4-Ethynylanisole | Alkynyls

Abstract: NIR dyes have become popular for many applications, including biosensing and imaging. For this reason, the mol. switch mechanism of the xanthene dyes makes them useful for in vivo detection and imaging of bioanalytes. Our group has been designing NIR xanthene-based dyes by the donor-acceptor-donor approach; however, the equilibrium between their opened and closed forms varies depending on the donors and spacer. We synthesized donor-acceptor-donor NIR xanthene-based dyes with an alkyne spacer via the Sonogashira coupling reaction to investigate the effects of the alkyne spacer and the donors on the maximum absorption wavelength and the mol. switching (ring opening) process of the dyes. We evaluated the strength and nature of the donors and the presence and absence of the alkyne spacer on the properties of the dyes. It was shown that the alkyne spacer extended the conjugation of the dyes, leading to absorption wavelengths of longer values compared with the dyes without the alkyne group. In addition, strong charge transfer donors shifted the absorption wavelength towards the NIR region, while donors with strong π-donation resulted in xanthene dyes with a smaller equilibrium constant DFT/TDDFT calculations corroborated the exptl. data in most of the cases. Dye 2 containing the N,N-dimethylaniline group gave contrary results and is being further investigated.

Keywords: donor-acceptor-donor ; NIR dyes ; xanthene dyes ; amine donors ; alkyne spacers

Purchased from AmBeed: 589-87-7 ; 768-60-5 ; 201802-67-7 ; 262861-81-4 ; 57102-42-8 ; 17573-94-3 ; 1066-54-2 ; 205877-26-5 ; 28611-39-4 ; 1195931-66-8

Transition Metal‐Free Catalytic C− H Silylation of Terminal Alkynes with bis (Trimethylsilyl) acetylene Initiated by KHMDS

Krzysztof Kuciński ; Grzegorz Hreczycho ;

DOI: 10.1002/cctc.202200794 ChemCatChem,2022,14(18):e202200794.

Abstract: Commercially available and inexpensive potassium bis(trimethylsilyl)amide (KHMDS) serves as an efficient transition metal-free catalyst for the catalytic sp C−H silylation of several terminal alkynes including two pharmaceuticals. Overall, the presented system allows the synthesis of various attractive silylacetylenes under mild conditions, making this approach an environmentally benign and sustainable alternative to existing synthetic solutions.

Purchased from AmBeed: 768-60-5 ; 40307-11-7 ; 171290-52-1 ; 766-83-6 ; 886363-40-2 ; 62452-73-7 ; 1945-84-2 ; 29079-00-3 ; 766-97-2 ; 705-31-7 ; 23152-99-0 ; 14630-40-1 ; 766-47-2 ; 873-73-4 ; 2510-23-8 ; 704-41-6 ; 67237-53-0 ; 160542-02-9 ; 766-49-4 ; 769-26-6

Product Details of [ 768-60-5 ]

CAS No. :	768-60-5
Formula :	C₉H₈O
M.W :	132.16
SMILES Code :	C1=C(C=CC(=C1)C#C)OC
MDL No. :	MFCD00168815
InChI Key :	KBIAVTUACPKPFJ-UHFFFAOYSA-N
Pubchem ID :	251020

Safety of [ 768-60-5 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 768-60-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	6
Fraction Csp3	0.11
Num. rotatable bonds	1
Num. H-bond acceptors	1.0
Num. H-bond donors	0.0
Molar Refractivity	40.87
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	9.23 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.32
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.54
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.76
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.37
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.46
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.29

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.64
Solubility	0.304 mg/ml ; 0.0023 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.38
Solubility	0.55 mg/ml ; 0.00416 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-2.57
Solubility	0.354 mg/ml ; 0.00268 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.3 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	2.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.38

Application In Synthesis of [ 768-60-5 ]

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

Downstream synthetic route of [ 768-60-5 ]

[ 768-60-5 ] Synthesis Path-Downstream 1~54

1
[ 3167-62-2 ]
[ 123-11-5 ]
[ 3167-63-3 ]
[ 477727-71-2 ]
[ 123098-29-3 ]
[ 768-60-5 ]

References: [1]Canadian Journal of Chemistry,1989,vol. 67,p. 1332 - 1343.

2
[ 3167-62-2 ]
[ 123-11-5 ]
[ 3167-63-3 ]
[ 18684-79-2 ]
[ 18684-94-1 ]
[ 768-60-5 ]

References: [1]Canadian Journal of Chemistry,1989,vol. 67,p. 1332 - 1343.

3
[ 615-43-0 ]
[ 768-60-5 ]
[ 157869-15-3 ]

Yield	Reaction Conditions	Operation in experiment
93%		General procedure: 2-iodoaniline (500.2 mg, 2.28 mmol, 1.0 equiv) was dissolved in Et3N (4.5 mL). The resulting solution was added with PdCl2(PPh3)2 (32.1 mg, 0.046 mol, 0.02 equiv) and CuI (17.4 mg, 0.091mmol, 0.04 equiv). The orange-yellow solution was degassed by bubbling with a stream of argon into the solution at room temperature for 30 min. After degassing, phenylacetylene (0.30 mL,279.0 mg, 2.73 mmol, 1.2 equiv) was added as a neat liquid into the solution via syringe. The resulting dark brown solution was allowed to stir at room temperature under argon atmosphere overnight. The reaction was quenched by addition of sat. aq. NH4Cl. The separated aqueousphase was extracted with EtOAc (3x times). The combined organic phases were washed with sat. aq. NaCl, dried over anh. Na2SO4, filtered and concentrated to a crude product. The crudeproduct was purified by SiO2 column chromatography eluting with 0-10% EtOAc-hexane to give 398.2 mg (90%) of 2-(phenylethynyl)aniline as an orange solid.
75%	With sodium hydroxide; In toluene; at 130℃; for 72h;	General procedure: To a stirred solution of the corresponding 2-iodoaniline (6, 1 mmol) in toluene (3 mL) under argon atmosphere were added Pd/CuO-Fe3O4 (50 mg), NaOH (400 mg, 10 mmol), and the corresponding alkyne (2, 1.5 mmol). The resulting mixture was stirred at 130 C until the end of reaction (see Table 6). The catalyst was removed by a magnet and the resulting mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to remove the solvent. The product was purified by chromatography on silica gel (hexane/ethyl acetate) to give the corresponding compounds 7. Yields are included in Table 6. Then, to a stirred solution of 7 (1 mmol) in toluene (4 mL) was added ZnBr2 (225 mg, 1 mmol). The resulting mixture was stirred at 130 C during 24 h. The mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to give the pure products 8 in quantitative yields. Physical and spectroscopic data for compounds 7 and 8, as well as literature for known compounds, follow.

References: [1]Dalton Transactions,2017,vol. 46,p. 1539 - 1545.
[2]Applied Organometallic Chemistry,2018,vol. 32.
[3]Beilstein Journal of Organic Chemistry,2011,vol. 7,p. 565 - 569.
[4]Angewandte Chemie - International Edition,2013,vol. 52,p. 11835 - 11839.
Angew. Chem.,2013,vol. 125,p. 12051 - 12055,5.
[5]New Journal of Chemistry,2018,vol. 42,p. 16886 - 16890.
[6]Tetrahedron Letters,2018,p. 675 - 680.
[7]Liebigs Annales,1995,p. 775 - 780.
[8]Applied Organometallic Chemistry,2014,vol. 28,p. 298 - 303.
[9]Journal of Organic Chemistry,2010,vol. 75,p. 3412 - 3419.
[10]Journal of Organic Chemistry,2019,vol. 84,p. 8121 - 8130.
[11]Tetrahedron,2012,vol. 68,p. 1393 - 1400.
[12]Synthesis,2009,p. 829 - 835.
[13]ChemMedChem,2016,vol. 11,p. 2347 - 2360.
[14]Tetrahedron Letters,2004,vol. 45,p. 35 - 38.
[15]Organic Letters,2008,vol. 10,p. 4887 - 4889.
[16]Journal of Organic Chemistry,2010,vol. 75,p. 7502 - 7504.
[17]Organic Letters,2011,vol. 13,p. 1098 - 1101.
[18]Journal of Organic Chemistry,2012,vol. 77,p. 617 - 625.
[19]Tetrahedron Letters,2013,vol. 54,p. 2357 - 2361.
[20]Chemistry - A European Journal,2013,vol. 19,p. 8294 - 8299.
[21]Journal of Organic Chemistry,2013,vol. 78,p. 10319 - 10328.
[22]Organic Letters,2013,vol. 15,p. 5940 - 5943.
[23]Chemical Communications,2014,vol. 50,p. 3024 - 3026.
[24]Chemistry - A European Journal,2015,vol. 21,p. 3193 - 3197.
[25]Organic Letters,2015,vol. 17,p. 5662 - 5665.
[26]Journal of Organic Chemistry,2016,vol. 81,p. 3994 - 4001.
[27]Chemical Communications,2017,vol. 53,p. 196 - 199.
[28]Advanced Synthesis and Catalysis,2017,vol. 359,p. 1373 - 1378.
[29]Advanced Synthesis and Catalysis,2017,vol. 359,p. 1844 - 1848.
[30]Chemical Communications,2017,vol. 53,p. 8533 - 8536.
[31]Chemical Communications,2017,vol. 53,p. 8980 - 8983.
[32]Organic Letters,2017,vol. 19,p. 3982 - 3985.
[33]Organic Letters,2017,vol. 19,p. 6128 - 6131.
[34]Journal of Organic Chemistry,2017,vol. 82,p. 12386 - 12394.
[35]Journal of Organic Chemistry,2018,vol. 83,p. 10453 - 10464.
[36]Organic Letters,2018,vol. 20,p. 6765 - 6768.
[37]Advanced Synthesis and Catalysis,2019,vol. 361,p. 490 - 495.
[38]Angewandte Chemie - International Edition,2019,vol. 58,p. 8882 - 8886.
Angew. Chem.,2019,vol. 131,p. 8974 - 8978,5.
[39]Advanced Synthesis and Catalysis,2019,vol. 361,p. 5558 - 5564.
[40]Chemical Communications,2020,vol. 56,p. 474 - 477.
[41]Organic Letters,2020,vol. 22,p. 814 - 817.
[42]Journal of Organic Chemistry,2020,vol. 85,p. 3224 - 3233.

4
[ 577-91-3 ]
[ 129397-83-7 ]
[ 108-24-7 ]
[ 768-60-5 ]
4-[2-(1-(S)-benzyl-2-hydroxy-ethylcarbamoyl)-2-phenyl-ethyl]-2,6-bis-(4-methoxyphenyl)ethynyl-phenyl acetate [ No CAS ]