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Agarwal, Devesh S. ; Beteck, Richard M. ; Ilbeigi, Kayhan , et al. DOI: PubMed ID:

Abstract: A library of imidazo[1,2-a]pyridine-appended chalcones were synthesized and characterized using 1H NMR,13C NMR and HRMS. The synthesized analogs were screened for their antikinetoplastid activity against Trypanosoma cruzi, Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense and Leishmania infantum. The analogs were also tested for their cytotoxicity activity against human lung fibroblasts and primary mouse macrophages. Among all screened derivatives, (E)-N-(4-(3-(2-chlorophenyl)acryloyl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide was found to be the most active against T. cruzi and T. b. brucei exhibiting IC50 values of 8.5 and 1.35 μM, resp. Against T. b. rhodesiense, (E)-N-(4-(3-(4-bromophenyl)acryloyl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide was found to be the most active with an IC50 value of 1.13 μM. All synthesized active analogs were found to be non-cytotoxic against MRC-5 and PMM with selectivity indexes of up to more than 50.

Keywords: antikinetoplastid ; chalcone ; drug likeliness properties ; imidazo[1,2-a]pyridine ; neglected tropical diseases (NTDs) ; Trypanosoma brucei brucei ; Trypanosoma brucei rhodesiense

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Product Details of [ 1122-91-4 ]

CAS No. :1122-91-4 MDL No. :MFCD00003377
Formula : C7H5BrO Boiling Point : -
Linear Structure Formula :- InChI Key :ZRYZBQLXDKPBDU-UHFFFAOYSA-N
M.W : 185.02 Pubchem ID :70741
Synonyms :

Calculated chemistry of [ 1122-91-4 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 39.53
TPSA : 17.07 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.9 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.71
Log Po/w (XLOGP3) : 2.16
Log Po/w (WLOGP) : 2.26
Log Po/w (MLOGP) : 2.21
Log Po/w (SILICOS-IT) : 2.68
Consensus Log Po/w : 2.2

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.78
Solubility : 0.31 mg/ml ; 0.00168 mol/l
Class : Soluble
Log S (Ali) : -2.15
Solubility : 1.31 mg/ml ; 0.00706 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.2
Solubility : 0.117 mg/ml ; 0.000634 mol/l
Class : Soluble

Medicinal Chemistry

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

Safety of [ 1122-91-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H317-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1122-91-4 ]

* 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.

  • Upstream synthesis route of [ 1122-91-4 ]
  • Downstream synthetic route of [ 1122-91-4 ]

[ 1122-91-4 ] Synthesis Path-Upstream   1~148

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Reference: [1] Tetrahedron Letters, 2010, vol. 51, # 2, p. 357 - 359
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  • [ 127406-56-8 ]
Reference: [1] Tetrahedron, 1998, vol. 54, # 7, p. 1289 - 1298
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  • [ 127406-56-8 ]
Reference: [1] Organic and Biomolecular Chemistry, 2014, vol. 12, # 2, p. 286 - 297
  • 4
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  • [ 127406-56-8 ]
Reference: [1] Organic Process Research and Development, 2008, vol. 12, # 1, p. 69 - 75
  • 5
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  • [ 50907-23-8 ]
Reference: [1] Applied Organometallic Chemistry, 2018, vol. 32, # 4,
[2] Tetrahedron Letters, 2016, vol. 57, # 5, p. 523 - 524
  • 6
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  • [ 132833-51-3 ]
Reference: [1] Advanced Synthesis and Catalysis, 2012, vol. 354, # 5, p. 870 - 878
[2] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 20, p. 2989 - 2992
[3] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 15, p. 4242 - 4247
  • 7
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  • [ 1204-86-0 ]
YieldReaction ConditionsOperation in experiment
64% With tetrabutylammomium bromide; palladium diacetate; potassium carbonate; 2,6-bis(diphenylphosphino)pyridine In N,N-dimethyl acetamide at 135℃; for 4 h; Inert atmosphere General procedure: A round bottomedflask was charged with bromobenzene (4 mmol), aniline (4 mmol),TBAB (3 mmol), and K2CO3 (4 mmol) under a dry nitrogen atmosphere. A solution of (Ph2P)2py (0.05 mol percent in 2 mL of DMAc) and a solution of palladiumacetate (0.025 mol percent in 2 mL of DMAc) was added through a rubber septum,and the resulting mixture was heated at 135 C for the appropriate time. Uponcompletion of the reaction, the mixture was cooled to room temperature and quenched with H2O. After extraction with CH2Cl2 (3 20 mL), the combinedorganic layer was dried over MgSO4. The solvent was evaporated and the cruderesidue was purified by silica gel chromatography, using n-hexane/EtOAc aseluent to provide the desired product. The products were characterized byNMR spectroscopy
Reference: [1] Journal of Organometallic Chemistry, 2009, vol. 694, # 9-10, p. 1473 - 1481
[2] Tetrahedron, 2008, vol. 64, # 40, p. 9507 - 9514
[3] Applied Organometallic Chemistry, 2018, vol. 32, # 1,
[4] Tetrahedron Letters, 2014, vol. 55, # 30, p. 4098 - 4101
[5] Advanced Synthesis and Catalysis, 2008, vol. 350, # 17, p. 2767 - 2777
[6] Inorganica Chimica Acta, 2010, vol. 363, # 6, p. 1262 - 1268
[7] Journal of Medicinal Chemistry, 2013, vol. 56, # 20, p. 8049 - 8065
  • 8
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  • [ 103858-53-3 ]
Reference: [1] Patent: US2002/68756, 2002, A1,
  • 9
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  • [ 1122-91-4 ]
  • [ 10040-98-9 ]
YieldReaction ConditionsOperation in experiment
67% With potassium carbonate In N,N-dimethyl-formamide at 152℃; for 26 h; General procedure: To a vigorously stirred suspension of the CuNPs/MagSilica catalyst (100 mg) in DMF (6 mL) under air, K2CO3 (276 mg, 2.0 mmol) and imidazole (136 mg, 2.0 mmol) were added. The reaction mixture was stirred for 30 min and then the corresponding aryl halide (1.0 mmol) was added and the reaction flask was immersed in an oil bath at the reflux temperature of DMF (152 °C). The reaction mixture was stirred at this temperature until no further conversion of the starting aryl halide was observed (TLC, GC). The catalyst was immobilized by means of a permanent magnet placed on the outer wall of the reaction flask, and washed twice with Et2O (10 mL each). Finally, the catalyst was dried under vacuum (5 Torr) for its recovery and reuse. The crude reaction mixture was evaporated under vacuum (15 Torr) and the resulting residue was purified by flash column chromatography (silica gel, hexane/AcOEt) to afford the corresponding N-aryl imidazoles (2a-j). All known compounds included in Table 1 were characterized by comparison of their chromatographic and spectroscopic data (1H, 13C NMR, and MS) either with those of the corresponding commercially available pure samples (2g) or with those described in the literature (2a,21 2b,212c,22 2d,21 2e,11a 2f,11a 2h,23 2i,24 2j25).
85 %Chromat. With C16H12ClN3OPdS; potassium hydroxide In dimethyl sulfoxide at 110℃; for 10 h; General procedure: Arylhalide (1.0 mM), nitrogen-containing heterocycle (1.2 mM), KOH (2 mM), and the catalyst (0.75 Mpercent) were stirred in dimethyl sulfoxide (DMSO) (4 mL) at 110 °C for 10 h. After completion of the reaction, the mixture was cooled to room temperature, diluted with ethyl acetate (10 mL) and filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel using hexane/ethyl acetate(70 : 30) as eluent to afford the desired product. The products have been characterized by 1H NMR spectroscopy.
Reference: [1] Tetrahedron, 2008, vol. 64, # 19, p. 4254 - 4259
[2] Tetrahedron, 2008, vol. 64, # 10, p. 2471 - 2479
[3] Tetrahedron Letters, 2006, vol. 47, # 23, p. 3897 - 3899
[4] Synthetic Communications, 2012, vol. 42, # 1, p. 114 - 121
[5] Chinese Journal of Chemistry, 2012, vol. 30, # 10, p. 2394 - 2400
[6] RSC Advances, 2015, vol. 5, # 12, p. 8571 - 8578
[7] Synthetic Communications, 2012, vol. 42, # 2, p. 279 - 284
[8] Research on Chemical Intermediates, 2016, vol. 42, # 10, p. 7501 - 7511
[9] Bulletin of the Chemical Society of Japan, 2008, vol. 81, # 4, p. 515 - 517
[10] Tetrahedron, 2014, vol. 70, # 36, p. 6082 - 6087
[11] Applied Organometallic Chemistry, 2017, vol. 31, # 11,
[12] Inorganic Chemistry, 2010, vol. 49, # 1, p. 331 - 338
[13] Tetrahedron, 2008, vol. 64, # 7, p. 1383 - 1387
[14] European Journal of Medicinal Chemistry, 2009, vol. 44, # 11, p. 4654 - 4660
[15] Journal of Coordination Chemistry, 2015, vol. 68, # 19, p. 3537 - 3550
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  • [ 10040-98-9 ]
Reference: [1] Monatshefte fur Chemie, 2004, vol. 135, # 4, p. 419 - 423
  • 11
  • [ 1670-14-0 ]
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  • [ 98-86-2 ]
  • [ 58536-46-2 ]
YieldReaction ConditionsOperation in experiment
30%
Stage #1: With sodium methylate In methanol; ethanol at 20℃; for 9 h; Inert atmosphere; Reflux
Stage #2: With sodium hydroxide In methanol; ethanol at 70℃; for 5 h;
4-bromobenzaldehyde (18.5 g, 100 mmol), acetophenone (12.0 g, 100 mmol), 1N-sodium methoxide/methanol solution (10 ml) and ethanol (200 ml) were stirred at room temperature for 5 hours at the room temperature under an Ar gas atmosphere. Subsequently, the reactant mixture was heated and stirred for another four hours at a reflux temperature. Next, benzamidine hydrochloride (9.4 g, 60 mmol) and sodium hydroxide (8.0 g, 200 mmol) were added thereto and stirred for five hours at 70 degrees C. After the reaction, the reactant mixture was filtered to separate an extract. The extract was refined by silica-gel column chromatography (a developing solvent: dichloromethane) to provide an intermediate body X7 as a white solid. A yield of the intermediate body X7 was 11.6 g and a yield rate thereof was 30percent
Reference: [1] Patent: EP2489664, 2012, A1, . Location in patent: Page/Page column 47
[2] Patent: US2016/343955, 2016, A1,
  • 12
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  • [ 58536-46-2 ]
Reference: [1] Patent: EP2415769, 2012, A1,
[2] Patent: EP2589596, 2013, A1,
[3] Patent: US9711732, 2017, B2,
[4] Journal of Materials Chemistry C, 2018, vol. 6, # 37, p. 10088 - 10100
  • 13
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  • [ 23449-08-3 ]
YieldReaction ConditionsOperation in experiment
68% With copper(II) acetate monohydrate; sodium carbonate In toluene at 100℃; for 24 h; General procedure: A mixture ofaldehyde 1 (6.8 mmol), amidine hydrochloride 2 (2 g,11.4 mmol), Na2CO3 (1.21 g, 11.4 mmol, 1.0 equiv) andCu(OAc)2 (10 molpercent) was stirred in toluene (20 mL) under100 °C in air for 24 h. After completion of the reaction, themixture was cooled to room temperature. The water wasadded to the reaction system and atmospheric distillation untiltoluene was evaporated. The resulting solution was filteredand residue with hot water washed 3 times. The crude productwas purified by column chromatography on silica gel usingpetroleum ether/EtOAc (100:1) as an eluent to give the correspondingproducts 7a-7x.
Reference: [1] Journal of Fluorescence, 2018, vol. 28, # 2, p. 707 - 723
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  • [ 534-85-0 ]
  • [ 2620-76-0 ]
YieldReaction ConditionsOperation in experiment
92% With sodium hydrogensulfite In N,N-dimethyl-formamide for 1 h; A solution of Ν-(4-phenyl)benzene-1,2-diamine (3.68 g, 20 mmol), 4-bromobenzaldehyde (3.70 g, 20 mmol) and sodium bisulfite (2.04 g, 10mmol) was dissolved in DMF (80 mL) and stirred in air for 1 h. After the completion of the reaction, the reaction solution was poured into water to precipitate the product. After standing for some time, the product was filtered and washed with a small amount of methanol. Finally, the crude product was purified by silica gel column chromatography using a mixture of n-hexane and ethyl acetate (1: 5) as eluent to give a white powdery solid product. Yield: 6.40 g, 92percent.
89% With sodium hydrogensulfite In N,N-dimethyl-formamide for 1 h; Reflux willN- (4-phenyl) benzene-1,2-diamine(3.68 g, 20 mmol),4-bromobenzaldehyde (3.70 g, 20 mmol) and sodium bisulfite (2.04 g, 10 mmol)Of the mixture was dissolved in DMF (80 mL)Mix in air for 1 h.Point plate test After the end of the reaction cooled to room temperature,The reaction solution was poured into water,Precipitation products.After standing for some time,Filter out the product,Wash with a small amount of methanol.At last,The crude product was mixed with n-hexane and ethyl acetate (1: 3)As a eluent by silica gel column chromatography to obtain a white powder solid product.Yield: 6.18 g, 89percent.
60% at 180℃; for 6 h; 4-bromo-benzaldehyde (8.3g, 45mmol) was dispersed in the benzene in 10ml of N-phenyl-1,2-phenylenediamine (N-phenyl-1,2-phenylenediamine, 8.3g, 45mmol ), which was heated at 180 °C for 6 hours. After cooling to room temperature, and then removed by distillation under reduced pressure to nitrobenzene, the resulting solid was filtered and dried in vacuo, washed with ethyl ether to obtain a compound A.
57.71% With toluene-4-sulfonic acid In toluene for 16 h; Heating / reflux Synthesis of 2-(4-bromophenyl)-1-phenyl-1H-benzo[d]imidazoleN-Phenyl-o-phenylenediamine 13.27 g (72 mmole), 4-bromobenzaldehyde 16 g (87 mmole), and 2.8 g of PTSA (14 mmole) was stirred in 150 ml of Toluene, the reaction mixture was then heated to reflux for 16 hours, after cooling, the reaction mixture was extracted with water, and then the organic layer was evaporated to dry, the residue was then recrystallized with acetone to get 14.51 g of product (yield=57.71percent).
49% for 12 h; Reflux Acetic acid (20 mL) was added to a flask containing N-phenyl-o-phenylenediamine (1.50 g, 8.14 mmol) and 4-bromobenzaldehyde (1.66 g, 8.96 mmol).
After the mixture was refluxed for 12 h, distilled water was added and the organic layer was extracted with dichloromethane.
The organic layer was washed with sodium bicarbonate and brine and dried using anhydrous sodium sulfate.
The filtrate was concentrated in vacuo to give a crude mixture, which was then subjected to column chromatography on silica gel using ethyl acetate and hexane (v/v 1:20) as the eluent.
Analytically pure 2-(4-bromophenyl)-1-phenyl-1H-benz[d]imidazole was isolated as a white solid (1.39 g, 49percent).
1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.4 Hz, 1H), 7.53-7.42 (m, 7 H), 7.35-7.21 (m, 5H).
13C NMR (CDCl3, 100 MHz) δ 151.21, 142.90, 137.25, 136.75, 131.55, 130.84, 130.01, 128.90, 128.77, 127.37, 124.04, 123.58, 123.15, 119.90, 110.48. MALDI-TOF MS: calcd for C19H13BrN2 348.03, found 349.20.
35% With Oxone In N,N-dimethyl-formamide at 20 - 40℃; Inert atmosphere c) 2-(4-Bromophenyl)-1-phenyl-1H-benzimidazole N-Phenyl-o-phenylenediamine (50 g, 0.27 mol) is dissolved in anhydrous DMF (400 ml) under N2, and 4-bromobenzaldehyde (45.5 g, 0.25 mol) is added dropwise. The reaction mixture is warmed to 40° C., and Oxone (potassium hydrogen monopersulfate, 98.1 g, 0.16 mol) is added in portions. After the mixture has been stirred at room temperature for 120 min., 1 l of water is added. The precipitated product is filtered off, washed with water and dried in vacuo. Recrystallisation from acetonitrile gives a cream-coloured solid (31 g, 35percent).
23.6% at 140℃; Inert atmosphere 2.1Weigh 7.36 g of 4-bromobenzaldehyde and 7.3 g of o-aminodiphenylamine in 200 mL of acetic acid.After charging and discharging nitrogen for 3 times, the temperature was set to 140 ° C to start the reaction;2.2After the reaction, the temperature was lowered to room temperature, and a large amount of gray solid was precipitated after pouring into water, and filtered.After the filter cake was added with 5 g of silica gel, the column was passed to obtain 3.2 g of a white solid powder, the yield was 23.6percent, HPLC 99.7percent;

Reference: [1] Patent: CN107011268, 2017, A, . Location in patent: Paragraph 0083; 0085; 0087; 0088
[2] Monatshefte fur Chemie, 2009, vol. 140, # 4, p. 375 - 380
[3] Patent: CN106905242, 2017, A, . Location in patent: Paragraph 0038; 0046; 0047; 0048
[4] Journal of Heterocyclic Chemistry, 2012, vol. 49, # 5, p. 1187 - 1195
[5] Patent: KR101597865, 2016, B1, . Location in patent: Paragraph 0115-0118
[6] Patent: US2008/265746, 2008, A1, . Location in patent: Page/Page column 6
[7] Organic Electronics: physics, materials, applications, 2013, vol. 14, # 10, p. 2497 - 2504
[8] Patent: US2012/292571, 2012, A1, . Location in patent: Page/Page column 37
[9] Patent: CN106800555, 2018, B, . Location in patent: Paragraph 0075; 0102; 0103
[10] Patent: WO2009/51390, 2009, A2, . Location in patent: Page/Page column 65-67
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YieldReaction ConditionsOperation in experiment
92% at 130℃; for 12 h; Sealed tube; Inert atmosphere General procedure: An oven dried pressure tube was chargedwith aryl bromide (1 mmol), CuI (1 mmol), DABCO (2 mmol) and dry DMSO (5 mL).Then the tube was sealed with a teflon cap and heated with stirring at 130 Cin N2 atmosphere for 12 – 36 h. The completions of reactions weremonitored by TLC. The reaction mixture was then cooled to room temperature. Themass was passed through celite bed, packed in a sinter funnel. Then thefiltered reaction mixture was extracted with ethyl acetate (3 X 20) washed withwater (3 X 20) and brine solution (3 X 10). Ethyl acetate part were collectedand dried over Na2SO4, and then evaporated under reducedpressure. The crude products were purified by column chromatography on silicagel to obtain pure product.
70% at 135℃; for 36 h; General procedure: An oven dried pressure tube was charged with aryl halide (0.5mmol), CuI (10–25molpercent), anhydrous Zn(OAc)2 (1.5–2equiv) and anhydrous DMSO (1.6mL). The tube was sealed with a Teflon screw cap and stirred at 135°C for 24–36h. The reaction mixture was then cooled to room temperature and stirred in 10mL of diethyl ether for 5min. It is filtered through a sintered funnel and the filtrate is washed with excess ice cold water and further extracted with diethyl ether (3×10mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product, which was purified by column chromatography using 200–400 mesh silica gel and a mixture of diethyl ether and hexane (or pentane, for Table 2, entries 2, 8, 10, 14, 16 and 24) as eluents to afford the desired products in good yields.
Reference: [1] Tetrahedron Letters, 2015, vol. 56, # 37, p. 5199 - 5202
[2] Chemical Communications, 2011, vol. 47, # 18, p. 5304 - 5306
[3] Tetrahedron, 2013, vol. 69, # 38, p. 8276 - 8283
  • 16
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Reference: [1] Advanced Synthesis and Catalysis, 2006, vol. 348, # 1-2, p. 236 - 242
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  • [ 589-17-3 ]
Reference: [1] Organic Letters, 2013, vol. 15, # 1, p. 108 - 111
[2] Organic and Biomolecular Chemistry, 2013, vol. 11, # 24, p. 4016 - 4024
[3] Patent: WO2015/95821, 2015, A1,
[4] Chemical Communications, 2017, vol. 53, # 54, p. 7545 - 7548
[5] Patent: WO2017/134188, 2017, A1,
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  • [ 53348-05-3 ]
Reference: [1] Comptes Rendus Chimie, 2017, vol. 20, # 8, p. 841 - 849
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  • [ 1122-91-4 ]
  • [ 18962-05-5 ]
YieldReaction ConditionsOperation in experiment
72% With hemicucurbituril supported [Bmim]Cl In toluene for 10 h; Reflux General procedure: A mixture of aryl halide (1 mmol) and sodium alkoxide(3.0 mmol) was refluxed in the presence of 200 mg ofHmCucSILP catalyst in toluene (5 mL) for an appropriatetime as indicated in Table 2. After completion of thereaction, the reaction mixture was filtered and solvent wasevaporated in vacuo to give the crude product, which waspurified by column chromatography over silica gel usinghexane/EtOAc as the eluent.
Reference: [1] Catalysis Letters, 2016, vol. 146, # 12, p. 2485 - 2494
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  • [ 71-36-3 ]
  • [ 5736-88-9 ]
Reference: [1] Journal of the American Chemical Society, 2010, vol. 132, # 33, p. 11592 - 11598
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  • [ 288-36-8 ]
  • [ 179056-04-3 ]
Reference: [1] Angewandte Chemie - International Edition, 2011, vol. 50, # 38, p. 8944 - 8947
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  • [ 26510-95-2 ]
Reference: [1] Journal of Organic Chemistry, 2004, vol. 69, # 22, p. 7599 - 7608
[2] Journal of Organic Chemistry, 2004, vol. 69, # 22, p. 7599 - 7608
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Reference: [1] Synthesis, 2008, # 11, p. 1685 - 1687
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  • [ 26510-95-2 ]
Reference: [1] RSC Advances, 2013, vol. 3, # 31, p. 12616 - 12620
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  • [ 776-99-8 ]
Reference: [1] Synlett, 2007, # 3, p. 374 - 380
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  • [ 22483-09-6 ]
  • [ 34784-05-9 ]
YieldReaction ConditionsOperation in experiment
35%
Stage #1: for 12 h; Reflux; Dean-Stark
Stage #2: With chloroformic acid ethyl ester In tetrahydrofuran at -10℃; for 0.166667 h;
A mixture of 4-bromobenzaldehyde (300.0 g, 1620.0 mmol) and amino acetaldehyde dimethyl acetal (170.4 g, 1620 mmol) in anhydrous toluene (1.5 L) was refluxed under a Dean-Stark condenser for 12 h. The solution was concentrated under vacuum. The residue was dissolved in anhydrous THF and cooled to -10 °C. Ethyl chloroformate (193.3 ml_, 1782 mmol) was added and stirred for 10 min at -10 °C, and then allowed to warm to room temperature. Subsequently trimethyl phosphite (249.6 ml_, 1782.0 mmol) was added dropwise to the reaction mixture and stirred for 10 h at room temperature. The solvent was evaporated under vacuum and the residue was dissolved in anhydrous DCM (1.5 L) and stirred for 30 minutes. The reaction mixture was cooled to 0 °C, and titanium tetrachloride (1.2 L, 6480 mmol) was added dropwise. The reaction mixture was stirred at 40 °C for 6 days. The reaction mixture was poured into ice and pH was adjusted to 8 - 9 with aqueous 6N NaOH solution. The suspension was extracted three times with EtOAc. The organic layer was extracted with 3 M HCI. The acidic aqueous solution was adjusted to pH to 7 - 8 with 3N NaOH solutions and extracted two times with EtOAc. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide the product. Crude compound was dissolved in minimum amount of DCM and mixed with pentane to get compound A1 as light brown solid. Yield: 90 g (35percent). Rf: 0.6 (30percent EtOAc in petroleum ether). LCMS m/z = 209 (M + 1 ). 1H NMR (400 MHz, cf6-DMSO): δ 7.82 (m, 2H), 8.1 1 (d, J = 8.8 Hz, 2H), 8.30 (br s, 1 H), 8.56 (d, J = 6.0 Hz, 1 H), 9.35 (s, 1 H).
14%
Stage #1: at 120℃; Dean-Stark
Stage #2: at 160℃; for 0.5 h;
General procedure: Aminoacetaldehyde dimethylacetal (3.0 eq.) was added to a solution of bromobenzaldehyde13b or 13c (1.0 eq.) in toluene (30 mL). Each reaction mixture was refluxed (Dean–Stark apparatus)at 120 °C. After consumption of the starting material, each reaction mixture was concentrated todryness, then dissolved in conc. H2SO4 (2 mL) and added to a cold solution of P2O5 in conc. H2SO4(0.5 mL). Each reaction mixture was heated at 160 °C for 30 min, allowed to cool to RT, neutralizedwith NaOH (10 M), extracted with EtOAc, and concentrated to dryness. Each residue was subjected toFCC to afford 6-bromoisoquinoline (14b, 30 mg, 0.14 mmol, 14percent) and 7-bromoisoquinoline (14c, 99 mg,0.47 mmol, 22percent) [20,21]. Ethylchloroformate (1.0 eq.) was added to a solution of isoquinoline 14b or14c (1.0 eq.) in DCM at 0 °C and stirred at the same temperature for 30 min, followed by additionof 2-trimethylsilylthiazole (1.0 eq.). Each reaction mixture was stirred at RT for 3 h, concentratedto dryness, and each residue was subjected to FCC. Each product was dissolved in benzene (5 mL),o-chloranil (1.0 eq.) was added, and each reaction mixture was refluxed for 5 h. Each reaction mixturewas diluted with 5percent NaOH (10 mL), extracted with DCM, and concentrated to dryness. Each reactionmixture residue was subjected to FCC to afford the products 9b and 9c.6-Bromo-1-(2-thiazolyl)isoquinoline (9b): 6-Bromoisoquinoline (14b, 30 mg, 0.14 mmol) was synthesizedstarting from 4-bromobenzaldehyde (13c, 200 mg, 1.08 mmol) in 14percent yield. Compound 9b wassynthesized starting from 6-bromoisoquinoline (14b, 100 mg, 0.48 mmol) in 15percent yield over two steps(21 mg, 0.07 mmol), obtained as an orange powder, m.p. 103–105 °C.
Reference: [1] Patent: WO2015/181676, 2015, A1, . Location in patent: Page/Page column 132-133
[2] Dalton Transactions, 2015, vol. 44, # 18, p. 8552 - 8563
[3] Molecules, 2017, vol. 22, # 8,
[4] Journal of the Chemical Society. Perkin Transactions 2, 1998, # 2, p. 437 - 447
  • 27
  • [ 1122-91-4 ]
  • [ 34784-05-9 ]
Reference: [1] Patent: WO2011/103196, 2011, A1,
  • 28
  • [ 110-89-4 ]
  • [ 1122-91-4 ]
  • [ 10338-57-5 ]
YieldReaction ConditionsOperation in experiment
92% With water; sodium t-butanolate In toluene at 105℃; for 4 h; Schlenk technique General procedure: An oven-dried Schlenk tube was charged with the aryl halide (2 mmol) and amine (2.5 mmol), FeOA–Pd (0.05 g, 0.04 mmol, 1.5 molpercent), base (3 mmol), solvent (5 mL) and additive. The resulting mixture was stirred for the appropriate time and temperature. After reaction completion the reaction mixture was then cooled to room temperature and the catalyst separated using a magnet, taken up in Et2O (4 mL), and washed with brine (5 mL). The resulting solution was dried over anhydrous MgSO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel.
Reference: [1] Tetrahedron Letters, 2016, vol. 57, # 2, p. 219 - 222
[2] Tetrahedron Letters, 1998, vol. 39, # 17, p. 2471 - 2474
  • 29
  • [ 123-75-1 ]
  • [ 1122-91-4 ]
  • [ 5543-27-1 ]
Reference: [1] Advanced Synthesis and Catalysis, 2016, vol. 358, # 16, p. 2631 - 2641
[2] Chemical Communications, 2017, vol. 53, # 73, p. 10212 - 10215
[3] Organic Letters, 2007, vol. 9, # 17, p. 3429 - 3432
[4] Journal of Organic Chemistry, 2009, vol. 74, # 6, p. 2575 - 2577
[5] Organic and Biomolecular Chemistry, 2016, vol. 14, # 29, p. 7028 - 7037
[6] Dalton Transactions, 2014, vol. 43, # 3, p. 1292 - 1304
[7] Organic Letters, 2014, vol. 16, # 21, p. 5812 - 5815
[8] RSC Advances, 2016, vol. 6, # 18, p. 14937 - 14947
[9] Photochemical and Photobiological Sciences, 2018, vol. 17, # 6, p. 750 - 762
  • 30
  • [ 1122-91-4 ]
  • [ 57699-28-2 ]
Reference: [1] Organic Letters, 2015, vol. 17, # 15, p. 3810 - 3813
  • 31
  • [ 507-19-7 ]
  • [ 1122-91-4 ]
  • [ 40150-98-9 ]
  • [ 939-97-9 ]
Reference: [1] Journal of the American Chemical Society, 2015, vol. 137, # 36, p. 11562 - 11565
  • 32
  • [ 1122-91-4 ]
  • [ 100-58-3 ]
  • [ 58-73-1 ]
Reference: [1] Medicinal Chemistry Research, 2012, vol. 21, # 11, p. 3532 - 3540
  • 33
  • [ 1122-91-4 ]
  • [ 25118-59-6 ]
Reference: [1] Journal of the Chemical Society, 1927, p. 25
  • 34
  • [ 110-05-4 ]
  • [ 1122-91-4 ]
  • [ 59247-47-1 ]
Reference: [1] RSC Advances, 2013, vol. 3, # 33, p. 13668 - 13670
  • 35
  • [ 75-91-2 ]
  • [ 1122-91-4 ]
  • [ 59247-47-1 ]
Reference: [1] Chemical Communications, 2014, vol. 50, # 36, p. 4751 - 4754
  • 36
  • [ 1122-91-4 ]
  • [ 536-74-3 ]
  • [ 57341-98-7 ]
YieldReaction ConditionsOperation in experiment
100%
Stage #1: for 0.0833333 h; Sealed tube; Sonication
Stage #2: for 3 h; Sealed tube
General procedure: In a tightly sealed tube (septa system),aryl halides (5.5 mmol) and 5percent nanocatalyst Pd/Cu, PPh3 (17 mg) were suspended in drytriethylamine (10 mL). The mixture was placed in an ultrasound bath and sonicated for 5 min.Then, the acetylene compound (5.6 mmol) was added and the mixture was stirred for 3 h. Themixture was cooled to room temperature and the catalyst was centrifuged, filtered and washedwith ethyl acetate (3 x 10 mL). The filtrate was washed three times with deionized water (3 x 15mL) and then dried over magnesium sulfate, filtered and concentrated under reduced pressureto give the product.
95% With potassium phosphate; C30H37Br2N3Pd(2-) In dimethyl sulfoxide at 100℃; for 1 h; General procedure: In a typical run, a 4 mL vial equipped with a magnetic stirrer bar was charged with a mixture of aryl halide (1 mmol), alkyne (2 mmol), Pd catalyst (0.01 mmol), K3PO4 (2 mmol), and 2 mL of DMSO in air. The mixture was stirred at 100 °C for 1 h, then cooled to room temperature and brine was added into it. The resulting mixture was extracted with ethyl acetate three times, and the crude product was obtained by removing the volatiles. The product was purified by flash column chromatography on silica gel.#10;
94% With copper(l) iodide; C26H24N6NiS4; triethylamine In N,N-dimethyl-formamide at 80℃; for 8 h; Inert atmosphere General procedure: In an oven-dried round bottom flask under an atmosphere of N2, a mixture of aryl halide (1 mmol), phenylacetylene (1.5 mmol), 1 (60.75 ppm or 0.05 molpercent), copper(I) iodide (5 mmol), and Et3N (3.0 mmol) in DMF (5 mL) was taken. The reaction mixture was stirred 80 °C for 2 h. At the end of the mentioned time, the reaction mixture was diluted with EtOAc (20 mL), washed with water (3 x 10 mL). The combinedorganic layer was dried over anhydrous Na2SO4, filtered and stripped off the solvent under reduced pressure. The residue was subjected to column chromatography on silica gel using ethyl acetate and n-hexane mixtures to afford the desired product in high purity. The products were characterized by 1H and 13C NMR analysis. The procedure for the Sonogashira reaction of aryl bromides was similar as mentioned above in the case of aryl iodides, where aryl bromide (1 mmol) and 1 (121.5ppm or 0.1 mol percent) were used and the reaction was carried out for 8 h.
93% With copper(l) iodide; C41H56ClNO4PdSe; potassium carbonate In N,N-dimethyl-formamide at 120℃; for 15 h; Inert atmosphere General procedure: A catalyst from 1-4 (10-2 M, 500 μL, 5 10-3 mmol, 0.5 molpercent) and (5 molpercent) of CuI were added to 3 mL degassed DMF taken in around bottom flask under nitrogen atmosphere. It was followed by the addition of aryl bromide (1.0 mmol), terminal alkyne (1.5 mmol) and K2CO3 (2.0 mmol). The reaction mixturewas heatedto 120 °C for 15 h under N2 atmosphere. Thereafter the mixture was cooled and extracted with ethyl acetate (15 mL). The extract was washed with water (10 mL) and dried over anhydrous Na2SO4. The solvent was evaporated with rotary evaporator and the resulting residue purified by a column chromatography on silica gel.
93% With Cu[9,9-dimethyl-4,5-bis(diphenylphosphine)xanthene]I; palladium diacetate; caesium carbonate In N,N-dimethyl-formamide at 60℃; for 16 h; Inert atmosphere General procedure: The mixture of aryl halides (1, 1.0 mmol) and alkynes (2, 1.2 mmol), Pd(OAc)2 (0.01mmol), Cu(Xantphos)I (0.01 mmol) and Cs2CO3 (2.0 mmol) in anhydrous DMF (5 mL) washeated at 60 oC for 16 h under argon atmosphere. After the reaction was finished, DMF was removed under reduced pressure. The mixture was extracted with ethyl acetate three times, then the combined organic layers were dried over anhydrous Na2SO4 and filtered. After removal of the solvent, the residue was purified by flash column chromatography on silica gel (hexane/ethyl acetate) to afford the pure product.
91% With nickel(II) ferrite; potassium carbonate In water at 100℃; for 2.5 h; General procedure: In a round-bottom flask equipped with a condenser for refluxingand a magnetic stirring bar, aryl/alkyl halide (1 mmol), phenylacetylene (1 mmol), K2CO3 (1.1 mmol), nickel ferrite nanoparticles(0.05 mmol) and water (3 ml) were added and heated at 100 °Cunder air atmosphere. The mixture was vigorously stirred underthese reaction conditions and its completion was monitored byTLC (EtOAc–n-hexane, 25:75).In each case, after completion of the reaction, the mixturewas dilutedwith diethyl ether and water. The organic layer was washed withbrine, dried over MgSO4, and concentrated under reduced pressureusing a rotary evaporator. The residue was purified by recrystallizationfrom ethanol and water.
91% at 85℃; for 24 h; Inert atmosphere; Green chemistry General procedure: To a mixture of the catalyst 3 (20mg containing 0.05molpercent Pd for aryl iodides and 40mg containing 0.1molpercent Pd for aryl bromides and chlorides), aryl halide (1mmol), alkyne (1.5mmol), and K2CO3 (1.5mmol, 207mg) was added PEG 200 (2mL) under argon atmosphere. The reaction mixture was stirred for the appropriate reaction time at 85 or 130°C (see, Table 2). The progress of the reaction was monitored by using gas chromatography. After completion of the reaction, pure products were obtained by using column chromatography with hexane and ethyl acetate as eluents.
90% With C37H29ClN3PPdS; triethylamine In N,N-dimethyl-formamide at 20℃; for 12 h; General procedure: In an oven-dried round bottom flask, a mixture of aryl halide (1 mmol), phenylacetylene (1.5 mmol), complex 1 (0.5 mol percent for aryl bromides, 1.0 mol percent for aryl chlorides) and Et3N (3.0 mmol) in DMF (5 mL) was taken. The reaction mixture was stirred at room temperature (12 h for aryl bromides, 24 h for aryl chlorides). At the end of the time period mentioned, the reaction mixture was diluted with EtOAc (20 mL) and washed with water (3 x 10 mL). The organic layer was dried over anhydrous Na2SO4, filtered and stripped off the solvent under reduced pressure. The residue was subjected to column chromatography on silica gel using ethyl acetate and n-hexane mixtures to afford the desired product in high purity. The products were characterized by 1H and 13C NMR analysis.
90% With sodium carbonate In 1-methyl-pyrrolidin-2-one; water at 60℃; for 1.05 h; General procedure: To a mixture of phenyl acetylene (0.5 gm, 4.9 mmol), arylhalide (5.4 mmol) and Na2CO3 (5.4 mmol) in N-methyl2-pyrrolidone (NMP):Water, the DHOC-PdNps (0.0077mmol) were added. The reaction mixture was then stirredat 60 C (Table 3). The reaction was monitored by TLC,and after completion of the reaction, the reaction mixturewas cooled to room temperature. Then, the reaction mixture was extracted with ethyl acetate (60 mL 9 2) andwashed with water (60 mL). The organic phase waswashed with brine (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. The products were purifiedusing 5 percent ethyl acetate in hexane as the eluent.
90% With C31H24NO3PPd; potassium carbonate In N,N-dimethyl-formamide at 80℃; for 5 h; General procedure: A mixture of aryl halide (1mmol), alkyne (1mmol) were placed in a 25-mL round-bottomed flask, followed by addition of K2CO3 (1mmol) and palladium(II) complex (0.08molpercent) in DMF (5mL). The resulting mixture was stirred at 80°C for 5–7h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature and the product was washed with water and extracted with ethyl acetate (3×10mL). The combined organic layers were dried over Na2SO4 and the solvent removed under reduced pressure to give crude product which was purified by column chromatography by using petroleum ether/ethyl acetate (4:1) as an eluent. The products were confirmed by 1H and 13C NMR.
88% With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 12 h; Green chemistry General procedure: A mixture of aryl halide (1mmol), terminal alkyne (1mmol), K2CO3 (2mmol) and MNPFemTriazNHCAg complex (6) (100mg) in DMF (5mL) was stirred at 100°C. The progress of reaction was monitored by TLC. After completion, the reaction mixture was quenched in ice cold water and 6 was separated by external magnet. The reaction mixture was extracted with ethyl acetate (3×25mL). Evaporation of solvent in vaccuo followed by column chromatography over silica gel using petroleum ether/ethyl acetate afforded desired Sonogashira coupling products.
87% With trans-{(1-ethyl-2-(4-bromophenyl)imidazol-3-ylidene[1,2-a]pyridine)}PdI2(pyridine); caesium carbonate In water; N,N-dimethyl-formamide at 90℃; for 3 h; Schlenk technique General procedure: In a typical catalysis run, performed in air, a 25mL round bottom flask charged with a mixture of the aryl bromide or iodide, terminal alkyne, Cs2CO3, and diethyleneglycol-di-n-butyl ether (internal standard) in the molar ratio of 1:2:2:1. Palladium complexes (1–4)b, or PdCl2 or (COD)PdCl2 (4molpercent) was added to the mixture followed by 10mL solvent (DMF–H2O (7:3 v/v) and the reaction mixture was heated at 90°C for 3h, after which an aliquot was filtered and the product analyzed by gas chromatography using diethyleneglycol-di-n-butyl ether internal standard.
87% With C59H51NO3P4Pd(2+)*3CF3O3S(1-); caesium carbonate In methanol at 60℃; for 24 h; General procedure: A mixture of an aryl halide (1 mmol), phenylacetylene (1.3 mmol), Cat. (0.001 molpercent), Cs2CO3 (2.5 mmol), and methanol (3 ml) was heated to 60 °C for 24 h. The reaction mixture was then cooled to room temperature and the solvent was removed under reduced pressure. The combined organic extracts were washed with brine and dried over CaCl2 and MgSO4. The solvent was evaporated and coupling product was obtained. The liquid residues were purified by silica gel column chromatography (n-hexane:EtOAc, 80:20) and the solid residues were purified by re-crystallization from ethanol and water.
85% With [N-benzyl DABCO]+[Cu4Cl5]-; potassium carbonate In N,N-dimethyl-formamide at 135℃; for 3.5 h; Inert atmosphere General procedure: Aryl halide (0.2 mmol) and K2CO3 (0.4 mmol) were added to a mixture of DMF (2 mL) and catalyst A (5 mol percent) in a round-bottom flask equipped with a condenser and under an N2 atmosphere. The mixture was heated in an oil bath at 135 °C and then phenylacetylene (0.22 mmol) was added in two portions. The mixture was stirred continuously during the reaction and monitored by thin-layer chromatography (TLC) and gas chromatography (GC). After the reaction was complete, the mixture was cooled to room temperature and diluted with EtOAc and H2O. The product was extracted with EtOAc and the organic phase dried over MgSO4, filtered, and concentrated. The arylalkynes obtained could be purified by silica gel column chromatography (hexane:EtOAc). The arylalkyne products were known compounds and were characterized from their IR, 1H NMR, and GC-MS.
85%
Stage #1: With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triphenylphosphine In N,N-dimethyl-formamide at 20℃; for 0.25 h; Inert atmosphere
Stage #2: With triethylamine In N,N-dimethyl-formamide at 20℃; for 0.5 h; Inert atmosphere
Stage #3: at 80℃; for 12 h; Inert atmosphere
To a solution of 4-bromobenzaldehyde (500 mg, 2.70 mmol) in DMF (9 mL) was added Pd(PPh3)2Cl2 (14 mg, 0.02 mmol), PPh3 (10.5 mg, 0.04 mmol) and copper iodide (5mg) under argon atmosphere, and the suspension was stirred at room temperature for 15 min. Triethylamine (2 mL) was added to the reaction mixture. After stirring for 30 min at room temperature, phenylacetylene (306 mg, 3.0 mmol) was added. The reaction mixture was heated at 80 °C for 12 h and allowed to cool to room temperature. All volatile materials were removed in vacuum, and the residue was extracted with diethyl ether (3 × 10 mL). The crude product was purified using column chromatography (silica gel/ethyl acetate:petroleum ether 20:80) afforded 1 (472 mg, 85percent) as a light yellow solid.
85% With potassium carbonate In ethanol; water at 90℃; for 0.583333 h; Microwave irradiation General procedure: Into a 10 mL vial, aryl halide (1.0 mmol), phenylacetylene(1.2 mmol), K2CO3 (3.0 mmol), ethanol (3.0 mL), water (1.0 mL) and resin-PdNPs catalyst (300 mg) were taken and heated in a CEM microwave (150 w, 90°C) for different intervals of time (Scheme 6.1). The reaction was quenched in 10 mL cold water. The resulting solution was extracted with Et2O. The combined ether extract dried over anhydrous MgSO4 and solvent removed using a rotaevaporator. The crude product thus isolated was recrystallized from appropriate solvents.The effect of various parameters was studied taking coupling of iodobenzene and phenylacetylene as the standard reaction.
84% With [PdCl2((C6H5)2PCH2P(C6H5)2CHC(O)C6H4NO2)]; potassium carbonate In N,N-dimethyl-formamide at 130℃; for 5 h; General procedure: A mixture of an aryl halide (1 mmol), phenylacetylene(1.3 mmol), catalyst (0.001 mol percent), K2CO3 (2.5 mmol), and DMF(2 ml) was heated to 130 C. The mixture was then cooled to roomtemperature and the solvent was removed under reduced pressure.The combined organic extracts were washed with brine and driedover CaCl2 or MgSO4. The solvent was evaporated and liquid residueswere purified by silica gel column chromatography (n-hexane:EtOAc, 80:20) and solid residues were purified byrecrystallization from EtOH and H2O. Products were identified bycomparison of their 1H and 13C NMR spectral data those reportedin the literature.
81% With copper(l) iodide; C31H26N4PPdS(1+)*Cl(1-); sodium hydroxide In ethanol; toluene at 110℃; for 17 h; General procedure: To slurry of aryl halide (1 mmol), cuprous iodide (10 molpercent) andpalladium catalyst (a known molpercent) in an appropriate solvent(4 mL), phenylacetylene (1.2 mmol) and NaOH (1.7 mmol) wasadded and heated at required temp. After completion of the reaction(monitored by TLC), the flask was removed from the oil bathand water (20 mL) added, followed by extraction with ether(4 10 mL). The combined organic layers were washed with water(3 10 mL), dried over anhydrous Na2SO4, and filtered. Solventwas removed under vacuum. The residue was dissolved in hexaneand analyzed by GC–MS using Elite-5 columns, which are fused silicacapillary columns coated with 5percent diphenyl and 95percent dimethylpolysiloxane.
81% With [(Pd{(κ2-C,N)-(3-(dimethylaminomethyl)indole)}µ-OAc)2]; potassium carbonate In water; N,N-dimethyl-formamide at 120℃; for 6 h; General procedure: A 50-mL round-bottom flask was charged with aryl halide (1 mmol), phenylacetylene (1.5 mmol), K2CO3 (2 mmol), DMF:H2O (1:1) (4 mL), and the C,N-palladacycle (0.1 molpercent Pd). The mixture was stirred at 100°C for the desired reaction time. The reaction was monitored by GC. After the reaction was complete, the mixture was cooled to room temperature and diluted with EtOAc and H2O. The product was extracted with EtOAc and the organic phase dried over MgSO4, filtered, and concentrated. The arylalkynes obtained could be purified by silica gel column chromatography (hexane:EtOAc).The arylalkyne products were known compounds and were characterized from their 1H NMR and 13C NMR.
80% at 60℃; To a solution of 4-bromobenzaldehyde (250 mg, 1.35 mmol, 1.0 equiv.), PdCl2(PPh3)2 (19.0 mg, 27.0 prnol, 4 molpercent) and Cul (10.3 mg, 54.0 Mmol, 2 molpercent) in degassed NEt.3 (12 mL) was added phenylacetylene (180 mg, 1.76 mmol, 1.3 equiv.). The reaction was stirred at 60 °C over night and the solvent removed under reduced pressure. The crude material was purified by flash column chromatography (S1O2; petrolether : ethylacetate = 50:1 ), followed by recrystallization in ChteCte/pentane, to afford the title compound 1i as colorless solid (223 mg, 1.08 mmol, 80percent).
77% With piperidine; [Pd{C6H4(CH2N(CH2Ph)2)}(μ-Br)]2 In 1-methyl-pyrrolidin-2-one at 100℃; for 0.133333 h; Microwave irradiation General procedure: A mixture of the aryl halide (0.5 mmol), phenylacetylene(0.5 mmol), piperidine (1 mmol), ortho-palladated catalyst(0.2 mol percent) was added to NMP (3 mL) in round-bottom flask equipped with condenser and placed into the Milestone microwave. Initially using a microwave power of 600 W the temperature was ramped from room temperature to 100 °C and then held at this temperature until the reaction was completed. During this time, the power was modulated automatically to keep the reaction mixture at 100 °C. The mixture was stirred continuously during the reaction and monitored by both TLC and GC. After the reaction was complete, the mixture was cooled to room temperature and was diluted with n-hexane and water. The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure using rotary evaporator. The residue was purified by silica gel column chromatography.
87 %Chromat. With piperidine In water at 100℃; for 6 h; General procedure: In a typical reaction, a mixture of aryl halides (1.0 mmol), phenylacetylene (1.5 mmol), piperidine (2.0 mmol), H2O (6 ml) and catalyst (0.5 molpercent of Pd) was stirred at 100 °C for appropriate time. Progress of the reaction was monitored by GC analysis at different time interval of the reaction. After the completion of the reaction, the mixture was cooled to room temperature, diluted with water, and extracted with CH2Cl2 for three times. The organic phase thuscollected was dried with Na2SO4 and concentrated. The crude product was purified by flash column chromatography on silica gel. The product was analyzed by GC/MS, 1H NMR and elemental analyses. All the products were known compounds and were identified by comparison of their physical and spectra data with those of authentic samples.
85 %Chromat. With copper(l) iodide; C18H14N2Pd; sodium hydroxide In ethanol; toluene at 25℃; for 5 h; General procedure: To slurry of aryl halide (1 mmol), cuprous iodide (10 molpercent) and palladium catalyst (a known molpercent) in 1:1 ethanol–toluene (4 mL), phenylacetylene (1.2 mmol) and NaOH (1.7 mmol) were added and heated at 25 °C. After completion of the reaction (monitored by TLC), the flask was removed from the oil bath and water (20 mL) added, followed by extraction with ether (4 × 10 mL). The combined organic layers were washed with water (3 × 10 mL), dried over anhydrous Na2SO4, and filtered. Solvent was removed under vacuum. The residue was dissolved in hexane and analyzed by GC–MS.#10;
100 %Spectr. at 100℃; for 5 h; Sealed tube General procedure: In a tightly sealed tube (septa system), aryl halides (5.4 mmol), the catalyst, PPh3 and CuI (compare Table 2 and Table 3 for the exact mixture compositions) were suspended in dry triethylamine (10 mL). The mixture was placed in an ultrasound bath and sonicated for 5 min. Then, the acetylene compound (5.6 mmol) was added and the mixture was stirred as indicated in Table 2 and Table 3. The mixture was cooled to room temperature, and the catalyst was centrifuged, filtered, and washed with deionized water (2×10 mL) and ethyl acetate (2×10 mL). The filtrate was poured into 15 mL of dilute hydrochloric acid solution and the aqueous layer was extracted three times with dichloromethane (3×15 mL). The collected organic layer was washed with deionized water (15 mL) and then dried over magnesium sulfate, filtered, and concentrated under reduced pressure, affording the product. The conversion and selectivity were determined by 1H NMR spectroscopy. The spectra was recorded on a Bruker Avance (400MHz or 500MHz) using deuterated solvents: CDCl3 and DMSO with TMS as internal standard.
99 %Chromat. With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl acetamide at 60℃; for 24 h; General procedure: Aryl halide and a terminal alkyne, with an equivalent molar ratioof 1.0–1.5, were added to a mixture of PdbisindoleSiO2Fe3O4(0.18 mmol, 20 mg) and DABCO (2.0 mmol, 224 mg) in a flask and2 mL DMA was added. The reaction mixture was stirred at 60C foraryl iodides and aryl bromides. The reaction temperature was setto 120C for aryl chlorides and 1 mmol TBAB was also added. Theprogress of the reaction was monitored by gas chromatography.After completion of the reaction, distilled water (2 mL) was addedto the reaction mixture and the crude product was extracted withethyl acetate (3 × 5.0 mL). The crude product was further purifiedby column chromatography using n-hexane and ethyl acetate as eluents.
100 %Chromat. With C18H20BrClN2O2Pd2S2; sodium acetate In water; dimethyl sulfoxide at 110℃; for 24 h; General procedure: A mixture of aryl halide (1.0 mmol), phenyl acetylene(1.5 mmol), precatalyst (2 molpercent), 2 mL solvent and 3 mmol basewas stirred under air atmosphere at 110 C for the desired timeuntil complete consumption of starting material as monitored byTLC. After the mixture was washed with water, extracted withethyl acetate (2 * 5 mL), dried over MgSO4, and injected to the GCchromatography. All of compounds have been characterized by1H NMR spectra.

Reference: [1] PLoS ONE, 2015, vol. 10, # 6,
[2] Angewandte Chemie - International Edition, 2013, vol. 52, # 44, p. 11554 - 11559[3] Angew. Chem., 2013, vol. 125, # 44, p. 11768 - 11773,6
[4] Dalton Transactions, 2017, vol. 46, # 44, p. 15235 - 15248
[5] Tetrahedron Letters, 2003, vol. 44, # 35, p. 6595 - 6599
[6] Applied Organometallic Chemistry, 2018, vol. 32, # 1,
[7] Organic Letters, 2003, vol. 5, # 11, p. 1841 - 1844
[8] Tetrahedron, 2013, vol. 69, # 25, p. 5178 - 5184
[9] Catalysis Letters, 2012, vol. 142, # 5, p. 594 - 600
[10] Catalysis Science and Technology, 2014, vol. 4, # 3, p. 746 - 751
[11] Tetrahedron Letters, 2016, vol. 57, # 44, p. 4893 - 4897
[12] Journal of Organic Chemistry, 2009, vol. 74, # 22, p. 8897 - 8900
[13] Journal of Organometallic Chemistry, 2014, vol. 753, p. 42 - 47
[14] Tetrahedron Letters, 2016, vol. 57, # 29, p. 3137 - 3139
[15] Applied Organometallic Chemistry, 2018, vol. 32, # 3,
[16] Organic Letters, 2014, vol. 16, # 14, p. 3724 - 3727
[17] RSC Advances, 2017, vol. 7, # 5, p. 2475 - 2479
[18] Synlett, 2008, # 20, p. 3239 - 3241
[19] Chinese Chemical Letters, 2012, vol. 23, # 2, p. 185 - 188
[20] New Journal of Chemistry, 2015, vol. 39, # 3, p. 2333 - 2341
[21] Catalysis Communications, 2014, vol. 60, p. 82 - 87
[22] New Journal of Chemistry, 2017, vol. 41, # 7, p. 2745 - 2755
[23] Inorganica Chimica Acta, 2018, vol. 483, p. 262 - 270
[24] Tetrahedron, 2009, vol. 65, # 36, p. 7440 - 7448
[25] Tetrahedron Letters, 2015, vol. 56, # 37, p. 5252 - 5256
[26] Catalysis Letters, 2016, vol. 146, # 8, p. 1581 - 1590
[27] Inorganica Chimica Acta, 2018, vol. 471, p. 345 - 354
[28] Organic Letters, 2002, vol. 4, # 9, p. 1411 - 1414
[29] Green Chemistry, 2009, vol. 11, # 11, p. 1821 - 1825
[30] Applied Organometallic Chemistry, 2014, vol. 28, # 8, p. 595 - 597
[31] Organic Letters, 2005, vol. 7, # 25, p. 5625 - 5628
[32] RSC Advances, 2014, vol. 4, # 62, p. 32826 - 32833
[33] Journal of Organometallic Chemistry, 2018, vol. 866, p. 112 - 122
[34] Polyhedron, 2013, vol. 64, p. 20 - 29
[35] Catalysis Communications, 2013, vol. 37, p. 114 - 121
[36] Dalton Transactions, 2016, vol. 45, # 28, p. 11445 - 11458
[37] European Journal of Organic Chemistry, 2018, vol. 2018, # 38, p. 5253 - 5259
[38] Angewandte Chemie, International Edition, 2009, vol. 48, # 25, p. 4610 - 4612
[39] Journal of Chemical Sciences, 2011, vol. 123, # 6, p. 937 - 942
[40] Tetrahedron Letters, 2014, vol. 55, # 24, p. 3459 - 3462
[41] Tetrahedron Letters, 2005, vol. 55, # 37, p. 5203 - 5206
[42] Applied Organometallic Chemistry, 2016, vol. 30, # 9, p. 748 - 752
[43] Journal of Molecular Catalysis A: Chemical, 2016, vol. 424, p. 171 - 180
[44] Tetrahedron Letters, 2013, vol. 54, # 35, p. 4656 - 4660
[45] Dalton Transactions, 2017, vol. 46, # 38, p. 13065 - 13076
[46] Organic and Biomolecular Chemistry, 2003, vol. 1, # 13, p. 2235 - 2237
[47] Catalysis Communications, 2012, vol. 17, p. 160 - 163
[48] Inorganica Chimica Acta, 2015, vol. 425, p. 67 - 75
[49] Turkish Journal of Chemistry, 2015, vol. 39, # 6, p. 1199 - 1207
[50] ChemCatChem, 2018, vol. 10, # 4, p. 758 - 762
[51] Chemistry - A European Journal, 2014, vol. 20, # 45, p. 14853 - 14867
[52] Dalton Transactions, 2015, vol. 44, # 32, p. 14293 - 14303
[53] Angewandte Chemie - International Edition, 2016, vol. 55, # 3, p. 1196 - 1199[54] Angew. Chem., 2016, vol. 55, # 128, p. 1212 - 1216,5
[55] Patent: WO2017/16653, 2017, A1, . Location in patent: Page/Page column 24
[56] Journal of the Iranian Chemical Society, 2015, vol. 12, # 7, p. 1163 - 1169
[57] Tetrahedron Letters, 2003, vol. 44, # 48, p. 8653 - 8656
[58] European Journal of Organic Chemistry, 2015, vol. 2015, # 20, p. 4389 - 4399
[59] Dalton Transactions, 2012, vol. 41, # 16, p. 5020 - 5025
[60] Green Chemistry, 2015, vol. 17, # 2, p. 1071 - 1076
[61] ChemPlusChem, 2015, vol. 80, # 6, p. 973 - 979
[62] European Journal of Organic Chemistry, 2014, vol. 2014, # 14, p. 3001 - 3008
[63] Synthetic Communications, 1990, vol. 20, # 13, p. 2059 - 2064
[64] Chemistry - A European Journal, 2003, vol. 9, # 19, p. 4661 - 4669
[65] European Journal of Organic Chemistry, 2008, # 23, p. 4050 - 4054
[66] Chemical Communications, 2013, vol. 49, # 42, p. 4827 - 4829
[67] Applied Organometallic Chemistry, 2014, vol. 28, # 9, p. 696 - 698
[68] RSC Advances, 2015, vol. 5, # 114, p. 94369 - 94374
[69] Green Chemistry, 2017, vol. 19, # 5, p. 1353 - 1361
[70] European Journal of Organic Chemistry, 2011, # 25, p. 4773 - 4787
[71] Journal of Organometallic Chemistry, 1975, vol. 93, p. 259 - 263
[72] Patent: EP1346993, 2003, A1,
[73] Advanced Synthesis and Catalysis, 2008, vol. 350, # 14-15, p. 2391 - 2400
[74] Journal of Organometallic Chemistry, 2009, vol. 694, # 21, p. 3477 - 3486
[75] European Journal of Inorganic Chemistry, 2009, # 12, p. 1608 - 1618
[76] Dalton Transactions, 2009, # 47, p. 10581 - 10591
[77] Dalton Transactions, 2011, vol. 40, # 1, p. 44 - 46
[78] Journal of Organometallic Chemistry, 2011, vol. 696, # 13, p. 2689 - 2692
[79] Journal of Molecular Catalysis A: Chemical, 2011, vol. 344, # 1-2, p. 62 - 73
[80] Journal of Organometallic Chemistry, 2013, vol. 736, p. 1 - 8
[81] Dalton Transactions, 2013, vol. 42, # 19, p. 6803 - 6809
[82] European Journal of Inorganic Chemistry, 2013, # 26, p. 4654 - 4661
[83] Journal of Catalysis, 2014, vol. 313, p. 1 - 8
[84] Catalysis Communications, 2013, vol. 40, p. 23 - 26
[85] Dalton Transactions, 2015, vol. 44, # 2, p. 725 - 732
[86] Chinese Journal of Catalysis, 2015, vol. 36, # 7, p. 1047 - 1053
[87] Chemical Communications, 2016, vol. 52, # 8, p. 1571 - 1574
[88] RSC Advances, 2016, vol. 6, # 58, p. 52656 - 52664
[89] Journal of Photochemistry and Photobiology A: Chemistry, 2016, vol. 326, p. 76 - 88
[90] Applied Catalysis A: General, 2016, vol. 525, p. 31 - 40
[91] New Journal of Chemistry, 2016, vol. 40, # 8, p. 6939 - 6945
[92] Inorganica Chimica Acta, 2016, vol. 451, p. 227 - 232
[93] RSC Advances, 2016, vol. 6, # 96, p. 93660 - 93672
[94] New Journal of Chemistry, 2017, vol. 41, # 12, p. 5105 - 5113
  • 37
  • [ 1122-91-4 ]
  • [ 2170-06-1 ]
  • [ 57341-98-7 ]
Reference: [1] Advanced Synthesis and Catalysis, 2006, vol. 348, # 15, p. 2101 - 2113
  • 38
  • [ 3757-88-8 ]
  • [ 1122-91-4 ]
  • [ 57341-98-7 ]
Reference: [1] Tetrahedron Letters, 1997, vol. 38, # 21, p. 3759 - 3762
[2] Molecular Catalysis, 2018, vol. 445, p. 87 - 93
  • 39
  • [ 1122-79-8 ]
  • [ 1122-91-4 ]
  • [ 57341-98-7 ]
Reference: [1] Tetrahedron, 1995, vol. 51, # 41, p. 11165 - 11176
  • 40
  • [ 1122-91-4 ]
  • [ 536-74-3 ]
  • [ 886-66-8 ]
  • [ 57341-98-7 ]
Reference: [1] Chemical Communications, 1997, # 14, p. 1275 - 1276
  • 41
  • [ 1122-91-4 ]
  • [ 637-44-5 ]
  • [ 57341-98-7 ]
Reference: [1] Advanced Synthesis and Catalysis, 2013, vol. 355, # 4, p. 705 - 710
  • 42
  • [ 21890-32-4 ]
  • [ 1122-91-4 ]
  • [ 57341-98-7 ]
Reference: [1] New Journal of Chemistry, 2017, vol. 41, # 8, p. 2910 - 2918
  • 43
  • [ 1122-91-4 ]
  • [ 536-74-3 ]
  • [ 4526-07-2 ]
  • [ 57341-98-7 ]
Reference: [1] Journal of Organic Chemistry, 1998, vol. 63, # 23, p. 8551 - 8553
  • 44
  • [ 1122-91-4 ]
  • [ 16184-89-7 ]
Reference: [1] Tetrahedron Letters, 2013, vol. 54, # 33, p. 4483 - 4486
[2] European Journal of Organic Chemistry, 2015, vol. 2015, # 19, p. 4071 - 4076
[3] Chemistry - An Asian Journal, 2016, vol. 11, # 17, p. 2470 - 2477
[4] Chemical Communications, 2018, vol. 54, # 78, p. 11017 - 11020
  • 45
  • [ 81290-20-2 ]
  • [ 1122-91-4 ]
  • [ 16184-89-7 ]
Reference: [1] Journal of Organic Chemistry, 2018,
  • 46
  • [ 75-07-0 ]
  • [ 1122-91-4 ]
  • [ 49678-04-8 ]
Reference: [1] Journal of the Indian Chemical Society, 2010, vol. 87, # 9, p. 1145 - 1148
[2] Organic Letters, 2016, vol. 18, # 1, p. 4 - 7
[3] Angewandte Chemie - International Edition, 2015, vol. 54, # 6, p. 1885 - 1887[4] Angew. Chem., 2014, vol. 54-126, # 6, p. 1905 - 1907,3
[5] European Journal of Organic Chemistry, 2017, vol. 2017, # 25, p. 3631 - 3634
  • 47
  • [ 75-07-0 ]
  • [ 1122-91-4 ]
  • [ 49678-04-8 ]
Reference: [1] Organic Letters, 2016, vol. 18, # 1, p. 4 - 7
  • 48
  • [ 1122-91-4 ]
  • [ 2136-75-6 ]
  • [ 49678-04-8 ]
Reference: [1] Angewandte Chemie - International Edition, 2011, vol. 50, # 8, p. 1910 - 1913
[2] Organic and Biomolecular Chemistry, 2014, vol. 12, # 43, p. 8588 - 8592
[3] Organic Letters, 2016, vol. 18, # 4, p. 752 - 755
[4] European Journal of Organic Chemistry, 2017, vol. 2017, # 3, p. 719 - 725
  • 49
  • [ 1122-91-4 ]
  • [ 49678-04-8 ]
Reference: [1] Synthetic Communications, 2011, vol. 41, # 2, p. 206 - 218
[2] Tetrahedron Letters, 2014, vol. 55, # 30, p. 4095 - 4097
  • 50
  • [ 79-24-3 ]
  • [ 1122-91-4 ]
  • [ 109-73-9 ]
  • [ 6186-22-7 ]
Reference: [1] Patent: US5332757, 1994, A,
  • 51
  • [ 1122-91-4 ]
  • [ 6186-22-7 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1978, p. 995 - 1001
[2] Chimica Therapeutica, 1968, vol. 3, p. 313 - 320
[3] Journal of the American Chemical Society, 1964, vol. 86, p. 684 - 687
[4] Patent: WO2017/29104, 2017, A1,
  • 52
  • [ 1122-91-4 ]
  • [ 4209-02-3 ]
  • [ 881650-48-2 ]
Reference: [1] Tetrahedron Letters, 2016, vol. 57, # 22, p. 2437 - 2440
  • 53
  • [ 1122-91-4 ]
  • [ 163596-75-6 ]
YieldReaction ConditionsOperation in experiment
94% at 10℃; for 2 h; Step 1. 4-Bromo-3-nitrobenzaldehyde; A 100-mL 3-necked round-bottom flask was charged with NaNO3 (5.48 g, 64.47 mmol, 1.19 equiv). To this was added H2SO4 (60 mL, 98percent). The resulting solution was stirred for 1.5 hours at 10° C. To the mixture was added 4-bromobenzaldehyde (10 g, 54.05 mmol, 1.00 equiv). The resulting solution was stirred for an additional 2 hours at 10° C. The reaction progress was monitored by TLC (EtOAc: PE=1:5). Upon completion, the reaction was then quenched by the addition of 200 g of ice. The solids were collected by filtration and washed with water (3.x.200 mL) affording 4-bromo-3-nitrobenzaldehyde as white solid (11.72 g, 94percent).
55% at 0 - 40℃; for 1 h; General procedure: The nitration of aldehydes was carried out in a three-neckedflask of 50 ml with magnetic stirrer. H2SO4 25 ml (0.47 M)were cooled to 0 °C, 3.1 ml (0.070 M) of HNO3 were added,and then the aldehyde (0.06 M) was slowly added. Thereaction was carried out at a temperature of 0–5 °C. Then,the mixture was heated at 40 °C for 1 h. The reaction waspoured into ice water and filtered under a vacuum; thenitrobenzaldehydes were purified by recrystallization. Thescheme of reaction is showed in Fig. 1 (Furniss et al. 1989).The spectrums of 1H NMR of nitrobenzaldehydes wereobtained in CDCl3 and TMS as reference.
Reference: [1] Patent: US8080566, 2011, B1, . Location in patent: Page/Page column 65
[2] Medicinal Chemistry Research, 2018, vol. 27, # 7, p. 1782 - 1791
[3] Recueil des Travaux Chimiques des Pays-Bas, 1926, vol. 45, p. 694[4] Recueil des Travaux Chimiques des Pays-Bas, 1929, vol. 48, p. 1137
[5] Journal of the Chemical Society, 1927, p. 25
[6] Chemische Berichte, 1891, vol. 24, p. 3768
[7] Patent: US2002/7059, 2002, A1,
[8] Patent: US6642222, 2003, B2,
[9] Patent: US6593335, 2003, B1,
[10] European Journal of Medicinal Chemistry, 2015, vol. 100, p. 162 - 175
[11] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 2, p. 261 - 265
  • 54
  • [ 1122-91-4 ]
  • [ 6319-40-0 ]
Reference: [1] Journal of the Chemical Society, 1927, p. 25
  • 55
  • [ 1122-91-4 ]
  • [ 4654-39-1 ]
Reference: [1] Chemical Communications, 2017, vol. 53, # 31, p. 4308 - 4311
  • 56
  • [ 56985-67-2 ]
  • [ 49660-93-7 ]
  • [ 1122-91-4 ]
YieldReaction ConditionsOperation in experiment
46% With chromium(VI) oxide; sulfuric acid In water; acetone for 2 h; 15.4 mi of a solution of Jones'reagent, prepared by dissolving 35 g of Cr03 in 98percent H2SO4 (31.6 ml), in 100 ml of water are added to a solution of 4.7 g (about 20.5 MMOL) of the alcohol obtained in preparation 4 (in a purity of 60percent, as results from the reaction for carrying out preparation 4) in 61 ml of acetone. After two hours, an analysis by thin layer chromatography shows that all the starting material has been consumed. The reaction medium is then filtered and concentrated under reduced pressure. The residue is taken up diethyl ether, washed with 1 N NAOH (twice), with water and with saturated aqueous salt SOLU- tion. The organic phase is then dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 2.85 g (about 46percent of 4-bromo- BENZALDEHYDE). The product is pure enough to be used without further purification.
Reference: [1] Patent: WO2004/37806, 2004, A1, . Location in patent: Page 38
  • 57
  • [ 1122-91-4 ]
  • [ 75-26-3 ]
  • [ 49660-93-7 ]
Reference: [1] Organic Letters, 2017, vol. 19, # 12, p. 3255 - 3258
  • 58
  • [ 1122-91-4 ]
  • [ 49660-93-7 ]
Reference: [1] Beilstein Journal of Organic Chemistry, 2015, vol. 11, p. 972 - 979
[2] Organic Letters, 2018, vol. 20, # 10, p. 2906 - 2910
  • 59
  • [ 1122-91-4 ]
  • [ 23703-22-2 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 2233 - 2237
  • 60
  • [ 2537-48-6 ]
  • [ 1122-91-4 ]
  • [ 57775-08-3 ]
YieldReaction ConditionsOperation in experiment
28.1 g
Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuran for 1 h; Inert atmosphere; Cooling with ice
Stage #2: at 20℃; Inert atmosphere
Stage #3: With sodium tetrahydroborate In methanol at 0 - 100℃; for 1 h; Inert atmosphere
(2) 3- (4-bromo-phenyl) pyridine of prop-2-ene nitrile E / Z mixture (34.8g) (0.63L) - in methanol (0.21L) solution, sodium borohydride at 0 ( 8.2g) was added, under a nitrogen gas atmosphere, the mixture was stirred for 1 hour at 100 . The reaction solution was concentrated, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and after filtration, the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 100: 0 → 65: 35), to thereby obtain 3- (4-bromophenyl) propanenitrile (28.1 g) as a yellow oil .
Reference: [1] Patent: JP2015/231988, 2015, A, . Location in patent: Paragraph 0328; 0329
  • 61
  • [ 85462-16-4 ]
  • [ 1122-91-4 ]
  • [ 27466-83-7 ]
  • [ 35452-54-1 ]
Reference: [1] Journal of Organic Chemistry, 1992, vol. 57, # 16, p. 4487 - 4490
  • 62
  • [ 1122-91-4 ]
  • [ 76287-49-5 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 2233 - 2237
  • 63
  • [ 1122-91-4 ]
  • [ 51554-93-9 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 2233 - 2237
[2] Journal of the American Chemical Society, 1937, vol. 59, p. 1176
  • 64
  • [ 1122-91-4 ]
  • [ 35656-89-4 ]
Reference: [1] Journal of Organometallic Chemistry, 2002, vol. 657, # 1-2, p. 129 - 135
  • 65
  • [ 1122-91-4 ]
  • [ 77047-87-1 ]
  • [ 28785-06-0 ]
  • [ 122-03-2 ]
Reference: [1] Chemical Communications, 2011, vol. 47, # 18, p. 5181 - 5183
  • 66
  • [ 124-38-9 ]
  • [ 1122-91-4 ]
  • [ 7099-87-8 ]
Reference: [1] Angewandte Chemie - International Edition, 2018, vol. 57, # 38, p. 12318 - 12322[2] Angew. Chem., 2018, vol. 130, # 38, p. 12498 - 12502,5
  • 67
  • [ 1122-91-4 ]
  • [ 40640-98-0 ]
Reference: [1] Chemistry - A European Journal, 2016, vol. 22, # 14, p. 4738 - 4742
[2] Chemical Communications, 2017, vol. 53, # 4, p. 732 - 735
  • 68
  • [ 27329-60-8 ]
  • [ 1122-91-4 ]
  • [ 18648-66-3 ]
Reference: [1] Patent: JP2005/298421, 2005, A, . Location in patent: Page/Page column 27-28
[2] Chemistry Letters, 2016, vol. 45, # 5, p. 517 - 519
[3] Angewandte Chemie - International Edition, 2018, vol. 57, # 20, p. 5695 - 5698[4] Angew. Chem., 2018, vol. 130, # 20, p. 5797 - 5800,4
  • 69
  • [ 1122-91-4 ]
  • [ 411235-57-9 ]
  • [ 20034-50-8 ]
YieldReaction ConditionsOperation in experiment
93.2% With potassium phosphate tribasic trihydrate; palladium diacetate; tricyclohexylphosphine In water; toluene at 80℃; for 15 h; Inert atmosphere [0188] To a mixture of 4-bromobenzaldehyde (13.5 g,0.0734 mol), cyclopropylboronic acid (6.3 g, 0.0734 mol),K3P04 .3H20 (33.3 g, 0.147 mol) and PCy3 (20.5 g, 0.0734mol) in toluene/H20 (180 mL, 5:1) was added Pd(OAc )2 (500mg) under N2 . The reaction was heated at 80° C. for 15 hrsunder N2 . The reaction was complete detected by LCMS.Toluene and H20 were removed by vacuum. The crude productwas purified by colunm chromatography on silica gel(eluted with PE:Et0Ac=20: 1) to give the title compound (5.0g, yield: 93.2percent) as a yellow oil. 1 H-NMR ( 400 MHz, CDC13 )oppm 9.94 (s, lH), 7.76 (d, 2H, 1=7.6 Hz), 7.18 (d, 2H, 1=7.6Hz), 2.00-1.94 (m, lH), 1.11-1.07 (m, 2H), 0.82-0.80 (m,2H).
80% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In water; toluene at 110℃; for 16 h; Inert atmosphere; Microwave irradiation 4-Cyclopropylbenzaldehyde was prepared in 80percent yield according to the Example 8, Step A substituting cyclohex-l-en-l-ylboronic acid for cyclopropylboronic acid and 6-(4-bromophenyl)-3-((2-chlorophenyl)thio)-6-(thiophen-3-yl) piperidine -2,4-dione for 4-bromobenzaldehyde
61% With potassium phosphate; palladium diacetate; tricyclohexylphosphine In toluene at 20 - 100℃; Inert atmosphere [0721] Synthesis of 4-cyclopropylbe yde: [0722] To a stirred solution of 4-bromobenzaldehyde (500 mg, 2.70 mmol) in toluene (20 mL) under argon atmosphere were added cyclopropyl boronic acid (300 mg, 3.51 mmol), potassium phosphate (1.72 g, 8.10 mmol) and tricyclohexyl phosphine (38 mg, 0.13 mmol) at RT and purged under argon for 30 min. Then palladium acetate (30 mg, 0.13 mmol) was added to the reaction mass; heated to 100 °C and stirred for 8 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was filtered through celite and the filtrate was concentrated in vacuo. The residue was diluted with ice cold water (25 mL) and extracted with EtOAc (2 x 30 mL). The combined organic extracts were washed with saturated NaHC03 solution (15 mL), dried over sodium sulfate, filtered and concentrated in vacuo to obtain the crude. The crude was purified through silica gel column chromatography using 10percent EtOAc/ Hexanes to afford 4- cyclopropylbenzaldehyde (240 mg, 61percent) as pale yellow liquid. [0723] 1H-NMR (CDC13, 400 MHz): δ 9.94 (s, 1H), 7.78 (d, 2H), 7.20 (d, 2H), 2.00-1.95 (m, 1H), 1.12-1.07 (m, 2H), 0.84-0.78 (m, 2H); TLC: 20percent EtOAc/ Hexanes (R 0.5).
1.70 g With potassium phosphate; triphenylphosphine In water; toluene at 100℃; for 18 h; To a solution of 4-bromobenzaldehyde (3.4 g, 0.0 180 mmol) in mixture of toluene:water (40 mL: 3.0 mL) was added tripotassium phosphate (9.5 g, 0.045 mmol), triphenylphosphine (0.719 g, 0.002 mmol) and cyclopropylboronic acid (2.3 g, 0.027 mmol). The reaction mixture was heated at 100°C for 18 h. The reaction mass wasquenched with water and extracted with EtOAc. The organic layer were washed with water and brine, dried over Na2504 and concentrated. The obtained solid was purified by column chromatography to afford 1.70 g of the title product. ‘H NMR (300 IVIHz, DMSO d6): 9.94 (s, 1H), 7.77-7.75 (d, J = 8.4 Hz, 2H), 7.20-7.17 (d, J = 7.8 Hz, 2H), 1.97 (m, 1H), 1.11-1.08 (m, 2H), 0.82-0.80 (m, 2H).

Reference: [1] Synthetic Communications, 2006, vol. 36, # 1, p. 121 - 128
[2] Patent: US2016/31892, 2016, A1, . Location in patent: Paragraph 0187-0188
[3] Tetrahedron Letters, 2002, vol. 43, # 39, p. 6987 - 6990
[4] Patent: WO2015/140133, 2015, A1, . Location in patent: Page/Page column 137
[5] Patent: WO2013/142269, 2013, A1, . Location in patent: Paragraph 0721; 0722; 0723
[6] Patent: EP1640360, 2006, A1, . Location in patent: Page/Page column 81
[7] Patent: WO2015/59618, 2015, A1, . Location in patent: Page/Page column 43
[8] Patent: US2010/331301, 2010, A1, . Location in patent: Page/Page column 22
  • 70
  • [ 1122-91-4 ]
  • [ 30314-45-5 ]
Reference: [1] Patent: WO2016/109501, 2016, A1,
  • 71
  • [ 1122-91-4 ]
  • [ 100-53-8 ]
  • [ 66176-39-4 ]
  • [ 78832-95-8 ]
Reference: [1] Patent: US5061717, 1991, A,
  • 72
  • [ 141-82-2 ]
  • [ 1122-91-4 ]
  • [ 39773-47-2 ]
YieldReaction ConditionsOperation in experiment
72.2% With ammonium acetate In ethanol at 75 - 80℃; for 10 h; To 30 mL of ethanol were added 5.00 g (27.0 mmol) of 4-bromobenzaldehyde, 2.80 g (27.0 mmol) of malonic acid and 3.10 g (40.2 mmol) of ammonium acetate, and the mixture was reacted while stirring under reflux (75 to 80°C) for 10 hours. After completion of the reaction, the obtained reaction mixture was stirred at room temperature for 1 hour and then filtered to give 4.8 g of 3-amino-3-(4-bromophenyl)propionic acid (racemic mixtures) (isolation yield based on 4-bromobenzaldehyde: 72.2percent) as white powder. Incidentally, physical properties of the 3-amino-3-(4-bromophenyl)propionic acid (racemic mixtures) were as follows. 1H-NMR (δ (ppm), D2O) : 2.93 (dd, 1H, J=17.1, 6.8Hz), 3.04 (dd, 1H, J=17.1, 7.8Hz), 4.63 (dd, 1H, J=7.8, 6.8Hz), 7.22 (s, 1H), 7.24 (s, 1H), 7.47 (s, 1H), 7.49 (s, 1H) 13C-NMR (δ (ppm), D2O) : 40.4, 53. 9, 126.0, 131.9, 135.3, 137.1, 175.9
72% With ammonium acetate In butan-1-olReflux General procedure: A mixture of appropriate aldehyde 2.40 g (1-15), 2.44 g ofmalonic acid and 3.54 g of ammonium acetate (1:1.1:2.3), in 200mLof the 1-butanol was refluxed for 1.5-2 h until the evolution of CO2ceased. The precipitate formed was filtered and washed withboiling 1-butanol (2 x 50 mL), boiling ethanol (2 x 50 mL) and100mL of water. Precipitates were dried at 80-100 °C for 8-10 h.Purity of product was checked by TLC, and yield obtained about65-80percent in each reaction.
Reference: [1] Advanced Synthesis and Catalysis, 2010, vol. 352, # 2-3, p. 395 - 406
[2] Advanced Synthesis and Catalysis, 2017, vol. 359, # 9, p. 1570 - 1576
[3] Patent: EP1621529, 2006, A1, . Location in patent: Page/Page column 33
[4] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 252 - 268
[5] Journal of the Chemical Society. Perkin Transactions 1, 2001, # 14, p. 1673 - 1695
[6] Journal of Organic Chemistry, 2009, vol. 74, # 23, p. 9152 - 9157
  • 73
  • [ 1122-91-4 ]
  • [ 39773-47-2 ]
Reference: [1] Patent: US6306909, 2001, B1,
[2] Patent: US2009/203582, 2009, A1,
  • 74
  • [ 141-82-2 ]
  • [ 1122-91-4 ]
  • [ 1200-07-3 ]
  • [ 39773-47-2 ]
Reference: [1] Tetrahedron, 2002, vol. 58, # 37, p. 7449 - 7461
  • 75
  • [ 141-82-2 ]
  • [ 1122-91-4 ]
  • [ 1200-07-3 ]
  • [ 39773-47-2 ]
Reference: [1] Russian Journal of Organic Chemistry, 2012, vol. 48, # 6, p. 860 - 863
  • 76
  • [ 1122-91-4 ]
  • [ 42860-06-0 ]
Reference: [1] Journal of the Chemical Society, 1927, p. 25
  • 77
  • [ 1122-91-4 ]
  • [ 10602-04-7 ]
Reference: [1] Russian Chemical Bulletin, 2002, vol. 51, # 1, p. 128 - 134[2] Izvestiya Akademi Nauk, Seriya Khimicheskaya, 2002, # 1, p. 122 - 127
[3] Patent: WO2011/21209, 2011, A1,
[4] Patent: US2012/101099, 2012, A1,
[5] Patent: US2017/202970, 2017, A1,
[6] Patent: CN107365254, 2017, A,
[7] Patent: WO2008/31157, 2008, A1,
  • 78
  • [ 79-24-3 ]
  • [ 1122-91-4 ]
  • [ 131981-75-4 ]
YieldReaction ConditionsOperation in experiment
18% at 120℃; Microwave irradiation General procedure: To a solution of the appropriate benzaldehyde (3.6 mmol) in glacial acetic acid (4 mL) was added the nitroalkane (7.2mmol) followed by cyclohexylamine (3.6 mmol, 0.4 mL). The reaction mixture was heated under microwave irradiation at 120 °C for 30 min. After cooling, water (10 mL) was added to the reaction and it was allowed to stand. The precipitated nitroethene was isolated by filtration. The filtrate was further diluted with water (20 mL) and extracted with dichloromethane (3 x 10 mL). The organic phases were combined and washed with saturated aqueous NaHCO3 (3 x10 mL). The solution was dried over anhydrous Na2SO4, filtered and all solvent removed in vacuo, to give an oil which was purified by flash column chromatography over silica gel (eluent: dichloromethane/hexane) and recrystallised from ethanol.
47% With ammonium acetate; sulfuric acid In toluene Preparation 37
2-(4-bromophenyl)-1-nitro-1-methylethylene
A solution of 30.0 g (162 mmol) of 4-bromobenzaldehyde, 116 mL (1.6 mole) of nitroethane, and 37.5 g (486 mmol) of ammonium acetate in 200 mL of toluene was heated under a Dean and Stark trap for 18 hours.
The mixture was then cooled to 80° C., 1 mL of concentrated sulfuric acid was added, and the mixture was stirred at 80° C. for 2 hours.
The mixture was then cooled to ambient temperature and washed with 200 mL of brine.
The organic layer was separated and the aqueous layer was extracted three times with 60 mL of diethyl ether.
The combined organics were dried (MgSO4), filtered and coincentrated in vacuo.
The residue was recrystallized from methanol to afford 18.7 g (47percent) of the title compound.
Reference: [1] Tetrahedron, 2008, vol. 64, # 27, p. 6294 - 6299
[2] Tetrahedron Letters, 1986, vol. 27, # 33, p. 3843 - 3844
[3] Chemical Communications, 2016, vol. 52, # 65, p. 10060 - 10063
[4] Medicinal Chemistry, 2018, vol. 14, # 2, p. 181 - 199
[5] Patent: US6303816, 2001, B1,
[6] Angewandte Chemie - International Edition, 2013, vol. 52, # 15, p. 4235 - 4238[7] Angew. Chem., 2013, vol. 125, # 15, p. 4329 - 4332,4
[8] Chemical Communications, 2014, vol. 50, # 64, p. 8878 - 8881
  • 79
  • [ 79-24-3 ]
  • [ 1122-91-4 ]
  • [ 623-00-7 ]
  • [ 25062-46-8 ]
  • [ 131981-75-4 ]
Reference: [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1991, vol. 40, # 2.2, p. 366 - 372[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1991, # 2, p. 426 - 433
  • 80
  • [ 1122-91-4 ]
  • [ 1208-87-3 ]
Reference: [1] Patent: CN107573288, 2018, A,
[2] Patent: CN107652238, 2018, A,
  • 81
  • [ 1122-91-4 ]
  • [ 74003-55-7 ]
Reference: [1] Journal of the Chemical Society, 1927, p. 25
  • 82
  • [ 1122-91-4 ]
  • [ 122-52-1 ]
  • [ 38186-51-5 ]
Reference: [1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 15, p. 2934 - 2936
  • 83
  • [ 1122-91-4 ]
  • [ 38186-51-5 ]
Reference: [1] Advanced Synthesis and Catalysis, 2012, vol. 354, # 14-15, p. 2659 - 2664
[2] Tetrahedron, 2013, vol. 69, # 3, p. 1065 - 1068
[3] Angewandte Chemie - International Edition, 2018, vol. 57, # 22, p. 6624 - 6628[4] Angew. Chem., 2018, vol. 130, # 22, p. 6734 - 6738,5
  • 84
  • [ 1122-91-4 ]
  • [ 41841-16-1 ]
Reference: [1] Journal of Organic Chemistry, 2016, vol. 81, # 19, p. 8673 - 8695
  • 85
  • [ 506-59-2 ]
  • [ 1122-91-4 ]
  • [ 6274-57-3 ]
Reference: [1] Organic Letters, 2017, vol. 19, # 19, p. 5122 - 5125
[2] Journal of Organic Chemistry, 2013, vol. 78, # 8, p. 3688 - 3696
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 3, p. 1320 - 1336
  • 86
  • [ 1122-91-4 ]
  • [ 124-40-3 ]
  • [ 6274-57-3 ]
Reference: [1] Synthetic Communications, 2000, vol. 30, # 11, p. 2001 - 2008
[2] Science, 2017, vol. 358, # 6361, p. 326 - 332
  • 87
  • [ 1122-91-4 ]
  • [ 124-40-3 ]
  • [ 103-83-3 ]
  • [ 6274-57-3 ]
Reference: [1] Patent: WO2015/32653, 2015, A1, . Location in patent: Page/Page column 34-35
[2] RSC Advances, 2018, vol. 8, # 27, p. 15202 - 15206
  • 88
  • [ 1122-91-4 ]
  • [ 74-89-5 ]
  • [ 699-03-6 ]
YieldReaction ConditionsOperation in experiment
91%
Stage #1: at 65℃; for 4 h; Autoclave
Stage #2: at 20℃; Autoclave
Preparation of (4-Bromo-benzyl)-methyl-amineMeNH2 In an autoclave, a mixture of 4-bromobenzaldehyde (2.08 g, 1 1.15 mmol) and methylamine 2M solution in methanol (25 ml_, 33.44 mmol) was stirred at 65°C for 4 h. After cooling to rt, sodium borohydride (633 mg, 16.72 mmol) was added portionwise. The reaction mixture was stirred at rt for 30 min, then concentrated in vacuo. The resulting residue was dissolved in EA (30 ml.) and the organic layer washed with a sat. NaHCO3 solution (10 ml_). The aq. phase was basified with few drops of 1 N NaOH (pH=13) and extracted twice with EA. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure to afford the title compound as a colorless oil (2.04 g, 91 percent), which was used for the next step without further purification.LC-MS (analytic A, Zorbax SB-AQ column, acidic conditions): tR = 0.61 min; [M+H]+ = 241.06 (MeCN adduct).
91%
Stage #1: at 65℃; for 4 h; autoclave
Stage #2: at 20℃; for 0.5 h;
Stage #3: With sodium hydrogencarbonate In ethyl acetate
In an autoclave, a mixture of 4-bromobenzaldehyde (2.08 g, 11.15 mmol) and methylamine 2M solution in methanol (25 mL, 33.44 mmol) was stirred at 65° C. for 4 h. After cooling to rt, sodium borohydride (633 mg, 16.72 mmol) was added portionwise. The reaction mixture was stirred at rt for 30 min, then concentrated in vacuo. The resulting residue was dissolved in EA (30 mL) and the organic layer washed with a sat. NaHCO3 solution (10 mL). The aq. phase was basified with few drops of 1N NaOH (pH=13) and extracted twice with EA. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure to afford the title compound as a colorless oil (2.04 g, 91percent), which was used for the next step without further purification.LC-MS (analytic A, Zorbax SB-AQ column, acidic conditions): tR=0.61 min; [M+H]+=241.06 (MeCN adduct).
Reference: [1] Patent: WO2010/58353, 2010, A1, . Location in patent: Page/Page column 77-78
[2] Patent: US2011/224210, 2011, A1, . Location in patent: Page/Page column 54
[3] Phosphorus, Sulfur and Silicon and the Related Elements, 1993, vol. 78, # 1-4, p. 141 - 152
[4] Organic Letters, 2014, vol. 16, # 2, p. 358 - 361
  • 89
  • [ 1122-91-4 ]
  • [ 699-03-6 ]
Reference: [1] Journal of Organic Chemistry, 2002, vol. 67, # 23, p. 8191 - 8196
[2] Journal of Medicinal Chemistry, 1984, vol. 27, # 9, p. 1111 - 1118
[3] Patent: US5455273, 1995, A,
[4] Organic Letters, 2011, vol. 13, # 4, p. 600 - 603
[5] Chemistry - A European Journal, 2014, vol. 20, # 52, p. 17565 - 17571
  • 90
  • [ 6274-57-3 ]
  • [ 699-03-6 ]
  • [ 1122-91-4 ]
Reference: [1] Journal of the Chemical Society, Chemical Communications, 1985, # 2, p. 64 - 65
[2] Journal of the Chemical Society, Chemical Communications, 1985, # 2, p. 64 - 65
  • 91
  • [ 1122-91-4 ]
  • [ 122-39-4 ]
  • [ 4181-05-9 ]
Reference: [1] Dyes and Pigments, 2012, vol. 95, # 2, p. 229 - 235
  • 92
  • [ 1122-91-4 ]
  • [ 62561-74-4 ]
Reference: [1] Advanced Synthesis and Catalysis, 2016, vol. 358, # 20, p. 3298 - 3306
  • 93
  • [ 1122-91-4 ]
  • [ 59016-93-2 ]
  • [ 87199-17-5 ]
Reference: [1] Journal of the American Chemical Society, 2012, vol. 134, # 28, p. 11667 - 11673
  • 94
  • [ 1450-14-2 ]
  • [ 1122-91-4 ]
  • [ 2199-32-8 ]
Reference: [1] Chemical Communications, 2000, # 19, p. 1895 - 1896
  • 95
  • [ 1122-91-4 ]
  • [ 107859-98-3 ]
Reference: [1] Patent: WO2014/131855, 2014, A1,
[2] Journal of Medicinal Chemistry, 2016, vol. 59, # 19, p. 8967 - 9004
  • 96
  • [ 1122-91-4 ]
  • [ 140-88-5 ]
  • [ 107859-98-3 ]
Reference: [1] Patent: WO2016/57731, 2016, A1,
[2] Patent: US2017/290800, 2017, A1,
  • 97
  • [ 1122-91-4 ]
  • [ 120077-69-2 ]
Reference: [1] Journal of the Chemical Society, 1927, p. 25
  • 98
  • [ 5927-18-4 ]
  • [ 1122-91-4 ]
  • [ 75567-84-9 ]
Reference: [1] Chemistry Letters, 1998, # 3, p. 203 - 204
  • 99
  • [ 1122-91-4 ]
  • [ 75567-84-9 ]
Reference: [1] Journal of Organometallic Chemistry, 2002, vol. 657, # 1-2, p. 129 - 135
[2] European Journal of Organic Chemistry, 2014, vol. 2014, # 33, p. 7347 - 7352
  • 100
  • [ 1122-91-4 ]
  • [ 6317-56-2 ]
Reference: [1] Patent: CN107573288, 2018, A,
[2] Patent: CN107652238, 2018, A,
  • 101
  • [ 1122-91-4 ]
  • [ 105-53-3 ]
  • [ 43153-12-4 ]
Reference: [1] Tetrahedron Letters, 2004, vol. 45, # 30, p. 5823 - 5825
  • 102
  • [ 6165-68-0 ]
  • [ 1122-91-4 ]
  • [ 107834-03-7 ]
YieldReaction ConditionsOperation in experiment
87% With C7H10N2*Pd(2+)*2Cl(1-); potassium carbonate In ethanol; water for 0.166667 h; Reflux; Schlenk technique 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 (0.001–0.2molpercent) 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.
40% With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In ethanol; water; tolueneReflux General procedure: Tetrakis(triphenylphosphine)palladium(0) (0.0168 mmol) was added to a solution of 4-bromobenzaldehyde (50, 5.6 mmol) in ethanol-toluene (40 mL, 1:1). After 15 min, the appropriate boronic acid 51b-m (6.75 mmol) was added, followed by sodium hydrogen carbonate (22.4 mmol) and water (11 mL). The resulting mixture was heated under reflux for 9-15 hours. After cooling, the reaction mixture was filtered through Celite.(R)., the organic phase was separated, washed with brine (2x20 mL), dried and the solvent evaporated in vacuo. The residue thus obtained was purified by flash-chromatography. Elution by light petroleum-ethyl acetate mixtures afforded the desired compounds.
Reference: [1] Chemistry of Heterocyclic Compounds, 2014, vol. 50, # 1, p. 19 - 25[2] Khim. Geterotsikl. Soedin., 2014, vol. 50, # 1, p. 24 - 31,7
[3] Russian Journal of General Chemistry, 2014, vol. 84, # 9, p. 1782 - 1792[4] Zh. Obshch. Khim., 2014, vol. 84, # 9, p. 1546 - 1556,11
[5] RSC Advances, 2015, vol. 5, # 85, p. 69776 - 69781
[6] Journal of Medicinal Chemistry, 2003, vol. 46, # 10, p. 1918 - 1930
[7] Catalysis Communications, 2016, vol. 79, p. 17 - 20
[8] European Journal of Organic Chemistry, 2006, # 17, p. 3938 - 3946
[9] Macromolecules, 2011, vol. 44, # 13, p. 5155 - 5167
[10] Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 6379 - 6397
[11] Advanced Synthesis and Catalysis, 2008, vol. 350, # 14-15, p. 2391 - 2400
[12] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 11, p. 3429 - 3445
[13] Journal of Medicinal Chemistry, 2014, vol. 57, # 20, p. 8445 - 8458
[14] European Journal of Medicinal Chemistry, 2016, vol. 115, p. 453 - 462
  • 103
  • [ 188290-36-0 ]
  • [ 1122-91-4 ]
  • [ 107834-03-7 ]
Reference: [1] Journal of Organic Chemistry, 2011, vol. 76, # 19, p. 8138 - 8142
[2] Synthetic Communications, 2011, vol. 41, # 23, p. 3524 - 3531
[3] European Journal of Organic Chemistry, 2017, vol. 2017, # 1, p. 111 - 123
[4] Heterocycles, 1990, vol. 31, # 11, p. 1951 - 1958
  • 104
  • [ 14221-01-3 ]
  • [ 1122-91-4 ]
  • [ 107834-03-7 ]
Reference: [1] Patent: US5849911, 1998, A,
  • 105
  • [ 1264696-96-9 ]
  • [ 1122-91-4 ]
  • [ 107834-03-7 ]
Reference: [1] European Journal of Organic Chemistry, 2011, # 1, p. 143 - 149
  • 106
  • [ 54663-78-4 ]
  • [ 1122-91-4 ]
  • [ 107834-03-7 ]
Reference: [1] Journal of Materials Chemistry A, 2013, vol. 1, # 38, p. 11909 - 11921
  • 107
  • [ 3437-95-4 ]
  • [ 1122-91-4 ]
  • [ 107834-03-7 ]
Reference: [1] Tetrahedron Letters, 2004, vol. 45, # 20, p. 3909 - 3912
  • 108
  • [ 1122-91-4 ]
  • [ 1066-54-2 ]
  • [ 63697-96-1 ]
YieldReaction ConditionsOperation in experiment
85.1%
Stage #1: With triethylamine In tetrahydrofuran for 0.75 h; Inert atmosphere
Stage #2: With copper(l) iodide; triphenylphosphine hydrochloride In tetrahydrofuran for 10 h; Inert atmosphere
Stage #3: With potassium carbonate In methanol at 20℃; for 5 h;
15.0 mmol (2.78 g) of p-bromobenzaldehyde was dissolved in 95 ml of a tetrahydrofuran and triethylamine mixed solution (1: 1 by volume) and placed in a 250 ml single-necked flask,The cells were ventilated for 45 minutes and then 18.0 mmol (1.76 g)Of trimethylsilylacetylene. Adding 97.2 mg of triphenylphosphonium dichloride,46.5mg cuprous iodide. Under argon, the reaction was carried out for 10 hours.After the reaction was stopped, the solvent was removed by distillation under reduced pressure and purified by silica gel column chromatography (developing solvent: dichloromethane: petroleum ether 1: 4), steamed and dried in vacuo to give 2.19 g of a white solid in 72.3percent yield.B: A solution of 8.0 mmol (1.62 g) of a product was dissolved in 30 mlMethanol and 60 ml of tetrahydrofuran, placed in a 250 ml single-necked round bottom flask,Then add anhydrous potassium carbonate,And the mixture was stirred at room temperature for 5 hours. The solvent was distilled off under reduced pressure,Silica gel column (developing solvent for petroleum ether and dichloromethane 1: 1 mixed solvent) crude purification;Dried in vacuo to give 0.88 g of a white solid in 85.1percent
Reference: [1] Patent: CN106588789, 2017, A, . Location in patent: Paragraph 0047-0049
[2] Dalton Transactions, 2013, vol. 42, # 40, p. 14374 - 14379
[3] Journal of Polymer Science, Part A: Polymer Chemistry, 2013, vol. 51, # 19, p. 4070 - 4075
[4] Polyhedron, 2015, vol. 86, p. 10 - 16
[5] Patent: CN107987094, 2018, A, . Location in patent: Paragraph 0038; 0039
  • 109
  • [ 1122-91-4 ]
  • [ 63697-96-1 ]
Reference: [1] Journal of Organic Chemistry, 2003, vol. 68, # 21, p. 8025 - 8036
[2] Russian Chemical Bulletin, 2002, vol. 51, # 1, p. 128 - 134[3] Izvestiya Akademi Nauk, Seriya Khimicheskaya, 2002, # 1, p. 122 - 127
[4] Journal of Organic Chemistry, 1981, vol. 46, # 11, p. 2280 - 2286
[5] Chemical Communications, 2011, vol. 47, # 4, p. 1282 - 1284
[6] Patent: WO2011/21209, 2011, A1,
[7] New Journal of Chemistry, 2011, vol. 35, # 1, p. 127 - 136
[8] Chemistry Letters, 2011, vol. 40, # 2, p. 184 - 185
[9] European Journal of Organic Chemistry, 2011, # 25, p. 4773 - 4787
[10] Patent: US2012/101099, 2012, A1,
[11] Journal of the American Chemical Society, 2012, vol. 134, # 40, p. 16671 - 16692
[12] Polymer, 2012, vol. 53, # 26, p. 6033 - 6038
[13] Chemical Communications, 2013, vol. 49, # 17, p. 1717 - 1719
[14] Letters in Organic Chemistry, 2013, vol. 10, # 1, p. 22 - 26
[15] Chemistry - An Asian Journal, 2011, vol. 6, # 6, p. 1604 - 1612
[16] Journal of Polymer Science, Part A: Polymer Chemistry, 2013, vol. 51, # 24, p. 5248 - 5256
[17] Tetrahedron Letters, 2014, vol. 55, # 11, p. 1946 - 1948
[18] Journal of Materials Chemistry A, 2013, vol. 1, # 34, p. 10008 - 10015
[19] Angewandte Chemie - International Edition, 2014, vol. 53, # 31, p. 8216 - 8220[20] Angew. Chem., 2014, vol. 126, # 31, p. 8355 - 8359,5
[21] Chemistry - A European Journal, 2014, vol. 20, # 44, p. 14282 - 14295
[22] Beilstein Journal of Organic Chemistry, 2014, vol. 11, p. 37 - 41
[23] Chemical Communications, 2015, vol. 51, # 25, p. 5257 - 5260
[24] Reactive and Functional Polymers, 2015, vol. 87, p. 46 - 52
[25] ChemPlusChem, 2014, vol. 79, # 9, p. 1352 - 1360
[26] Chemistry - A European Journal, 2016, vol. 22, # 16, p. 5583 - 5597
[27] Chemical Communications, 2016, vol. 52, # 13, p. 2843 - 2845
[28] ChemPhysChem, 2016, p. 2066 - 2078
[29] Journal of Molecular Structure, 2017, vol. 1128, p. 361 - 367
[30] Journal of the American Chemical Society, 2016, vol. 138, # 51, p. 16703 - 16710
[31] Patent: CN106946838, 2017, A,
[32] Angewandte Chemie - International Edition, 2017, vol. 56, # 42, p. 13094 - 13098[33] Angew. Chem., 2017, vol. 56, p. 13274 - 13278,5
[34] Patent: US2017/202970, 2017, A1,
[35] New Journal of Chemistry, 2018, vol. 42, # 1, p. 555 - 563
[36] Patent: CN107365254, 2017, A,
[37] European Journal of Organic Chemistry, 2018, vol. 2018, # 15, p. 1756 - 1760
[38] Chemical Communications, 2018, vol. 54, # 35, p. 4465 - 4468
  • 110
  • [ 1066-26-8 ]
  • [ 1122-91-4 ]
  • [ 63697-96-1 ]
Reference: [1] Liebigs Annales, 1996, # 12, p. 2107 - 2113
  • 111
  • [ 1122-91-4 ]
  • [ 80793-25-5 ]
Reference: [1] Chemical Communications, 2011, vol. 47, # 27, p. 7875 - 7877
[2] Chinese Chemical Letters, 2016, vol. 27, # 4, p. 555 - 558
  • 112
  • [ 1122-91-4 ]
  • [ 140-88-5 ]
  • [ 1417403-46-3 ]
  • [ 30913-87-2 ]
Reference: [1] Synthetic Communications, 2013, vol. 43, # 6, p. 848 - 858
  • 113
  • [ 1122-91-4 ]
  • [ 1066-54-2 ]
  • [ 77123-57-0 ]
YieldReaction ConditionsOperation in experiment
100% With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In tetrahydrofuran at 20℃; Inert atmosphere To a solution of 4-bromobenzaldehyde 7 (3.70 g, 20.0 mmol), CuI (380 mg, 2.00 mmol) and Pd(PPh3)4 (924 mg, 800 mol) in THF (60 mL) were added Et3N (11.2 mL, 80.3 mmol) and trimethylsilylacetylene (4.24 mL, 30.0 mmol). The reaction mixture was stirred at room temperature under Ar overnight and filtered, and the solids were washed with EtOAc (30 mL). The filtrate and EtOAc washing were combined and concentrated under reduced pressure, and the residue was purified by flash column chromatography (silica gel, petroleum benzine ramping to petroleum benzine:EtOAc = 98:2) to give 4-((trimethylsilyl)ethynyl)benzaldehyde as a pale brown solid (4.04 g, 100percent). RF (petroleum benzine:EtOAc = 4:1) 0.87. m.p. 6667 °C (lit. [7] m.p. 70 °C). IR νmax/cm-1 2960, 2899, 2832, 2733, 2159, 1702, 1600, 1563, 1412, 1384, 1303, 1251, 1205, 1165, 862, 842. 1H NMR (300 MHz, CDCl3) δ 0.19 (s, 9H, Si(CH3)3), 7.47 (d, 2H, J 8.1, Ph-H), 7.68 (d, 2H, J 7.8, Ph-H), 9.87 (s, 1H, CHO). 13C NMR(75 MHz, CDCl3) δ 0.3, 98.8, 103.8, 129.1, 129.3, 132.3, 135.5, 191.0 (four carbon signals overlapping or obscured). MS (GC-EI) 187.1 ([MCH3]+, 100percent), 202.0 (M+, 8percent). The spectroscopic data were in agreement with those in the literature. [7]
100%
Stage #1: for 0.0833333 h; Sealed tube; Sonication
Stage #2: for 3 h; Sealed tube
General procedure: In a tightly sealed tube (septa system),aryl halides (5.5 mmol) and 5percent nanocatalyst Pd/Cu, PPh3 (17 mg) were suspended in drytriethylamine (10 mL). The mixture was placed in an ultrasound bath and sonicated for 5 min.Then, the acetylene compound (5.6 mmol) was added and the mixture was stirred for 3 h. Themixture was cooled to room temperature and the catalyst was centrifuged, filtered and washedwith ethyl acetate (3 x 10 mL). The filtrate was washed three times with deionized water (3 x 15mL) and then dried over magnesium sulfate, filtered and concentrated under reduced pressureto give the product.
99% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 40℃; for 2 h; p-bromobenzaldehyde (1.85 g, 10 mmol) was dissolved in 15 mL of anhydrous THF and trimethylsilylacetylene was added.(1.47 g, 15 mmol), bistriphenylphosphine dichloropalladium (70 mg, 0.1 mmol), cuprous iodide (38 mg, 0.2 mmol), and 5 ml triethylamine.Reaction at 40 °C for 2 h. Spin-dry the THF, and column-purify with PE and DCM (2:1 by volume) to obtain 2.0 g of compound 4 as a white solid. The yield is 99percent.
98.6% for 2 h; Heating / reflux Example 4Part A: Synthesis of 4- [(TrimethylsilyDethynyll benzaldehydeA deaerated solution of 24.5 g (132 mmol) of 4-bromobenzaldehyde and 1.00 g of triphenylphosphine in 300 ml of anhydrous triethylamine was treated with 20.0 g (204 mmol) of ethynyltrimethylsilane and then 0.3 g of palladium(II)acetate under argon. The mixture was heated at reflux for 2 h, cooled and filtered to give 24.Og (100 percent) of triethylamine hydrobromide. The filtrate was concentrated to an oil which solidified into long needles. The crude material was dissolved in hexane and filtered through silica gel to give 26.3 g (130 mmol, 98.6 percent) of 4-[(trimethylsilyl)ethynyl]benzaldehyde. The material was used in the next step without any further purification. 1H-NMR (CDCl3, 400 MHz): δ[ppm] = 0.21(s, 9 H), 7.60 (q, 4 H, J = 7.0 Hz), 9.85 (s, 1 H)
96.1% With triphenylphosphine In triethylamine for 2 h; Heating / reflux To a solution of 4-bromobenzaldehyde (10.00 g, 54.08 mmol) and triphenylphosphine (0.500 g, 1.91 mmol) in anhydrous triethylamine (80 mL) under Angon, were added ethynyltrimethylsilane (6.00 g, 61.09 mmol) and palladium (II) acetate (0.100 g, 0.445 mmol). The final mixture was heated to reflux for 2 hours, and then it was cooled down to room temperature and filtrated. The filtrate was concentrated under vacuum to a thick oil, which was purified by column chromatography (dichloromethane/petroleum ether 1:4) and recrystallized from cold cyclohexane to give 10.5 g (96.1percent yield) of 4-(trimethylsilylethynyl)benzaldehyde; MS m/e 187.2 (M+); 1H-NMR (CDCl3) ? ppm: 0.27 (s, 9H, SiMe3), 7.60 (d, 2H, ArH, J=8.1 Hz), 7.82 (d, 2H, ArH, J=8.1 Hz), 10.00 (s, 1H, CHO)].
96% With copper(l) iodide; triethylamine; triphenylphosphine; palladium dichloride In tetrahydrofuran for 2 h; Reflux To a stirred mixture of 3 (4.61 g, 24.9 mmol), CuI (193 mg,1.01 mmol, 0.041 equiv.), PdCl2 (93 mg, 0.52 mmol, 0.021 equiv.),and PPh3 (405 mg, 1.54 mmol, 0.062 equiv.) in 25 mL of THF was addedEt3N (5.2 mL, 37.3 mmol, 1.5 equiv.)and trimethylsilylacetylene(6 mL, 42.5 mmol, 1.7 equiv.). The mixture was stirred for 2 hours at refluxtemperature, then poured into water and extracted with CHCl3. TheCHCl3 layer was washed with brine, dried over Na2SO4,and filtered. The filtrate was evaporated, and silica gel flash column chromatography(n-hexane to n-hexane/AcOEt = 20/1) of the residue gave 4.82 g (96percent) of 4 as a brown solid: 1H NMR(CDCl3 500 MHz, δ; ppm) 10.00 (1H, s), 7.82 (2H, dd, J = 6.7 Hz, 1.8 Hz), 7.61 (2H, d, J = 8.2 Hz), 0.27 (9H, s).
92% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 40℃; Inert atmosphere Trimethylsilylacetylene (5mL, 4.03g, 41.0mmol) was added to a solution of 4-bromobenzaldehyde (5.00g, 27.0mmol), Pd(PPh3)2Cl2 (50mg, 0.07mmol), and CuI (25mg, 0.13mmol) in distilled THF (40mL) under argon. Then, triethylamine (6.5mL) was added and the reaction mixture was heated at 40°C overnight. The solvent was evaporated under reduced pressure. The obtained residue was extracted in DCM, washed in water, dried with MgSO4, and then taken into dryness. The solid was then purified by column chromatography on silica gel using a mixture of heptane/DCM (1:1) as eluent. The compound 9 was obtained as a pale yellow solid to yield 5.04g (92percent). 1H NMR (400MHz, CDCl3, δ in ppm): 10.01 (s, 1H, CHO), 7.83 (d, 2H, Hphenyl, 3JHH=7.6Hz), 7.62 (d, 2H, Hphenyl, 3JHH=7.2Hz), 0.29 (s, 9H, (CH3)3Si).
89% for 6 h; Reflux A deaerated solution of 4-bromobenzaldehyde (3, 4.87 g, 25 mmol),triphenylphosphine (0.33 g, 1.25 mmol), PdCl2 (45 mg, 0.25 mmol), and Cu(OAc)2 (48 mg, 0.25 mmol) inanhydrous triethylamine (60 mL) was treated with trimethylsilylacetylene (5.5 mL, 38 mmol). The mixture wasbrought to reflux for 6 h. After cooling, the precipitated triethylamine hydrobromide was filtered off, and thesolvent was evaporated. The crude material was purified by silica gel column chromatography (silica gel 120 g,hexanes/ethyl acetate = 90/10), affording 4-((trimethylsilyl)ethynyl)benzaldehyde (4.49 g, 89percent yield) as a yellowsolid. 4-((Trimethylsilyl)ethynyl)benzaldehyde (4.05 g, 20 mmol) was treated with K2CO3 (2.28 mg, 2 mol) inMeOH (24 mL) at room temperature for 24 h. The solvent was removed in vacuo. The crude material was purifiedby silica gel column chromatography (silica gel 120 g, hexanes/ethyl acetate = 90/10), affording 4-ethynylbenzaldehyde (5; 2.20 g, 85percent yield) as a yellow solid.
88% With copper(l) iodide; N-cyclohexyl-cyclohexanamine In tetrahydrofuran at 30℃; for 17 h; [Example A-18] Synthesis of 4-[(trimethylsilyl)ethynyl]benzaldehyde from 4-bromobenzaldehyde and trimethylsilylacetylene (Synthesis in which tri-tert-butylphosphonium tetraphenylborate was handled in air) A 50-ml four-necked flask was equipped with a stirrer, a thermometer and a reflux condenser. 0.034 g (0.15 mmol) of palladium (II) acetate, 0.019 g (0.1 mmol) of copper (I) iodide, 1.088 g (6 mmol) of dicyclohexylamine and 9 ml of tetrahydrofuran were weighed in the flask, followed by stirring. Further, 0.157 g (0.3 mmol) of tri-tert-butylphosphonium tetraphenylborate obtained in Example A-1 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 30°C for 30 minutes. 0.925 g (5 mmol) of 4-bromobenzaldehyde and 0.589 g (6 mmol) of trimethylsilylacetylene were added, followed by stirring at 30°C for 17 hours. After the completion of the reaction, 10 ml of tetrahydrofuran, 5 ml of toluene and 15 ml of saturated sodium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.893 g of 4-[(trimethylsilyl)ethynyl]benzaldehyde (yield: 88 molpercent based on 4-bromobenzaldehyde). The identification of the product was made by 1H-NMR and 13C-NMR. (1) 1H-NMR spectrum (δ in CDCl3) 0.26 ppm (s, 9H, H3C) 7.59 ppm (d, J=8.1 Hz, 2H, ring proton) 7.81 ppm (d, J=8.1 Hz, 2H, ring proton) 9.99 ppm (s, 1H, HC) (2) 13C-NMR spectrum (δ in CDCl3) -0.2, 99.0, 103.8, 129.3, 129.4, 132.5, 135.6, 191.4 ppm
88% With copper(l) iodide; N-cyclohexyl-cyclohexanamine In tetrahydrofuran at 30℃; for 17 h; In argon atmosphere [Comparative Example 33] Synthesis of 4-[(trimethylsilyl)ethynyl]benzaldehyde from 4-bromobenzaldehyde and trimethylsilylacetylene (Synthesis in which tri-tert-butylphosphine was handled in argon) The procedures in Example A-18 or B-36 were repeated except that 0.157 g (0.3 mmol) of tri-tert-butylphosphonium tetraphenylborate of Example A-18 or 0.174 g (0.3 mmol) of tri-tert-butylphosphonium tetra-para-tolylborate of Example B-36 was replaced with 0.061 g (0.3 mmol) of tri-tert-butylphosphine, and except that the procedures were carried out in a glove box in which an argon atmosphere was strictly maintained. Consequently, 0.894 g of 4-[(trimethylsilyl)ethynyl]benzaldehyde was obtained (yield: 88 molpercent based on 4-bromobenzaldehyde). The identification of the product was made by 1H-NMR and 13C-NMR, and the results were in agreement with those of Example A-18 or B-36.
88% With copper(l) iodide; N-cyclohexyl-cyclohexanamine In tetrahydrofuran at 30℃; for 17 h; [Example B-36] [Similar to Example A-18] Synthesis of 4-[(trimethylsilyl)ethynyl]benzaldehyde from 4-bromobenzaldehyde and trimethylsilylacetylene (Synthesis in which tri-tert-butylphosphonium tetra-para-tolylborate was handled in air) A 50-ml four-necked flask was equipped with a stirrer, a thermometer and a reflux condenser. 0.034 g (0.15 mmol) of palladium (II) acetate, 0.019 g (0.1 mmol) of copper (I) iodide, 1.088 g (6 mmol) of dicyclohexylamine and 9 ml of tetrahydrofuran were weighed in the flask, followed by stirring. Further, 0.174 g (0.3 mmol) of tri-tert-butylphosphonium tetra-para-tolylborate obtained in Example B-3 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 30°C for 30 minutes. 0.925 g (5 mmol) of 4-bromobenzaldehyde and 0.589 g (6 mmol) of trimethylsilylacetylene were added, followed by stirring at 30°C for 17 hours. After the completion of the reaction, 10 ml of tetrahydrofuran, 5 ml of toluene and 15 ml of saturated sodium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.890 g of 4-[(trimethylsilyl)ethynyl]benzaldehyde (yield: 88 molpercent based on 4-bromobenzaldehyde). The identification of the product was made by 1H-NMR and 13C-NMR. (1) 1H-NMR spectrum (δ in CDCl3) 0.26 ppm (s, 9H, H3C) 7.59 ppm (d, J=8.1 Hz, 2H, ring proton) 7.81 ppm (d, J=8.1 Hz, 2H, ring proton) 9.99 ppm (s, 1H, HC) (2) 13C-NMR spectrum (δ in CDCl3) -0.2, 99.0, 103.8, 129.3, 129.4, 132.5, 135.6, 191.4 ppm
85% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; for 24 h; To a mixture of PdCl2(PPh3)2 (175 mg, 0.3 mmol) andCuI (190 mg, 1.0 mmol) in THF (30 mL), 4-bromobenzaldehyde (1.85 g, 10 mmol), trimethylsilyl acetylene(1.12 mL, 12 mmol), and NEt3 (10 mL) were added.The resulted mixture was stirred for 24 h at room temperature.The solvent was removed and 30 mL CH2Cl2 wasadded. The mixture was washed with water (3 30 mL). Theorganic phase was dried with MgSO4 and the solvent wasremoved by rotary evaporation. Purification by columnchromatography (Silica gel, CH2Cl2/hexane 1:2) gave 4-(2-(trimethylsilyl)ethynyl) -benzaldehyde derivative as whitesolid (yield 85percent).To a stirred solution of 4-(2-(trimethylsilyl)ethynyl) benzaldehyde(5 mmol) in CH3OH (30 mL), K2CO3 (69 mg, 0.5mmol) was added. The mixture was stirred for 24 h at roomtemperature, and the solvent was removed. The residue wasdiluted with 30 mL Et2O and washed with water (3 30mL). The organic phase was dried over MgSO4 and the solventwas removed by rotary evaporation. Purification by aflash colum chromatography (Silica gel, Et2O) provide 5 aswhite solid (546 mg, yield 84percent).1H NMR (400 MHz, CDCl3)
81% With triethylamine In tetrahydrofuran at 25 - 30℃; for 3 - 20.5 h; Example 1; Synthesis of 4-trimethylsilanylethynyl-benzaldehyde (2); 4-Bromobenzaldehyde (1) (185 g, 1.0 mole) was dissolved in THF (1 L) followed by addition of copper (I) iodide (7.6 g, 0.04 mol), dicholobis(triphenylphospine) palladium (II) (14.02 g, 0.02 mol) and triethylamine (151.5 g, 1.5 mol). Ethynyltrimethylsilane (109.1 g, 1.11 mol) was added from addition funnel as a solution in THF (0.2 L). The reaction was stirred at 30° C. for 30 min and then at 25° C. for 20 hours. Analysis by HPLC indicated the completion of the reaction. THF was removed and the residue was treated with hexane (1.8 L). The solid was removed by filtration and the filter cake washed with hexane (0.3 L). The combined hexane solution was washed with water (2.x.0.5 L). Hexane was removed in a rotovap. The residue was dissolved in EtOH (0.5 L) at 50° C. The solution was then slowly cooled to 16° C. and was stirred for 30 minutes. Product started to crystallize. The mixture was further cooled to 5° C. 1:1 of EtOH/H2O (0.24 L) was added slowly. The mixture was stirred at 5° C. for 30 minutes. Solid was collected by filtration, washed with 4:1 of EtOH/H2O (0.2 L) and dried to provide 137.0 g of product. The mother liquor was concentrated to dryness. The residue was partitioned between hexane (0.5 L) and brine (0.25 L). Hexane layer was separated and concentrated to dryness. The residue was crystallized from hexane (40 ml) and further recrystallized from 4:1 of EtOH/H2O (0.1 L) to provide second crop of aldehyde 2 (27.0 g). The combined yield for aldehyde 2 was 81percent. 1H NMR (300 MHz, CDCl3) δ 0.081(s, 9H), 7.41(d, 2H, J=8.1 Hz), 7.63(d, 2H, J=8.4 Hz), 9.81 (s, 1H).
80% at 20℃; Inert atmosphere; sealed tube; Reflux B. 4-ethynylbenzaldehyde; A degassed solution of 4-bromobezaldehyde (6.0 g, 32.4 mmol) and triphenylphosphine (0.17 g, 0.65 mmol) in 60 mL of anhydrous triethylamine was added ethynyltrimethylsilane (26.7 mL, 48.6 mmol) followed by palladium (II) acetate (0.072 g, 0.32 mmol) at room temperature under argon atmosphere. The reaction mixture was heated at reflux for 2 h in sealed tube. The reaction mass was cooled to room temperature and the precipitated solid was filtered. The filtrate was concentrated to provide crude compound. The crude compound was purified by column chromatography (silica gel, 100-200 mesh) by using 1percent ethyl acetate in pet-ether as mobile phase to provide 4- ((trimethylsilyl)ethynyl)benzaldehyde (5.2 g, 80percent). This compound was taken up in methanol (100 mL), to which potassium carbonate (0.341 g, 2.47 mmol) was added at room temperature. The reaction mass was stirred for 2 h. The solvent was removed under reduced pressure and the residue was diluted with dichloromethane (50 mL). The organic solution was washed with water (50 mL), brine solution (25 mL), dried over anhydrous magnesium sulfate and evaporated under reduced pressure to get 4-ethynylbenzaldehyde as light brown solid (3.0 g, 94percent).LC-MS: [M+H]+ 131.2 Mass: calculated for C9H6O, 130.15IH NMR (400 MHz, δ ppm, CDC13): δ 10.02 (s, IH), 7.85 (d, 2H), 7.65 (d, 2H), 3.29 (s, IH)
80% Reflux To a solution of 4-bromobenzaldehyde (10.0 g, 54.04 mmol) in diisopropylamine (600 mL) were added bistriphenylphosphine palladium (II) chloride (380 mg, 0.54 mmol) and Cul (205 mg, 1.08 mmol). The reaction mixture was degassed for 20 min. Then the reaction mixture was cooled to ice temperature and trimethyl silylacetalide (11.2 mL, 81.06 mmol) was added drop wise at same temperature for 30 min and it was refluxed over a period of 3 h. Diisopropylamine was evaporated under reduced pressure and the residue was diluted with ethyl acetate (1000 mL). The ethyl acetate layer was washed with IN Hydrochloric acid (2X100 mL), saturated sodium bicarbonate (1X100 mL) and water (2X 200 mL). Organic layer was dried over sodium sulphate and it was evaporated under reduced pressure to obtain crude product. The crude product was further purified by column chromatography to give 4-Trimethylsilanylethynyl-benzaldehyde as a colorless solid (8.5 g, 80 percent).
80% at 0℃; for 3.5 h; Reflux To a solution of 4-bromobenzaldehyde (10.0 g, 54.04 mmol) in diisopropylamine (600 mL) were added bistriphenylphosphine palladium (II) chloride (380 mg, 0.54 mmol) and CuI (205 mg, 1.08 mmol).
The reaction mixture was degassed for 20 min.
Then the reaction mixture was cooled to ice temperature and trimethyl silylacetalide (11.2 mL, 81.06 mmol) was added drop wise at same temperature for 30 min and it was refluxed over a period of 3 h.
Diisopropylamine was evaporated under reduced pressure and the residue was diluted with ethyl acetate (1000 mL).
The ethyl acetate layer was washed with 1N Hydrochloric acid (2*100 mL), saturated sodium bicarbonate (1*100 mL) and water (2*200 mL).
Organic layer was dried over sodium sulphate and it was evaporated under reduced pressure to obtain crude product.
The crude product was further purified by column chromatography to give 4-Trimethylsilanylethynyl-benzaldehyde as a colorless solid (8.5 g, 80percent).
74% at 40℃; Trimethylsilylacetylene (19.4 mL, 135.9 mmol) was added to a mixture of 4-bromobenzaldehyde (5.0 g, 27.18 mmol), Pd(PPh3)2Cl2 (950 mg, 1.36 mmol) and CuI (520 mg, 2.72 mmol) in Et3N (60 mL). The mixture was stirred overnight at 40 °C. After cooling to room temperature, the resulting   ammonium salt was filtered off, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography with petroleum ether as eluent to afford 4-((trimethylsilyl)ethynyl)benzaldehyde as a yellow powder after removal of the solvent (4.0 g, 74percent). 1H NMR (300 MHz, CDCl3) δ 10.00 (s, 1H), 7.82 (d, J = 8.5 Hz, 2H), 7.60 (d, J = 8.2 Hz, 2H), 0.27 (s, 9H).
70% at 0 - 20℃; for 3.5 h; Reflux A solution of 548 4-bromobenzaldehyde (10 g, 54.64 mmol) in 549 diisopropyl amine (500 mL) was charged with 550 bis(triphenylphosphine)palladium(II) dichloride (380 mg, 0.546 mmol) and 314 copper iodide (205 mg, 1.09 mmol) and degassed for 20 min. The reaction mixture was cooled to 0° C. and followed by dropwise addition of 551 trimethyl silyl acetylene (11.2 mL, 81.06 mmol) for a period of 30 min. The reaction mixture was allowed to attain room temperature and further refluxed for 3 h. The reaction mixture was cooled to room temperature and HBr salt formed was filtered. The filtrate was concentrated in vacuo, diluted with ethyl acetate and washed with 1N HCl solution followed by saturated 125 sodium bicarbonate and water. The separated organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo resulting in the crude 545 compound which was purified by column chromatography on silica gel eluting with 0-5percent ethyl acetate in n-hexane to afford 7.7 g, 70percent yield, of the title compound as an off white solid. 1H NMR (400 MHz, CDCl3) δ=10.00 (s, 1H), 7.82 (d, J=8.31 Hz, 2H), 7.60 (d, J=7.83 Hz, 2H), 0.27 (s, 9H); MS (ES+): m/z=244.16 [M+H]+; LCMS: tR=3.58 min.
1.2 g With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In tetrahydrofuran at 18 - 25℃; Inert atmosphere A suspension of 4-bromobenzaldehyde (1 g, 5mmol), Pd(PPh3 ) 4 (0.23 g, 0.2 mmol). Cui (95 mg, 0.5mmol), triethylamine (2.02 g, 20 mmol) and ethynyltrimethylsilane(0.79 g, 8 mmol) in THF (20 mL) under a N2atmosphere was stirred at RT overnight. The mixture wasfiltered and the filtrate was concentrated. The residue waspurified by silica-gel colunm chromatography to give 1.2 gof 4-((trimethylsilyl)ethynyl)benzaldehyde as a light brownsolid.

Reference: [1] Advanced Synthesis and Catalysis, 2006, vol. 348, # 15, p. 2101 - 2113
[2] Beilstein Journal of Organic Chemistry, 2014, vol. 11, p. 37 - 41
[3] PLoS ONE, 2015, vol. 10, # 6,
[4] Chemistry - A European Journal, 2010, vol. 16, # 25, p. 7389 - 7394
[5] Chemical Communications, 2011, vol. 47, # 4, p. 1282 - 1284
[6] Chemistry - A European Journal, 2013, vol. 19, # 6, p. 1996 - 2004
[7] Journal of the American Chemical Society, 2016, vol. 138, # 51, p. 16703 - 16710
[8] New Journal of Chemistry, 2017, vol. 41, # 16, p. 8016 - 8025
[9] Patent: CN107365254, 2017, A, . Location in patent: Paragraph 0115-0118
[10] Journal of Organic Chemistry, 1981, vol. 46, # 11, p. 2280 - 2286
[11] ChemPlusChem, 2014, vol. 79, # 9, p. 1352 - 1360
[12] Patent: WO2008/31157, 2008, A1, . Location in patent: Page/Page column 64
[13] Journal of Organic Chemistry, 2003, vol. 68, # 21, p. 8025 - 8036
[14] Chemical Communications, 2013, vol. 49, # 17, p. 1717 - 1719
[15] Patent: US2004/14737, 2004, A1, . Location in patent: Page 5
[16] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 16, p. 3172 - 3175
[17] Journal of Organic Chemistry, 2000, vol. 65, # 22, p. 7323 - 7344
[18] Tetrahedron Letters, 2000, vol. 41, # 7, p. 1015 - 1018
[19] Tetrahedron, 2013, vol. 69, # 34, p. 7112 - 7124
[20] Chemical Communications, 2014, vol. 50, # 6, p. 695 - 697
[21] Organometallics, 2015, vol. 34, # 4, p. 673 - 682
[22] RSC Advances, 2014, vol. 4, # 107, p. 62532 - 62543
[23] Journal of Organometallic Chemistry, 2006, vol. 691, # 7, p. 1389 - 1401
[24] Tetrahedron Letters, 2014, vol. 55, # 11, p. 1946 - 1948
[25] European Journal of Organic Chemistry, 2015, vol. 2015, # 1, p. 91 - 108
[26] European Journal of Organic Chemistry, 2018, vol. 2018, # 15, p. 1756 - 1760
[27] Patent: EP1688424, 2006, A1, . Location in patent: Page/Page column 61-62
[28] Patent: EP1688424, 2006, A1, . Location in patent: Page/Page column 98
[29] Patent: EP1688424, 2006, A1, . Location in patent: Page/Page column 84
[30] Green Chemistry, 2009, vol. 11, # 11, p. 1821 - 1825
[31] Journal of the American Chemical Society, 2014, vol. 136, # 3, p. 970 - 977
[32] Tetrahedron, 2008, vol. 64, # 50, p. 11420 - 11432
[33] Journal of the American Chemical Society, 2014, vol. 136, # 6, p. 2280 - 2283
[34] Letters in Organic Chemistry, 2013, vol. 10, # 1, p. 22 - 26
[35] Chemical Communications, 2016, vol. 52, # 13, p. 2843 - 2845
[36] ChemPhysChem, 2016, p. 2066 - 2078
[37] New Journal of Chemistry, 2018, vol. 42, # 1, p. 555 - 563
[38] Macromolecules, 2011, vol. 44, # 13, p. 5155 - 5167
[39] Journal of Materials Chemistry A, 2013, vol. 1, # 34, p. 10008 - 10015
[40] Patent: US2006/63926, 2006, A1, . Location in patent: Page/Page column 5; 7
[41] Angewandte Chemie - International Edition, 2017, vol. 56, # 42, p. 13094 - 13098[42] Angew. Chem., 2017, vol. 56, p. 13274 - 13278,5
[43] Journal of the American Chemical Society, 2009, vol. 131, # 2, p. 634 - 643
[44] Patent: WO2010/100475, 2010, A1, . Location in patent: Page/Page column 48-49
[45] Patent: WO2011/21209, 2011, A1, . Location in patent: Page/Page column 35; 36
[46] Patent: US2012/101099, 2012, A1, . Location in patent: Page/Page column 12
[47] Journal of Organometallic Chemistry, 2009, vol. 694, # 14, p. 2153 - 2162
[48] Journal of Materials Chemistry C, 2016, vol. 4, # 22, p. 5010 - 5018
[49] Polymer, 2012, vol. 53, # 26, p. 6033 - 6038
[50] Chemistry - A European Journal, 2008, vol. 14, # 11, p. 3467 - 3480
[51] Chemistry - A European Journal, 2014, vol. 20, # 44, p. 14282 - 14295
[52] Journal of Materials Chemistry C, 2016, vol. 4, # 14, p. 2843 - 2853
[53] Journal of the American Chemical Society, 2012, vol. 134, # 40, p. 16671 - 16692
[54] Chemical Communications, 2015, vol. 51, # 25, p. 5257 - 5260
[55] Patent: US2017/202970, 2017, A1, . Location in patent: Paragraph 0728; 0738; 0739
[56] Angewandte Chemie, International Edition, 2009, vol. 48, # 25, p. 4610 - 4612
[57] New Journal of Chemistry, 2011, vol. 35, # 1, p. 127 - 136
[58] Journal of the Chemical Society. Perkin Transactions 2, 1998, # 3, p. 715 - 723
[59] Tetrahedron Letters, 2000, vol. 41, # 40, p. 7623 - 7627
[60] Journal of Organic Chemistry, 2006, vol. 71, # 22, p. 8500 - 8509
[61] Patent: EP1688424, 2006, A1, . Location in patent: Page/Page column 98
[62] European Journal of Organic Chemistry, 2008, # 27, p. 4598 - 4606
[63] Journal of Organic Chemistry, 2009, vol. 74, # 6, p. 2417 - 2424
[64] Chemistry - A European Journal, 2010, vol. 16, # 28, p. 8285 - 8290
[65] Chemistry Letters, 2011, vol. 40, # 2, p. 184 - 185
[66] European Journal of Organic Chemistry, 2011, # 25, p. 4773 - 4787
[67] Tetrahedron, 2012, vol. 68, # 31, p. 6338 - 6342
[68] Organometallics, 2013, vol. 32, # 15, p. 4366 - 4381
[69] Chemistry - An Asian Journal, 2011, vol. 6, # 6, p. 1604 - 1612
[70] Journal of Polymer Science, Part A: Polymer Chemistry, 2013, vol. 51, # 24, p. 5248 - 5256
[71] Reactive and Functional Polymers, 2015, vol. 87, p. 46 - 52
[72] Journal of Catalysis, 2014, vol. 313, p. 1 - 8
[73] Journal of the American Chemical Society, 2014, vol. 136, # 29, p. 10499 - 10507
[74] Angewandte Chemie - International Edition, 2014, vol. 53, # 31, p. 8216 - 8220[75] Angew. Chem., 2014, vol. 126, # 31, p. 8355 - 8359,5
[76] Journal of Materials Chemistry C, 2014, vol. 2, # 45, p. 9720 - 9736
[77] Phosphorus, Sulfur and Silicon and the Related Elements, 2016, vol. 191, # 3, p. 411 - 416
[78] Chemistry - A European Journal, 2016, vol. 22, # 16, p. 5583 - 5597
[79] Patent: CN105348303, 2016, A, . Location in patent: Paragraph 0029; 0054
[80] Journal of Molecular Structure, 2017, vol. 1128, p. 361 - 367
[81] Journal of Organometallic Chemistry, 2017, vol. 835, p. 25 - 30
[82] Patent: CN106946838, 2017, A, . Location in patent: Paragraph 0065; 0066; 0067
[83] Chemical Communications, 2018, vol. 54, # 35, p. 4465 - 4468
[84] Patent: US2018/258065, 2018, A1, . Location in patent: Paragraph 0129; 0255
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YieldReaction ConditionsOperation in experiment
96.1% With triphenylphosphine In triethylamine 4-Ethynylbenzaldehyde (13):
To a solution of 4-bromobenzaldehyde (10.00 g, 54.08 mmol) and triphenylphosphine (0.500 g, 1.91 mmol) in anhydrous triethylamine (80 mL) under argon were added ethynyltrimethylsilane (6.00 g, 61.09 mmol) and palladium (II) acetate (0.100 g, 0.445 mmol).
The final mixture was heated to reflux for 2 hours, and was then cooled to room temperature and filtered.
The filtrate was concentrated under vacuum to a thick oil, which was purified by column chromatography (dichloromethane/petroleum ether 1:4) and recrystallized from cold cyclohexane to give 10.5 g (96.1percent yield) of 4-(trimethylsilylethynyl)benzaldehyde [MS m/e 187.2 (M+); 1H-NMR (CDCl3) δ ppm: 0.27 (s, 9H, SiMe3), 7.60 (d, 2H, ArH, J=8.1 Hz), 7.82 (d, 2H, ArH, J=8.1 Hz), 10.00 (s, 1H, CHO)].
96.1% With triphenylphosphine In triethylamine 4-Ethynylbenzaldehyde (13):
To a solution of 4-bromobenzaldehyde (10.00 g, 54.08 mmol) and triphenylphosphine (0.500 g, 1.91 mmol) in anhydrous triethylamine (80 mL) under argon were added ethynyltrimethylsilane (6.00 g, 61.09 mmol) and palladium (II) acetate (0.100 g, 0.445 mmol).
The final mixture was heated to reflux for 2 hours, and was then cooled to room temperature and filtered.
The filtrate was concentrated under vacuum to a thick oil, which was purified by column chromatography (dichloromethane/petroleum ether 1:4) and recrystallized from cold cyclohexane to give 10.5 g (96.1percent yield) of 4-(trimethylsilylethynyl)benzaldehyde [MS m/e 187.2 (M+); 1H-NMR (CDCl3) δ ppm: 0.27 (s, 9H, SiMe3), 7.60 (d, 2H, ArH, J=8.1 Hz), 7.82 (d, 2H, ArH, J=8.1 Hz), 10.00 (s, 1H, CHO)].
Reference: [1] Patent: US2004/106592, 2004, A1,
[2] Patent: US2004/116385, 2004, A1,
  • 115
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  • [ 1066-54-2 ]
  • [ 4526-07-2 ]
  • [ 77123-57-0 ]
Reference: [1] Journal of Organic Chemistry, 1998, vol. 63, # 23, p. 8551 - 8553
  • 116
  • [ 1993-03-9 ]
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  • [ 57592-42-4 ]
Reference: [1] European Journal of Medicinal Chemistry, 2016, vol. 115, p. 453 - 462
[2] Patent: EP3202759, 2017, A1, . Location in patent: Paragraph 0050
[3] Patent: WO2009/129625, 2009, A1, . Location in patent: Page/Page column 31
  • 117
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  • [ 73183-34-3 ]
  • [ 128376-64-7 ]
YieldReaction ConditionsOperation in experiment
95% With bis-triphenylphosphine-palladium(II) chloride; potassium acetate In 1,4-dioxane at 80℃; for 15 h; Inert atmosphere To a stirring solution of co pound Z 1 (2 c 8 g , 0.15 mol), compound 2,2 (45.7 g , 0.18 mo) and PdCa(PPha}2 (5.26 g, 7.5 mmof) in 1 ,4-dioxane (500 ml), was added KOAc (22.0 gt 0.225 mo) under an argon atmosphere and the mixture was stirred at 80CC for 15 fir. The solvent was removed under reduced pressure, and the residue was diluted with PE (500 nL). Solids were removed by filtration, and the filtrate was concentrated under reduced pressure to give a crude, which was purified by flash chromatography (siiica gel/ FE:EA 1 Q- 1) to give 4-(4t4,5,5-tetramethy-1 3.2- dioxgborolan-2-yi)ben2aid©hyd (2.3, 32.5 g, 95percent) as a white solid.
1.12 g With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In toluene at 90 - 100℃; for 6 h; Sealed tube Pd(dppf)Cl2.CH2Cl2 (0.48 g, 0.0005 mole) was added to a sealed tube containing a mixture of 4-bromobenzaldehyde (1 g, 0.005 mole), potassium acetate (1.31 g, 0.013 mole) and bis(pinacolato)diboron (1.6 g, 0.006 mole) in toluene (20 mL) and the contents were heated at 90 - 100 °C for 6 hours and then cooled to room temperature. The reaction mass filtered through a pad of celite and washed with ethyl acetate (20 mL x 2). The filtrate was concentrated under vacuum to obtain the crude compound that was further purified by flash chromatography using ethyl acetate:hexanes (10:90) to obtain 4-(4,4,5,5- tetramethyl-[l,3,2]dioxaborolan-2-yl)benzaldehyde. Yield: 1.12 g; l - NMR (CDC13, 400 MHz) δ ppm: 1.36 (s, 12H), 7.85 - 7.87 (d, J = 7.72 Hz, 2H), 7.95 - 7.97 (d, J = 7.8 Hz, 2H), 10.05 (s, 1H); Mass (m/z): 233.0 (M+H)+.
Reference: [1] Advanced Synthesis and Catalysis, 2016, vol. 358, # 6, p. 977 - 983
[2] Patent: WO2013/170165, 2013, A1, . Location in patent: Page/Page column 93
[3] Applied Organometallic Chemistry, 2011, vol. 25, # 7, p. 537 - 541
[4] Organic Letters, 2016, vol. 18, # 20, p. 5248 - 5251
[5] Journal of the American Chemical Society, 2016, vol. 138, # 1, p. 84 - 87
[6] Synthetic Communications, 2007, vol. 37, # 5, p. 667 - 674
[7] Journal of Materials Chemistry, 2011, vol. 21, # 14, p. 5451 - 5456
[8] Angewandte Chemie - International Edition, 2012, vol. 51, # 2, p. 536 - 539
[9] Patent: WO2018/42362, 2018, A1, . Location in patent: Page/Page column 51
[10] Patent: WO2018/195321, 2018, A1, . Location in patent: Page/Page column 493; 494
  • 118
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Reference: [1] Chemistry - A European Journal, 2014, vol. 20, # 1, p. 263 - 271
  • 119
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  • [ 73183-34-3 ]
  • [ 100-52-7 ]
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Reference: [1] Green Chemistry, 2012, vol. 14, # 3, p. 661 - 667
  • 120
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  • [ 215453-51-3 ]
Reference: [1] Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537
  • 121
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  • [ 223671-15-6 ]
Reference: [1] Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537
[2] Journal of the American Chemical Society, 2015, vol. 137, # 33, p. 10464 - 10467
  • 122
  • [ 668987-38-0 ]
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  • [ 128376-65-8 ]
YieldReaction ConditionsOperation in experiment
10% at 100℃; for 18 h; A round-bottom flask charged with the aryl halide (5.0 mmol, 1.0 equiv), Ni (For exact amount of catalyst and co-ligand see Table 8; 10percent loading was used for Ni catalysts not specified in Table 8). (NiCl2(L)x , Ni(COD)2) or Pd (No co-ligand was used for Pd catalyst) catalysts (PdCl2(dppf)) (0.5 mmol, 0.1 to 0.02 equiv), ligand (L: dppp, dppe, dppf, PPh3, Et3N, bpy, PCy3) (0.5 mmol, 0.1 equiv), and a Teflon.(R). coated stir bar was evacuated three times for 10 min under high vacuum and backfilled with N2. Toluene (5 mL) and base (Et3N or (i-Pr)2EtN (15.0 mmol, 3.0 equiv) were added to the reaction mixture at rt. Freshly prepared neopentylglycolborane (10.0 mmol, 2.0 equiv in 5 ml toluene) was added to the red colored suspension via syringe at 23 0C. The reaction mixture was heated to 100 0C and the conversion was followed by GC. After 2 h-12 h (reaction time depends on the type of the aryl halide; iodo derivatives were found to react faster, in 2-4 h , while bromo derivatives in 8-12h), the reaction mixture was quenched via slow addition of saturated aqueous ammonium chloride (10 mL). The quenched reaction mixture was three times washed with saturated aqueous ammonium chloride and extracted with ethyl acetate (50 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The crude product was purified by silica gel chromatography or recrystallization.
Reference: [1] Patent: WO2009/137322, 2009, A2, . Location in patent: Page/Page column 20; 30; 32; 33
[2] Organic Letters, 2008, vol. 10, # 21, p. 4879 - 4882
  • 123
  • [ 1122-91-4 ]
  • [ 201733-56-4 ]
  • [ 128376-65-8 ]
Reference: [1] Tetrahedron Letters, 2012, vol. 53, # 46, p. 6230 - 6235,6
  • 124
  • [ 1122-91-4 ]
  • [ 1066-54-2 ]
  • [ 275386-60-2 ]
Reference: [1] Patent: WO2008/31157, 2008, A1,
  • 125
  • [ 1122-91-4 ]
  • [ 111829-72-2 ]
  • [ 158435-41-7 ]
Reference: [1] Journal of the American Chemical Society, 2017, vol. 139, # 2, p. 888 - 896
  • 126
  • [ 1122-91-4 ]
  • [ 206055-91-6 ]
Reference: [1] Journal of Medicinal Chemistry, 2003, vol. 46, # 2, p. 284 - 302
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 3, p. 765 - 781
[3] Patent: WO2014/117090, 2014, A1,
[4] Chemical Papers, 2015, vol. 69, # 11, p. 1500 - 1511
[5] Ultrasonics Sonochemistry, 2017, vol. 36, p. 343 - 353
[6] European Journal of Medicinal Chemistry, 2017, vol. 126, p. 929 - 936
[7] Patent: WO2008/108602, 2008, A1,
  • 127
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  • [ 364794-79-6 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 20, p. 2989 - 2992
  • 128
  • [ 59020-10-9 ]
  • [ 1122-91-4 ]
  • [ 127406-55-7 ]
YieldReaction ConditionsOperation in experiment
93% With copper(l) iodide; C37H51ClFeNPPd; cesium fluoride In N,N-dimethyl-formamide at 80℃; for 12 h; Inert atmosphere General procedure: 4.3.10
4-(Pyridin-3-yl)benzaldehyde (3ja)
White solid, mp 50-51 °C; 1H NMR (400 MHz, CDCl3): δ=10.09 (s, 1H), 8.90 (d, J=1.76 Hz, 1HAryl halide (0.5 mmol), base (1 mmol), CuI (20 mol percent), alkylstannylpyridine(0.75 mmol), and catalyst (1 mol percent) were dissolvedin DMF (2 mL) in a 10 mL vial and heated at a specific temperatureunder N2 for 12 h. After the reaction was complete, and thenquenched with water. The mixture was diluted with ethyl acetate(10 mL), filtered through a pad of Celite, and followed by extractionwith ethyl acetate for three times. The combined organic layer wasdried over anhydrous Na2SO4, filtered, and evaporated under reducedpressure. The residual was purified by flash chromatographyon silica gel (ethyl acetate/hexane) to give the desired product.), 8.68-8.66 (m, 1H), 8.00 (d, J=8.24 Hz, 2H), 7.93 (d, J=7.88 Hz, 1H), 7.76 (d, J=8.20 Hz, 2H), 7.41-7.44 (m, 1H); 13C NMR (100 MHz, CDCl3): δ=123.8, 127.8, 127.8, 130.5, 130.5, 134.6, 135.3, 135.8, 143.8, 148.4, 149.6, 191.8; HRMS-ESI (m/z): [M+H]+ calcd for C12H10NO+: 184.0757, found: 184.0758.
Reference: [1] Tetrahedron, 2013, vol. 69, # 2, p. 902 - 909
  • 129
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  • [ 127406-55-7 ]
Reference: [1] European Journal of Organic Chemistry, 2009, # 13, p. 2051 - 2054
[2] Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 224 - 239
[3] Dalton Transactions, 2007, # 35, p. 3952 - 3958
[4] European Journal of Medicinal Chemistry, 2016, vol. 115, p. 453 - 462
  • 130
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  • [ 127406-55-7 ]
YieldReaction ConditionsOperation in experiment
45% With copper(I) oxide; tetrakis(triphenylphosphine) palladium(0); 1,10-Phenanthroline In N,N-dimethyl acetamide at 60 - 180℃; for 4 h; Inert atmosphere; Glovebox; Microwave irradiation General procedure: In an argon-filled glovebox, a 10 mL microwave vial was charged with Pd(PPh3)4 (14.35 mg,0.0125 mmol), Cu2O (21.3 mg, 0.15 mmol), 1,10-phenanthroline (8.95 mg,0.05 mmol), the potassium pyridylcarboxylate (0.50 mmol), aryl bromide(0.75 mmol) and anhydrous DMA (3.0 mL). The resulting solution wasirradiated in a microwave reactor (Biotage Initiator Eight EXP) with a 2 minprestirring period, followed by 10 min at 60 C. The reaction was then heatedat 180 C for 3 h 50 min. The maximum pressure noted was 3 bar. Aftercompletion of the reaction, H2O was added to the mixture which was thenextracted with EtOAc (3 10 mL). The combined organic layers were washedwith brine (5 mL), dried over Na2SO4, filtered, and the volatiles removed invacuo. The residue was purified by column chromatography on silica gel,yielding the corresponding biaryl product.
Reference: [1] Tetrahedron Letters, 2015, vol. 56, # 11, p. 1293 - 1296
  • 131
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  • [ 160688-99-3 ]
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Reference: [1] Journal of Organic Chemistry, 2004, vol. 69, # 6, p. 2210 - 2212
  • 132
  • [ 1120-90-7 ]
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  • [ 127406-55-7 ]
Reference: [1] Tetrahedron Letters, 2004, vol. 45, # 20, p. 3909 - 3912
  • 133
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  • [ 111829-72-2 ]
  • [ 158435-41-7 ]
Reference: [1] Journal of the American Chemical Society, 2017, vol. 139, # 2, p. 888 - 896
  • 134
  • [ 1423-27-4 ]
  • [ 1122-91-4 ]
  • [ 198205-95-7 ]
Reference: [1] Journal of Medicinal Chemistry, 2013, vol. 56, # 7, p. 2975 - 2990
[2] Patent: WO2005/118542, 2005, A1, . Location in patent: Page/Page column 59
  • 135
  • [ 444-29-1 ]
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  • [ 198205-95-7 ]
Reference: [1] Tetrahedron Letters, 2004, vol. 45, # 20, p. 3909 - 3912
  • 136
  • [ 5720-06-9 ]
  • [ 1122-91-4 ]
  • [ 421553-62-0 ]
YieldReaction ConditionsOperation in experiment
87% With sodium carbonate In methanol at 20℃; for 3 h; Sealed tube; Inert atmosphere General procedure: To a round bottom flask with stir bar were added phenylboronic acid (275 mmol), 1-bromo-4-nitrobenzene (250 mmol), base (375 mmol), 1.0 molpercent catalyst 6 (9.2 mg), and solvent 4mL. The entrance was sealed with septum, and inside air was was exchanged with N2. After the mixture was stirred at room temperature for a certain period, the mixture was diluted with H2O (5ml) and Et2O (5 ml). Organic layer was concentrated in vacuo.
Reference: [1] Journal of Chemical Research, 2004, # 9, p. 593 - 595
[2] Advanced Synthesis and Catalysis, 2004, vol. 346, # 13-15, p. 1669 - 1673
[3] Synthesis, 2005, # 4, p. 537 - 542
[4] Tetrahedron Letters, 2018, vol. 59, # 31, p. 2989 - 2993
[5] ChemCatChem, 2016, vol. 8, # 4, p. 743 - 750
[6] Organometallics, 2011, vol. 30, # 8, p. 2411 - 2417
[7] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 11, p. 3429 - 3445
[8] Tetrahedron, 2017, vol. 73, # 1, p. 64 - 69
  • 137
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  • [ 421553-62-0 ]
Reference: [1] RSC Advances, 2016, vol. 6, # 2, p. 1012 - 1017
  • 138
  • [ 1046478-89-0 ]
  • [ 1122-91-4 ]
  • [ 439811-37-7 ]
YieldReaction ConditionsOperation in experiment
66% With caesium carbonate In 1,4-dioxane at 110℃; Inert atmosphere Compound B6.1 (1.00 g; 2.721 mmol), 4-bromobenzaldehyde (0.604 g;3.266 mmol) and cesium carbonate (0.436 ml; 5.443 mmol) weresuspended in dry 1,4-dioxane (10.0 mL) under argon atmosphere. The mixture was heated to 110 °C and stirred overnight at this temperature. The reaction mixture was cooled to room temperature, quenched with water (30 mL) and extracted with MTB-ether. The combined organic layerswere washed with 5percent citric acid solution, saturated NaHCO3 solution and brine, dried with sodium sulfate, filtered by suction and evaporated to dryness. The solid residue was triturated with petrolether/MTB-ether (1:1), filtered by suction, washed with petrolether/MTB-ether (3:1) and dried.From the filtrate further product was isolated by flash chromatography (Companion RF; 40 g Si50 silica gel column). Yield: 657 mg (66percent) colorless solid; LC/MS (A), Rt: 2.72 mm; (M+H-t-Bu) 312.0/314.0
Reference: [1] Organic Letters, 2014, vol. 16, # 11, p. 3064 - 3067
[2] Patent: WO2017/76484, 2017, A1, . Location in patent: Page/Page column 58
  • 139
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  • [ 457889-46-2 ]
Reference: [1] Patent: EP2725024, 2014, A1,
[2] Patent: US2014/171431, 2014, A1,
  • 140
  • [ 17933-03-8 ]
  • [ 1122-91-4 ]
  • [ 400744-83-4 ]
Reference: [1] Applied Organometallic Chemistry, 2017, vol. 31, # 4,
[2] Journal of Mass Spectrometry, 2008, vol. 43, # 4, p. 542 - 546
  • 141
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  • [ 1088410-99-4 ]
Reference: [1] Organic Process Research and Development, 2014, vol. 18, # 12, p. 1702 - 1713
[2] Organic Process Research and Development, 2014, vol. 18, # 12, p. 1702 - 1713
  • 142
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  • [ 1088410-99-4 ]
Reference: [1] Organic Process Research and Development, 2014, vol. 18, # 12, p. 1702 - 1713
[2] Organic Process Research and Development, 2014, vol. 18, # 12, p. 1702 - 1713
  • 143
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  • [ 1254319-51-1 ]
Reference: [1] Organic Letters, 2014, vol. 16, # 2, p. 358 - 361
[2] Organic Letters, 2014, vol. 16, # 2, p. 358 - 361
  • 144
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  • [ 1254319-51-1 ]
  • [ 1247891-93-5 ]
Reference: [1] Organic Letters, 2014, vol. 16, # 2, p. 358 - 361
[2] Organic Letters, 2014, vol. 16, # 2, p. 358 - 361
  • 145
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  • [ 1254319-51-1 ]
  • [ 1520080-47-0 ]
Reference: [1] Organic Letters, 2014, vol. 16, # 2, p. 358 - 361
  • 146
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  • [ 1234319-14-2 ]
Reference: [1] Patent: US2012/214791, 2012, A1,
  • 147
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  • [ 1082674-24-5 ]
Reference: [1] Patent: WO2015/181676, 2015, A1,
  • 148
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  • [ 377053-86-6 ]
Reference: [1] Patent: WO2014/117090, 2014, A1,
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