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Chemical Structure| 288-88-0
Chemical Structure| 288-88-0
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Product Details of [ 288-88-0 ]

CAS No. :288-88-0 MDL No. :MFCD00005228
Formula : C2H3N3 Boiling Point : -
Linear Structure Formula :- InChI Key :NSPMIYGKQJPBQR-UHFFFAOYSA-N
M.W :69.07 Pubchem ID :9257
Synonyms :

Calculated chemistry of [ 288-88-0 ]

Physicochemical Properties

Num. heavy atoms : 5
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 16.38
TPSA : 41.57 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.73 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : -0.01
Log Po/w (WLOGP) : -0.2
Log Po/w (MLOGP) : -1.1
Log Po/w (SILICOS-IT) : 1.21
Consensus Log Po/w : -0.02

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.0
Solubility : 6.88 mg/ml ; 0.0996 mol/l
Class : Very soluble
Log S (Ali) : -0.41
Solubility : 26.6 mg/ml ; 0.386 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.71
Solubility : 13.3 mg/ml ; 0.193 mol/l
Class : Soluble

Medicinal Chemistry

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

Safety of [ 288-88-0 ]

Signal Word:Danger Class:N/A
Precautionary Statements:P201-P202-P264-P270-P273-P280-P301+P312+P330-P305+P351+P338-P312-P337+P313-P405-P501 UN#:N/A
Hazard Statements:H302-H313-H319-H360-H402 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 288-88-0 ]

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

  • Upstream synthesis route of [ 288-88-0 ]
  • Downstream synthetic route of [ 288-88-0 ]

[ 288-88-0 ] Synthesis Path-Upstream   1~46

  • 1
  • [ 288-88-0 ]
  • [ 74-88-4 ]
  • [ 6086-21-1 ]
  • [ 10570-40-8 ]
Reference: [1] Bulletin des Societes Chimiques Belges, 1988, vol. 97, # 8-9, p. 573 - 598
[2] Tetrahedron Letters, 2000, vol. 41, # 8, p. 1297 - 1301
[3] Acta Chemica Scandinavica, 1990, vol. 44, # 10, p. 1050 - 1057
  • 2
  • [ 288-88-0 ]
  • [ 616-38-6 ]
  • [ 10570-40-8 ]
YieldReaction ConditionsOperation in experiment
4.74 g at 120℃; for 16 h; Inert atmosphere Step 1. 250 mmol of dimethyl carbonate was added to a mixture of 50 mmol of 1,2,4-triazole and 12.5 mmol of sodium carbonate, and the resulting suspension was stirred at 120 ° C under a nitrogen atmosphere and refluxed for 16 h. Volatilization in the residual liquid in the vacuumWashing the residue with chloroform, filtering solid impurities, and spinning the filtrate.4.74 g of 4-methyl-1,2,4-triazole was obtained as a colorless liquid.
Reference: [1] Patent: CN108250227, 2018, A, . Location in patent: Paragraph 0025; 0028
  • 3
  • [ 288-88-0 ]
  • [ 74-88-4 ]
  • [ 10570-40-8 ]
Reference: [1] Organic Letters, 2010, vol. 12, # 13, p. 3002 - 3005
  • 4
  • [ 288-88-0 ]
  • [ 77-78-1 ]
  • [ 6086-21-1 ]
  • [ 10570-40-8 ]
Reference: [1] Acta Chemica Scandinavica, 1990, vol. 44, # 10, p. 1050 - 1057
  • 5
  • [ 21034-55-9 ]
  • [ 74-88-4 ]
  • [ 288-88-0 ]
  • [ 6086-21-1 ]
  • [ 10570-40-8 ]
Reference: [1] Russian Journal of Organic Chemistry, 1995, vol. 31, # 8, p. 1118 - 1121[2] Zhurnal Organicheskoi Khimii, 1995, vol. 31, # 8, p. 1227 - 1230
  • 6
  • [ 288-88-0 ]
  • [ 616-38-6 ]
  • [ 6086-21-1 ]
  • [ 10570-40-8 ]
Reference: [1] Organometallics, 2012, vol. 31, # 12, p. 4565 - 4573
  • 7
  • [ 288-88-0 ]
  • [ 75-44-5 ]
  • [ 41864-22-6 ]
Reference: [1] Justus Liebigs Annalen der Chemie, 1957, vol. 609, p. 75,82
  • 8
  • [ 288-88-0 ]
  • [ 75-03-6 ]
  • [ 16778-70-4 ]
YieldReaction ConditionsOperation in experiment
70% With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 20℃; Cooling with ice Example 3. Synthesis of 1 -Ethyl- 1 H- 1.2,4-triazole (26a).Scheme 6. Preparation of Intermediate 26a.\\16a 18a 26a[111] Step 1. l-Ethyl-lH-l,2,4-triazole d8a): To an ice-cold solution of 1,2,4- triazole (5 g, 72.4 mmol) in anhydrous TΗF (50 mL) was added ethyl iodide (7 mL, 86.9 mmol). DBU (10.8 mL, 72.4 mmol) was added dropwise to the cloudy system over 10-20 min. The reaction was allowed to slowly warm to room temperature and was stirred overnight. The mixture was filtered through a Celite pad and the filtrate was concentrated under reduced pressure to give 10 g of crude material as a yellow liquid. The crude material was Kugelrohr-distilled (at approximately 300 mtorr, 35- 40 0C) to provide 4.9 g (70percent) of 18a as clear liquid.
Reference: [1] Patent: WO2011/5520, 2011, A1, . Location in patent: Page/Page column 31-32
[2] European Journal of Organic Chemistry, 2018, vol. 2018, # 31, p. 4331 - 4337
[3] Journal of Medicinal Chemistry, 2005, vol. 48, # 23, p. 7089 - 7092
[4] Patent: WO2010/67125, 2010, A1, . Location in patent: Page/Page column 85
  • 9
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  • [ 74-96-4 ]
  • [ 16778-70-4 ]
YieldReaction ConditionsOperation in experiment
4.47 g
Stage #1: With sodium ethanolate In ethanol at 30℃; for 0.666667 h;
Stage #2: at 75℃; for 14 h;
adding 60 mmol of sodium ethoxide into 50 mmol of 1, 2, 4-triazole (shown in the formula II)) and 50 mL of ethanol solution, stirring for 40 minutes at the temperature of 30 DEG c, and dropwise adding 60 mmol of bromoethane, carrying out condensation reflux for 14 hours at the temperature of 75 DEG c, removing volatile matters in the reaction raffinate, washing the dichloromethane, and filtering the solid impurities, and carrying out rotary evaporation to remove the washing solvent to obtain colorless liquid 1-ethyl -1,2,4-triazole 4.47 g
Reference: [1] Gazzetta Chimica Italiana, 1905, vol. 35 I, p. 378
[2] Journal of Organic Chemistry, 2013, vol. 78, # 8, p. 4196 - 4201
[3] Journal of Physical Chemistry B, 2014, vol. 118, # 33, p. 9944 - 9951
[4] Patent: CN108484654, 2018, A, . Location in patent: Paragraph 0027; 0030
  • 10
  • [ 288-88-0 ]
  • [ 74-96-4 ]
  • [ 43183-55-7 ]
  • [ 16778-70-4 ]
Reference: [1] Tetrahedron Letters, 2000, vol. 41, # 8, p. 1297 - 1301
  • 11
  • [ 288-88-0 ]
  • [ 75-03-6 ]
  • [ 43183-55-7 ]
  • [ 16778-70-4 ]
Reference: [1] Tetrahedron Letters, 2000, vol. 41, # 8, p. 1297 - 1301
  • 12
  • [ 288-88-0 ]
  • [ 75-03-6 ]
  • [ 16778-70-4 ]
Reference: [1] Patent: US6630471, 2003, B1,
  • 13
  • [ 591-50-4 ]
  • [ 288-88-0 ]
  • [ 16227-12-6 ]
YieldReaction ConditionsOperation in experiment
99% With copper(II) acetate monohydrate; caesium carbonate In N,N-dimethyl-formamide at 110℃; for 24 h; Inert atmosphere General procedure: To a solution of Cu(OAc)2*H2O (0.01 mmol) in DMF (2 mL) were added aryl iodide (1.2 mmol), nitrogen-containing heterocycle (1.0 mmol), and Cs2CO3 (2 mmol) under nitrogen atmosphere. The mixture was stirred at 110 °C for 24 h. After cooling to ambient temperature, the mixture was partitioned between water and ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel.
Reference: [1] Tetrahedron, 2011, vol. 67, # 29, p. 5282 - 5288
  • 14
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  • [ 13423-60-4 ]
YieldReaction ConditionsOperation in experiment
96% With potassium phosphate; copper(l) iodide; N,N`-dimethylethylenediamine In N,N-dimethyl-formamide at 110℃; for 72 h; Inert atmosphere General procedure: A mixture of CuI (0.10 g, 0.50 mmol), the required azole(10 mmol), K3PO4 (4.4 g, 20 mmol), the required halide (12 mmol)and N,N0-dimethylethylenediamine (0.11 mL, 1.0 mmol) in DMF(5 mL) was degased and heated under argon at 110 C for 72 h.After filtration over celite (washing using AcOEt) and removal ofthe solvents, the crude product is purified by chromatography oversilica gel (the eluent is given in the product description). 4.3.1
1-Phenyl-1H-1,2,4-triazole (2a)
Compound 2a was prepared from 1,2,4-triazole (0.69 g) and iodobenzene (1.4 mL) using the general procedure 1, and was isolated (eluent: heptane/AcOEt 7:3) in 96percent yield as a yellow powder: mp 48 °C (lit.
28
46 °C); 1H NMR (CDCl3, 300 MHz) 7.42 (m, 1H), 7.53 (m, 2H), 7.71 (m, 2H), 8.15 (s, 1H), 8.74 (s, 1H); 13C NMR (CDCl3, 75 MHz) 120.1 (2CH), 128.3 (CH), 129.9 (2CH), 137.1 (C), 140.9 (CH), 152.7 (CH).
91% With caesium carbonate In DMF (N,N-dimethyl-formamide) at 50 - 82℃; for 24 - 72 h; Example 1.17 [0636] Preparation of 1-phenyl-1H-1,2,41 triazole [0637] Operating protocol A (82 C., 48 hours) was followed using 117 mg of Chxn-Py-Al (0.4 mmoles), 336 ?l of iodobenzene (3 mmoles), 138 mg of 1,2,4-triazole (2 mmoles), 1.042 g of caesium carbonate (3.2 mmoles) and 1.2 ml of DMF. [0638] The degree of transformation and selectivity were 100percent and 98percent respectively. [0639] The residue obtained following treatment was purified by silica gel chromatography (eluent: hexane/dichloromethane, 100/0 to 50/50). [0640] 264 mg of a dark yellow solid was obtained in a yield of 91percent. [0641] Pale yellow needles were obtained after re-crystallisation from chloroform. [0642] The compound obtained had the following formula: [CHEMMOL-00056] [0643] The characteristics were as follows: [0644] MPt: 46 C. (CHCl3) (Lit: 46-47 C. given by Micetich, R G; Spevak, P; Hall, T W; Bains, B K; Heterocycles 1985, 23, 1645-1649); [0645] H NMR/CDCl3:? 8.52 (wide s, 1H, HI), 8.04 (wide s, 1H, H2), 7.53-7.65 (m, 2H, H4,8), 7.26-7.51 (m, 3H, H5,6,7); [0646] 13C NMR/CDCl3: ? 152.55 (C1), 140.88 (C2), 139.96 (C3), 129.73 (C5 and C7), 128.15 (C6), 119.99 (C4 and C8); [0647] GC/MS: Rt=14.02 min, M/Z=145, purity=100percent; [0648] Rf=0.21 (eluent: dichloromethane/ethyl acetate, 90/10). Example 1.18 [0649] Preparation of 1-phenyl-1H-[1,2,4]triazole [0650] Operating protocol A (82 C., 24 hours) was followed using 117 mg of Chxn-Py-Al (0.4 mmoles), 336 ?l of iodobenzene (3 mmoles), 138 mg of 1,2,4-triazole (2 mmoles), 1.042 g of caesium carbonate (3.2 mmoles) and 1.2 ml of DMF. [0651] The degree of transformation and selectivity were 79percent and 99percent respectively. [CHEMMOL-00057] Example 1.19 [0652] Preparation of 1-phenyl-1H-[1,2,4]triazole Example 1.18 was repeated, operating at 50 C. (72 hours). The degree of transformation and selectivity for 1-phenyl-1H-[1,2,4-triazole] were 75percent and 99percent respectively. [0653] [CHEMMOL-00058]
91%
Stage #1: at 100℃;
Stage #2: at 50 - 82℃; for 24 - 72 h;
Operating protocol A (82° C., 48 hours) was followed using 117 mg of Chxn-Py-Al (0.4 mmoles), 336 μl of iodobenzene (3 mmoles), 138 mg of 1,2,4-triazole (2 mmoles), 1.042 g of caesium carbonate (3.2 mmoles) and 1.2 ml of DMF. The degree of transformation and selectivity were 100percent and 98percent respectively. The residue obtained following treatment was purified by silica gel chromatography (eluent: hexane/dichloromethane, 100/0 to 50/50). 264 mg of a dark yellow solid was obtained in a yield of 91percent. Pale yellow needles were obtained after re-crystallisation from chloroform. The compound obtained had the following formula: The characteristics were as follows: MPt: 46° C. (CHCl3) (Lit: 46-47° C. given by Micetich, R G; Spevak, P; Hall, T W; Bains, B K; Heterocycles 1985, 23, 1645-1649); 1H NMR/CDCl3: δ8.52 (wide s, 1H, H1), 8.04 (wide s, 1H, H2), 7.53-7.65 (m, 2H, H4,8), 7.26-7.51 (m, 3H, H5,6,7); 13C NMR/CDCl3: δ 152.55 (C1), 140.88 (C2), 139.96 (C3), 129.73 (C5 and C7), 128.15 (C6), 119.99 (C4 and C8); GC/MS: Rt=14.02 min, M/Z=145, purity=100percent; Rf=0.21 (eluent: dichloromethane/ethyl acetate, 90/10). Example 1.18; Preparation of 1-phenyl-1H-[1,2,4]triazole; Operating protocol A (82° C., 24 hours) was followed using 117 mg of Chxn-Py-Al (0.4 mmoles), 336 μl of iodobenzene (3 mmoles), 138 mg of 1,2,4-triazole (2 mmoles), 1.042 g of caesium carbonate (3.2 mmoles) and 1.2 ml of DMF. The degree of transformation and selectivity were 79percent and 99percent respectively. ; Example 1.19; Preparation of 1-phenyl-1H-[1,2,4]triazole; Example 1.18 was repeated, operating at 50° C. (72 hours). The degree of transformation and selectivity for 1-phenyl-1H-[1,2,4-triazole] were 75percent and 99percent respectively.
83% With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 30 h; sealed tube Preparation of 1-phenyl-1H-[1,2,4]triazole [0220] Following General Procedure A (90 0C, 30 hours), 1/-/-[1 ,2,4]triazole (104 mg, 1.5 mmol) is coupled with iodo-benzene (112 μL, 1.0 mmol). The crude brown oil is purified by flash chromatography on silica gel (eluent: dichloromethane/hexanes = 50/50) to provide 120 mg (83 percent isolated yield) of the desired product as a light yellow solid. <n="50"/>007/001836_ 49 -IdentificationMp: 460C.1H NMR (400 MHz, CDCI3): δ 8.49 (s, 1 H1 H8), 8.03 (s, 1H, H7), 7.58-7.61 (m, 2H, H2i6), 7.40-7.44 (t, 2H1 H3,5), 7.31-7.33 (t, 1 H, H4).13C NMR (100 MHz, CDCI3): δ 152.62 (C7), 140.91 (C8), 136.99 (C1), 129.77 (C3,5), 128.21 (C4), 120.04 (C2i6).IR (KBr) : v (cm'1) = 3105, 2924, 2852, 1600, 1514, 1416, 1359, 1278, 1223,1152, 1055, 981 , 876, 754, 681 , 671 , 503.GC/MS: rt = 15.28 min, M/Z = 145.HRMS: 146.0721 (M+H). Theoretical: 146.0718
71%
Stage #1: Inert atmosphere
Stage #2: at 120℃; for 64 h; Inert atmosphere
A flask was charged with K2CO3 (12.1689 g, 88 mmol), 1H-1,2,4-triazole (2.0042 g, 29 mmol), Cu2O(430 mg, 3 mmol) and 1,10-phenanthroline (1.0452 g, 5.8 mmol) and then evacuated and back-filled with N2. Then, anhydrous DMF (20 ml) and iodobenzene (8.9764 g, 4.92 ml, 44 mmol) were added and the resulting mixture was heated to 120 °C for 64 h and then diluted with CH2Cl2 (40 ml). The mixture was filtered through a pad of Celite and the residue washed with CH2Cl2 (20 ml). The resulting organic layer was washed with water (20 ml) and brine (20 ml), dried over MgSO4 and concentrated under reduced pressure. The crude mixture was purified by column chromatography (cyclohexane/ethyl acetate 8/0→2/0) to yield the product as a pale yellow solid (2.986 g, 71percent).
65%
Stage #1: With phenanthroline monohydrate; potassium carbonate In N,N-dimethyl-formamideInert atmosphere
Stage #2: at 100℃; for 48 h;
EXAMPLE 108
1-phenyltriazole 1 g (0.0145 mol) triazole 2, 0.21 g (0.00145 mol) copper(I)oxide, 0.29 g (0.00145 mol) phenantroline monohydrate and 6.01 g (0.044 mol) potassium carbonate are weighed into a Schlenk flask. After repeated evacuating and flushing with argon, 10 ml dry DMF is added. Evacuating and flushing with argon are repeated several times. Subsequently, 2.42 ml (4.43 g, 0.022 mol) of iodobenzene is added. The reaction mixture is stirred for 48 h at 100° C. under argon. After cooling 20 ml DCM is added and filtered. The solvent is removed in vacuum and the product is obtained after purification by column chromatography (KG 60, gradient petroleum ether/EtOAc 8:2 to EtOAc) as a yellowish-white solid.M 145.17 C8H7N3 Yield: 1.362 g (65percent)1H-NMR DM-94 (300 MHz/DMSO): (ppm)=7.41 (t, 1H, 6-H); 7.58 (t, 2H, 5/5'-H); 7.87 (d, 2H, 4-H); 8.25 (s, 1H, 1-H); 9.31 (s, 1H, 2-H)13C-NMR DM-94 (75.475 MHz/DMSO): (ppm)=119.37 (5/5'-C); 127.78 (6-C); 129.77 (4/4'-C); 136.74 (3-C); 142.27 (2-C); 152.39 (1-C)

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[2] Journal of Organic Chemistry, 2007, vol. 72, # 8, p. 2737 - 2743
[3] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 19, p. 6355 - 6363
[4] RSC Advances, 2014, vol. 4, # 83, p. 44105 - 44116
[5] Journal of Organic Chemistry, 2004, vol. 69, # 17, p. 5578 - 5587
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[7] Organic and Biomolecular Chemistry, 2016, vol. 14, # 46, p. 10861 - 10865
[8] Chemistry - A European Journal, 2004, vol. 10, # 22, p. 5607 - 5622
[9] Patent: US2003/236413, 2003, A1, . Location in patent: Page 24-25
[10] Patent: US2005/234239, 2005, A1, . Location in patent: Page/Page column 23; 28-29
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[12] ChemPlusChem, 2013, vol. 78, # 12, p. 1491 - 1502
[13] RSC Advances, 2014, vol. 4, # 14, p. 7321 - 7329
[14] Angewandte Chemie - International Edition, 2007, vol. 46, # 6, p. 934 - 936
[15] Patent: WO2008/4088, 2008, A2, . Location in patent: Page/Page column 48-49
[16] Synthesis, 2010, # 9, p. 1505 - 1511
[17] Chemistry - An Asian Journal, 2014, vol. 9, # 1, p. 166 - 178
[18] Advanced Synthesis and Catalysis, 2007, vol. 349, # 17-18, p. 2673 - 2676
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[20] Journal of Organic Chemistry, 2011, vol. 76, # 1, p. 305 - 308
[21] Patent: US2011/105761, 2011, A1, . Location in patent: Page/Page column 38-39
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[24] Tetrahedron Letters, 2007, vol. 48, # 37, p. 6573 - 6576
  • 15
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YieldReaction ConditionsOperation in experiment
93% With copper(I) 3-metthylsalicylate; potassium carbonate In dimethyl sulfoxide at 110℃; for 3 h; General procedure: A dry flask was charged with the nitrogen containing heterocycles (1.5 mmol), aryl halides (1 mmol), potassium carbonate(2 mmol) and CuMeSal (0.01 mmol) then anhydrous DMSO (5 ml) was added. The reaction mixture was stirred at 110°C, open to air, for 3h , cooled to room temperature, filtered, and the precipitate was washed with DMSO (2 ml) then stirred with ice water (30 ml) and extracted with ethyl acetate (3 × 50 ml),dried over sodium sulfate and the solvent was removed under reduced pressure.The residue was purified by chromatography or recrystallization as indicated with each compound.
6.32 g
Stage #1: With sodium methylate In methanol at 40℃; for 1 h;
Stage #2: at 90℃; for 16 h;
, adding 50 mmol of sodium methoxide into 50 mmol of 1, 2, 4-triazole (shown in the formula II)) and 50 mL of methanol solution, stirring for 60 minutes at 40 DEG c, and dropwise adding 60 mmol of bromobenzene, carrying out condensation reflux for 16 hours at the temperature of 90 DEG c, removing volatile matters in the reaction raffinate, washing the carbon tetrachloride, and filtering the solid impurities, and carrying out rotary evaporation to remove the washing solvent to obtain colorless liquid 1-phenyl -1,2,4-triazole 6.32g
Reference: [1] Journal of Organic Chemistry, 2008, vol. 73, # 22, p. 9121 - 9124
[2] Tetrahedron Letters, 2014, vol. 55, # 19, p. 3049 - 3051
[3] Green Chemistry, 2012, vol. 14, # 5, p. 1268 - 1271
[4] ChemCatChem, 2014, vol. 6, # 8, p. 2373 - 2383
[5] Journal of Organic Chemistry, 2007, vol. 72, # 22, p. 8535 - 8538
[6] Synthesis, 2008, # 11, p. 1707 - 1716
[7] Angewandte Chemie - International Edition, 2007, vol. 46, # 6, p. 934 - 936
[8] Dalton Transactions, 2015, vol. 44, # 18, p. 8433 - 8443
[9] Patent: CN108484654, 2018, A, . Location in patent: Paragraph 0057; 0060
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Reference: [1] Organic and Biomolecular Chemistry, 2018, vol. 16, # 46, p. 8984 - 8988
  • 17
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  • [ 28899-97-0 ]
  • [ 13423-60-4 ]
Reference: [1] Tetrahedron Letters, 1999, vol. 40, # 14, p. 2747 - 2748
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  • [ 2996-92-1 ]
  • [ 13423-60-4 ]
Reference: [1] Tetrahedron Letters, 2007, vol. 48, # 44, p. 7845 - 7848
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  • [ 288-88-0 ]
  • [ 62-53-3 ]
  • [ 13423-60-4 ]
Reference: [1] Chemistry - A European Journal, 2014, vol. 20, # 45, p. 14619 - 14623
  • 20
  • [ 288-88-0 ]
  • [ 696-62-8 ]
  • [ 13423-60-4 ]
Reference: [1] RSC Advances, 2015, vol. 5, # 51, p. 40628 - 40635
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  • [ 540-37-4 ]
  • [ 6523-49-5 ]
Reference: [1] RSC Advances, 2014, vol. 4, # 83, p. 44105 - 44116
  • 22
  • [ 288-88-0 ]
  • [ 98-59-9 ]
  • [ 13578-51-3 ]
YieldReaction ConditionsOperation in experiment
83.7% With triethylamine In dichloromethane 1-(p-toluenesulfonyl)-1,2,4-triazole (10) 1,2,4-triazole (9.28 g) was suspended in dichloromethane (110 mL) dried over molecular sieves. Triethylamine (13.6 g) was added; the triazole dissolved after triethylamine addition. Tosylchloride (25.62 g;) was added to the reaction mixture over approx. 30 min. The reaction mixture was stirred overnight. Precipitated salt was filtered off. Filtrate was washed with water and dried with Na2SO4. The drying agent was filtered off and filtrate was evaporated on rotary evaporator. Cyclohexane (300 mL) was added to the residue and the mixture was allowed to crystallise overnight. Product was separated by filtration, washed with cyclohexane (50 mL), and dried in oven at 50° C. to give the title compound as white crystalline powder, 25.1 g (83.7percent of theoretical yield; m.p. 105-107° C.
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[2] Journal of Organic Chemistry, 2010, vol. 75, # 8, p. 2722 - 2725
[3] Patent: US2008/76933, 2008, A1, . Location in patent: Page/Page column 3-5
[4] Patent: EP1258480, 2002, A1, . Location in patent: Page 37
[5] Journal of Chemical Research, 2016, vol. 40, # 2, p. 101 - 106
  • 23
  • [ 288-88-0 ]
  • [ 824-79-3 ]
  • [ 13578-51-3 ]
YieldReaction ConditionsOperation in experiment
55% With N-Bromosuccinimide In 1,4-dioxane at 25℃; for 12 h; General procedure: Azoles 1 (0.5 mmol), sodium sulfinate 2 (1.0 mmol) and NBS (0.5 mmol) were dissolved in 2 mL of 1,4-dioxane solvent. the reaction mixture was stirred at room temperature under air for 12 h. After the reaction, the resulting mixture was extracted with EtOAc. The combined organic phase was dried over anhydrous Na2SO4 and the solvent was then removed under vacuum. The residue was purified by flash column chromatography on silica gel (petroleumether/ethyl acetate, 3:1) to afford the corresponding product.
Reference: [1] Tetrahedron, 2017, vol. 73, # 17, p. 2504 - 2511
  • 24
  • [ 288-88-0 ]
  • [ 1576-35-8 ]
  • [ 13578-51-3 ]
Reference: [1] Organic and Biomolecular Chemistry, 2015, vol. 14, # 2, p. 590 - 597
  • 25
  • [ 288-88-0 ]
  • [ 30955-05-6 ]
  • [ 13578-51-3 ]
Reference: [1] Nucleosides and Nucleotides, 1997, vol. 16, # 7-9, p. 1067 - 1071
  • 26
  • [ 288-88-0 ]
  • [ 7411-23-6 ]
YieldReaction ConditionsOperation in experiment
90%
Stage #1: With bromine; sodium hydroxide In dichloromethane; water at 25℃; for 12 h;
Stage #2: With hydrogenchloride In dichloromethane; water for 1 h;
To a solution of 1,2,4-triazole, 1 (27.6 g, 399.6 mmol) in dichloromethane (80 mL) was simultaneously added bromine in dichloromethane (50percentv/v, 80 mL) and an aqueous solution of sodium hydroxide (50percent w/v,96 mL). The rate of addition was such that the temperature of the reaction mass was maintained between 10-15°C. After the complete addition, the temperature was raised to 25°C and the stirring was continued for an additional 12 h. Into this was then added 6 N aq.HCl and stirring continued for 1 h.The solid thus precipitated was filtered, and dried under vacuum at 50°C to afford 2 as an off-white solid(80 g, 90percent). The product was used without further purification.
65% With bromine; sodium hydroxide In dichloromethane; water at 0 - 20℃; Intermediate 1 3,5-Dibromo-lH-l,2,4-triazole Solutions of bromine (6.1 mL, 119 mmol) in DCM (15 mL) and sodium hydroxide (6.78 g, 169 mmol) in water (20 mL) were simultaneously added dropwise to a stirred mixture of 1H-1,2,4- triazole (3.9 g, 56 mmol), water (50 mL) and DCM (15 mL) at 0°C while keeping the reaction temperature below 20°C. The mixture was stirred at ambient temperature over night. Hydrochloric acid (cone, 2.0 mL, 66 mmol) was added. The solid was isolated by filtration, washed with water and dried in vacuum to yield the title compound as a solid (8.3 g, 65percent). MS (ESI ) m/z 224 [M-H]".
65% With bromine; sodium hydroxide In dichloromethane; water at 0 - 20℃; Intermediate 1 3,5-Dibromo-lH-l,2,4-triazole lH-l,2,4-Triazole (3.9 g, 56 mmol) was mixed in water (50 mL) and DCM (15 mL) at 0°C. A solution of dibromine (6.1 mL, 119 mmol) in DCM (15 mL) and a solution of sodium hydroxide (6.78 g, 169 mmol) in water (20 mL) were added dropwise simultaneously while keeping the reaction temperature below 20°C. The mixture was stirred at ambient temperature over night. Hydrochloric acid (cone, 2.0 mL, 66 mmol) was added. The solid was isolated by filtration, washed with water and dried under vacuum to yield the title compound as a solid (8.3 g, 65percent). MS (ESI ) m/z 224 [M-H]".
Reference: [1] Synthesis, 1998, # 9, p. 1357 - 1361
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2014, vol. 53, # 5, p. 610 - 618
[3] Patent: WO2014/195321, 2014, A1, . Location in patent: Page/Page column 15; 16
[4] Patent: WO2014/195322, 2014, A1, . Location in patent: Page/Page column 15
[5] Patent: US2010/240619, 2010, A1, . Location in patent: Page/Page column 68
  • 27
  • [ 288-88-0 ]
  • [ 459-57-4 ]
  • [ 27996-86-7 ]
YieldReaction ConditionsOperation in experiment
72% With potassium carbonate In N,N-dimethyl-formamide at 110℃; General procedure: A mixture of 4-fluoro acetophenone/4-fluorobenzaldehyde (10 mmol) and imidazole/triazole (10 mmol) were dissolved in dry DMF (20 mL). K2CO3 (12 mmol) was added in small portion within a period of 15 min to the above stirred solution. Mixture was stirred for 10-12 h at 110 °C. Heating discontinued, K2CO3 was filtered off, filtrate extracted with ethyl acetate (3 .x. 15 mL). Organic layer was washed with water (3 .x. 15 mL), dried over anhydrous sodium sulphate and concentrated to given an oil which was purified on silica gel column (60-120 mesh) taking methanol: chloroform (1:99) as an eluent.
65% With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 6 h; Example 91Preparation of 4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI5); To a stiffing solution of 4-fluorobenzaldehyde (10.0 g, 80.6 mmol) in DMF (150 mL) were added K2CO3 (13.3 g, 96.7 mmol) and 1,2,4-triazole (6.67 g, 96.7 mmol) and the resultant reaction mixture was stirred at 120° C. for 6 h. After completion of reaction (by TLC), the reaction mixture was diluted with H2O and extracted with EtOAc (3.x.100 mL). The combined EtOAc layer was washed with H2O and brine, dried over Na2SO4, and concentrated under reduced pressure to afford the title compound as a solid (9.0 g, 65percent): mp 145-149° C.: 1H NMR (400 MHz, CDCl3) δ 10.08 (s, 1H), 8.70 (s, 1H), 8.16 (s, 1H), 8.06 (d, J=8.0 Hz, 2H), 7.92 (d, J=8.0 Hz, 2H); ESIMS m/z 173.9 ([M+H]+).
65% With potassium carbonate In N,N-dimethyl-formamide Example 91
Preparation of 4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI5)
To a stirring solution of 4-fluorobenzaldehyde (10.0 g, 80.6 mmol) in DMF (150 mL) were added K2CO3 (13.3 g, 96.7 mmol) and 1,2,4-triazole (6.67 g, 96.7 mmol) and the resultant reaction mixture was stirred at 120° C. for 6 h.
After completion of reaction (by TLC), the reaction mixture was diluted with water and extracted with EtOAc (3*100 mL).
The combined EtOAc layer was washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure to afford the title compound as a solid (9.0 g, 65percent): mp 145-149° C.: 1H NMR (400 MHz, CDCl3) δ 10.08 (s, 1H), 8.70 (s, 1H), 8.16 (s, 1H), 8.06 (d, J=8.0 Hz, 2H), 7.92 (d, J=8.0 Hz, 2H); ESIMS m/z 173.9 ([M+H]+).
65% With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 6 h; Example 91: Preparation of 4-(lH-l,2,4-triazol-l-yl)benzaldehyde (DI5) To a stirring solution of 4-fluorobenzaldehyde (10.0 g, 80.6 mmol) in DMF (150 mL) were added K2CO3 (13.3 g, 96.7 mmol) and 1,2,4- triazole (6.67 g, 96.7 mmol) and the resultant reaction mixture was stirred at 120 °C for 6 h. After completion of reaction (by TLC), the reaction mixture was diluted with H20 and extracted with EtOAc (3 xlOO mL). The combined EtOAc layer was washed with H20 and brine, dried over Na2S04, and concentrated under reduced pressure to afford the title compound as a solid (9.0 g, 65percent): mp 145-149 °C: ]H NMR (400 MHz, CDC13) δ 10.08 (s, IH), 8.70 (s, IH), 8.16 (s, IH), 8.06 (d, J = 8.0 Hz, 2H), 7.92 (d, J = 8.0 Hz, 2H); ESIMS m/z 173.9 ([M+H]+).
65% With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 6 h; To a stiffing solution of 4-fluorobenzaldehyde (10.0 g, 80.6 mmol) in DMF (150 mL) were added K2CO3 (13.3 g, 96.7 mmol) and 1,2,4-triazole (6.67 g, 96.7 mmol) and the resultant reaction mixture was stirred at 120° C. for 6 h. After completion of reaction (by TLC), the reaction mixture was diluted with H2O and extracted with EtOAc (3×100 mL). The combined EtOAc layer was washed with H2O and brine, dried over Na2SO4, and concentrated under reduced pressure to afford the title compound as a solid (9.0 g, 65percent): mp 145-149° C.: 1H NMR (400 MHz, CDCl3) δ 10.08 (s, 1H), 8.70 (s, 1H), 8.16 (s, 1H), 8.06 (d, J=8.0 Hz, 2H), 7.92 (d, J=8.0 Hz, 2H); ESIMS m/z 173.9 ([M+H]+).
65% With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 6 h; To a stiffing solution of 4-fluorobenzaldehyde (10.0 g, 80.6 mmol) in DMF (150 mL) were added K2CO3 (13.3 g, 96.7 mmol) and 1,2,4-triazole (6.67 g, 96.7 mmol) and the resultant reaction mixture was stirred at 120° C. for 6 h.
After completion of reaction (by TLC), the reaction mixture was diluted with H2O and extracted with EtOAc (3*100 mL).
The combined EtOAc layer was washed with H2O and brine, dried over Na2SO4, and concentrated under reduced pressure to afford the title compound as a solid (9.0 g, 65percent): mp 145-149° C.: 1H NMR (400 MHz, CDCl3) δ 10.08 (s, 1H), 8.70 (s, 1H), 8.16 (s, 1H), 8.06 (d, J=8.0 Hz, 2H), 7.92 (d, J=8.0 Hz, 2H); ESIMS m/z 173.9 ([M+H]+).
65% With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 6 h; Example 91 Preparation of 4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI5) To a stirring solution of 4-fluorobenzaldehyde (10.0 g, 80.6 mmol) in DMF (150 mL) were added K2CO3 (13.3 g, 96.7 mmol) and 1,2,4-triazole (6.67 g, 96.7 mmol) and the resultant reaction mixture was stirred at 120° C. for 6 h. After completion of reaction (by TLC), the reaction mixture was diluted with water and extracted with EtOAc (3×100 mL). The combined EtOAc layer was washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure to afford the title compound as a solid (9.0 g, 65percent): mp 145-149° C.: 1H NMR (400 MHz, CDCl3) δ 10.08 (s, 1H), 8.70 (s, 1H), 8.16 (s, 1H), 8.06 (d, J=8.0 Hz, 2H), 7.92 (d, J=8.0 Hz, 2H); ESIMS m/z 173.9 ([M+H]+).

Reference: [1] European Journal of Medicinal Chemistry, 2009, vol. 44, # 7, p. 2930 - 2935
[2] European Journal of Medicinal Chemistry, 2011, vol. 46, # 9, p. 4302 - 4310
[3] Patent: US2012/329649, 2012, A1, . Location in patent: Page/Page column 72
[4] Patent: US2014/171314, 2014, A1, . Location in patent: Page/Page column
[5] Patent: WO2014/100163, 2014, A1, . Location in patent: Page/Page column 131
[6] Patent: US2014/171308, 2014, A1, . Location in patent: Paragraph 0656-0657
[7] Patent: US2014/171312, 2014, A1, . Location in patent: Paragraph 0821; 0822
[8] Patent: US9211280, 2015, B2, . Location in patent: Page/Page column 132-133
[9] Tetrahedron, 2001, vol. 57, # 22, p. 4781 - 4785
[10] Journal of Medicinal Chemistry, 1998, vol. 41, # 13, p. 2390 - 2410
[11] Asian Journal of Chemistry, 2014, vol. 26, # 1, p. 257 - 260
[12] Crystal Growth and Design, 2012, vol. 12, # 9, p. 4663 - 4668
[13] Journal of Organic Chemistry, 2013, vol. 78, # 7, p. 3222 - 3234
[14] Patent: US2014/107094, 2014, A1, . Location in patent: Paragraph 0593; 0594
[15] Patent: US2015/105366, 2015, A1, . Location in patent: Paragraph 0567; 0568
[16] Patent: WO2015/57205, 2015, A1, . Location in patent: Page/Page column 158
[17] Medicinal Chemistry Research, 2017, vol. 26, # 7, p. 1506 - 1515
[18] Molecules, 2017, vol. 22, # 8,
[19] Patent: CN107056716, 2017, A, . Location in patent: Paragraph 0032; 0033
[20] Patent: CN104119286, 2017, B, . Location in patent: Paragraph 0033
  • 28
  • [ 288-88-0 ]
  • [ 459-57-4 ]
  • [ 27996-86-7 ]
Reference: [1] Patent: US6451973, 2002, B1,
[2] Patent: US5977075, 1999, A,
[3] Patent: US7138432, 2006, B1, . Location in patent: Page/Page column 44
[4] Patent: US5703106, 1997, A,
  • 29
  • [ 459-57-4 ]
  • [ 288-88-0 ]
  • [ 27996-86-7 ]
Reference: [1] Journal of Medicinal Chemistry, 1987, vol. 30, # 6, p. 1023 - 1029
[2] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1695 - 1697
  • 30
  • [ 288-88-0 ]
  • [ 76-83-5 ]
  • [ 31250-99-4 ]
YieldReaction ConditionsOperation in experiment
93%
Stage #1: With triethylamine In N,N-dimethyl-formamide for 0.0833333 h;
j0185j Triethylamine (5.49 g, 54.30 mmol) is added to a solution of 1,2,4-triazole (3.0 g, 43.44 mmol) in DMF (50 mL) at rt. After stirring for 5 minutes, trityl chloride (12.11 g, 43.44 mmol) is added as a solid and the mixture is stirred overnight. The solvent is distilled off under reduced pressure and the crude is partitioned between dichloromethane (50 mL) and water (50 mL). The organic layer is separated and the aqueous layer is extracted with dichloromethane (3 x 50 mL). The combined organic layers are washed with water (3 x 40 mL). The organic layer is dried over Na2SO4 and concentrated under reduced pressure to afford the product 1-trytil-1H- 1,2,4-triazole (12.6 g, 93 percent). n-BuLi (4.5 mL, 11.24 mmol; 2.5 M solution in hexanes) is added to a solution of 1-trityl-1H-1,2,4-triazole (3.5 g, 11.24 mmol) in THF (120 mL) at -78°C and the solution is stirred for 45 mm. Bromine (1.76 g, 11.02 mmol) is added dropwise over a period of 5 minutes and the solution is stirred for 2 h allowed to warm to -20 °C and quenched by adding saturated NH4C1 solution (30 mL). The reaction mixture ias diluted with water (60 mL) and dichloromethane (40 mL). The organic layer is separated and the aqueous layer is extracted with CH2C12 (4 x 50 mL).The combined organic extract was dried over Na2SO4 and the solvent evaporated under reduced pressure to afford crude which is used as such for the next step (4.2 g, 95 percent). 7.09-7.16 (m, 6H), 7.27-7.40 (m, 9H), 7.86 (s, 1H).
Reference: [1] Patent: WO2014/159248, 2014, A1, . Location in patent: Paragraph 0185
[2] European Journal of Medicinal Chemistry, 2009, vol. 44, # 7, p. 3064 - 3067
[3] Tetrahedron, 1997, vol. 53, # 30, p. 10289 - 10312
[4] MedChemComm, 2014, vol. 5, # 1, p. 72 - 81
[5] Patent: US6620841, 2003, B1,
[6] Patent: EP1219607, 2002, A1,
[7] Heterocycles, 1985, vol. 23, # 11, p. 2895 - 2906
[8] Patent: US5393732, 1995, A,
  • 31
  • [ 288-88-0 ]
  • [ 76-83-5 ]
  • [ 136633-98-2 ]
  • [ 31250-99-4 ]
Reference: [1] Recueil des Travaux Chimiques des Pays-Bas, 1991, vol. 110, # 9, p. 369 - 373
[2] Tetrahedron Letters, 2000, vol. 41, # 8, p. 1297 - 1301
  • 32
  • [ 77287-34-4 ]
  • [ 302-01-2 ]
  • [ 288-88-0 ]
  • [ 628-36-4 ]
Reference: [1] Journal of the American Chemical Society, 1955, vol. 77, p. 621,623
  • 33
  • [ 5818-15-5 ]
  • [ 288-88-0 ]
  • [ 758-96-3 ]
Reference: [1] Journal fuer Praktische Chemie - Practical Applications and Applied Chemistry (Germany), 2000, vol. 342, # 7, p. 682 - 699
  • 34
  • [ 288-88-0 ]
  • [ 41253-21-8 ]
YieldReaction ConditionsOperation in experiment
98% With sodium methylate In methanol for 4 h; Heating / reflux [0061] Catalyst 1: Sodium 1,2,4-triazolate [0062] A three-necked-flask stirring apparatus with mechanical stirrer, internal thermometer and reflux condenser was charged under dry nitrogen with 200 ml of dry methanol and 45 ml of a 30percent strength methanolic solution of sodium methoxide, corresponding to 0.25 mol of sodium methoxide. 17.4 g (0.25 mol) of 1,2,4-triazole was added thereto in portions at room temperature. After the end of addition of the 1,2,4-triazole the reaction mixture was stirred at reflux temperature for 4 h. The solvent was subsequently distilled off under reduced pressure and the oily residue which remained was admixed at room temperature with 200 ml of methylene chloride. The mixture was stirred at room temperature for 15 min and the precipitated solid product was filtered off. This gave 22.5 g of sodium 1,2-4-triazolate (yield: 98percent of theory) in the form of a colourless powder. The product was pure according to its 1H-NMR spectrum and free of the 1,2,4-triazole used.
Reference: [1] Liebigs Annalen der Chemie, 1994, # 2, p. 145 - 150
[2] Patent: US2004/49028, 2004, A1, . Location in patent: Page 5
[3] Chemistry of Heterocyclic Compounds, 1998, vol. 34, # 2, p. 252 - 253
[4] Journal of the American Chemical Society, 1927, vol. 49, p. 1999
[5] Patent: WO2005/105762, 2005, A1, . Location in patent: Page/Page column 8; 9-10
[6] Patent: US2003/13872, 2003, A1,
[7] Patent: WO2006/108155, 2006, A2, . Location in patent: Page/Page column 16-17
[8] Patent: US2010/143455, 2010, A1, . Location in patent: Page/Page column 9-10
[9] Patent: WO2006/137083, 2006, A1, . Location in patent: Abstract
[10] Patent: US2003/236419, 2003, A1, . Location in patent: Page 10
  • 35
  • [ 288-88-0 ]
  • [ 41253-21-8 ]
Reference: [1] Patent: US4421758, 1983, A,
  • 36
  • [ 288-88-0 ]
  • [ 872-50-4 ]
  • [ 41253-21-8 ]
Reference: [1] Patent: EP2719695, 2014, A1, . Location in patent: Page/Page column
  • 37
  • [ 288-88-0 ]
  • [ 50-00-0 ]
  • [ 74205-82-6 ]
YieldReaction ConditionsOperation in experiment
89% at 140℃; for 0.5 h; Step 1.
Preparation of (1H-1,2,4-triazol-1-yl)methanol
A mixture of 1H-1,2,4-triazole (7.04 g, 102 mmol), paraformaldehyde (3.06 g, 102 mmol) and catalytic amount of triethylamine was heated to molten condition and stirred at the same temperature (140° C.) for 0.5 hour.
Reaction mixture was then cooled to 30° C. to obtain the product (9.0 g, 89percent) as white solid.
79% at 20℃; for 13 h; Reflux The compound was synthesized with some modifications compared to Ref. [14]: (1,2,4)-triazole [98 percent(Aldrich), 1,73 g, 25 mmol] in 20 ml of ethanol (absolute ethanol, ≥99.8 percent, Sigma-Aldrich) and 3.5 ml of formaldehyde solution (≥36,5 percent, Sigma-Aldrich) were stirred, refluxed for 1 h, and mixing was continued at room temperature for 12 h. After the elimination of the solvent under reduced pressure, the obtained residue was treated with cold water. A white solid appeared, which was collected by filtration, washed with diethyl ether (99 percent, Sigma-Aldrich) and dried under vacuum to yield the pure product (79 percent).
Reference: [1] Heterocyclic Communications, 2001, vol. 7, # 6, p. 577 - 582
[2] Phosphorus and Sulfur and the Related Elements, 1987, vol. 33, p. 41 - 52
[3] Tetrahedron, 2010, vol. 66, # 47, p. 9145 - 9150
[4] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1980, vol. 16, # 2, p. 189 - 194[5] Khimiya Geterotsiklicheskikh Soedinenii, 1980, vol. 16, # 2, p. 251 - 256
[6] Patent: US2016/83380, 2016, A1, . Location in patent: Paragraph 0240; 0241
[7] Structural Chemistry, 2016, vol. 27, # 2, p. 697 - 704
  • 38
  • [ 288-88-0 ]
  • [ 446-52-6 ]
  • [ 138479-53-5 ]
Reference: [1] Australian Journal of Chemistry, 1991, vol. 44, # 8, p. 1097 - 1114
  • 39
  • [ 288-88-0 ]
  • [ 451-46-7 ]
  • [ 143426-48-6 ]
Reference: [1] European Journal of Medicinal Chemistry, 1992, vol. 27, # 3, p. 219 - 228
  • 40
  • [ 288-88-0 ]
  • [ 451-46-7 ]
  • [ 167626-25-7 ]
  • [ 143426-48-6 ]
Reference: [1] Patent: US6359134, 2002, B1, . Location in patent: Referential example 17
  • 41
  • [ 288-88-0 ]
  • [ 461-82-5 ]
  • [ 103962-05-6 ]
Reference: [1] Patent: US4925863, 1990, A,
  • 42
  • [ 288-88-0 ]
  • [ 80443-63-6 ]
  • [ 107534-96-3 ]
YieldReaction ConditionsOperation in experiment
95% at 108 - 128℃; for 15 h; Into a clean 1000ml four-necked flask 200g of 2- (4-chlorophenethyl) -2-t-butyl ethylene oxide,200g triazole,90 g PEG-7000, 38 g KOH and 0.6 g 18-crown-6,To the dropping funnel, 400 g of 2- (4-chlorophenethyl) -2-t-butyl-oxirane were added dropwise.Turn on stirringWhen heated to 108 ° C,Begin with the dropwise addition of 2- (4-chlorophenethyl) -2-t-butyl-oxirane,Control the reaction flask temperature does not exceed 112 ,Dropping 2h, after the addition was completed,The reaction flask temperature was controlled at 108 ~ 112 ,Insulation 5h;Then warmed to 125 ~ 128 ,Insulation 8h, sample testing,Raw material peak is less than 0.5percent4-H isomer 0.3percentTo the reaction flask was added enough water and methylcyclohexane,Wherein the mass ratio of water and methylcyclohexane is 1: 3.5;After stratification, the water cooled crystallization of PEG,Suction filtered solid PEG recovery applied;The organic layer was cooled to crystallize tebuconazole, filtered with suction,Filter cake was washed to pH 7 to 8,The filter cake was dried to give 772 g of 1H-tebuconazole.
94% With potassium hydroxide In neat (no solvent) at 130℃; for 7 h; In 250ml three bottles,23.8 g of 2-tert-butyl-2- (4-chlorophenethyl) oxirane was added,2.0 g of potassium hydroxide and 800 g of PEG were added,And 8.0 g of 1,2,4-triazole was added,Temperature and control the temperature 130 ,Reaction for 7 hours,Stop the reaction.The filter mother liquor in Example 6 was added and the temperature was adjusted to 30 ° C for 3 hours and evacuated.The filter cake was dried to obtain 29.1 g of tebuconazole (white solid)Content of 98.1percent,Yield 94.0percent.
Reference: [1] Patent: CN107176929, 2017, A, . Location in patent: Paragraph 0024; 0025; 0026; 0027; 0028; 0029; 0030-0040
[2] Patent: CN106588791, 2017, A, . Location in patent: Paragraph 0041; 0042
[3] Patent: US4668660, 1987, A,
  • 43
  • [ 288-88-0 ]
  • [ 764-28-3 ]
  • [ 107534-96-3 ]
Reference: [1] Patent: US4626594, 1986, A,
  • 44
  • [ 288-88-0 ]
  • [ 226944-49-6 ]
  • [ 104206-82-8 ]
Reference: [1] Patent: US6218579, 2001, B1,
  • 45
  • [ 288-88-0 ]
  • [ 75-75-2 ]
  • [ 1175536-50-1 ]
YieldReaction ConditionsOperation in experiment
89.7%
Stage #1: for 1 h;
In the 1L added three-opening bottle 52.9g (0.24 µM) trimethyl protoiodide sulphone, 2.15g (0.014 µM) L - menthol, 6.3g (0.024 µM) triphenylphosphine, 9.6g (0.48 µM) LiOH, 350gTHF, nitrogen protection, stirring cooling to -20 °C, dropwise 64.8g compound III of the tetrahydrofuran solution, then completing, -20 °C insulation 20h, sampling HPLC detection, compound III 0.03percent, compound compound IV 99.8percent, ee value 99.3percent. The temperature to 20 °C, adding 16.5g (0.24 µM) 1, 2, 4 - triazole, thermal insulation 1h, adding 300g water, for 300g * 2 ethyl acetate extraction twice, combined with the organic phase, the organic phase is used for the 300g saturated sodium chloride washing, and organic 20g dried with anhydrous sodium sulfate 2h, filtering to remove the drying agent, the organic phase PH=8, to the organic adds by drops 50g methanesulfonic acid adjusting PH to strongly acidic, a large number of solid precipitation, filtering to obtain yellow solid 78.6g, HPLC purity 99percent, yield 89.7percent. Taking 23g the above yellow solid, adding 100g THF, stirring cooling to -10 °C, solid not soluble, dropping 19.3g triethylamine, dropped exothermic, needs to control the dripped under for the -5 °C, dropwise 10.8g a chloride, heat release during the dropping, temperature control of the -5 °C, then completing insulation 1h, system by large floc, the heat preservation finishes, no raw material remaining TLC ((Rf raw material=0.6, Rf (reaction solution)=0.7, developing solvent: toluene: ethanol=4:1, volume ratio)), to the system adds by drops 40g 10percent of sodium hydroxide solution, canada finishes clear system, thermal insulation 0.5h, liquid, organic uses 80g saturated sodium chloride wash, liquid, organic phase turns on lathe does (0.09 mpa, 50 °C) get 18g yellow solid, solid then 20percent ethanol solution of recrystallized a, shall be 13.4g white needle crystal compound V, HPLC purity 99.8percent, ee value 99.1percent, the overall yield 71percent (calculated to lactic acid methyl ester).
Reference: [1] Patent: CN106749202, 2017, A, . Location in patent: Paragraph 0037; 0042; 0046
  • 46
  • [ 288-88-0 ]
  • [ 75-75-2 ]
  • [ 1774-47-6 ]
  • [ 127001-03-0 ]
  • [ 1175536-50-1 ]
Reference: [1] Organic Process Research and Development, 2009, vol. 13, # 4, p. 716 - 728
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Reason: Stable Isotope

Related Parent Nucleus of
[ 288-88-0 ]

Triazoles

Chemical Structure| 41253-21-8

[ 41253-21-8 ]

Sodium 1,2,4-triazol-1-ide

Similarity: 0.95

Chemical Structure| 6086-21-1

[ 6086-21-1 ]

1-Methyl-1,2,4-triazole

Similarity: 0.77

Chemical Structure| 7170-01-6

[ 7170-01-6 ]

3-Methyl-1H-1,2,4-triazole

Similarity: 0.67

Chemical Structure| 6818-99-1

[ 6818-99-1 ]

3-Chloro-1,2,4-triazole

Similarity: 0.67

Chemical Structure| 3179-31-5

[ 3179-31-5 ]

1H-1,2,4-Triazole-3-thiol

Similarity: 0.65