -20 - 0℃; for 2h;
  • 11
  • [ 202476-26-4 ]
  • [ 1204-44-0 ]
  • N-(4'-chlorobiphenyl)-1,3-dimethyl-5-fluoropyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In tetrahydrofuran; di-isopropyl ether; cyclohexane; water 2 N-(4'-chlorobiphenyl)-1,3-dimethyl-5-fluoropyrazole-4-carboxamide N-(4'-chlorobiphenyl)-1,3-dimethyl-5-fluoropyrazole-4-carboxamide At +5° C., a solution of 1.15 g (7 mmol) of 1,3-dimethyl-5-fluoropyrazole-4-carbonyl chloride in 3 ml of tetrahydrofuran was added dropwise to a solution of 1.42 g (7 mmol) of 2-amino-4'-chlorobiphenyl and 0.71 g (7 mmol) of triethylamine in 7 ml of tetrahydrofuran, and the mixture was then stirred for 20 minutes at +5° C. and for 2 hours at room temperature. The mixture was stirred into 140 ml of water and the precipitated was filtered off by suction. Digestion with a mixture of diisopropyl ether and cyclohexane (1:2) gave 1.5 g of the title compound (m.p.: 146-150° C., no. 1.10 in the table below).
  • 12
  • [ 463-71-8 ]
  • [ 1204-44-0 ]
  • [ 139769-03-2 ]
YieldReaction ConditionsOperation in experiment
In 1,4-dioxane; water 67 EXAMPLE 67 EXAMPLE 67 Reaction of 2-amino-4'-chlorobiphenyl (8.7 g) and thiophosgene (7.4 g) in a mixture of dioxane (10 ml) and water (10 ml) at 0°-5° C. for 20 minutes and then at ambient temperature for 3 hours yielded 4'-chloro-2-biphenylylisothiocyanate (m.p. 63° C.) as a yellow solid.
  • 13
  • C6H7ClF2N2O [ No CAS ]
  • [ 1204-44-0 ]
  • N-[2-(4-chlorophenyl)phenyl]-3-(difluoromethyl)-1-methyl-4,5-dihydro-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane at 20℃; for 16h; P1.c S-Difluoromethyl-i -methyM.δ-dihydro-I H-pyrazole^-carboxylic acid (0.1 g, 0.5 mmol) was dissolved in 2 ml of dichloromethane containing 1 drop of N, N- dimethylformamide. A solution of oxalyl chloride (78 mg, 0.6 mmol) in 2 ml of dichloromethane was added dropwise at room temperature. This mixture was stirred for 2 h at the same temperature and subsequently slowly added to a mixture of 4'-chloro-biphenyl-2- ylamine (0.1 1 g, 0.5 mmol) and triethylamine (85 mg, 0.8 mmol) in 2 ml of dichloromethane. After stirring the reaction mixture for 16 h at room temperature, it was poured on ice and extracted with dichloromethane. The combined organic layer was washed with brine, dried over magnesium sulfate and evaporated. The remaining oil was purified by silica gel chromatography using ethyl acetate and hexane as eluents, giving 40 mg of 3- difluoromethyl-1 -methyl-4,5-dihydro-1 H-pyrazole-4-carboxylic acid (4'-chloro-biphenyl-2-yl)- amide (Compound No.1.006).
40 mg With triethylamine In dichloromethane at 20℃; for 16h; Inert atmosphere; N-[2-(4-Chlorophenyl)phenyl]-3-(difluoromethyl)-1-methyl-4,5-dihydro-1H-pyrazole-4-carboxamide (9, C18-H16ClF2N3O) 3-(Difluoromethyl)-1-methyl-4,5-dihydro-1H-pyrazole-4-carboxylic acid (0.1 g, 0.6 mmol) was dissolvedin 2 cm3 of dichloromethane containing one drop ofN,N-dimethylformamide. A solution of 78 mg oxalyl chloride(0.6 mmol) in 2 cm3 of dichloromethane was added atroom temperature. This mixture was stirred for 1 h at roomtemperature and then slowly added to a mixture of 0.11 g 40-chlorobiphenyl-2-amine (0.6 mmol) and 85 mg triethylamine(0.8 mmol) in 2 cm3 of dichloromethane. The reactionmixture was stirred for 16 h at room temperature, thenpoured on water and extracted with dichloromethane. Theorganic layer was washed with brine, dried over sodiumsulfate, and evaporated under reduced pressure. The residuewas purified by chromatography on silica gel, using ethylacetate/heptane 1:3 as eluent, to deliver 40 mg N-[2-(4-chlorophenyl)phenyl]-3-(difluoromethyl)-1-methyl-4,5-dihydro-1H-pyrazole-4-carboxamide (9, 0.2 mmol, 35%). 1HNMR (400 MHz, CDCl3): d = 2.83 (s, 3H), 3.59-3.68 (m,2H), 5.72 (t, 1H, J = 54.5 Hz), 6.44 (s, 1H), 7.12-7.22 (m,5H), 7.31-7.43 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3):d = 24.7, 108.3, 110.0, 113.2, 117.5, 117.9, 121.8, 123.6,124.8, 126.1, 129.2, 129.7, 130.4, 133.3, 134.02, 135.1,136.7, 160.6 ppm; LC-MS: tR = 1.73 min; MS: m/z = 364([M?1]?).
  • 14
  • 3-(trifluoromethyl)pyrazine-2-carbonyl chloride [ No CAS ]
  • [ 1204-44-0 ]
  • N-(4'-chlorobiphenyl-2-yl)-3-trifluoromethyl-pyrazine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In tetrahydrofuran at 20℃; for 2h; 2 Example 2 : Production of N- ( 4 ' -chlorobiphenyl-2-yl) -3-trifluoromethyl- pyrazine-2-carboxamide (Compound No. 3-6); Triethylamine ( 0.32 g : 1.5 mmole ) was added to a solution of 4 ' -chlorobiphenyl-2-ylamine (0.3 g: 1.5 mmole) and 3-trifluoromethylpyrazine-2-carboxylic acid chloride (0.32 g: 1.5 mmole) in THF (10 mL), followed by stirring at room temperature for 2 hours . Water was added to the reaction mixture to suspend the reaction, followed by extraction with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated in vacuo, and the residue was purified by silica gel column chromatography to give the subject compound (0.47 g) .Yield: 85 %Typical physical properties: melting point of 144 to 145" C
  • 15
  • [ 79-37-8 ]
  • [ 1204-44-0 ]
  • [ 113100-53-1 ]
  • [ 344429-50-1 ]
YieldReaction ConditionsOperation in experiment
With triethylamine;N,N-dimethyl-formamide; In water-jet-vacuum; dichloromethane; water; ethyl acetate; Reference Example 1 1-Methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (4'-chlorobiphenyl-2-yl) amide A solution of <strong>[113100-53-1]1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid</strong> (0.68 g) and oxalyl chloride (0.49 g) in methylene chloride (30 ml) is stirred for 2 hours at room temperature in the presence of a catalytic amount of DMF. The resulting acid chloride solution is then added to a solution of 4'-chlorobiphenyl-2-ylamine (0.71 g) and triethylamine (0.36 g) in 15 ml of methylene chloride at 0C. The reaction mixture is then stirred for 4 hours at room temperature. After distilling off the solvent in a water-jet-vacuum, the residue is taken up in ethylacetate/water. The ethylacetate phase is extracted twice with water. After drying of the organic phase with Na2SO4, the solvent is distilled off in a water-jet-vacuum and the residue purified by column chromatography (silica gel; eluant: ethylacetate/hexane=1:1). 0.8 g of <strong>[113100-53-1]1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid</strong> (4'-chlorobiphenyl-2-yl) amide are obtained in the form of slightly brownish crystals having a melting point of 144-146C.
  • 16
  • [ 400743-82-0 ]
  • [ 20012-63-9 ]
  • [ 39643-31-7 ]
  • [ 728918-72-7 ]
  • C8H7F4N [ No CAS ]
  • C33H29IN5O4Pol [ No CAS ]
  • [ 91646-45-6 ]
  • [ 4273-98-7 ]
  • [ 2264-92-8 ]
  • [ 1204-44-0 ]
  • [ 68817-71-0 ]
  • [ 369-36-8 ]
  • [ 37750-29-1 ]
  • [ 55751-54-7 ]
  • [ 18595-14-7 ]
  • [ 52562-19-3 ]
  • [ 62532-99-4 ]
  • [ 21627-58-7 ]
  • [ 73818-73-2 ]
  • [ 54705-91-8 ]
  • [ 26286-54-4 ]
  • [ 177171-13-0 ]
  • [ 99-55-8 ]
  • [ 23491-48-7 ]
  • [ 400750-84-7 ]
  • C42H37N8O4Pol [ No CAS ]
  • C42H37N8O4Pol [ No CAS ]
  • C43H43N6O4Pol [ No CAS ]
  • C42H39N6O4Pol [ No CAS ]
  • C43H37N6O4PolS [ No CAS ]
  • C40H36N7O6Pol [ No CAS ]
  • C42H39N6O6Pol [ No CAS ]
  • C39H33FN7O6Pol [ No CAS ]
  • C44H39N6O5Pol [ No CAS ]
  • C45H38ClN6O4Pol [ No CAS ]
  • C46H41N6O4Pol [ No CAS ]
  • C43H42N7O4Pol [ No CAS ]
  • C46H41N6O5Pol [ No CAS ]
  • C45H38FN6O4Pol [ No CAS ]
  • C45H38ClN6O4Pol [ No CAS ]
  • C41H35F4N6O4Pol [ No CAS ]
  • C45H39N6O6PolS [ No CAS ]
  • C45H38ClN6O4PolS [ No CAS ]
  • C44H44N7O4Pol [ No CAS ]
  • C47H41N6O5Pol [ No CAS ]
  • C45H39ClN7O4Pol [ No CAS ]
  • C47H41N6O6Pol [ No CAS ]
  • C45H45N8O5Pol [ No CAS ]
  • C44H44N9O6Pol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In ISOPROPYLAMIDE; at 60℃;Combinatorial reaction / High throughput screening (HTS); Step 2. Catalytic amination of the solid supported 8-iodo-l-methyl-4,5-dihydro- lH-pyrazolo [4,3-h] quinazoline-3-carboxamide; <n="82"/>Using a 4 niL Argonaut Trident synthesizer cassette, 200 mg (0.11 mmol) of the resin from step 1 above, were charged into separate vials. To each of the reactor vials flushed with argon, finely divided potassium carbonate (0.15 g, 1.1 mmol), palladium acetate [Pd(OAc)2] (2.5mg, 0.011 mmol, 10%), (HK)-BINAP (6.8 mg, 0.011 mmol, 10%) and the corresponding amine (0.22 mmol, 2 equivalents) in degassed (argon) dimethyacetamide (2 mL) were added. The resulting mixture was agitated at 600C for 10 hours on the Argonaut Trident Automated Library Synthesizer (ALS) station. The Trident ALS station was programmed to continuously mechanically agitate the resin at 6O0C while a nitrogen gas "sparge" was incorporated to re-suspend the scarcely soluble potassium carbonate. Nitrogen gas sparging was incorporated once per hour, for a 30 second duration, throughout the 16-hour heating cycle.The resin was drained from the synthesis cocktail and washed using the Argonaut Trident External Agitation Thermal Unit (EATU) synthesis station with DMA (3 x 2 mL, 5 min.). The above catalytic amination cycle was repeated a second time using the previously described procedure.Upon completion of the second amination cycle, the resin was drained from the synthesis cocktail and washed using the Argonaut Trident EATU synthesis station with DMF (1 x 2 mL, 5 min.), with water (1 x 2 mL, 5 min.), with DMF/water (1 : 1) (3 x 2 mL, 5 min.), with DMF (3 x 2 mL, 5 min.), with methanol (3 x 2 mL, 5 min.) and with DCM (3 x 2 mL, 5 min.).
  • 17
  • C11H11F3N2O [ No CAS ]
  • [ 1204-44-0 ]
  • 3-(4'-chloro-biphenyl-2-ylamino)-3-(1-methyl-4-trifluoromethyl-1H-pyrrol-3-yl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With sodium hexamethyldisilazane In tetrahydrofuran at 20℃; for 16h;
  • 18
  • [ 49609-84-9 ]
  • [ 1204-44-0 ]
  • [ 188425-85-6 ]
YieldReaction ConditionsOperation in experiment
95% In isopropyl alcohol; at 40 - 65℃; for 4h; [0049] Boscalid was prepared following the same general reaction sequence as in Example 1 above.100501 3.5 g of 2-chloro-nicotinoyl chloride was dripped into a solution of 5.0 g of 4- chloro-biphenyl-2-ylamine in 30 ml iso-propanol held in a reaction flask at 40 C. The reaction flask was connected to an external HCL adsorber containing anadsorbent comprising activated alumina and an alkali metal promoter. The mixture was then heated to 65 C and maintained at this temperature for 2 hours with stirring.100511 The resulting mixture was then cooled with stirring to room temperature and boscalid solid allowed to crystallize out of solution. The boscalid solid was recovered in an amount equivalent to a yield of 95% based on the 2-chloro-nicotinoyl chlorideused.
93% With triethylamine; In tetrahydrofuran; at 25℃; for 1h; To a solution of chloronicotinic acid chloride (1.85g, 10.1mmol) in THF (10 mL) was added a solution of aniline 4 (2.04g, 10 mmol) in THF (10 mL) followed by Et3N (1.10g, 11 mmol). The reaction mixture was stirred for 1 h at room temperature and concentrated under vacuum. Purification of the residue by flash chromatography gave 5 as a white solid, 3.19g.
92.3% In 5,5-dimethyl-1,3-cyclohexadiene; for 5h;Reflux; (3) 6.1 g (0.03 mol) of 4'-chloro-2-aminobiphenyl and 40 mL of xylene were charged into a 100 mL three-Stirred and heated to reflux, and a solution of 6.3 g (0.036 mol) of 2-chloronicotinoyl chloride in 20 mL of xylene was slowly added dropwise,Drip after the incubation reaction 5h. After cooling to room temperature, the mixture was washed and washed with water,Concentrated cooling gave 9.5 g of 2-chloro-N- (4'-chlorobiphenyl-2-yl) nicotinamide in a yield of 92.3%
91% With sodium carbonate; aniline; In water; at 75 - 90℃; for 1h; Example 7The 153.6g 2- (4- chlorophenyl) aniline (0.738mol) was dissolved in 152.5g xylene solution, and adding 686 water and 65.7g of sodium carbonate, heated to 75 deg. C . Then afterwards, 139.2g 2-chloronicotinoyl chloride (0.775mol) was dissolved in a solution of 423g of xylene. After heating to 75 deg. C slowly put in a mixture of aniline, xylene, water and sodium carbonate. Control system temperature to reach 90 deg. C .Under stirring speed of 10r / min using an anchor stirrer, maintain temperaturefor 1h. After heating, at a 20 / h cooling rate, cool to 30 deg. C , and then the mixture was suction filtered, the product placed in an oven 90 adjust dried, and finally dried sample was 234.0g, purity 98.4%, yield 91.0%, by differential thermal analysisa melting point of 148 deg. C.
91.7% at 50℃; 20.4g (0.10mol) of 2-(4-chlorophenyl)aniline was added to the reaction flask, and the temperature was raised to 50 degrees. 21.1 g (0.12 mol) of 2-chloronicotinoyl chloride was added in portions, and the reaction was continued by HPLC. The raw material is completely reacted, added to the solvent, cooled, and suction filtered.The white solid was dried to 31.5 g, yield 91.7%.
87% With triethylamine; In dichloromethane; for 6h;Reflux; 0394] To a solution of 4?-chlorobiphenyl-2-amine (0.28 mmol, 58 mg) and triethylamine (1.40 mmol, 0.20 ml) in dichloromethane (4.4 ml) was slowly added, at 0 C., a solution of 2-chloronicotinyl chloride (0.41 mmol, 72 mg) in methylene chloride (0.9 ml). The mixture was allowed to thaw to room temperature for 3 h, stirred for a further hour and then heated to reflux for 2 h. The organic phase was washed with water and saturated sodium chloride solution and dried over sodium sulfate. After concentration under reduced pressure, the crude product was purified by means of column chromatography (silica gel, hexane/EtOAc=3:1) to obtain 2-chloro-N-(4?-chlorobiphenyl-2-yl)-nicotinamide (0.25 mmol; 85 mg; 87%). [0395] Rf 0.4 (hexane/EtOAc=3:2) [UV]. [0396] 1H NMR (600 MHz, CDCl3): delta=7.26-7.28 (m, 2H), 7.34 (d, J=8.4 Hz, 2H), 7.35 (m, 1H), 7.43 (d, J=8.5 Hz, 2H), 7.45-7.48 (m, 1H), 8.13 (dd, J=1.9 Hz, J=7.7 Hz, 1H), 8.14-8.17 (m, 1H), 8.41 (d, J=8.2 Hz, 1H), 8.44 (dd, J=1.9 Hz, J=4.7 Hz, 1H).
87% With triethylamine; In dichloromethane; for 6h;Reflux; To a solution of 4'-chlorobiphenyl-2-amine (0.28 mmol, 58 mg) and triethylamine (1.40 mmol, 0.20 ml) indichloromethane (4.4 ml) at 0 C was slowly added 2-chloro Nicotinyl chloride (0.41 mmol, 72 mg) indichloromethane (0.9 ml). The mixture was stirred to room temperature and held for 3 hours, stirred for an additional hour, then heated to reflux and held for 2 hours. The organic phase was washed with water andsaturated sodium chloride solution and dried over sodium sulfate. After purification under reduced pressure, thecrude product was purified by column chromatography (silica gel, hexane / EtOAc = 3: 1) to give 2-chloro-N-(4'-chlorobiphenyl-2-yl) nicotinamide (0.25 mmol;85mg ; 87%).
60% With sodium carbonate; In dichloromethane; at 20℃; for 3h; 0.1 mol of sodium carbonate and 1.1 mol of 2-(4-chlorophenyl)aniline obtained in the third step were added to the reaction kettle, and 36 mL of 2-chloronicotinoyl chloride dissolved in dichloromethane was slowly added dropwise to the reaction kettle at room temperature under stirring. Stir for 3 hours,Add 100 mL of water to wash and separate the water layer.The oil layer is desolvated to recover dichloromethane, and then re-crystallized with 50 mL of ethanol.Filtration, washing, and drying to obtain boscalid, in terms of p-chlorobromobenzene.The total synthetic yield is over 60%.The product content reaches 98%.
With triethylamine; In dichloromethane; at 20℃; for 3h; The 2- (4-chlorophenyl) aniline intermediate and triethylamine were dissolved in dichloromethane to obtain a mixed solution Liquid, at room temperature, A solution of 2-chloronicotinoyl chloride in dichloromethane was slowly added to the mixed solution, After adding, the reaction was stirred for 3 h, Separate the organic phase, the organic phase were washed with saturated sodium carbonate, Washed with water, washed with saturated saline, dried over anhydrous magnesium sulfate, Filtration, the filtrate evaporated to obtain the second solvent after the crude product, Then recrystallized with methanol to give boscalid, 2- (4-chlorophenyl) aniline, triethylamine, The molar ratio of 2-chloronicotinyl chloride organic solvent and the second solvent is 1: 5: 1: 35,2_ chloronicotinyl chloride in dichloromethane The molar ratio of 2-chloronicotinoyl chloride to methylene chloride is 1:12.

  • 19
  • [ 89566-59-6 ]
  • [ 615-36-1 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
Stage #1: di-(p-chlorophenyl)borinic acid With sodium hydroxide In tetrahydrofuran; water at 20℃; for 1h; Stage #2: With triphenylphosphine In tetrahydrofuran; water at 20℃; for 0.5h; Stage #3: 2-bromoaniline With hydrogenchloride In tetrahydrofuran; water at 100℃; for 12h;
  • 20
  • [ 6271-80-3 ]
  • [ 1204-44-0 ]
  • [ 90-41-5 ]
YieldReaction ConditionsOperation in experiment
With 10% palladium on activated carbon; hydrogen In methanol at 40℃;
With 10 % platinum on carbon; hydrogen In water; <i>tert</i>-butyl alcohol at 60℃;
With 10% Pt/activated carbon; hydrogen In water; ethyl acetate at 45℃; for 0.5h;
  • 21
  • [ 141573-96-8 ]
  • [ 1204-44-0 ]
  • [ 188425-85-6 ]
YieldReaction ConditionsOperation in experiment
73% In toluene; xylene; at 10 - 95℃; under 150.015 Torr; Example 8 Synthesis of 2-chloro-N-(4'-chlorobiphenyl-2-yl)nicotinamide 100.0 g (0.557 mol, 98% pure) of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride were dissolved at 25 C. in 80.0 g of toluene. The solution was evacuated to 200 mbar and heated to 95 C. Subsequently, within 2.5 hours, 396.8 g (0.541 mol, 28% strength) of xylenic 4'-chlorobiphenyl-2-ylamine solution were metered in and the reaction mixture was stirred for a further 1 hour. After venting and cooling to 87 C., the mixture was seeded with 1 g of 2-chloro-N-(4'-chlorobiphenyl-2-yl)nicotinamide and the temperature was maintained for 1 hour. Subsequently, the mixture was cooled to 25 C. with a ramp of 5 C/h. After further cooling to 10-15 C., the solids were filtered off, washed with cold xylene and dried at 80 C. under reduced pressure. The yield (without further processing of the mother liquor) was 166.4 g (73%). HPLC shows the desired product and the diacylated product in a ratio of 85:15 area %.
  • 22
  • [ 1679-18-1 ]
  • [ 615-36-1 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
97% With palladium diacetate; anhydrous sodium carbonate In ethanol; lithium hydroxide monohydrate at 100℃; for 24h; 1-18 Example 2 Place o-bromoaniline (1 mmol), p-chlorophenylboronic acid (2 mmol), sodium carbonate (3 mmol), and palladium acetate (2 mol%) in a 25 mL round bottom flask, add water / ethanol (volume ratio 1: 1) ) 6 mL of the mixed solution, stirred at 100 oC for 24 h. After the reaction was completed, it was cooled to room temperature, and then extracted with ether. After spin-drying the organic solvent,The product is obtained after separation,The yield is 97%.
97% With tetrabutylammonium bromide; C32H26Cl2N8O4Pd2; potassium carbonate In methanol; lithium hydroxide monohydrate for 0.166667h; Reflux;
95% With tripotassium phosphate tribasic; 1,3-bis[(methyl-2-methoxy-3-deoxy-4,6-dioxabenzylidene-α-D-altropyranos-3-yl)imidazol-2-ylcarbene]allylpalladium(II) chloride In dodecane; lithium hydroxide monohydrate; toluene at 130℃; for 12h; 1-19 General procedure for Suzuki-Miyaura reaction General procedure: Weigh 4-chlorophenylboronic acid (235 mg, 1.5 mmol), potassium phosphate (424 mg, 2.0 mmol), 2-bromoaniline (172 mg, 1.0 mmol) into a pressure-resistant bottle (15 mL) with magnetons in sequence , Dodecane (85 mg, 0.5 mmol), water (3.0 mmol), toluene (2 mL) and catalyst (0.00006 mmol), the reaction was stirred at 130 . After the reaction solution was cooled to room temperature, ethyl acetate (2 mL) was added dropwise and stirred for 10 minutes to terminate the reaction. Saturated brine (10 mL) was added and extracted with ethyl acetate (10 mL * 3). The combined organic phases were dried over anhydrous sulfuric acid. Sodium was dried, the solvent was evaporated under reduced pressure, and the product was purified by silica gel column chromatography.
95% With tetrabutylammonium bromide; potassium carbonate In lithium hydroxide monohydrate at 100℃; for 0.75h; 2-Amino-4-chlorobiphenyl Following the general procedure,the reaction of 2-bromoaniline (1.72 g, 10 mmol) with 4-chlorophenylboronic acid (1.72 g, 11 mmol) in the presence of K2CO3 (3.45 g, 25 mmol) and Bu4NBr (0.0322 g, 0.1 mmol, 1 mol.%) acting as the phase transfer carrier was carried out in H2O (100 mL) in the presence of the Pd-Fe-Co-NiPd composite (50 mg , 1 mol.% Pd). The reaction mixture was refluxed with stirring for 15 min; according to TLC data, this time was long enough for the reaction to complete. Then, the mixture was diluted with water (100 mL), heated to 100 and kept at this temperature for an additional 30 min, cooled to room temperature and filtered to separate the cross-coupling products and the catalyst. Hexane (50 mL) was added to the residue, the mixture was heated until complete dissolution of the reaction productand the catalyst (48 mg) was separated using an external magnet.The solution thus obtained was cooled at 2-3 C for 3 h, the crystals that precipitated were filtered off and dried at room temperature in air for 12 h. White crystalline powder (1.94 g,95%) was obtained, m.p. 48-49 C (cf. 47-48 C according to Ref. 33). Foun d (%): C, 70.69; H, 5.01; N, 6.84. C12H10NCl.Calculated (%): C, 70.77; H, 4.95; N, 6.88; Cl, 17.41. 1H NMR(400 MHz, CDCl3, δ): 3.63 (br.s, 2 H, NH2); 6.78 (dd, 1 H,J = 7.9 Hz, J = 1.0 Hz); 6.85 (td, 1 H, J = 7.6 Hz, J = 1.0 Hz);7.11 (dd, 1 H, J = 7.6 Hz, J = 1.5 Hz); 7.19 (td, 1 H, J = 7.9 Hz,J = 1.0 Hz); 7.38-7.46 (m, 4 H). 13C NMR (100 MHz, CDCl3,δ): 115.7, 118.7, 126.2, 128.8, 128.9, 130.3, 130.4, 133.0, 137.8,143.4. Mass spectrum, m/z (I (%)): 205 [37Cl - M]+ (27),204 (12), 203 [35Cl - M]+ (100), 202 (13), 169 (17), 168 (55),167 (34), 166 (16), 83 (26).
92% With [Pd(N-(3-chloro-2-quinoxalinyl)-N'-(2,6-diisopropylphenyl)imidazolium)(PPh3)Cl2]; potassium carbonate In lithium hydroxide monohydrate at 70℃; for 3h;
91% With anhydrous sodium carbonate; triphenylphosphine In lithium hydroxide monohydrate at 80℃; for 18h; Schlenk technique; Suzuki-Miyaura cross-coupling reaction General procedure: A mixture of aryl halide (0.25 mmol), phenylboronicacid (0.3 mmol), Na2CO3 (0.25 mmol), PPh3 (0.025 mmol)and Pd(at)PAAs-CD (0.5 mg, 0.2 mol% Pd per mol of arylhalide) were placed into a 10 mL Schlenck tube with1 mL H2O. The reaction mixture was reacted at 80 °C for18 h, and the reaction progress was monitored via gaschromatography mass spectrometry (GC-MS). The reactionmixture was allowed to cool to room temperature, andthen 3 mL water was added, and the product was extractedwith ethyl acetate (3 mL × 3). The organic layers werecombined and dried over anhydrous Na2SO4 and solventswere evaporated via rotary evaporator. The crude productwas purified by column chromatography (200-300 meshsilica) using a mixture of petroleum ether/ethyl acetate(10:1, v:v) as eluent. The structures of the products wereconfirmed by 1H NMR and 13C NMR spectroscopies.
91% With tert-butyldicyclohexylphosphine; palladium diacetate; anhydrous sodium carbonate In cyclohexane; lithium hydroxide monohydrate at 100℃; for 5h; Sealed tube; Inert atmosphere;
89% With C13H22N2*Pd(2+)*2Cl(1-); potassium carbonate In lithium hydroxide monohydrate; ethylene glycol for 0.25h; Reflux; Schlenk technique; 2.1 General procedure General procedure: A 20mL Schlenk tube with a magnetic stir bar was charged with aryl halide (2mmol), arylboronic acid (2.4mmol), K2CO3 (5mmol), 10mL of solvent [H2O, H2O-MeOH (1:1), H2O-EtOH (1:1), H2O-EG (1:1)] and an aliquot of 0.01M solution of palladium complexes PdCl2(L)2 or Pd[(L)4]Cl2 in MeOH (0.001-0.2mol%) under air atmosphere. The reaction mixture was placed in a preheated oil bath: at 100°C for MeOH-H2O, at 110°C for EtOH-H2O, at 140°C for H2O and at 160°C for EG-H2O; and stirred under reflux for the given time. After this time, the mixture was cooled, acidified by 5M HCl (in the case of acids) and diluted with 10mL of H2O and 10mL of Et2O (or EtOAc). The organic phase was separated, and the aqueous layer was extracted with Et2O EtOAc) (2×10mL). The combined organic layers were washed with H2O (10mL), brine (10mL), and dried over Na2SO4. The pure products were obtained by a simple filtration of ether solution through silica gel pad and evaporation of a solvent.
88% With C30H32NO6P2S2(1-)*2Na(1+)*Br(1-); anhydrous sodium carbonate; palladium (II) chloride In lithium hydroxide monohydrate at 20℃; for 8h;
85% With palladium diacetate; anhydrous sodium carbonate In lithium hydroxide monohydrate; propan-2-one at 35℃; for 12h;
84% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate In 1,2-dimethoxyethane; lithium hydroxide monohydrate at 80℃;
84% Stage #1: p-chlorobenzeneboronic acid; 2-bromoaniline With potassium carbonate In 1,2-dimethoxyethane; lithium hydroxide monohydrate for 0.5h; Stage #2: With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) In 1,2-dimethoxyethane; lithium hydroxide monohydrate at 80℃;
72% With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In ethanol; lithium hydroxide monohydrate; toluene at 100℃; Inert atmosphere; 1.1-A 1-A) Synthesis of Intermediate 1-A-1 Under a stream of nitrogen, a round bottom flask was charged with 2-bromoaniline (2-bromoaniline, 100 g, 581.3 mmol) (4-chlorophenyl)boronic acid (90.87 g, 581.3 mmol), K2CO3 (200.86 g, 1453.3 mmol), Pd(PPh3)4 (13.43 g, 11.62 mmol), toluene (800 mL), ethanol (200 mL) and water (400 mL), and then reacted at 100°C with stirring. After the completion of the reaction, the organic layer was separated, and after dewatering and filtration, it was purified by silicagel column chromatography and recrystallization to prepare 85.23 g of Intermediate 1-A-1 (yield: 72%).
68% With palladium 10% on activated carbon; potassium carbonate In 1,4-dioxane; lithium hydroxide monohydrate at 95℃; for 6h;
68% With palladium 10% on activated carbon; potassium carbonate In 1,4-dioxane; lithium hydroxide monohydrate at 95℃; for 6h;
With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In ethanol; lithium hydroxide monohydrate; toluene at 100℃; for 16h;
With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In ethanol; lithium hydroxide monohydrate; toluene at 95℃; for 16h; Inert atmosphere;
With tetrakis-(triphenylphosphine)-palladium; potassium phosphate heptahydrate In tetrahydrofuran at 80℃; Inert atmosphere; Schlenk technique;
With palladium diacetate; anhydrous sodium carbonate In lithium hydroxide monohydrate; propan-2-one at 35℃; for 12h;
With palladium diacetate; anhydrous sodium carbonate In lithium hydroxide monohydrate; propan-2-one at 35℃; for 12h; 4.2. General procedure for preparation of biphenylamine derivatives General procedure: A vessel with a magnetic stir bar was charged with Na2CO3 (2.120 g, 20 mmol, 2.0 equiv), Pd(OAc)2 (112 mg, 0.500 mmol, 5 mol%), 2-bromoaniline (10 mmol, 1.0 equiv), arylboronic acid (15 mmol, 1.5 equiv), distilled water (35 mL), and acetone (30 mL). Then the mixture was stirred for 12 h at 35 °C. Afterward the resulting solution was filtered through a plug of Celite and the residue was washed with ethyl acetate (30 mL). The filtrate was extracted three times with diethyl ether (3x30 mL). The combined organic phases were washed with brine (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash column chromatography with ethyl acetate (EA) and petroleum ether (Pet) as eluent to afford the corresponding 2-amidobiphenyl derivatives (1b-1k, 1m-1o, and 1q).
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 80℃; for 24h; Inert atmosphere;
With tetrakis-(triphenylphosphine)-palladium; potassium phosphate heptahydrate In tetrahydrofuran at 100℃; for 12h; Inert atmosphere; Schlenk technique;
Stage #1: p-chlorobenzeneboronic acid; 2-bromoaniline With potassium carbonate In 1,2-dimethoxyethane; lithium hydroxide monohydrate at 20℃; for 0.5h; Inert atmosphere; Stage #2: With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) In 1,2-dimethoxyethane; lithium hydroxide monohydrate at 20 - 80℃; Inert atmosphere;
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 80℃; for 24h; Inert atmosphere;
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 80℃; for 12h; Inert atmosphere;
Stage #1: p-chlorobenzeneboronic acid; 2-bromoaniline With potassium carbonate In 1,2-dimethoxyethane; lithium hydroxide monohydrate at 20℃; for 0.5h; Inert atmosphere; Stage #2: With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) In 1,2-dimethoxyethane; lithium hydroxide monohydrate at 80℃; Inert atmosphere;
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 90℃; for 24h; Sealed tube; Inert atmosphere;
With di-tert-butyl(phenyl)phosphonium tetrafluoroborate; palladium(II) 2,4-pentanedionate; potassium carbonate In lithium hydroxide monohydrate; butan-1-ol at 60℃; for 20h; Inert atmosphere; General procedure: Under argon, a mixture of N-(2-bromo-4-fluorophenyl)acetamide (1.00 g, 4.27 mmol), bis(3,4-dichlorophenyl)borinic acid (0.685 g, 2.14 mmol), potassium carbonate (1.03 g, 7.44 mmol), [(t-Bu)2PhPH]BF4 (1.6 mg, 5.2 μmol), Pd(acac)2 (1.6 mg, 5.3 μmol) was heated to 60° C. in 8 ml of water and 2 ml of 1-butanol. The reaction mixture was stirred at 60° C. for about 13 hours, cooled to room temperature and acidified with 1 N hydrochloric acid. After extracting the reaction mixture twice with ethyl acetate, the combined organic phases were dried over magnesium sulphate. The solvent was distilled off under reduced pressure. 1.21 g of crude product were obtained (90.8 area % HPLC, 86% yield).
With di-tert-butyl(phenyl)phosphonium tetrafluoroborate; palladium (II) 2,4-pentanedionate; potassium carbonate In lithium hydroxide monohydrate; butan-1-ol at 60℃; for 13h; Inert atmosphere; Preparation of N- (3',4'-dichloro-5-fluorobiphenyl-2-yl)acetamide General procedure: N- (2-bromo-4-fluorophenyl) acetamide (1.00 g, 4.27 mmol), bis (3,4-dichlorophenyl) boronic acid (0.685 g, 2.14 mmol) A mixture of potassium carbonate (1.03 g, 7.44 mmol), [(t-Bu) 2 PhhPH] BF4 (1.6 mg, 5.2 μmol) and Pd (acac) 2 (1.6 mg, 5.3 μmol)8 ml of water and 2 ml of 1-butanol was heated to 60 ° C. The reaction mixture was stirred at 60 deg.] C for about 13 hours, cooled to room temperature, acidified with 1N hydrochloric acid. The reaction mixture was extracted twice with ethyl acetate and the combined organic phases were dried over magnesium sulfate. The solvent was distilled off under reduced pressure. 1.21 g of crude product was obtained (90.8 area% HPLC, 86% yield).
With tetrakis-(triphenylphosphine)-palladium; carbon monoxide; oxygen; potassium carbonate In ethanol; lithium hydroxide monohydrate at 90℃; for 24h; Schlenk technique;
Stage #1: p-chlorobenzeneboronic acid; 2-bromoaniline With potassium carbonate In 1,2-dimethoxyethane; lithium hydroxide monohydrate at 20℃; for 0.5h; Inert atmosphere; Stage #2: With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) In 1,2-dimethoxyethane; lithium hydroxide monohydrate at 80℃; Inert atmosphere;
With palladium diacetate; N,N-diisopropylamine In lithium hydroxide monohydrate at 100℃; for 0.5h;
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate In 1,2-dimethoxyethane at 80℃; Inert atmosphere;
With tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate In ethanol; lithium hydroxide monohydrate; toluene at 80℃; for 6h; Inert atmosphere; Schlenk technique; 3. Typical procedures for the synthesis of 1a-1v. (A) General procedure: Taking 1d as an example: (A) Under a nitrogen atmosphere, a 100 mL Schlenk flask was charged with 2-bromoaniline (0.86 g, 5.0 mmol), 4-tert-butylphenylboronic acid (1.07 g, 6.0 mmol), Na2CO3 (1.33 g, 12.5 mmol), and a solvent mixture of toluene/EtOH/H2O (24 mL, 1:1:1 (v/v/v)) with stirring. Pd(PPh3)4 (0.29 g, 0.25 mmol) was added. Then, the mixture was stirred at 80 °C for 6 h, cooled to room temperature, quenched with saturated NH4Cl, and extracted with EtOAc (3 × 25 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of petroleum ether and ethyl acetate (10:1 (v/v)) as eluents to afford 4'-(tert-butyl)-[1,1'-biphenyl]-2-amine as a yellow oil (0.88 g, 78%).
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate In ethanol; lithium hydroxide monohydrate at 20℃; for 2h; Inert atmosphere; Reflux;
With palladium diacetate; N,N-diisopropylamine In lithium hydroxide monohydrate at 100℃; for 0.5h;
Stage #1: p-chlorobenzeneboronic acid; 2-bromoaniline With potassium carbonate In 1,2-dimethoxyethane; lithium hydroxide monohydrate for 0.5h; Stage #2: With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) In 1,2-dimethoxyethane; lithium hydroxide monohydrate at 80℃; General procedure (GP3): General procedure: Arylboronic acid (1.2 equiv.) and an aq. solution of K2CO3 (2 M, 4.5equiv.) were added to a mixture of 2-bromoaniline (1.0 equiv.) in 1,2-dimethoxyethane (0.5 M) andthe reaction mixture was stirred for 30 min. After addingbis(triphenylphosphine)palladium(II)chloride (2 mol%), the mixture was heated to 80 °C and stirredovernight. The reaction mixture was cooled to room temperature, filtered through a short pad ofsilica and eluted with EtOAc. The filtrate was washed with water and the organic phase dried overMgSO4. Filtration, concentration in vacuo and FC (PE/EtOAc) afforded the desired 2-aminobiphenyl.
Stage #1: p-chlorobenzeneboronic acid; 2-bromoaniline With potassium carbonate In 1,2-dimethoxyethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) In 1,2-dimethoxyethane at 80℃; Inert atmosphere;

Reference: [1]Current Patent Assignee: UNIV DEZHOU - CN111039796, 2020, A Location in patent: Paragraph 0017-0034
[2]Bumagin, Nikolay A.; Dikusar, Evgenij A.; Ivashkevich, Ludmila S.; Kletskov, Alexey V.; Kolesnik, Iryna A.; Lyakhov, Alexander S.; Petkevich, Sergey K.; Potkin, Vladimir I. [Inorganic Chemistry, 2020]
[3]Current Patent Assignee: GUANGDONG UNIVERSITY OF PETROCHEMICAL TECHNOLOGY - CN111056951, 2020, A Location in patent: Paragraph 0018
[4]Bumagin, N. A. [Russian Chemical Bulletin, 2021, vol. 70, # 8, p. 1483 - 1488][Izv. Akad. Nauk, Ser. Khim., 2021, # 8, p. 1483 - 1488]
[5]Ramakrishna; Dastagiri Reddy [Dalton Transactions, 2017, vol. 46, # 26, p. 8598 - 8610]
[6]Zhang, Wei; Yao, Zi-Jian; Deng, Wei [Journal of the Brazilian Chemical Society, 2019, vol. 30, # 8, p. 1667 - 1677]
[7]Goetz, Roland; Hashmi, A. Stephen K.; Orecchia, Patrizio; Petkova, Desislava Slavcheva; Rominger, Frank; Schaub, Thomas [Green Chemistry, 2021, vol. 23, # 20, p. 8169 - 8180]
[8]Bumagin, Nikolay A. [Catalysis Communications, 2016, vol. 79, p. 17 - 20]
[9]Qiu, Pei; Zhao, Jing Yang; Shi, Xu; Duan, Xin Hong [New Journal of Chemistry, 2016, vol. 40, # 8, p. 6568 - 6572]
[10]Liang, Zunjun; Feng, Ruokun; Yin, Hong; Zhang, Yuhong [Organic Letters, 2013, vol. 15, # 17, p. 4544 - 4547]
[11]Leifert, Dirk; Daniliuc, Constantin Gabriel; Studer, Armido [Organic Letters, 2013, vol. 15, # 24, p. 6286 - 6289]
[12]Lübbesmeyer; Leifert; Schäfer; Studer [Chemical Communications, 2018, vol. 54, # 18, p. 2240 - 2243]
[13]Current Patent Assignee: MAT SCIENCE CO LTD - CN114573546, 2022, A Location in patent: Paragraph 0161-0164
[14]Kim, Byung Seok; Jang, Chungsik; Lee, Dong Jin; Youn, So Won [Chemistry - An Asian Journal, 2010, vol. 5, # 11, p. 2336 - 2340]
[15]Kim, Byung Seok; Lee, Sun Young; Youn, So Won [Chemistry - An Asian Journal, 2011, vol. 6, # 8, p. 1952 - 1957]
[16]Cho, Seung Hwan; Yoon, Jungho; Chang, Sukbok [Journal of the American Chemical Society, 2011, vol. 133, # 15, p. 5996 - 6005]
[17]Tang, Conghui; Jiao, Ning [Journal of the American Chemical Society, 2012, vol. 134, # 46, p. 18924 - 18927]
[18]Xiao, Tiebo; Dong, Xichang; Tang, Yanchi; Zhou, Lei [Advanced Synthesis and Catalysis, 2012, vol. 354, # 17, p. 3195 - 3199]
[19]Liang, Zunjun; Ju, Long; Xie, Yongju; Huang, Lehao; Zhang, Yuhong [Chemistry - A European Journal, 2012, vol. 18, # 49, p. 15816 - 15821]
[20]Liang, Zunjun; Zhang, Jitan; Liu, Zhanxiang; Wang, Kai; Zhang, Yuhong [Tetrahedron, 2013, vol. 69, # 31, p. 6519 - 6526]
[21]Suzuki, Chiharu; Hirano, Koji; Satoh, Tetsuya; Miura, Masahiro [Organic Letters, 2013, vol. 15, # 15, p. 3990 - 3993] Naveen, Kanagaraj; Nikson, Savariyappan Albert; Perumal, Paramasivan Thirumalai [Advanced Synthesis and Catalysis, 2017, vol. 359, # 14, p. 2407 - 2413]
[22]Wang, Qile; Dong, Xichang; Xiao, Tiebo; Zhou, Lei [Organic Letters, 2013, vol. 15, # 18, p. 4846 - 4849]
[23]Zhu, Tong-Hao; Wang, Shun-Yi; Tao, Yang-Qing; Wei, Tian-Qi; Ji, Shun-Jun [Organic Letters, 2014, vol. 16, # 4, p. 1260 - 1263]
[24]Xia, Zhonghua; Huang, Jinbo; He, Yimiao; Zhao, Jiaji; Lei, Jian; Zhu, Qiang [Organic Letters, 2014, vol. 16, # 9, p. 2546 - 2549]
[25]Takamatsu, Kazutaka; Hirano, Koji; Satoh, Tetsuya; Miura, Masahiro [Organic Letters, 2014, vol. 16, # 11, p. 2892 - 2895] Suzuki, Chiharu; Hirano, Koji; Satoh, Tetsuya; Miura, Masahiro [Organic Letters, 2015, vol. 17, # 6, p. 1597 - 1600]
[26]Li, Jian; Wang, Hongni; Sun, Jiangtao; Yang, Yang; Liu, Li [Organic and Biomolecular Chemistry, 2014, vol. 12, # 40, p. 7904 - 7908]
[27]Wan, Wen; Ma, Guobin; Li, Jialiang; Chen, Yunrong; Hu, Qingyang; Li, Minjie; Jiang, Haizhen; Deng, Hongmei; Hao, Jian [Chemical Communications, 2016, vol. 52, # 8, p. 1598 - 1601]
[28]Wang, Sheng; Shao, Peng; Du, Gaixia; Xi, Chanjuan [Journal of Organic Chemistry, 2016, vol. 81, # 15, p. 6672 - 6676]
[29]Current Patent Assignee: BAYER AG - US2016/280635, 2016, A1 Location in patent: Paragraph 0244-0245; 0249; 0250
[30]Current Patent Assignee: BAYER AG - CN105392791, 2016, A Location in patent: Paragraph 0270; 0275; 0278; 0283; 0286; 0291; 0293
[31]Shi, Renyi; Niu, Huiying; Lu, Lijun; Lei, Aiwen [Chemical Communications, 2017, vol. 53, # 11, p. 1908 - 1911]
[32]Wan, Wen; Xu, Xiaochen; Chen, Yunrong; Jiang, Haizhen; Wang, Yong; Deng, Hongmei; Hao, Jian [European Journal of Organic Chemistry, 2017, vol. 2017, # 22, p. 3145 - 3151]
[33]Gao, Yuzhen; Cai, Zhihua; Li, Shangda; Li, Gang [Organic Letters, 2019, vol. 21, # 10, p. 3663 - 3669]
[34]Liu, Shuyang; Pan, Wenna; Wu, Songxiao; Bu, Xiubin; Xin, Shigang; Yu, Jipan; Xu, Hao; Yang, Xiaobo [Green Chemistry, 2019, vol. 21, # 11, p. 2905 - 2910]
[35]Zhao, Cheng-Long; Shi, Jin; Lu, Xiuqiang; Wu, Xun; Zhang, Cheng-Pan [Journal of Fluorine Chemistry, 2019, vol. 226]
[36]Liu, Yan; Chen, Xiao-Lan; Li, Xiao-Yun; Zhu, Shan-Shan; Li, Shi-Jun; Song, Yan; Qu, Ling-Bo; Yu, Bing [Journal of the American Chemical Society, 2021, vol. 143, # 2, p. 964 - 972]
[37]Elsherbini, Mohamed; Moran, Wesley J. [Organic and Biomolecular Chemistry, 2021, vol. 19, # 21, p. 4706 - 4711]
[38]He, Xiang-Kui; Li, Lei; Lu, Juan; Xuan, Jun; Ye, Hai-Bing [Molecules, 2021, vol. 26, # 22]
[39]Du, Pengcheng; Sun, Qianqian; Li, Hongxiao; Zhang, Jianhua; Deng, Hongmei; Jiang, Haizhen [Chemistry - An Asian Journal, 2022, vol. 17, # 10]
  • 23
  • [ 1204-44-0 ]
  • [ 75-36-5 ]
  • N-[4’-chloro-(1,1’-biphenyl)-2-yl]acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere;
66% With triethylamine In dichloromethane at 0 - 20℃;
  • 24
  • [ 89346-58-7 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: 4′-chloro-1,1′-biphenyl-2yl-carbonitrile With dihydrogen peroxide; sodium hydroxide In ethanol; water Stage #2: With sodium hypochlorite; sodium hydroxide In ethanol; water
  • 25
  • [ 106-46-7 ]
  • [ 615-36-1 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
70% Stage #1: para-dichlorobenzene With magnesium; ethylene dibromide; lithium chloride In tetrahydrofuran at 25℃; for 0.5h; Stage #2: With zinc(II) chloride In tetrahydrofuran at 25℃; for 0.5h; Stage #3: 2-bromoaniline With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate In tetrahydrofuran at 25℃; for 3h;
  • 26
  • [ 1204-44-0 ]
  • [ 98-59-9 ]
  • [ 1312447-96-3 ]
YieldReaction ConditionsOperation in experiment
81% With pyridine at 0 - 25℃; for 1h;
  • 27
  • [ 1204-44-0 ]
  • [ 1410064-29-7 ]
YieldReaction ConditionsOperation in experiment
64% With tert.-butylhydroperoxide; trimethylsilylazide; copper(I) bromide In acetonitrile at 30℃; for 10h; Inert atmosphere; regioselective reaction;
  • 28
  • [ 1204-44-0 ]
  • [ 98-83-9 ]
  • [ 1435476-56-4 ]
YieldReaction ConditionsOperation in experiment
56% With copper carbonate hydroxide; acetic acid; palladium dichloride In 2,2,2-trifluoroethanol at 20 - 90℃; for 6.33333h;
  • 29
  • [ 1204-44-0 ]
  • [ 292638-85-8 ]
  • [ 1435476-30-4 ]
YieldReaction ConditionsOperation in experiment
48% With copper carbonate hydroxide; acetic acid; palladium dichloride In 2,2,2-trifluoroethanol at 20 - 90℃; for 6.33333h;
  • 30
  • [ 201230-82-2 ]
  • [ 1204-44-0 ]
  • [ 26844-83-7 ]
YieldReaction ConditionsOperation in experiment
57% With copper (II) trifluoroacetate hydrate; palladium diacetate In 2,2,2-trifluoroethanol at 70℃; for 3h; 4.3. General procedure for carbonylation of biphenylamines General procedure: Pd(OAc)2 (3 mg, 0.015 mmol), Cu(TFA)2*xH2O (217 mg, 0.75 mmol), biphenylamine (0.5 mmol), and trifluoroethanol (1.0 mL) was added to a three-necked flask equipped with a magnetic stirring bar and reflux condenser. Then a toy balloon filled with carbon monoxide gas was connected to the flask. The mixture was stirred for 3 h at 70 °C. After cooled to room temperature, the mixture was filtered through a plug of Celite, and the residue was washed with ethyl acetate (2x20 mL). The filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel with ethyl acetate (EA) and petroleum ether (Pet) as eluent to afford the corresponding products.
53% With dichloro bis(acetonitrile) palladium(II); copper(II) trifluoroacetate; trifluoroacetic acid In 1,4-dioxane at 110℃;
  • 31
  • [ 62-53-3 ]
  • [ 1073-69-4 ]
  • [ 135-68-2 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
1: 41% 2: 13% With manganese(IV) oxide In acetonitrile at 20℃; Overall yield = 54 %; regioselective reaction;
  • 32
  • [ 201230-82-2 ]
  • [ 615-43-0 ]
  • [ 1679-18-1 ]
  • [ 2894-51-1 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
1: 92 %Chromat. 2: 7 %Chromat. With potassium carbonate at 80℃; for 12h; Green chemistry;
1: 88 %Chromat. 2: 10 %Chromat. With potassium carbonate at 80℃; for 12h; Green chemistry; 3 2.2.4. Typical procedure for the carbonylative Suzuki couplingreaction General procedure: A mixture of aryl iodide (0.5 mmol), arylboronic acid (0.6 mmol),K2CO3(1.5 mmol), and 2 mol% palladium catalyst in anisole (5 mL)were stirred at 80C under 1 atm pressure of CO. An aliquot wastaken with a syringe and subjected to GC analysis and1H NMR (seethe supplementary material). Yields were calculated against theconsumption of the aryl iodides.
  • 33
  • [ 1204-44-0 ]
  • [ 492-17-1 ]
YieldReaction ConditionsOperation in experiment
83% Stage #1: 2-(4-chlorophenyl)aniline With [(k2-P,N-di(1-adamantyl)-2-morpholinophenylphosphine)Pd(Ph)Cl]; sodium t-butanolate In 1,4-dioxane Inert atmosphere; Glovebox; Stage #2: With ammonia In 1,4-dioxane at 24℃; for 36h; Inert atmosphere; Glovebox;
  • 34
  • [ 66715-65-9 ]
  • [ 1204-44-0 ]
  • C17H13ClN2O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine In tetrahydrofuran at 0 - 20℃; for 12h; Inert atmosphere;
  • 35
  • [ 1204-44-0 ]
  • [ 501-65-5 ]
  • [ 1448169-46-7 ]
YieldReaction ConditionsOperation in experiment
78% With dichloro(benzene)ruthenium(II) dimer; silver hexafluoroantimonate; acetic acid In 1,4-dioxane at 80℃; for 1h; Inert atmosphere; regioselective reaction;
  • 36
  • [ 591-50-4 ]
  • [ 1204-44-0 ]
  • [ 1452574-34-3 ]
YieldReaction ConditionsOperation in experiment
56% With silver(I) acetate; palladium diacetate; trifluoroacetic acid at 100℃; for 12h;
  • 37
  • [ 1204-44-0 ]
  • [ 1453097-99-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: tetrahydrofuran / 1 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 2: trichlorophosphate; triethylamine / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere; Cooling with ice; Schlenk technique 3: [bis(acetoxy)iodo]benzene; sodium acetate; p-benzoquinone / 1-methyl-pyrrolidin-2-one / 4 h / 20 °C / Inert atmosphere; Schlenk technique
Multi-step reaction with 3 steps 1: acetic anhydride / tetrahydrofuran / 2 h / 0 - 20 °C 2: triethylamine; trichlorophosphate / tetrahydrofuran / 2 h / 0 °C 3: tetrabutyl ammonium fluoride / 1,4-dioxane / 80 °C / Electrochemical reaction
Multi-step reaction with 3 steps 1: acetic anhydride / tetrahydrofuran / 12 h / 20 °C 2: trichlorophosphate; triethylamine / tetrahydrofuran / 0 - 20 °C 3: dimethylglyoxal / ethyl acetate / 12 h / 20 °C / Inert atmosphere; Irradiation
Multi-step reaction with 3 steps 1: acetic anhydride / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 2: triethylamine; trichlorophosphate / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 3: dipotassium peroxodisulfate; sodium carbonate / ethyl acetate / 36 h / 20 °C / Inert atmosphere; Irradiation; Schlenk technique; Green chemistry

  • 38
  • [ 1204-44-0 ]
  • [ 1453098-10-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: tetrahydrofuran / 1 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 2: trichlorophosphate; triethylamine / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere; Cooling with ice; Schlenk technique
Multi-step reaction with 2 steps 1.1: acetic anhydride / 55 °C 1.2: 2 h / 0 - 20 °C 2.1: triethylamine; trichlorophosphate / tetrahydrofuran / 2 h / 0 °C
Multi-step reaction with 2 steps 1: tetrahydrofuran / 2 h / 0 - 20 °C 2: triethylamine; trichlorophosphate / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 2: triethylamine; trichlorophosphate / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 2: triethylamine; trichlorophosphate / tetrahydrofuran / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 2: triethylamine; trichlorophosphate / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: acetic anhydride / tetrahydrofuran / 2 h / 0 - 20 °C 2: triethylamine; trichlorophosphate / tetrahydrofuran / 2 h / 0 °C
Multi-step reaction with 2 steps 1: acetic anhydride / tetrahydrofuran / 12 h / 20 °C 2: trichlorophosphate; triethylamine / tetrahydrofuran / 0 - 20 °C
Multi-step reaction with 2 steps 1: acetic anhydride / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 2: triethylamine; trichlorophosphate / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: 2 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 2: triethylamine; bis(trichloromethyl) carbonate / dichloromethane / 2.5 h / 0 - 20 °C
Multi-step reaction with 2 steps 1: tetrahydrofuran / 3 h / 0 - 20 °C 2: triethylamine; trichlorophosphate / tetrahydrofuran / 0 - 20 °C
Multi-step reaction with 2 steps 1: tetrahydrofuran / 2 h / 0 - 20 °C 2: trichlorophosphate; triethylamine / tetrahydrofuran / 2 h / 0 °C
Multi-step reaction with 2 steps 1: dichloromethane / 2 h / 20 °C / Inert atmosphere 2: triethylamine; trichlorophosphate / chloroform / 2 h / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: tetrahydrofuran / 3 h / 0 - 20 °C 2: trichlorophosphate; triethylamine / tetrahydrofuran / 4 h / 0 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: tetrahydrofuran / 2 h / 0 - 20 °C 2: triethylamine; trichlorophosphate / tetrahydrofuran / 2 h / 0 °C
Multi-step reaction with 2 steps 1: tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere

Reference: [1]Wang, Qile; Dong, Xichang; Xiao, Tiebo; Zhou, Lei [Organic Letters, 2013, vol. 15, # 18, p. 4846 - 4849]
[2]Leifert, Dirk; Daniliuc, Constantin Gabriel; Studer, Armido [Organic Letters, 2013, vol. 15, # 24, p. 6286 - 6289]
[3]Xia, Zhonghua; Huang, Jinbo; He, Yimiao; Zhao, Jiaji; Lei, Jian; Zhu, Qiang [Organic Letters, 2014, vol. 16, # 9, p. 2546 - 2549]
[4]Wan, Wen; Ma, Guobin; Li, Jialiang; Chen, Yunrong; Hu, Qingyang; Li, Minjie; Jiang, Haizhen; Deng, Hongmei; Hao, Jian [Chemical Communications, 2016, vol. 52, # 8, p. 1598 - 1601]
[5]Feng, Shangbiao; Li, Tao; Du, Chenglong; Chen, Peng; Song, Dengpeng; Li, Jinlai; Xie, Xingang; She, Xuegong [Chemical Communications, 2017, vol. 53, # 33, p. 4585 - 4588]
[6]Wan, Wen; Xu, Xiaochen; Chen, Yunrong; Jiang, Haizhen; Wang, Yong; Deng, Hongmei; Hao, Jian [European Journal of Organic Chemistry, 2017, vol. 2017, # 22, p. 3145 - 3151]
[7]Lübbesmeyer; Leifert; Schäfer; Studer [Chemical Communications, 2018, vol. 54, # 18, p. 2240 - 2243]
[8]Li, Jianbin; Caiuby, Clarice A. D.; Paixão, Márcio W.; Li, Chao-Jun [European Journal of Organic Chemistry, 2018, vol. 2018, # 20, p. 2498 - 2503]
[9]Liu, Shuyang; Pan, Wenna; Wu, Songxiao; Bu, Xiubin; Xin, Shigang; Yu, Jipan; Xu, Hao; Yang, Xiaobo [Green Chemistry, 2019, vol. 21, # 11, p. 2905 - 2910]
[10]Zhao, Cheng-Long; Shi, Jin; Lu, Xiuqiang; Wu, Xun; Zhang, Cheng-Pan [Journal of Fluorine Chemistry, 2019, vol. 226]
[11]Zhuang, Yan-Jun; Qu, Jian-Ping; Kang, Yan-Biao [Journal of Organic Chemistry, 2020, vol. 85, # 6, p. 4386 - 4397]
[12]Chen, Jia-Yi; Li, Xin; Lin, Li-Ting; Liu, Guo-Kai; Qin, Wen-Bing; Wong, Henry N. C.; Xiong, Wei [Journal of Organic Chemistry, 2020, vol. 85, # 16, p. 10479 - 10487]
[13]Shi, Wei; Ma, Fang; Li, Pinhua; Wang, Lei; Miao, Tao [Journal of Organic Chemistry, 2020, vol. 85, # 21, p. 13808 - 13817]
[14]Liu, Yan; Chen, Xiao-Lan; Li, Xiao-Yun; Zhu, Shan-Shan; Li, Shi-Jun; Song, Yan; Qu, Ling-Bo; Yu, Bing [Journal of the American Chemical Society, 2021, vol. 143, # 2, p. 964 - 972]
[15]He, Xiang-Kui; Li, Lei; Lu, Juan; Xuan, Jun; Ye, Hai-Bing [Molecules, 2021, vol. 26, # 22]
[16]Du, Pengcheng; Sun, Qianqian; Li, Hongxiao; Zhang, Jianhua; Deng, Hongmei; Jiang, Haizhen [Chemistry - An Asian Journal, 2022, vol. 17, # 10]
  • 39
  • [ 1204-44-0 ]
  • [ 2258-42-6 ]
  • N-(4′-chloro-[1,1′-biphenyl]-2-yl)formamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% In dichloromethane at 20℃; for 2h; Inert atmosphere;
In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere; Schlenk technique;
In tetrahydrofuran at 0 - 20℃; for 2h;
In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;
In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;
In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;
at 0 - 20℃; for 2h; Inert atmosphere; Schlenk technique; 3. Typical procedures for the synthesis of 1a-1v. (B) General procedure: (B) Under a nitrogen atmosphere, a 100 mL Schlenk flask was charged with 4'-(tert-butyl)-[1,1'-biphenyl]-2-amine (0.56g, 2.5 mmol) and THF (10 mL) at 0 oC with stirring. Acetic formic anhydride (2 mL), which was prepared from the reaction of acetic anhydride with formic acid (1.1 equiv) at 55 °C for 2 h, was added dropwise with syringe. Then, the reaction mixture was warmed to room temperature for 2 h, treated with saturated NaHCO3, and extracted with EtOAc (3 × 25 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of petroleum ether and ethyl acetate (3:1 (v/v)) as eluents to afford N-(4'-(tert-butyl)-[1,1'-biphenyl]-2-yl)formamide as a yellow oil (0.60 g 95%).
In tetrahydrofuran at 0 - 20℃; for 2h;
In tetrahydrofuran at 0 - 20℃; for 3h;
In tetrahydrofuran at 0 - 20℃; for 2h; General procedure (GP4): General procedure: An equimolar mixture of acetic anhydride and formic acid was stirredat 55 °C to form in situ acetic formic anhydride (2.0 equiv.). After cooling to room temperature itwas added dropwise to a stirred solution of 2-aminobiphenyl in THF (0.3-0.6 M) at 0 °C. Afterstirring 2 h at room temperature, the reaction was stopped by the addition of a saturated aq. solutionof NaHCO3. The aqueous phase was extracted three times with EtOAc and the combined organicphases were dried over MgSO4, filtered and concentrated in vacuo.Without further purification the residue was dissolved in THF (0.6 M) and triethylamine (6.0equiv.) was added. The reaction mixture was cooled to 0 °C and phosphoryl chloride (1.5 equiv.)was added dropwise. After stirring two hours at this temperature a saturated solution of aq. Na2CO3 was added to the mixture and stirred for 1 h at room temperature. The aqueous phase was extractedthree times with DCM. The combined organic phases were dried over MgSO4 and filtered.Purification via FC (PE/EtOAc) afforded the desired 2-isocyanobiphenyl.
In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;

Reference: [1]Shi, Wei; Ma, Fang; Li, Pinhua; Wang, Lei; Miao, Tao [Journal of Organic Chemistry, 2020, vol. 85, # 21, p. 13808 - 13817]
[2]Wang, Qile; Dong, Xichang; Xiao, Tiebo; Zhou, Lei [Organic Letters, 2013, vol. 15, # 18, p. 4846 - 4849]
[3]Xia, Zhonghua; Huang, Jinbo; He, Yimiao; Zhao, Jiaji; Lei, Jian; Zhu, Qiang [Organic Letters, 2014, vol. 16, # 9, p. 2546 - 2549]
[4]Wan, Wen; Ma, Guobin; Li, Jialiang; Chen, Yunrong; Hu, Qingyang; Li, Minjie; Jiang, Haizhen; Deng, Hongmei; Hao, Jian [Chemical Communications, 2016, vol. 52, # 8, p. 1598 - 1601]
[5]Feng, Shangbiao; Li, Tao; Du, Chenglong; Chen, Peng; Song, Dengpeng; Li, Jinlai; Xie, Xingang; She, Xuegong [Chemical Communications, 2017, vol. 53, # 33, p. 4585 - 4588]
[6]Wan, Wen; Xu, Xiaochen; Chen, Yunrong; Jiang, Haizhen; Wang, Yong; Deng, Hongmei; Hao, Jian [European Journal of Organic Chemistry, 2017, vol. 2017, # 22, p. 3145 - 3151]
[7]Zhao, Cheng-Long; Shi, Jin; Lu, Xiuqiang; Wu, Xun; Zhang, Cheng-Pan [Journal of Fluorine Chemistry, 2019, vol. 226]
[8]Chen, Jia-Yi; Li, Xin; Lin, Li-Ting; Liu, Guo-Kai; Qin, Wen-Bing; Wong, Henry N. C.; Xiong, Wei [Journal of Organic Chemistry, 2020, vol. 85, # 16, p. 10479 - 10487]
[9]Liu, Yan; Chen, Xiao-Lan; Li, Xiao-Yun; Zhu, Shan-Shan; Li, Shi-Jun; Song, Yan; Qu, Ling-Bo; Yu, Bing [Journal of the American Chemical Society, 2021, vol. 143, # 2, p. 964 - 972]
[10]He, Xiang-Kui; Li, Lei; Lu, Juan; Xuan, Jun; Ye, Hai-Bing [Molecules, 2021, vol. 26, # 22]
[11]Du, Pengcheng; Sun, Qianqian; Li, Hongxiao; Zhang, Jianhua; Deng, Hongmei; Jiang, Haizhen [Chemistry - An Asian Journal, 2022, vol. 17, # 10]
  • 40
  • [ 615-43-0 ]
  • [ 1679-18-1 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
92% With palladium diacetate; potassium carbonate In water; acetone at 65℃; Inert atmosphere;
88% With D-glucose; palladium diacetate; caesium carbonate In water; N,N-dimethyl-formamide at 100℃; for 16h; Sealed tube;
84% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,2-dimethoxyethane at 80℃; for 16h; Inert atmosphere; Schlenk technique;
81% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,2-dimethoxyethane; water at 80℃; for 18h; Inert atmosphere; Sealed tube;
81% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; toluene at 70℃; for 16h; Inert atmosphere;
72% With palladium diacetate; potassium carbonate In water; acetone at 65℃; for 20h;
With sodium methylate In 1,4-dioxane at 100℃; for 25h; Schlenk technique;
With Graphite oxide supported palladium nanoparticles In 1,4-dioxane at 100℃; for 24h; Inert atmosphere;
With palladium diacetate; potassium carbonate In water; acetone at 65℃; Sealed tube; Inert atmosphere;
Stage #1: 2-iodophenylamine; 4-Chlorophenylboronic acid With potassium carbonate In 1,2-dimethoxyethane; water at 20℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: With bis-triphenylphosphine-palladium(II) chloride In 1,2-dimethoxyethane; water at 20 - 80℃; for 12h; Schlenk technique; Inert atmosphere;
With palladium diacetate; benzaldehyde In N,N-dimethyl acetamide at 20℃; for 0.3h; 1.1 Preparation of 2- (4-chlorophenyl) aniline intermediate p-Chlorophenylboronic acid, O-iodoaniline, Benzaldehyde and palladium acetate catalyst were dissolved in Ν, N-methylacetamide, Stirred at room temperature for 18 min, Adding 30% mass percentage concentration of sodium carbonate solution was refluxed for 8h, Cooled to 25 ° C, standing stratification, to obtain an organic phase, To the resulting organic phase was added sulfuric acid mass percentage concentration of 30% Static stratification, The organic phase was prepared by adjusting the pH value to 11 with a potassium hydroxide solution with a mass percentage concentration of 40% Ethyl acetate extractant, dried with anhydrous calcium chloride desiccant, N, N-methylacetamide, Recrystallization from diisopropyl ether gave 2- (4-chlorophenyl) aniline, Chlorobenzene boronic acid, o-iodoaniline, Benzaldehyde, catalyst, the first solvent and the mass percentage concentration 30% sodium carbonate solution molar ratio of 1.5: 2: 1: 0.03: 15:16;
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In ethanol at 100℃;
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; tetrabutylammomium bromide; potassium carbonate In 1,4-dioxane; water at 130℃; for 1h; Microwave irradiation; 3 General method A: preparation of biphenylamine derivatives 3a-3aa General procedure: Substituted 2-iodoaniline 1 (1.0 eq.), substituted phenylboronicacid 2 (1.2 eq.), K2CO3 (3.0 eq.), tetrabutylammonium bromide (0.1eq.), PdCl2(dppf) (0.1 eq.) and dioxane/H2O (9:1) (0.5 M) wereadded to a 10 mL microwave-vial. The vial was sealed with a capand placed in a Cem Discover-microwave cavity. After irradiation at130 C for 1 h and subsequent cooling, the solvent was removed invacuo. The residue was taken up into EtOAc (30 mL) and washedonce withwater and brine. The organic layerwas dried over MgSO4,filtered, and concentrated. The crude product was purified by flashcolumn chromatography using 0e10% EtOAc/petroleum benzine togive the biphenylamine product 3a-3aa.
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In ethanol for 24h; Reflux; Inert atmosphere;
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; sodium carbonate In 1,4-dioxane; water at 65℃; Schlenk technique;
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In ethanol for 12h; Inert atmosphere; Reflux;
Stage #1: 2-iodophenylamine; 4-Chlorophenylboronic acid With potassium carbonate In 1,2-dimethoxyethane; water at 20℃; for 0.5h; Inert atmosphere; Stage #2: With bis-triphenylphosphine-palladium(II) chloride In 1,2-dimethoxyethane; water at 80℃; Inert atmosphere;
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; sodium carbonate In 1,4-dioxane; water at 65℃; Schlenk technique; Inert atmosphere;

Reference: [1]Jiang, Hang; Zhang, Yu; Chen, Dushen; Zhou, Bo; Zhang, Yanghui [Organic Letters, 2016, vol. 18, # 9, p. 2032 - 2035]
[2]Camp, Jason E.; Dunsford, Jay J.; Dacosta, Oliver S. G.; Blundell, Rebecca K.; Adams, James; Britton, Joshua; Smith, Robert J.; Bousfield, Thomas W.; Fay, Michael W. [RSC Advances, 2016, vol. 6, # 20, p. 16115 - 16121]
[3]Shi, Wei; Ma, Fang; Li, Pinhua; Wang, Lei; Miao, Tao [Journal of Organic Chemistry, 2020, vol. 85, # 21, p. 13808 - 13817]
[4]Parisien-Collette, Shawn; Cruché, Corentin; Abel-Snape, Xavier; Collins, Shawn K. [Green Chemistry, 2017, vol. 19, # 20, p. 4798 - 4803]
[5]Porta, Federica; Gelain, Arianna; Barlocco, Daniela; Ferri, Nicola; Marchianò, Silvia; Cappello, Valentina; Basile, Livia; Guccione, Salvatore; Meneghetti, Fiorella; Villa, Stefania [Chemical Biology and Drug Design, 2017, vol. 90, # 5, p. 820 - 839]
[6]Gillespie, James E.; Morrill, Charlotte; Phipps, Robert J. [Journal of the American Chemical Society, 2021, vol. 143, # 25, p. 9355 - 9360]
[7]Santra, Subhankar; Hota, Pradip Kumar; Bhattacharyya, Rangeet; Bera, Parthasarathi; Ghosh, Prasenjit; Mandal, Swadhin K. [ACS Catalysis, 2013, vol. 3, # 12, p. 2776 - 2789]
[8]Current Patent Assignee: MANDAL, Dr. Swadhin K.; SANTRA, Subhankar - WO2014/174397, 2014, A2 Location in patent: Paragraph 0045
[9]Shi, Guangfa; Chen, Dushen; Jiang, Hang; Zhang, Yu; Zhang, Yanghui [Organic Letters, 2016, vol. 18, # 12, p. 2958 - 2961]
[10]Feng, Shangbiao; Li, Tao; Du, Chenglong; Chen, Peng; Song, Dengpeng; Li, Jinlai; Xie, Xingang; She, Xuegong [Chemical Communications, 2017, vol. 53, # 33, p. 4585 - 4588]
[11]Current Patent Assignee: WUXI JIABAO PESTICIDE PHARMACEUTICAL - CN107216287, 2017, A Location in patent: Paragraph 0017; 0019
[12]Wang, Ming; Fan, Qiaoling; Jiang, Xuefeng [Organic Letters, 2018, vol. 20, # 1, p. 216 - 219]
[13]Nguyen, Nghi; Wilson, Danny W.; Nagalingam, Gayathri; Triccas, James A.; Schneider, Elena K.; Li, Jian; Velkov, Tony; Baell, Jonathan [European Journal of Medicinal Chemistry, 2018, vol. 148, p. 507 - 518]
[14]Ling, Fei; Zhang, Chaowei; Ai, Chongren; Lv, Yaping; Zhong, Weihui [Journal of Organic Chemistry, 2018, vol. 83, # 10, p. 5698 - 5706]
[15]Xu, Yankun; Liu, Xiaodong; Chen, Wenqi; Deng, Guobo; Liang, Yun; Yang, Yuan [Journal of Organic Chemistry, 2018, vol. 83, # 22, p. 13930 - 13939]
[16]Wang, Gang; Xiong, Biquan; Zhou, Congshan; Liu, Yu; Xu, Weifeng; Yang, Chang-An; Tang, Ke-Wen; Wong, Wai-Yeung [Chemistry - An Asian Journal, 2019, vol. 14, # 23, p. 4365 - 4374]
[17]Chen, Jia-Yi; Li, Xin; Lin, Li-Ting; Liu, Guo-Kai; Qin, Wen-Bing; Wong, Henry N. C.; Xiong, Wei [Journal of Organic Chemistry, 2020, vol. 85, # 16, p. 10479 - 10487]
[18]Zhang, Minghao; Deng, Wenbo; Sun, Mingjie; Zhou, Liwei; Deng, Guobo; Liang, Yun; Yang, Yuan [Organic Letters, 2021, vol. 23, # 15, p. 5744 - 5749]
  • 41
  • [ 64-18-6 ]
  • [ 1204-44-0 ]
  • N-(4′-chloro-[1,1′-biphenyl]-2-yl)formamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: formic acid With acetic anhydride at 55℃; Stage #2: 2-(4-chlorophenyl)aniline In tetrahydrofuran at 0 - 20℃; for 2h;
With acetic anhydride In tetrahydrofuran at 0 - 20℃; for 2h;
With acetic anhydride In tetrahydrofuran at 20℃; for 12h;
With acetic anhydride In tetrahydrofuran at 20℃; for 2h; Inert atmosphere;

  • 42
  • [ 2028-74-2 ]
  • [ 62-53-3 ]
  • [ 135-68-2 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
1: 44% 2: 12% With sodium hydroxide In water at 75℃; II.13 II.13 4′-Chlorobiphenyl-2-amine and 4′-chlorobiphenyl-4-amine 0344] 4′-Chlorobiphenyl-2-amine and 4′-chlorobiphenyl-4-amine were synthesized from aniline (20.0 mmol, 2.33 g) and 4-chlorophenyldiazonium chloride (2.00 mmol, 5.00 ml of the 0.4 M aryldiazonium chloride solution prepared by general method GM 1) analogously to general method GM 3 at 75° C. Diethyl ether was used for extraction. Excess aniline was removed by means of vacuum distillation. The two regioisomers were separated by means of column chromatography (silica gel, hexane/EtOAc=4:1). 4′-Chlorobiphenyl-2-amine (0.88 mmol, 179 mg, 44%) and 4′-chlorobiphenyl-4-amine (0.24 mmol, 49 mg, 12%) were obtained. RRN 65 4′-Chlorobiphenyl-2-amine [0345] Rf 0.6 (hexane/EtOAc=4:1) [UV] [0346] 1H NMR (360 MHz, CDCl3): δ=6.76 (dd, J=0.9 Hz, J=8.0 Hz, 1H), 6.82 (dt, J=1.1 Hz, J=7.47 Hz, 1H), 7.09 (dd, J=1.4 Hz, J=7.6 Hz, 1H), 7.16 (ddd, J=1.6 Hz, J=7.4 Hz, J=8.0 Hz, 1H), 7.37-7.45 (m, 4H). [0347] 13C NMR (90.6 MHz, CDCl3): δ=115.7 (CH), 118.8 (CH), 126.3 (Cq), 128.8 (CH), 129.0 (2×CH), 130.3 (CH), 130.4 (2×CH), 133.1 (Cq), 137.9 (Cq), 143.4 (Cq). [0348] MS (EI) m/z (%): 205 (29) [37Cl-M+], 204 (10), 203 (100) [35Cl-M+], 202 (12), 169 (17), 168 (56), 167 (37), 166 (14), 83 (29). [0349] HRMS (EI) calculated for C12H10ClN [M+]: 203.0502. found: 203.0502. RRN 66 4′-Chlorobiphenyl-4-amine [0350] Rf 0.3 (hexane/EtOAc=4:1) [UV] [0351] 1H NMR (600 MHz, CDCl3): δ=6.75 (d, J=8.6 Hz, 2H), 7.35 (d, J=8.6 Hz, 2H), 7.37 (d, J=8.6 Hz, 2H), 7.45 (d, J=8.5 Hz, 2H). [0352] 13C NMR (151 MHz, CDCl3): δ=115.4 (2×CH), 127.5 (2×CH), 127.8 (2×CH), 128.7 (2×CH), 130.2 (Cq), 132.1 (Cq), 139.6 (Cq), 146.1 (Cq). [0353] MS (EI) m/z (%): 205 (32) [37Cl-M+], 204 (18), 203 (100) [35Cl-M+], 169 (12), 168 (9), 167 (24), 139 (10), 101 (11), 83 (21). [0354] HRMS (EI) calculated for C12H10ClN [M+]: 203.0502. found: 203.0502.
  • 43
  • [ 7188-38-7 ]
  • [ 1204-44-0 ]
  • [ 1559070-52-8 ]
YieldReaction ConditionsOperation in experiment
47% With oxygen; cobalt acetylacetonate In 1,4-dioxane at 100℃;
  • 44
  • [ 1073-70-7 ]
  • [ 62-53-3 ]
  • [ 135-68-2 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
1: 51% 2: 9% With oxygen; sodium hydroxide In water at 60℃; for 33h; regioselective reaction;
  • 45
  • [ 1204-44-0 ]
  • [ 109394-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: tetrahydrofuran / 2 h / 0 - 20 °C 2: triethylamine; trichlorophosphate / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 3: dibenzoyl peroxide; sodium acetate; N,N`-dimethylethylenediamine; tert.-butylnitrite / 3.08 h / 20 - 70 °C / Schlenk technique; Inert atmosphere
Multi-step reaction with 3 steps 1: sodium nitrite; hydrogenchloride; potassium iodide / water / 0 - 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 2 h / 0 - 20 °C 3: copper(II) bis(trifluoromethanesulfonate) / 1,2-dichloro-ethane / 20 h / 150 °C / Sealed tube
  • 46
  • [ 1204-44-0 ]
  • [ 39901-94-5 ]
  • [ 1609211-15-5 ]
YieldReaction ConditionsOperation in experiment
With dmap; triethylamine In dichloromethane at 20℃; for 24h; Inert atmosphere;
  • 48
  • [ 106-39-8 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium(0); potassium hydroxide; tetrabutylammomium bromide / water / 0.07 h / 100 °C / Microwave irradiation 2: tetrakis(triphenylphosphine) palladium(0); potassium hydroxide; tetrabutylammomium bromide; copper(l) iodide / water / 0.1 h / 100 °C / Microwave irradiation 3: tin(ll) chloride; hydrogenchloride / water / 0.07 h / 50 °C / Microwave irradiation
Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / acetonitrile / 80 °C / Inert atmosphere 2: tin(II) chloride dihdyrate / ethanol / 5 h / 75 °C
  • 49
  • [ 190788-59-1 ]
  • [ 1204-44-0 ]
  • 50
  • [ 1204-44-0 ]
  • [ 26844-83-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 1 h / -10 - 25 °C / Inert atmosphere 2: sodium hydroxide / methanol / 0.5 h / 25 °C 3: sodium persulfate / dimethyl sulfoxide / 36 h / 110 °C
Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 3 h / 20 °C 2: cobalt(II) chloride; sodium pivalate; oxygen / 1,4-dioxane / 24 h / 130 °C / 760.05 Torr
  • 51
  • [ 5781-53-3 ]
  • [ 1204-44-0 ]
  • C15H12ClNO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane at -10 - 25℃; for 1h; Inert atmosphere;
  • 52
  • [ 1679-18-1 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / toluene / 0.17 h / 20 °C / Inert atmosphere 1.2: Inert atmosphere; Reflux 2.1: ammonium chloride; iron / water; isopropyl alcohol / Reflux; Inert atmosphere
Multi-step reaction with 2 steps 1: tert.-butylnitrite; methoxybenzene / methanol / 24 h / 25 °C 2: hydrogen / 40 °C
Multi-step reaction with 2 steps 1.1: sodium hydroxide / hexane / 0.17 h / Inert atmosphere 1.2: 6 h / 50 °C / Inert atmosphere 2.1: iron; ammonium chloride; acetic acid / methanol; water / 5 h / 40 °C
Multi-step reaction with 2 steps 1: palladium diacetate; triphenylphosphine; silver tetrafluoroborate / toluene / 80 °C 2: Red-Al / toluene / 110 °C
Multi-step reaction with 2 steps 1: C35H47O3P*C15H16N(1-)*CH3O3S(1-)*Pd(2+); triethylamine / water; tetrahydrofuran / 24 h / 45 °C 2: iron; ammonium chloride / water; tetrahydrofuran / 12 h / 45 °C
Multi-step reaction with 2 steps 1: dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium phosphate monohydrate / water; tetrahydrofuran / 12 h / 55 °C / Inert atmosphere 2: iron; ammonium chloride / water / 12 h / 45 °C
Multi-step reaction with 2 steps 1: sodium carbonate; sodium acetate; tetrabutylammomium bromide; C50H63Cl2N3Pd / ethanol; water / 24 h / 90 °C 2: zinc; hydrogenchloride; acetic acid / water; ethyl acetate / 4 h / 70 °C / Inert atmosphere

  • 53
  • [ 5256-74-6 ]
  • [ 1204-44-0 ]
  • ethyl 9-chloro-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepine-7-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; acetic acid In ethanol at 60℃; for 24h;
  • 54
  • [ 1204-44-0 ]
  • [ 119520-01-3 ]
  • benzyl 9-chloro-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepine-7-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; acetic acid In ethanol at 60℃; for 24h;
  • 55
  • [ 124-38-9 ]
  • [ 1204-44-0 ]
  • [ 26844-83-7 ]
YieldReaction ConditionsOperation in experiment
88% With chloro(1,5-cyclooctadiene)rhodium(I) dimer; potassium <i>tert</i>-butylate; tris(para-trifluoromethyl)phenyl phosphine In N,N-dimethyl-formamide at 150℃; for 24h; Sealed tube; Schlenk technique;
48% Stage #1: carbon dioxide; 2-(4-chlorophenyl)aniline With 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine In 1,2-dichloro-benzene at 20℃; for 1h; Sealed tube; Stage #2: With methyl trifluoromethanesulfonate In 1,2-dichloro-benzene at 140℃; for 12h; Sealed tube; Stage #3: With hydrogenchloride; water In 1,2-dichloro-benzene
  • 56
  • [ 873-77-8 ]
  • [ 95-51-2 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
91.6% With 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); zinc(II) chloride In tetrahydrofuran at 10 - 15℃; for 7h; Inert atmosphere; 11.2 Example 1 Step 2 Preparation of Preparation of 4'-chloro-2-aminobiphenyl In another four 1L reaction flask, a nitrogen atmosphere, followed by adding 219.54g of tetrahydrofuran,67.87g (0.532mol) o-chloroaniline, 0.73g (0.00532mol) zinc chloride, 0.29g (0.000532mol)(Dppp) NiCl2, open stirring, cooling to 10 ~ 15 reaction system, generated in Step 1 was added dropwise4-chlorophenyl magnesium bromide Grignard reagent to the system, maintaining the temperature 10 ~ 15 , dropwise for 3 hours,After addition was complete, heat 4h, sampling to detect completion of the reaction, the solution of dilute hydrochloric acid to the reaction mixture to quench the reaction,Stirred for 10min, allowed to stand, stratification, the organic layer was washed with 5% sodium chloride solution, allowed to stand for separation, the organicLayer was added activated carbon, heated to reflux, filtered hot and the filtrate was concentrated under reduced pressure is not off to a tetrahydrofuranStop, cooling to 20 ~ 25 , to give a white flaky solid, as 4'-chloro-2-aminobiphenyl, solid weighed was 98.9g, 91.6% yield (in terms of o-chloroaniline ), purity (GC) ≥99.0%.
91.6% With bis(triphenylphosphine)nickel(II) chloride; zinc(II) chloride In tetrahydrofuran at 10 - 15℃; for 7h; Inert atmosphere; 11.2 Step 2 Preparation of 4'-chloro-2-aminobiphenyl In another 1L four-neck reaction flask, under the protection of nitrogen, 219.54 g of tetrahydrofuran was added in sequence.67.87g (0.532mol) o-chloroaniline, 0.73g (0.00532mol) zinc chloride, 0.29g (0.000532mol) (dppp)NiCl2, the stirring is started, the reaction system is cooled to 10-15 ° C, and the step 1 is added dropwise. 4-chlorophenylmagnesium bromide reagent into the system,Maintain the temperature of 10 ~ 15 ° C, the addition time is 3 hours, add dropwise, heat preservation 4h,After the sampling and detection reaction is completed, dilute hydrochloric acid is added dropwise to the reaction solution, the reaction is quenched, stirred for 10 min, allowed to stand, layered, and the organic layer is washed with 5% sodium chloride solution, left to stand layering, and the organic layer is added with activated carbon to heat up. After refluxing, the mixture was filtered while hot, and the filtrate was concentrated under reduced pressure to dryness, and then evaporated to 20 to 25 ° C to obtain a white flaky solid.It was 4'-chloro-2-aminobiphenyl, and the solid was weighed to 98.9 g, the yield was 91.6% (calculated as o-chloroaniline), and the purity (GC) was ≥99.0%.
  • 57
  • [ 1212-08-4 ]
  • [ 7188-38-7 ]
  • [ 1204-44-0 ]
  • N-tert-butyl-N'-(4'-chloro[1,1'-biphenyl]-2-yl)-S-phenylisothiourea [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% With copper(l) iodide In 2-methyltetrahydrofuran at 75℃; for 20h; Microwave irradiation; Molecular sieve;
  • 58
  • [ 1204-44-0 ]
  • [ 188425-85-6 ]
  • 59
  • 2-amino-benzeneboronic acid hydrochloride [ No CAS ]
  • [ 637-87-6 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: 2-amino-benzeneboronic acid hydrochloride; 1-Chloro-4-iodobenzene With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; triphenylphosphine In ethanol; toluene at 20℃; for 0.0833333h; Stage #2: In ethanol; water; toluene at 120℃; for 2h; Inert atmosphere; Sealed tube; 4.2 2'-Bromo-[1,1'-biphenyl]-2-amine (1b) 4.4.2 4'-Chloro-[1,1'-biphenyl]-2-amine (1d) 37 A solution of 1-chloro-4-iodobenzene (86 mg, 0.5 mmol), (2-aminophenyl)boronic acid hydrochloride (173.0 mg, 1.0 mmol), Pd(PPh3)2Cl2 (70.2 mg, 0.1 mmol), PPh3 (52.5 mg, 0.2 mmol) and K2CO3 (552 mg, 4 mmol) in toluene:ethanol (10:4 mL) was stirred at room temperature for 5 min. H2O (2 mL) was added, and the resulting mixture was slightly degassed, sealed and stirred at 120 °C for 2 h. After being cooled to room temperature, the mixture was extracted with Et2O or EtOAc. The extracts were combined, dried over Na2SO4, and filtered. After removal of volatile components from the filtrate, the resulting crude product was purified by column chromatography on silica gel eluting with pentane/EtOAc (100:0→80:20%). Light yellow oil was obtained in 75% yield (153 mg, 0.75 mmol). 1H NMR (400.16 MHz, CDCl3): δ 7.40-7.35 (m, 4H), 7.14 (t, J=7.6, 1H), 7.06 (d, J=7.6, 1H), 6.80 (t, J=7.6, 1H), 6.73 (d, J=8.0, 1H), 3.68 (br s, 2H); 13C NMR (100.62 MHz, CDCl3): δ 143.3, 137.8, 132.9, 130.3(x2), 130.2, 128.8(x2), 128.7, 126.1, 118.6, 115.6.
  • 60
  • [ 1204-44-0 ]
  • C11H16N2O3S [ No CAS ]
  • C23H24ClN3O2S [ No CAS ]
  • C23H24ClN3O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: C11H16N2O3S With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 25℃; for 1h; Stage #2: 2-(4-chlorophenyl)aniline In N,N-dimethyl-formamide at 25℃; for 72h; Overall yield = 50 %; 41 Example 41 General procedure: Thiazole bisamide compounds were prepared in the same manner as in Examples 1 to 28 except that the R3 diphenyl ether group was replaced with biphenyl group, as shown in Table 4; The results of the prepared products of formula as (I-2), as well as the numbers of the prepared compounds, R1, R2, R5, R6 and the yields thereof are shown in Table 3. The intermediate of formula (II) (0.5 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 0.6 mmol), hydroxybenzotriazole (HOBt, 0.6 mmol) was dissolved in 5 mL of N, N-dimethylformamide, the reaction temperature 25 deg. C 1h; Then, the reactant (0.6 mmol) represented by R3-NH2 was added to the above solution, the reaction temperature was 25 deg. C 72h; after completion of the reaction, the solvent was removed under reduced pressure, column chromatography to obtain the target product, thiazole bisamide compound.
  • 61
  • [ 1204-44-0 ]
  • C9H12N2O3S [ No CAS ]
  • C21H20ClN3O2S [ No CAS ]
  • C21H20ClN3O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: C9H12N2O3S With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 25℃; for 1h; Stage #2: 2-(4-chlorophenyl)aniline In N,N-dimethyl-formamide at 25℃; for 72h; Overall yield = 57 %; 40 Example 40 General procedure: Thiazole bisamide compounds were prepared in the same manner as in Examples 1 to 28 except that the R3 diphenyl ether group was replaced with biphenyl group, as shown in Table 4; The results of the prepared products of formula as (I-2), as well as the numbers of the prepared compounds, R1, R2, R5, R6 and the yields thereof are shown in Table 3. The intermediate of formula (II) (0.5 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 0.6 mmol), hydroxybenzotriazole (HOBt, 0.6 mmol) was dissolved in 5 mL of N, N-dimethylformamide, the reaction temperature 25 deg. C 1h; Then, the reactant (0.6 mmol) represented by R3-NH2 was added to the above solution, the reaction temperature was 25 deg. C 72h; after completion of the reaction, the solvent was removed under reduced pressure, column chromatography to obtain the target product, thiazole bisamide compound.
  • 62
  • [ 1204-44-0 ]
  • [ 74-88-4 ]
  • 4'-chloro-N,N-dimethylbiphenyl-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With potassium carbonate In N,N-dimethyl-formamide at 65 - 120℃; for 23h; Inert atmosphere;
With carbon monoxide; oxygen; potassium carbonate In N,N-dimethyl-formamide at 65 - 120℃; for 28h;
  • 63
  • [ 1204-44-0 ]
  • [ 501-65-5 ]
  • 9-chloro-6,7-diphenyl-7H-dibenzo[b,d]azepine [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With copper diacetate; palladium diacetate In dimethyl sulfoxide at 120℃; for 5h; Sealed tube;
  • 64
  • N-(4'-chloro-[1,1'-biphenyl]-2-yl)pivalamide [ No CAS ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
93% With hydrogen bromide; Aliquat 336 In octane; water at 130℃; for 12h; Inert atmosphere;
  • 65
  • [ 1204-44-0 ]
  • [ 2732-25-4 ]
YieldReaction ConditionsOperation in experiment
73% With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; copper diacetate; Trimethylacetic acid In 1-methyl-pyrrolidin-2-one at 120℃; for 3h;
  • 66
  • [ 1679-18-1 ]
  • [ 88-73-3 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-Chlorophenylboronic acid; 2-Chloronitrobenzene With potassium ion Stage #2: With hydrogen; platinum 1 (1) main reaction With p-chlorobenzeneboronic acid and p-chloronitrobenzene as the starting material,Preparation of 2-(4-chlorophenyl)aniline by suziki, hydrogenation reduction two-step reaction.
  • 67
  • [ 1204-44-0 ]
  • [ 79-04-9 ]
  • C14H11Cl2NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice; 1.3 (3) In a 250 ml round bottom flask,Join4'-chloro-2-aminobiphenyl (10.81 g, 53.08 mmol)With 50 ml of dry methylene chloride dissolved completely,Triethylamine (14.7 ml, 106.16 mmol) was added.Chloroacetyl chloride (4.4 ml, 58.39 mmol) was diluted with 30 ml of dry dichloromethane,Stirring in the ice bath,Slowly drip into the reaction flask with a dropping funnel.After dripping,Remove the ice bath,The reaction was stirred at room temperature for 1 h.TLC (petroleum ether: ethyl acetate = 5: 1) After the reaction was complete, the stirring was stopped.Quenched with water and extracted twice with methylene chloride. The organic phases were combined and dried over anhydrous sodium sulfate. The column was concentrated to give 12.34 g of the compound represented by the formula IV as a pale orange solid in 83% yield.
  • 68
  • [ 1204-44-0 ]
  • 4’-chloro-2-azidobiphenyl [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% Stage #1: 2-(4-chlorophenyl)aniline With acetic acid; sodium nitrite In water at 0℃; for 1h; Stage #2: With sodium azide In water at 0 - 20℃; for 1h; Inert atmosphere;
  • 69
  • [ 1204-44-0 ]
  • [ 329-15-7 ]
  • 4-trifluoromethyl-N-(4'-chloro-[1,1'-biphenyl]-2-yl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% Stage #1: 2-(4-chlorophenyl)aniline With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Inert atmosphere; Stage #2: 4-trifluoromethyl-phenyl acetyl chloride In N,N-dimethyl-formamide; mineral oil at 60℃; for 12h; Inert atmosphere;
  • 70
  • C13H9ClF3NO2S [ No CAS ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
75% With Red-Al In toluene at 110℃;
  • 71
  • [ 49609-84-9 ]
  • [ 1204-44-0 ]
  • boscalid [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine In tetrahydrofuran at 20℃;
  • 72
  • [ 1204-44-0 ]
  • 3-chlorodibenzo[b,d]iodol-5-ium trifluoromethanesulfonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: hydrogenchloride; NaNO2 / lithium hydroxide monohydrate; tetrahydrofuran / 1 h / 0 - 5 °C 1.2: 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 0 - 20 °C
Multi-step reaction with 2 steps 1.1: hydrogenchloride; NaNO2 / lithium hydroxide monohydrate; tetrahydrofuran / 0.33 h / 0 °C 1.2: 1 h / 0 - 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1.1: hydrogenchloride / lithium hydroxide monohydrate; tetrahydrofuran / 0 °C / Inert atmosphere 1.2: 0.33 h / 0 °C / Inert atmosphere 1.3: 1.17 h / 0 - 20 °C / Inert atmosphere 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1.1: hydrogenchloride; NaNO2 / lithium hydroxide monohydrate / 2 h / 0 - 5 °C 1.2: 0 - 20 °C 2.1: acetonitrile / 4.02 h / Electrochemical reaction; Green chemistry
Multi-step reaction with 2 steps 1.1: hydrogenchloride; NaNO2 / lithium hydroxide monohydrate / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 12 h / 20 °C / Inert atmosphere 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3 h / 0 - 20 °C

  • 73
  • [ 448236-05-3 ]
  • [ 1204-44-0 ]
  • N-[2-(4-chlorophenyl)phenyl]-4-(difluoromethyl)-1-methylpyrrole-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% With 1,4-diaza-bicyclo[2.2.2]octane In acetonitrile at 110℃; for 3h; Inert atmosphere; N-[2-(4-Chlorophenyl)phenyl]-4-(difluoromethyl)-1-methylpyrrole-3-carboxamide (10, C19H15ClF2N2O) Amixture of 0.23 g 4-(difluoromethyl)-1-methylpyrrole-3-carbonyl fluoride (22, 1.3 mmol), 0.27 g 40-chlorobiphenyl-2-amine (1.3 mmol), and 0.2 g 1,4-diazabicyclo[2]octane (DABCO, 1.9 mmol) in 5 cm3 of acetonitrilewas heated to 110 C for 3 h. The reaction mixture wascooled to room temperature, taken up in ethyl acetate,washed with water, dried over sodium sulfate, and evaporatedunder reduced pressure. The residue was purifiedby chromatography on silica gel, using ethyl acetate/heptane 1:2 as eluent, to deliver 0.29 g N-[2-(4-chlorophenyl)phenyl]-4-(difluoromethyl)-1-methylpyrrole -3-carboxamide (10, 0.8 mmol, 62%). M.p.: 175-177 C; 1HNMR (400 MHz, CDCl3): d = 3.66 (s, 3H), 6.77-6.96(m, 2H), 7.19-7.45 (m, 8H), 8.27-8.32 (m, 1H) ppm; 13CNMR (100 MHz, CDCl3): d = 36.9, 109.2, 111.7, 114.0,117.9, 118.5, 122.3, 123.2, 124.1, 124.6, 128.5, 129.2,130.1, 130.8, 131.6, 134.0, 134.9, 136.8, 161.6 ppm; LC-MS: tR = 1.81 min; MS: m/z = 361 ([M?1]?).
  • 74
  • [ 1204-44-0 ]
  • 3-(difluoromethyl)-5-methylthiophene-2-carbonyl fluoride [ No CAS ]
  • N-[2-(4-chlorophenyl)phenyl]-3-(difluoromethyl)-5-methylthiophene-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With 1,4-diaza-bicyclo[2.2.2]octane In neat (no solvent) at 110℃; for 2h; Inert atmosphere; N-[2-(4-Chlorophenyl)phenyl]-3-(difluoromethyl)-5-methylthiophene-2-carboxamide (11, C19H14ClF2-NOS) A mixture of 0.38 g 3-(difluoromethyl)-5-methylthiophene-2-carbonyl fluoride (27, 0.9 mmol),0.19 g 40-chlorobiphenyl-2-amine (0.9 mmol), and 0.16 g1,4-diazabicyclo[2]octane (DABCO, 1.4 mmol) washeated without solvent to 110 C for 2 h. The reactionmixture was cooled to room temperature, taken up in ethylacetate, washed with water, dried over sodium sulfate, andevaporated under reduced pressure. The residue was purifiedby chromatography on silica gel, using ethyl acetate/heptane 1:4 as eluent, to deliver 0.24 g N-[2-(4-chlorophenyl)phenyl]-3-(difluoromethyl)-5-methylthiophene-2-carboxamide (11, 0.6 mmol, 67%). M.p.: 149-151 C; 1HNMR (400 MHz, CDCl3): d = 2.49 (s, 3H), 7.03 (s, 1H),7.18-7.52 (m, 8H), 8.31 (d, 1H, J = 11.6 Hz) ppm; 13CNMR (100 MHz, CDCl3): d = 15.6, 107.4, 110.0, 112.2,121.9, 125.0, 125.8, 128.8, 129.3, 130.1, 130.5, 131.7,132.6, 134.1, 134.2, 136.2, 139.8, 143.3, 159.0 ppm; LC-MS: tR = 1.76 min; MS: m/z = 378 ([M?1]?).
  • 75
  • 4'-chloro-[1,1'-biphenyl]-2-carboxamide [ No CAS ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
92.6% With sodium hypochlorite; sodium hydroxide In ethanol at 10 - 50℃; Cooling with ice; 4 4. Preparation of 2-(4-chlorophenyl)aniline 50g (0.125mol) NaOH solution (10%) and ethanol (50ml) were added to the reaction flask, and the ice water bath was cooled to below 10 °C, and 6.1 g (0.05 mol) of 2-(4-chlorophenyl)benzamide was accompanied. Stir slowly into the reaction flask, add sodium hypochlorite (37.4g, 0.058moles), control the temperature during the addition process does not exceed 10 ° C, drop the temperature to 50 ° C reaction, HPLC detection of the complete reaction of the reaction, distillation of some solvents under reduced pressure It was cooled to 0 ° C to obtain a white solid of 17.2 g, yield 92.6%.
88% Stage #1: 4'-chloro-[1,1'-biphenyl]-2-carboxamide With sodium hydroxide In methanol for 0.5h; Stage #2: With sodium hypochlorite In methanol at 0 - 50℃; for 2.5h; 10-11 The synthetic route of 2-(4'-chlorophenyl)aniline in this example is as follows: Specifically: adding 23g (0.1mol) 2-(4'-chlorophenyl)benzamide prepared in Example 4 or 5, 16g (0.2mol) 50wt% sodium hydroxide and 300mL methanol into the reaction flask, Stir for 0.5h,Pre-cool to 0,Drop 200g (0.27mol) of sodium hypochlorite solution with active chlorine content of 10wt%,Incubate at 0-5°C for 0.5h, then heat to 50°C and stir for 2h,After the reaction was monitored by HPLC, 100 mL of saturated sodium sulfite solution was added, stirred for 1 h, then part of the organic solvent was removed under reduced pressure, and 150 mL of toluene was added for extraction, the organic phase was collected and concentrated, and then slurried in a mixture of petroleum ether and ethyl acetate to obtain 2-( 4'-chlorophenyl)aniline, the mass purity is 97%, and the yield is 88%.
40% With sodium hypochlorite; sodium hydroxide In toluene at 40℃; 10 Example 10: Synthesis of 4'-chloro-[1,1'-biphenyl]-2-amine Sodium hydroxide (36.5 g) was added to a mixture of water (36.5 g) and toluene (300 g), and 4'-chloro-[1,1'-biphenyl]-2-carboxamide (73 g) was added at room temperature (by repeating several times) Example 8), 10% active sodium hypochlorite solution (370 ml) was added dropwise under stirring at 40°C, the reaction was monitored by LCMS, the system was spontaneously phase-separated, the toluene phase was collected, and dried with sodium sulfate, Filtration, concentrated to a viscous state, then added toluene (40 ml) and cooled to -15C, after centrifugation, a dark yellow solid was obtained, the form was slightly sticky, added toluene (40 ml) again, beating at -15C, then centrifuged After separation and vacuum drying, yellow 4'-chloro-[1,1'-biphenyl]-2-amine (26 g, purity 99%, yield 40%) was obtained.
6 g With water; bromine; sodium hydroxide at 0 - 5℃; for 1h; 4 Example 4: Preparation of 4'-chloro-2-aminobiphenyl 5.6 g (135.8 mmol) of sodium hydroxide was dissolved in 45 mL of water and stirred to cool to 0 ° C.Control the temperature 0-5 ° C dropwise 5.4g (33.8mmol) of bromine, 2h drop,After the completion of the drop, keep warm for 1 h. Control temperature 0-5 ° C,A mixed solution of 7.4 g (31.9 mmol) of 4'-chloro-2-amidobiphenyl and 10 mL of methanol was added dropwise.After the addition, the temperature was kept for 1 h, then slowly heated to above 45 ° C, and kept warm until the analysis was qualified. The reaction is over,To the reaction flask, 4.2 g (33.3 mmol) of sodium sulfite and 30 mL of toluene were added, and the mixture was stirred for 0.5 h, and then allowed to stand for stratification.The oil layer was washed twice with 20 mL × 2 water. The oil layer was dried toluene to obtain 6.0 g of 4'-chloro-2-aminobiphenyl, and the content was 97%.The yield is 93% or more.
With sodium hypochlorite at 20℃; for 6h; 1-3 Example 2 In a 500 ml three-necked flask,Add 250 ml of trimethylbenzene, add 0.2 mol of 9-fluorenone, 0.36 mol of potassium hydroxide, warm to reflux, reflux for 8 h, reduce to room temperature, add 200 ml of water, stir well, then separate the organic layer, and acidify the pH with hydrochloric acid to pH. =1 to 2, add 250 ml of dichloroethane,After thoroughly stirring, the aqueous layer was separated, and the dichloroethane layer was dried over anhydrous sodium sulfate.Add 0.1 g of antimony trichloride and warm to 60 ° C.First pass nitrogen to drive off the air in the reaction bottle.Then pass chlorine gas,After the end of the chlorination reaction (TLC tracking),Passing nitrogen to remove excess chlorine,Drop to room temperature, pass ammonia,After the reaction is completed, the solution is decomposed by distillation under reduced pressure.Sodium hypochlorite solution was added to the residue, and the mixture was stirred at room temperature for 6 hours, and then worked up to give the title compound, 98.3%, and the total yield was 75.4% (based on 9-fluorenone).
Multi-step reaction with 2 steps 1: sodium hydroxide; sodium hypochlorite / water / 1 h / 20 °C / Cooling with ice 2: sodium hydroxide; methanol / 1 h / 90 °C

  • 76
  • [ 667-27-6 ]
  • [ 1204-44-0 ]
  • [ 1610500-89-4 ]
YieldReaction ConditionsOperation in experiment
77% With 1,10-Phenanthroline; copper(II) bis(trifluoromethanesulfonate); sodium carbonate In acetonitrile at 120℃; for 20h; Inert atmosphere; Sealed tube; Schlenk technique;
  • 77
  • [ 1679-18-1 ]
  • [ 5570-18-3 ]
  • [ 958-96-3 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
1: 55% 2: 20% With potassium carbonate In water; acetonitrile at 70℃; Schlenk technique; chemoselective reaction;
  • 78
  • [ 486-25-9 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: chlorine / 1,2-dichloro-ethane / 50 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h 2.2: 0.5 h 3.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 0.83 h / 45 °C 3.2: 0.5 h / 0 °C 4.1: sodium hydroxide; sodium hypochlorite / ethanol / 10 - 50 °C / Cooling with ice
Multi-step reaction with 4 steps 1: potassium hydroxide / toluene / 8 h / Reflux 2: antimony(III) chloride; chlorine / 60 °C 3: ammonia 4: sodium hypochlorite / 6 h / 20 °C
Multi-step reaction with 4 steps 1.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 25 °C 1.2: pH 1 - 2 2.1: sulfuryl dichloride / 1,2-dichloro-ethane / 6 h / 70 °C 3.1: thionyl chloride / toluene / 4 h / 25 °C 3.2: 2 h / 0 - 20 °C 4.1: sodium hydroxide / methanol / 0.5 h 4.2: 2.5 h / 0 - 50 °C
Multi-step reaction with 5 steps 1: potassium hydroxide / toluene / 1 h / 105 - 124 °C 2: thionyl chloride / toluene / 3 h / 80 °C 3: benzylamine; ammonium hydroxide / toluene; dichloromethane / 2 h / 0 °C 4: iron(III) chloride; chlorine / 1,2-dichloro-ethane / 3.5 h / 50 °C 5: sodium hydroxide; sodium hypochlorite / toluene / 40 °C
Multi-step reaction with 6 steps 1: potassium hydroxide / toluene / 1 h / 105 - 124 °C 2: thionyl chloride / toluene / 3 h / 80 °C 3: benzylamine; ammonium hydroxide / toluene; dichloromethane / 2 h / 0 °C 4: iron(III) chloride; chlorine / 1,2-dichloro-ethane / 3.5 h / 50 °C 5: sodium hydroxide; sodium hypochlorite / water / 1 h / 20 °C / Cooling with ice 6: sodium hydroxide; methanol / 1 h / 90 °C

  • 79
  • [ 104326-73-0 ]
  • [ 1204-44-0 ]
  • C19H12ClF3N2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine In acetonitrile at 60℃; 4 Example 4 20.5 g (0.10 mol) of 4'-chloro-2-aminobiphenyl and 12.1 g (0.12 mol) of triethylamine and 150 ml of acetonitrile were added to a four-necked reaction flask, and the temperature was raised to 60 ° C, and 23.1 g (0.11) was slowly added dropwise. A mixture of mol of 4-trifluoromethylnicotinyl chloride and 55 ml of acetonitrile is added dropwise in about 1 to 2 hours. After the completion of the dropwise addition, the mixture was kept for 2 h, and the liquid phase was detected to have a 4'-chloro-2-aminobiphenyl content of less than 1%. Then, the solvent was evaporated under reduced pressure, washed with water (200 ml), filtered, and then recrystallized from methanol drying to obtain white solid 34.4 g, content 99.0%, yield 90%
  • 80
  • [ 1204-44-0 ]
  • [ 312-94-7 ]
  • C20H13ClF3NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With potassium carbonate In 1,2-dichloro-ethane; N,N-dimethyl-formamide at 80℃; 3 example 3 20.5 g (0.10 mol) of 4'-chloro-2-aminobiphenyl and 16.7 g (0.12 mol) of potassium carbonate and 150 ml of DMF were placed in a four-necked reaction flask, and the temperature was raised to 80 ° C, and 23.0 g (0.11 mol) was slowly added dropwise. A mixture of o-trifluoromethylbenzoyl chloride and 55 ml of dichloroethane is added dropwise in about 1 to 2 hours. After the completion of the dropwise addition, the mixture was kept for 2 h, and the liquid phase was detected to have a 4'-chloro-2-aminobiphenyl content of less than 1%. Then, the solvent was evaporated under reduced pressure, washed with water (200 ml), filtered, and then recrystallized from methanol to afford white solid 36.1. g, content 99.0%, yield 95%
  • 81
  • [ 49609-84-9 ]
  • [ 1679-18-1 ]
  • [ 88-73-3 ]
  • [ 1204-44-0 ]
YieldReaction ConditionsOperation in experiment
93% Stage #1: 4-Chlorophenylboronic acid; 2-Chloronitrobenzene With potassium phosphate; C46H52Cl3N3O2Pd In tetrahydrofuran; water at 60℃; for 4h; Stage #2: With hydrogenchloride; zinc Stage #3: 2-Chloronicotinoyl chloride
  • 82
  • [ 1204-44-0 ]
  • [ 107-13-1 ]
  • [ 1360593-24-3 ]
YieldReaction ConditionsOperation in experiment
78% With silver hexafluoroantimonate; [RhCl2(p-cymene)]2; mesitylenecarboxylic acid; copper(II) acetate monohydrate In tetrahydrofuran at 80℃; for 48h; Glovebox; Inert atmosphere;
  • 83
  • [ 5535-48-8 ]
  • [ 1204-44-0 ]
  • 8-chloro-6-((phenylsulfonyl)methyl)phenanthridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With silver hexafluoroantimonate; [RhCl2(p-cymene)]2; mesitylenecarboxylic acid; copper(II) acetate monohydrate In 1,4-dioxane at 80℃; for 48h; Glovebox; Inert atmosphere;
  • 84
  • [ 28383-65-5 ]
  • [ 1204-44-0 ]
  • ethyl 8-chlorophenanthridine-6-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With oxygen; trifluoroacetic acid at 120℃; 6 Example 6Preparation of Ethyl 8-chlorophenanthridine-6-carboxylate Add 0.2 mmol of 4'-chloro-1,1'-diphenyl-2-amine, 1.5 equivalents of ethyl 2-diazobenzoylacetate, and 1.6 mL of CF3COOH to a 15 mL pressure-resistant tube (with magnetic stir bar) ),Stir at 120 ° C under oxygen and monitor the progress of the reaction by TLC.After the reaction was completed, it was extracted three times with 15 mL of ethyl acetate and saturated 15 * 3 mL of sodium bicarbonate solution. The organic phases were combined and concentrated, and separated by silica gel column chromatography.27.4 mg of a yellow solid compound was obtained with a yield of 48%,The structure of the obtained product is as follows:
  • 85
  • [ 2942-59-8 ]
  • [ 1204-44-0 ]
  • N-(4'-chloro-[1,1'-biphenyl]-2-yl)-2-hydroxynicotinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
85.57% With m-nitrobenzene boronic acid In toluene at 120℃; for 10h; Large scale; 1-10 Example 1 Synthesis method of 2-hydroxy-N- (4'-chlorobiphenyl-2-yl) nicotinamide Using 2-chloronicotinic acid and 4'-chloro-2-aminobiphenyl as raw materials, it reacts with catalyst 3-nitrophenylboronic acid in toluene solution at 120 to produce 2-hydroxy-N- (4'-chlorobiphenyl- 2-yl) nicotinamide, the specific synthetic route is as follows:Step 1): Measure 1.56kg (ie 10mol) of 2-chloronicotinic acid, 1.02kg (ie 5mol) of 4'-chloro-2-aminobiphenyl, 0.42kg (ie 2.5mol) of 3-nitrobenzene Boric acid, spare;Measure 30L of toluene, add 2-chloronicotinic acid to toluene, stir and dissolve at room temperature, add 4'-chloro-2-aminobiphenyl, stir and mix, then add 3-nitrophenylboronic acid, heat to 120 ° C, After maintaining the reaction at 120 ° C for 10 hours, solution B was prepared, and solution B was naturally cooled to room temperature;Step 2): Add 30L of saturated sodium bicarbonate aqueous solution to the solution B, wash with stirring at room temperature for 10 min, separate the phases to obtain the organic phase and the aqueous phase, and repeat the above operation to wash the organic phase three times to obtain the organic phase C;Add 30L of saturated sodium chloride aqueous solution to the organic phase C, wash with stirring at room temperature for 10min, separate the phases to obtain the organic phase and the aqueous phase, and repeat the above operation to wash the organic phase three times to obtain the organic phase D;After the organic phase was dried over anhydrous magnesium sulfate with D, it was distilled to dryness at 40 ° C and 0.1MPa under reduced pressure to obtain 1.02kg of 2-hydroxy-N- (4'-chlorobiphenyl-2-yl) nicotinamide. The yield was 60.1%. The 1H NMR chart of 2-hydroxy-N- (4'-chlorobiphenyl-2-yl) nicotinamide is shown in Figure 1, and the high resolution liquid quality chart is shown in Figure 2.Step 3): Take 0.50kg of 2-hydroxy-N- (4’-chlorobiphenyl-2-yl) nicotinamide and set aside;Measure 5L of ethyl acetate, add 2-hydroxy-N- (4'-chlorobiphenyl-2-yl) nicotinamide, stir to dissolve, and slowly add petroleum ether dropwise until crystals precipitate (the amount of petroleum ether is about 4.0L );Reduce the temperature to 0 , and maintain the crystallization at 0 for 1h, filter, wash with a small amount of petroleum ether (about 1L), and dry at 40 for 4h to constant weight to obtain 0.43kg of 2-hydroxy-N- (4'- Chlorinated biphenyl-2-yl) nicotinamide boutique, the yield is 85.57%, the total yield is 51.43%, see the liquid diagram of 2-hydroxy-N- (4'-chlorobiphenyl-2-yl) nicotinamide Figure 4.
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 1204-44-0 ]

Aryls

Chemical Structure| 30273-39-3

[ 30273-39-3 ]

(4-Chloro-2-ethylphenyl)amine

Similarity: 0.95

Chemical Structure| 3843-97-8

[ 3843-97-8 ]

5-Chloro-2-ethylaniline

Similarity: 0.93

Chemical Structure| 108047-39-8

[ 108047-39-8 ]

2-(Aminomethyl)-4-chloroaniline

Similarity: 0.89

Chemical Structure| 67330-62-5

[ 67330-62-5 ]

3-Chloro-2,6-diethylaniline

Similarity: 0.85

Chemical Structure| 20782-94-9

[ 20782-94-9 ]

4-Chloro-2,5-dimethylaniline

Similarity: 0.84

Chlorides

Chemical Structure| 30273-39-3

[ 30273-39-3 ]

(4-Chloro-2-ethylphenyl)amine

Similarity: 0.95

Chemical Structure| 3843-97-8

[ 3843-97-8 ]

5-Chloro-2-ethylaniline

Similarity: 0.93

Chemical Structure| 108047-39-8

[ 108047-39-8 ]

2-(Aminomethyl)-4-chloroaniline

Similarity: 0.89

Chemical Structure| 67330-62-5

[ 67330-62-5 ]

3-Chloro-2,6-diethylaniline

Similarity: 0.85

Chemical Structure| 20782-94-9

[ 20782-94-9 ]

4-Chloro-2,5-dimethylaniline

Similarity: 0.84

Amines

Chemical Structure| 30273-39-3

[ 30273-39-3 ]

(4-Chloro-2-ethylphenyl)amine

Similarity: 0.95

Chemical Structure| 3843-97-8

[ 3843-97-8 ]

5-Chloro-2-ethylaniline

Similarity: 0.93

Chemical Structure| 108047-39-8

[ 108047-39-8 ]

2-(Aminomethyl)-4-chloroaniline

Similarity: 0.89

Chemical Structure| 67330-62-5

[ 67330-62-5 ]

3-Chloro-2,6-diethylaniline

Similarity: 0.85

Chemical Structure| 20782-94-9

[ 20782-94-9 ]

4-Chloro-2,5-dimethylaniline

Similarity: 0.84