103755-58-4|(1-Phenyl-1H-1,2,3-triazol-4-yl)methanol| Ambeed

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Quality Control of [ 103755-58-4 ] Purity: 95% SDS Specification

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Product Details of [ 103755-58-4 ]

CAS No. :	103755-58-4
Formula :	C₉H₉N₃O
M.W :	175.19
SMILES Code :	OCC1=CN(C2=CC=CC=C2)N=N1
MDL No. :	MFCD00100214
Boiling Point :	No data available
InChI Key :	UBFOXHGJGFQOFV-UHFFFAOYSA-N
Pubchem ID :	708707

Safety of [ 103755-58-4 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 103755-58-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	11
Fraction Csp3	0.11
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	47.49
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	50.94 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.88
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	0.5
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.61
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.	0.81
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	0.84
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.93

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.74
Solubility	3.22 mg/ml ; 0.0184 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.14
Solubility	12.7 mg/ml ; 0.0725 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very 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	-2.38
Solubility	0.729 mg/ml ; 0.00416 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.	-7.01 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	1.0
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	0.0 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)	1.91

Application In Synthesis of [ 103755-58-4 ]

* 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.

Downstream synthetic route of [ 103755-58-4 ]

[ 103755-58-4 ] Synthesis Path-Downstream 1~35

1
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References: [1]Chemische Berichte,1941,vol. 74,p. 1680,1685.

2
5-hydroxymethyl-3-phenyl-3<i>H</i>-[1,2,3]triazole-4-carboxylic acid [ No CAS ]
[ 103755-58-4 ]

References: [1]Atti della Accademia Nazionale dei Lincei, Classe di Scienze Fisiche, Matematiche e Naturali, Rendiconti,1953,vol. <8>14,p. 95,96,275.

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Yield	Reaction Conditions	Operation in experiment
35%	at 90℃; for 2h;	EXAMPLE 9: Preparation of jV-((lH-benzo[d]imidazol-2-yl)methyl)-jV-(4-aminobutyl)- 5,6,7,8-tetrahydroquinolin-8-amine tetrahydrochloride (Y).Step a: Preparation of (l-phenyl-lH-l,2,3-triazol-4-yl)methanol (7). Phenyl azide (2.02 g, 17.0 mmol) was dissolved in neat propargyl alcohol (3 mL) and the mixture was heated to 9O0C for 2h. The reaction mixture was cooled to room temperature and the reaction mixture was diluted into diethyl ether and left overnight during which time 7 precipitated as a crystalline solid to afford 1.03 g (35%) of the desired product 7 while the mother liquor contained primarily the regioisomer 9: 1H NMR (400 MHz, CDCl3) delta 7.97, (s, IH), 7.70, (d, J= 8.40 Hz, 2H), 7.50, (m, 2H), 7.41 (m, IH), 4.88, (d, J= 6.00 Hz, 2H), 2.70, (bs, IH).

References: [1]Journal of Heterocyclic Chemistry,1990,vol. 27,p. 2021 - 2027.
[2]Patent: WO2009/121063,2009,A2 .Location in patent: Page/Page column 143.
[3]Helvetica Chimica Acta,1952,vol. 35,p. 167,175.
[4]Inorganic Chemistry,2013,vol. 52,p. 5838 - 5850.
[5]RSC Advances,2014,vol. 4,p. 46040 - 46048.

4
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Yield	Reaction Conditions	Operation in experiment
99%	With manganese(IV) oxide; In dichloromethane; at 20℃;	Step 2 Synthesis of 1-Phenyl-1H-[1,2,3]triazole-4-carbaldehyde MnO2 (1.23 g, 14.14 mmol) was added to a stirred solution of <strong>[103755-58-4](1-phenyl-1H-[1,2,3]triazol-4-yl)-methanol</strong> (245 mg, 1.4 mmol) in DCM (15 mL) and the resulting mixture was stirred at room temperature overnight. The mixture was filtered over a celite bed, and the filtrate was concentrated under reduced pressure to afford 271 mg (99%) of 1-phenyl-1H-[1,2,3]triazole-4-carbaldehyde.
78%	With pyridinium chlorochromate; In dichloromethane; at 20℃; for 1.5h;	A solution of 8.75 g (0.05 mol) of <strong>[103755-58-4](1-phenyl-1H-1,2,3-triazol-4-yl)methanol</strong> (11) in 100 mL of methylene chloride was added in one portion with thorough stirring to a suspension of 16.15 g (0.075 mol) of freshly prepared pyridinium chlorochromate (PCC) in 200 mL of anhydrous methylene chloride. The mixture was stirred for 90 min at room temperature, 200 mL of anhydrous diethyl ether was added, the solution was separated from the black precipitate by decanting, and the precipitate was washed with diethyl ether (2 × 50 mL). The combined extracts were filtered through 20 g of silica gel, the solvent was distilled off under reduced pressure, and the residue was recrys-tallized from carbon tetrachloride. Yield 6.75 g (78%). mp 96-97C. 1 H NMR spectrum (500 MHz, DMSO-d 6 ), delta, ppm: 7.57 t (1H, p-H, J = 7.2 Hz), 7.65 t (2H, m-H, J = 7.2 Hz), 8.03 d (2H, o-H, J = 7.2 Hz), 9.59 s (1H, 5-H), 10.24 s (1H, CHO). Mass spectrum: m/z 174 [M + H] + . Found, %: C 62.45; H 4.14; N 24.21. C 9 H 7 N 3 O. Calculated, %: C 62.42; H 4.07; N 24.27.
	With manganese(IV) oxide; In dichloromethane; at 20℃; for 72h;	Step b: Preparation of l-phenyl-lH-l,2,3-triazole-4-carbaldehyde (9). To a solution of (1- phenyl-lH-l,2,3-triazol-4-yl)methanol, 7, (1.03 g, 5.87 mmol) in CH2Cl2 (50 mL) was added MnO2 (2.05g, 23.5 mmol). The reaction mixture was stirred for 3 days at room temperature. The reaction mixture was then filtered through Celite and the resulting filtrate was concentrated in vacuo. The crude material was purified by silica gel chromatography (0-5% methanol/dichloromethane) yielding 0.83g (82%) of 9: 1H NMR (400 MHz, CDCl3) delta 10.22 (s, IH), 8.51 (s, IH), 7.53, (d, J= 9.6 Hz, 2H), 7.58-7.49, (m, 3H).

	With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione; In dimethyl sulfoxide; at 20℃; for 4h;	General procedure: Into a round-bottom flask equipped with a magnetic stirring bar already containing a solution of 10mmolof 1,2,3-triazoles type 12 in 27.5mL of DMSO was added 11mmolof IBX. This mixture was stirred at room temperature for 4h. Next, distilled water (20mL) was added, and stirring was continued for 15minat room temperature. Subsequently, the mixture was filtered, extracted with ethyl acetate and dried over with MgSO4. The product was purified via silica-gel column chromatography using gradient mixture of hexane-ethyl acetate to afford the pure derivatives 11 and 15a-b.
	With Jones reagent; In acetone; at 0℃; for 0.583333h;	General procedure: The 1-substituted-1,2,3-triazol-4-yl-methanol 1 (4mmol) was taken in dry acetone (10mL), cooled to 0C and the Jones reagent (CrO3+H2SO4+Acetone) (4mmol) was added slowly over a period of 15min. The reaction mixture was stirred for 20min at 0C. After completion of reaction, filtered through the short pad of celite and the filtrate was collected and concentrated under vacuum. The residue was purified by passing through a column packed with silica gel using petroleum ether/EtOAc (8:2) as eluents.
	With chromium(VI) oxide; acetic acid; In water; at 100℃; for 1h;	General procedure: Propynyl alcohol (2.2 g, 0.04 mol), cuprous iodide (0.4 g, 2.0 mmol) andN,N-diisopropylethylamine (5.2 g, 0.04 mol) were sequentially added into a stirred solution of intermediate9a-9l(0.04 mol) in absolute ethanol (10 v/w) at 25oCfor 24 h. The insoluble matter removed by filtration, and the filtrate is concentrated. Next the filtrate was poured into water, extracted with dichloromethane, and the combined organic layer was washed with water, dried over anhydrous Na2SO4and evaporated to dryness to give compounds10a-10l. Intermediate10a-10l(0.10 mol) without purification was dissolved in glacial acetic acid (10 v/w), chromium trioxide (2 mL, 0.01 mol) was added dropwise and the mixture was stirred 1 h at 100oC.After cooling to r.t., solvent was removed by concentrate under reduced pressure. The residue was added to water under stirring, the precipitates were collected by filtration and washed with water to obtain compounds11a-11l.

References: [1]Patent: US2010/160323,2010,A1 .Location in patent: Page/Page column 30.
[2]Archiv der Pharmazie,2015,vol. 348,p. 796 - 807.
[3]Journal of Heterocyclic Chemistry,1990,vol. 27,p. 2021 - 2027.
[4]Russian Journal of Organic Chemistry,2019,vol. 55,p. 1310 - 1321.
    Zh. Org. Khim.,2019,vol. 55,p. 1393 - 1405,13.
[5]Chemical Communications,2016,vol. 52,p. 815 - 818.
[6]MedChemComm,2015,vol. 6,p. 1494 - 1500.
[7]Patent: WO2009/121063,2009,A2 .Location in patent: Page/Page column 142; 143.
[8]Journal of Medicinal Chemistry,2011,vol. 54,p. 5988 - 5999.
[9]European Journal of Medicinal Chemistry,2014,vol. 74,p. 461 - 476.
[10]European Journal of Medicinal Chemistry,2014,vol. 80,p. 184 - 191.
[11]Organic and Biomolecular Chemistry,2015,vol. 13,p. 477 - 486.
[12]Russian Journal of General Chemistry,2016,vol. 86,p. 1419 - 1423.
    Zh. Obshch. Khim.,2016,vol. 86,p. 1419 - 1423,5.
[13]Journal of Molecular Catalysis A: Chemical,2017,vol. 426,p. 474 - 489.
[14]Russian Journal of General Chemistry,2016,vol. 86,p. 2845 - 2848.
    Zh. Obshch. Khim.,2016.
[15]European Journal of Medicinal Chemistry,2017,vol. 139,p. 698 - 717.
[16]Journal of the Chinese Chemical Society,2017,vol. 64,p. 1197 - 1202.
[17]MedChemComm,2018,vol. 9,p. 1114 - 1130.
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[26]Molecules,2020,vol. 25.

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[ 103755-58-4 ]

References: [1]Advanced Synthesis and Catalysis,2005,vol. 347,p. 811 - 815.

7
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[ 103755-58-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With copper(ll) sulfate pentahydrate; hydrazine hydrate; In water; acetonitrile; at 20℃; for 0.666667h;	General procedure: Azide (1 equiv.), alkyne (1.5 equiv.) and CuSO4?5H2O (0.1 equiv.) were dissolved in a mixture of water and acetonitrile (12 mL; 2:1, v/v) at room temperature. Hydrazine hydrate (1 equiv.) was added dropwise to the above solution under vigorous stirring. The reaction mass turned to pale yellow or light green in color. After a few minutes (see Table 3 for exact reaction time) TLC showed completion of the reaction. Usually the product got precipitated as colorless solid (unless mentioned). The reaction mixture was diluted with excess of water and filtered. The precipitated product was washed with water and dried. The solid thus obtained could be crystallized or passed through a small pad of celite after dissolving in an appropriate solvent to get analytically pure product.
93%	With copper nanoparticles supported on nanocellulose; In glycerol; at 20℃; for 3h;Catalytic behavior;	General procedure: To a mixture of azide 1 (1 mmol, 1 equiv.) and acetylene 2(1.1 mmol, 1.1 equiv.) in glycerol (2 mL) was added the catalyst(20 mg, 3.31 wt%, 1.05 mol%). The mixture was stirredat room temperature for an appropriate time. The progressof the reaction was monitored by TLC. After completion ofthe reaction it was extracted with EtOAc (2x20 mL), washedwith brine, dried over anhydrous sodium sulfate. The solventwas removed under reduced pressure to give the crudeproduct and purified through silica gel column chromatography(10-20% EtOAc/hexanes) to get the desired product.The products were characterized by 1H and 13C NMR spectroscopy.
90%	With Cu(II)-tetrakis(aminophenyl)porphyrin immobilized onto graphene oxide; In ethanol; water; at 60℃; for 0.25h;Sonication;	General procedure: To a solution of azide (1.10mol) and terminal alkyne (1.0mol) in a mixture of H 2 O/EtOH (1:1; 2mL), GO-CuPPh catalyst (5.0mg) was added and the mixture was irradiated at 60C for 5-30min. Reaction progress was monitored by thin-layer chromatography (TLC) and upon reaction completion, the reaction mixture was diluted with EtOAc and the catalyst was centrifuged, and separated from the reaction mixture. The organic layer was dried over anhydrous Na 2 SO 4 , followed by evaporation under reduced pressure to remove the solvent. The residue was purified by recrystallization from ethanol to afford corresponding 1,4-disubsti-tuted 1,2,3-triazoles. The product was identified by melting point, 1 H-NMR, and 13 C-NMR spectroscopy.

89%	With CuNP(at)hydrotalcite; In ethylene glycol; at 20℃; for 1.75h;	General procedure: To a mixture of azide 1 (1 mmol, 1 equiv.) and acetylene 2 (1.1 mmol, 1.1 equiv.) in ethylene glycol (3 mL) was added the catalyst (15 mg, 1.87 wt%). The mixture was stirred at room temperature for different time. The progress of the reaction was monitored by TLC. The product was extracted with ethyl acetate and dried over anhydrous Na2SO4. The product was purified by column chromatography over silica gel using n-hexane/ethyl acetate to get the desired product. The products were characterized by 1H & 13C NMR spectroscopy.
88%	With silver trifluoromethanesulfonate; copper; In acetonitrile; at 20℃; for 3h;Inert atmosphere;	General procedure: In a typical experiment, alkyne (1mmol) and azide (1 mmol) were dissolved in anhydrous acetonitrile (5 mL) under nitrogen atmosphere. AgOTf (15 mol%) and copper powder (50 mol%) were added to the reaction mixture and stirring continued at r.t. for 3 hr. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The product was extracted with DCM. The organic layer was washed with water, dried over sodium sulphate, concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluent.
87%	With copper(l) iodide; triethylamine; In water; tert-butyl alcohol; at 20℃;	General procedure: The corresponding azide (1 mmol) and terminal alkyne (1 mmol or 2 mmol in the reactions with diazides) were dissolved in 5 mL of THF or tert-butyl alcohol. Water was added to the solution until an emulsion began to form, and a cata-lytic amount of copper(I) iodide (1-10 mol %, de-pending on the azide reactivity) was added. In the reac-tions with weakly reactive azides, 0.4 mL (2.8 mmol) of triethylamine as a co-catalyst was added. The mix-ture was stirred at room temperature until the initial azide disappeared (according to the TLC or IR data). The mixture was treated with 15 mL of water and 15 mL of concentrated aqueous ammonia and extracted with methylene chloride (3 × 10 mL). The extract was dried over Na 2 SO 4 , and the solvent was evaporated under reduced pressure. If necessary, the product was purified by recrystallization or column chromatog-raphy. Compounds 3d-3g were obtained as the only products: 3d, yield 95%; 3e, yield 89%; 3f, yield 91%; 3g, yield 67%.
70%	With copper(l) iodide; N,N,N',N'',N'''-pentamethyldiethylenetriamine; In tetrahydrofuran; at 20℃;Sonication; Inert atmosphere;	General procedure: In a 50 mL two-neck flask under a nitrogen atmosphere, a propargyl alcohol solution (0.28 g, 0.3 mL, 5 mmol) was added with a dissolved organic azide (1.2 equiv, 6 mmol) in THF (8 mL) and the copper catalyst (1 equiv, 5 mmol). The reaction was then put in a ultrasound bath for homogenization, followed by the addition of PMDETA (1.03 g, 1.25 mL, 6 mmol) drop by drop until the starting material was consumed, followed by TLC. The resulting aqueous phase was washed with ethyl acetate, the organic phase was dried with MgSO4, filtered and the solvent was evaporated under vacuum. The crude product was purified by column chromatography using as the eluent a mixture of hexane/ethyl acetate (2/8) (see refPreviewPlaceHolderSupplementary data for reaction time).
63%		To a mixture of DMSO: H2O (9:1) (40mL) solution phenyl azide (4.09g, 34.33mmol, 1.1equiv.) and copper iodide (1.19g, 6.24mmol, 0.2equiv.) were added and stirred for 10min. To this propargyl alcohol (1.75g, 31.21mmol, 1equiv.) was added and stirred additionally for 24h. Upon adding the reaction mixture to ice cold water pale green solid was precipitated. Solvent was filtered off and precipitate was washed with water (5×100mL), acetone (10mL) and dried under vacuo to give 1 as a pale green solid in (3.4g) 63% yield. Mp: 102C (decomposed); IR (KBr): 3381 (nuOH), 2924, 1594, 1011cm-1; 1H NMR (400MHz, CDCl3) delta: 8.01 (s, 1H), 7.69-7.66 (m, 2H), 7.49-7.39 (m, 3H), 4.87 (-CH2-OH) (d, 2H, J=4.4Hz), 3.91 (broad, s, 1H) (-OH); 13C NMR (100MHz, CDCl3) delta: 148.6, 137.0, 129.7, 128.9, 120.5, 120.3, 56.3 (-CH2-OH).
	With copper(ll) sulfate pentahydrate; sodium L-ascorbate; In water; tert-butyl alcohol; at 20℃;	General procedure: To a round-bottom flask equipped with a magnetic stirring bar were added an aromatic azide (0.83mmol), propargyl alcohol (0.75mmol), tert-butanol (0.7mL), copper sulfate pentahydrate (0.04mmol), sodium ascorbate (0.11mmol) and water (0.7mL). The reaction mixture was stirred for 48-72hat room temperature. Next, the mixture was extracted with ethyl acetate and the combined organic extracts were washed with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The product was purified via silica-gel column chromatography, using gradient mixture of hexane-ethyl acetate, to afford the pure derivatives 12a-d.
	With copper diacetate; In water; tert-butyl alcohol; at 20℃; for 18h;Inert atmosphere;	General procedure: In an argon atmosphere, alkyl/aryl azide (5.4mmol), propargyl alcohol (8mmol) were taken in t-BuOH (5mL) followed by addition of an aqueous Cu(OAc)2 solution (5mol%, 1mL). The reaction was stirred for 18h at room temperature and monitored by TLC. The resulting mixture was diluted with dichloromethane; the organic layer was separated and washed with water. Dried over sodium sulfate and purified by passing through a column packed with silica gel using n-hexane: ethyl acetate (6:4) as solvents.
	In water; at 25℃; for 5h;	General procedure: Phenylboronic acid 1a (1.5 mmol), NaN3 (1.5 mmol), and catalyst(0.03 mmol) were added to a solution of H2O (5 ml). The mixturewas stirred at ambient temperature for 7 h a correspondingtime. The progress was monitored by TLC. After this, phenylacetylene3a (1.0 mmol) was added, and the mixture was stirredat ambient temperature until complete. The reaction mixturewas adjusted to pH 12 with 1 M NaOH and then filtered. The filtercake was washed with EtOAc and THF twice each. The filtrate wasdiluted with water and extracted with EtOAc several times. Theorganic layer was separated, washed with saturated brine, anddried over anhydrous sodium sulfate and the solvent was removedunder vacuum. The crude residue was purified by flash chromatographyon silica gel to give the final product, 4a.
	With copper(l) iodide; sodium L-ascorbate; In acetonitrile; at 80℃; for 5h;Sealed tube;	General procedure: 1-Azido-4-methylbenzenes 1 (0.3 mmol), propargyl alcohol 2 (0.36 mmol), CuI (0.03 mmol),NaAsc (0.06 mmol), and 2 mL solvent were added to a 15 mL pressure tube. The tube was thensealed, and the mixture was stirred at 80 C for 5 hours. After the reaction completed, the abovesystem was added with KMnO4 (0.75 mmol) and Na2CO3 (0.45 mmol), and stirred at 80 C for 8h until the reaction completed. Then, Ag2O (0.03 mmol) and K2S2O7 (0.6 mmol) were added tothe tube and the mixture was conducted at 100 C for 24 h until the transformation finished byTLC analysis. H2O (25 mL) was added to the mixture and the system was extracted with EtOAc (3× 20 mL). The combined organic layer was washed with brine (3 × 5 mL), dried with Na2SO4, andconcentrated under reduced pressure to afford the crude product. Purification by columnchromatography on silica gel with EtOAc-PE (1:3) afforded the desired product 3.
	With copper(l) iodide; N-ethyl-N,N-diisopropylamine; In ethanol; at 25℃; for 4h;	General procedure: Propynyl alcohol (2.2 g, 0.04 mol), cuprous iodide (0.4 g, 2.0 mmol) andN,N-diisopropylethylamine (5.2 g, 0.04 mol) were sequentially added into a stirred solution of intermediate9a-9l(0.04 mol) in absolute ethanol (10 v/w) at 25oCfor 24 h. The insoluble matter removed by filtration, and the filtrate is concentrated. Next the filtrate was poured into water, extracted with dichloromethane, and the combined organic layer was washed with water, dried over anhydrous Na2SO4and evaporated to dryness to give compounds10a-10l. Intermediate10a-10l(0.10 mol) without purification was dissolved in glacial acetic acid (10 v/w), chromium trioxide (2 mL, 0.01 mol) was added dropwise and the mixture was stirred 1 h at 100oC.After cooling to r.t., solvent was removed by concentrate under reduced pressure. The residue was added to water under stirring, the precipitates were collected by filtration and washed with water to obtain compounds11a-11l.

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