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Chemical Structure| 50907-23-8 Chemical Structure| 50907-23-8
Chemical Structure| 50907-23-8

5-(4-Bromophenyl)-1H-tetrazole

CAS No.: 50907-23-8

4.5 *For Research Use Only !

Cat. No.: A165748 Purity: 98%

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Product Details of [ 50907-23-8 ]

CAS No. :50907-23-8
Formula : C7H5BrN4
M.W : 225.05
SMILES Code : BrC1=CC=C(C2=NN=NN2)C=C1
MDL No. :MFCD00991874
InChI Key :YMZMDMWMKVPGDP-UHFFFAOYSA-N
Pubchem ID :766141

Safety of [ 50907-23-8 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H318
Precautionary Statements:P264-P270-P280-P301+P312+P330-P305+P351+P338+P310-P501
Class:8
UN#:1759
Packing Group:

Calculated chemistry of [ 50907-23-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 11
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 47.31
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

54.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.23
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.9
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.63
Log Po/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.

2.14
Log Po/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

2.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.83

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.04
Solubility 0.203 mg/ml ; 0.000902 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.

-2.67
Solubility 0.485 mg/ml ; 0.00216 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

-3.87
Solubility 0.0306 mg/ml ; 0.000136 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

No
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.

-6.32 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

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.56

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)

1.79

Application In Synthesis [ 50907-23-8 ]

* 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 [ 50907-23-8 ]

[ 50907-23-8 ] Synthesis Path-Upstream   1~7

  • 1
  • [ 25062-46-8 ]
  • [ 50907-23-8 ]
YieldReaction ConditionsOperation in experiment
95% With diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In 5,5-dimethyl-1,3-cyclohexadiene for 4 h; Reflux; Green chemistry General procedure: DPPA (0.15 mmol) and DBU (0.30 mmol) were added to a solution of the appropriate aldoxime (0.10 mmol) in xylenes (0.5 mL). After stirring for 2–16 h at reflux, the mixture was cooled to r.t. and sat. aq NaHCO3 (2.0 mL) was added. After stirring for 5 min, the mixture was diluted with water (20 mL). The aqueous layer was then washed with EtOAc (25 mL) and acidified with 1 N aq HCl to pH 2. The aqueous layer was extracted with EtOAc (2 x 30 mL) and the combined organic extracts were washed with brine (30 mL) and dried over Na2SO4. Concentration of the solvent in vacuo followed by purification of the residue on a short column (silica gel, EtOAc–n-hexane, 1:1 to 3:1) gave the desired tetrazole.
82% With indium(III) chloride; sodium azide In N,N-dimethyl-formamide at 120℃; for 20 h; General procedure: InCl3 (3 molpercent) was added to a stirred solution of the appropriate aldoxime (1 mmol) and NaN3 (1.5 mmol) in DMF (5 mL), and the mixture was heated to 120 °C. When the reaction was complete(TLC), the mixture was cooled to r.t., H2O (5 mL), 2 M aq HCl (10mL), and EtOAc (10 mL) were successively added, and the mixture was stirred vigorously for 15 min. The organic layer was separated, and the aqueous layer was extracted with EtOAc(3 × 15 mL). The combined organic extracts were washed with H2O, dried (Na2SO4), and filtered. The solvent was evaporated under reduced pressure, and the crude product was purified by column chromatography [silica gel, EtOAc–hexane (9:1)].
81% With diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene for 16 h; Reflux General procedure: DPPA (0.30 mmol) and DBU (0.60 mmol) were added to a solution of aldoxime (0.20 mmol) intoluene (1.0 mL). After stirring for 16 h at reflux, the mixture was cooled to room temperature andsaturated NaHCO3 aq. (2.0 mL) was added. After stirring for 5 min, the mixture was diluted withwater (20 mL). The aqueous layer was then washed with AcOEt (25 mL) and acidified with 1.0 NHCl aq. to pH 2. The aqueous layer was extracted with AcOEt (30 mL × 2), and the combinedorganic extracts were washed with brine (30 mL) and dried over Na2SO4. The concentration of thesolvent in vacuo followed by the purification of the residue through a short silica gel column(AcOEt:n-hexane 1:1-3:1) gave desired tetrazole
References: [1] Synthesis (Germany), 2018, vol. 50, # 6, p. 1293 - 1300.
[2] Synlett, 2016, vol. 27, # 8, p. 1241 - 1244.
[3] Synlett, 2016, vol. 27, # 15, p. 2225 - 2228.
[4] Tetrahedron Letters, 2016, vol. 57, # 5, p. 523 - 524.
  • 2
  • [ 623-00-7 ]
  • [ 50907-23-8 ]
YieldReaction ConditionsOperation in experiment
98% With sodium azide; ammonium cerium (IV) nitrate In N,N-dimethyl-formamide at 110℃; for 6 h; Inert atmosphere; Green chemistry General procedure: sodiumazide (1.5 mmol) was added to a magnetically stirred solution of nitrile 1a(1 mmol) in anhydrous DMF and the CAN (10 mmol percent) was added. The reactionmixture was constantly stirred for another 6 h at 110 C under nitrogenatmosphere. After the completion of reaction as seen by TLC, the reactionmixture was brought to room temperature and the solvent was evaporatedunder vacuum. The crude thus obtained, was dissolved in ethyl acetate (20 mL)and solution was washed with acidified water (4 M HCl, 15 mL) twice.Separated organic layer was washed with brine solution dried overanhydrous Na2SO4, and solvent was removed under high vacuum to obtaintetrazole 1b as a white crystalline solid in 97percent yield.
98% With bismuth(III) chloride; sodium azide In water; isopropyl alcohol at 160℃; for 4 h; Microwave irradiation General procedure: 2-Furonitrile 1m (186 mg, 2 mmol), NaN3 (260 mg, 4 mmol), BiCl3 (126 mg, 0.4 mmol), and 8 mL of a 3:1 isopropanol/water mixture were added to a 30-mL Pyrex microwave vessel, which was then capped. The microwave vessel was then placed in a Milestone Start Synth microwave reactor. The reaction was magnetically stirred and heated for 1 h at 150°C. The reaction was monitored by thin-layer chromatography (TLC) using an ether/hexane mixture (typically 50/50) for development. The reaction mixture was then diluted with saturated aqueous sodium bicarbonate (20 mL) and was hed with ethyl acetate (2×15 mL). The aqueous sodium bicarbonate layer was cooled with ice and acidified to a pH of 2 or less with concentrated hydrochloric acid, which was added dropwise. The precipitate formed was extracted with ethyl acetate (3×15 mL). The combined organic layers were dried with anhydrous sodium sulfate and decanted into a tared round-bottom flask. The organic layer was concentrated under reduced pressure by rotary evaporation at 40°C and then under high vacuum. The tetrazole product was recrystallized from ethyl acetate and hexane.
98% at 120℃; for 0.5 h; Green chemistry General procedure: To a suspension of the catalyst (0.004 g) in PEG (2 mL), nitrile (1 mmol) and sodium azide (1.2 mmol) were added and the mixture was stirred vigorously at 120 °C for the required time (Table 6). After the reaction was completed (as monitored by TLC), the catalyst was separated with a magnet. HCl (4 N, 10 mL) was then added to the residue, and the tetrazole was extracted with ethyl acetate. The organic extract was washed with distilled water, dried over anhydrous Na2SO4 and then evaporated to give the desired tetrazole.
97.2% at 85℃; for 18 h; at 85 °C, a mixtureof Tetrabutylammonium fluoride trihydrate (TABF3H2O) (1.31 g,5 mmol), 4-bromobenzonitrile (1.82 g, 10 mmol) and trimethylsilylazide (TMSN3) (1.73 g, 15 mmol) was under vigorous stirring conditionsfor 18 h. After completion of the reaction, the mixture was allowedto cool to room temperature, added with ethyl acetate and washedby 3×150 mL hydrochloric acid. The organic layer was isolatedand the remaining aqueous phase was further extracted with ethylacetate. The organic phases were combined and dried using anhydrousMgSO4 to afford 5-(4-bromophenyl)-1H-tetrazole. Yield 97.2percent. Meltingpoint (MP): 260–261 °C. 1H NMR (400 MHz, DMSO‑d6): δ8.19–7.89 (m,2H), 7.83 (d, J=8.6 Hz, 2H). 13C NMR (400 MHz, DMSO‑d6): δ 132.98(s), 129.36 (s), 125.20 (s).
95% With sodium azide; ammonium acetate In N,N-dimethyl-formamide at 70℃; for 3 h; General procedure: The [AMWCNTs-O–Cu(II)–PhTPY] heterogeneous catalyst was subjected to 5 successive reuses under the reaction conditions: For each reaction, nitrile (1.0mmol), NaN3 (1.3mmol) and NH4OAc (1.0mmol) were mixed and stirred in DMF (1mL) in the presence of 4mol-percent of [AMWCNTs-O–Cu(II)–PhTPY] at 70°C in an uncapped vial. After the completion of the reaction, as monitored by TLC using n-hexane/ethyl acetate, the mixture was diluted by H2O (5mL), then the mixture was vacuum-filtered onto a sintered-glass funnel, and the residue was consecutively washed with ethyl acetate (30mL), water (5mL). The heterogeneous catalyst was recharged for another reaction run. The combined supernatant and organic washings were extracted with ethyl acetate (3×10mL), the combined organic layer was dried over anhydrous Na2SO4. Removal of the solvent under vacuum, followed by purification on silica gel using hexane/ethyl acetate as the eluent afforded the pure products.
95% With sodium azide In N,N-dimethyl-formamide at 90℃; for 3.5 h; General procedure: In a double-necked round bottom flask (100 mL) equippedwith a condenser was added a mixture consisting ofnitrile (0.005 mol), NaN3 (0.006 mol), and monodisperse Pt NPsVC in DMF (1.5 mL). The mixture washeated at reflux until TLC monitoring indicated no furtherimprovement in the conversion. The reaction mixture wasthen cooled to room temperature, vacuum-filtered usinga sintered-glass funnel and the residue was washed withethyl acetate (3×10 mL). The filtrate was treated with5 mL HCl (4 mol L−1 to reach pH= 3 and it was allowedto stir for 30 minutes. Subsequently, the organic layer wasseparated, dried over anhydrous Na2SO4 and evaporated.The crude product was purified by recrystallization and/orcolumn chromatography on silica gel eluted with propersolvents to get pure 5-Phenyl 1H-tetrazole.
95% With sodium azide; aminosulfonic acid In N,N-dimethyl-formamide at 120℃; for 5 h; General procedure: A mixture of 4-nitrobenzonitrile (0.296 g, 2 mmol), sodium azide (0.195 g, 3 mmol), and sulfamic acid (0.0097 g, 0.1 mmol) was stirred at 120°C in DMF (5 mL) for the appropriate time (Table 2) until TLC (4:1 n-hexane:ethyl acetate) indicated no further progress in the conversion. After completion of the reaction (as monitored by TLC), the reaction mixture was cooled to room temperature, then 20 mL diethyl ether was added to the mixture and stirred for 10 minutes. The catalyst was separated by simple gravity filtration, washed with diethyl ether (2 £ 10 mL) and dried at 40°C for 30 min. The recovered catalyst wasused for three additional cycles and gave the tetrazole in 95, 85 and 75percent (with 4-nitrobenzonitrile). The filtrate was treated with ethyl acetate (30 mL) and 6 N HCl(20 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc (20 mL). The combined organic layers were dried over anhydrous sodium sulfate and evaporated under reduced pressure to give 5-(4-nitrophenyl) tetrazole (0.363 g), 95percent yield.
94% at 140℃; for 1.33333 h; Green chemistry General procedure: NaN3 (0.975 g, 15 mmol)was dissolved in DES (10 mL) at room temperature by stirring until a clear solution was formed. Then benzonitrile (10 mmol) was added. The reaction mixture was constantly stirred at 140 °C and monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature and poured into the cold water (10 mL). The solid was obtained and filtered. The obtained solid is taken into cold water (10 mL). Then it was acidified carefully to pH 5 with 5 M HCl. The organic material was extracted thrice with ethyl acetate; the resultant organic layer was washed with distilled water, dried over anhydrous sodium sulfate, and concentrated to give the crude solid crystalline 5-substituted 1H-tetrazole. The resulting product, although evident as a single compound by TLC, was purified by simple recrystallization from aqueous ethanol giving pure 5-substituted 1H-tetrazoles.
94% With sodium azide; C19H17N3O4(2-)*Cu(2+) In ethylene glycol at 120℃; for 3 h; General procedure: In 25mL round-bottomed flask, sodium azide (0.076g, 1.2mmol) and polymeric copper (II) complex (0.005g) were added to a solution of benzonitrile (0.103g, 1mmol) in ethylene glycol (3mL) with stirring at room temperature. The reaction temperature was raised up to 120°C for 3h. The reaction was monitored by TLC at regular intervals. After completion of the reaction, the reaction mixture was cooled to room temperature and treated with 10mL HCl (2N) and extracted with 10mL ethyl acetate. The resulted organic layers were separated and washed with 2×10mL distilled water, dried over anhydrous sodium sulphate and evaporated under reduced pressure. The residue was then purified by column chromatography on silica gel (100–200 mesh) to afford the corresponding products.
92% With sodium azide In N,N-dimethyl-formamide at 110℃; for 3 h; General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol), Cu complex catalyst (0.4 molpercent) and DMF (3 mL) was taken in a round-bottomed flask and stirred at 110 °C temperature. After completion of the reaction the catalyst was separated from the reaction mixture with an external magnet and reaction mixture was treated with ethyl acetate (2 × 20 mL) and 1 N HCl (20 mL). The resultant organic layer was separated and the aqueous layer was again extracted with ethyl acetate (2 × 15 mL). The combined organic layers were washed with water, concentrated, and the crude material was chromatographed on silica gel (Hexane-EtoAc, 1:1) to afford the pure product.
92% With indium(III) chloride; sodium azide In water; isopropyl alcohol at 160℃; for 4 h; Microwave irradiation General procedure: Synthesis of 4-acetylbenzotetrazole (2c). 4-Acetylbenzonitrile 3c (290 mg, 2 mmol), NaN3 (260 mg, 4 mmol), InCl3(89 mg, 0.4 mmol), and 8 mL of a 3:1 isopropanol/water mixture were added to a 30-mL Pyrex microwave vessel and capped. The microwave vessel was then placed in a Milestone Start Synth microwave reactor. The reaction was magnetically stirred and heated for 1 hour at 160 oC. The pressure in the vessels was not determined. The reaction was monitored by TLC using an ether/hexane mixture (typically50/50) for development. After cooling, the reaction mixture was diluted with saturated aqueous sodium bicarbonate (20mL) and washed with ethyl acetate (2 x 15 mL). The aqueous sodium bicarbonate layer was cooled to 0 oC and acidified to a pH of 2 or less with concentrated hydrochloric acid,which was added drop-wise. The precipitate formed was extracted with ethyl acetate (3 x 15 mL). The combined organic layers were dried over anhydrous sodium sulfate and decanted into a tared round bottom flask. The organic layer was concentrated under reduced pressure. The tetrazole product was recrystallized from ethyl acetate and hexane. All reagents mentioned above were used unpurified
90% With sodium azide; copper(II) ferrite In N,N-dimethyl-formamide at 120℃; for 12 h; General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol), catalyst (40 molpercent) and DMF (3 mL) was taken in a round-bottomed flask and stirred at 120 °C temperature for 12 h. After completion of the reaction the catalyst was separated from the reaction mixture with an external magnet and reaction mixture was treated with ethyl acetate (30 mL) and 5 N HCl (20 mL). The resultant organic layer was separated and the aqueous layer was again extracted with ethyl acetate (20 mL). The combined organic layers were washed with water, concentrated, and the crude material was chromatographed on silica gel (Hexane-EtoAc, 1:1) to afford the pure product. refText
90% With sodium azide; copper(l) chloride In N,N-dimethyl-formamide at 120℃; for 12 h; General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol) and copper(I) chloride (4 mole percent) in DMF (2 mL) was stirred at 120 °C for the appropriate time period. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled and treated with 5 mL of HCl (4 mol L−1) and 10 mL of ethyl acetate, successively. The ethyl acetate extract was washed with water, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The product thus obtained was recrystallised from acetic acid to afford pure 5-substituted 1H-tetrazoles.
90% at 120℃; for 3 h; General procedure: To a stirred mixture of sodium azide (1.2 mmol) in PEG-400(2 mL), a nitrile compound (1 mmol) and NiNP-PNF (200 mL) were added and heated at 120°C under atmospheric conditions.The reaction progress was monitored by TLC. Upon reaction completion, the mixture was allowed to cool to ambient temperature and then filtered and extracted with ethyl acetate. The organic layer was washed with 1N HCl, dried with anhydrous Na2SO4, and filtered to afford pure 5-substituted tetrazoles.
89% With sodium azide; activated Fuller’s earth In dimethyl sulfoxide at 120℃; for 2 h; Green chemistry General procedure: To a DMSO (3 ml) solution of nitrile (1 mmol), and sodium azide (1.5 mmol), was added catalyst (10 wt percent). The reaction mixture was stirred to 120 0C in an oil bath. The reaction was monitored by TLC. After completion of the reaction, the mixture was filtered to separate the catalyst. The filtrate was quenched with water (30 ml), acidified with 5N HCl (20 ml) to precipitate the product, extracted with ethyl acetate (2 X 20 ml). The combined organic layers were washed with water, dried over sodium sulphate and evaporated under reduced pressure to give the product.
89% at 120℃; for 9 h; General procedure: A mixture of the required nitrile (1 mmol), sodium azide(1 mmol) and the catalyst MNP (0.05 g) was stirred at 120° C in PEG (1 mL) as solvent. After completion of the reaction, as indicated by TLC, the mixture was cooled to room temperature and diluted with 1:1 H2O:Ethyl acetate(10 mL) and then stirred at ambient temperature (10 min). The catalyst was removed by applying a magnetic field, and the decantate was treated with HCl (4 N, 10 mL). The organic layer was separated, washed with water, dried over sodium sulfate and concentrated to precipitate the crude crystalline solid. The pure tetrazoles were characterized bytheir spectroscopic data and melting points.
88% With sodium azide In N,N-dimethyl-formamide at 120℃; for 6.5 h; General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol) and catalyst (0.02 g, contains 0.4 molpercent of Cu(II)) in DMF (3 mL) was taken in a round-bottomed flask and stirred at 120 °C. The progress of the reaction was followed by thin-layer chromatography (TLC). After completion of the reaction, the reaction mixture was cooled to room temperature and diluted with ethyl acetate (3×20 mL). The catalyst was removed by using magnetic field or filtration and then the resulting solution was washed with 1N HCl, dried over anhydrous Na2SO4 and then was evaporated. The crude products were obtained in excellent yields. All products were characterized by 1H, 13C NMR, FT-IR, and melting point which were in agreement with literature. We have reported the spectral data of some aromatic and heteroaromatic synthesized compounds
88% at 120℃; for 15 h; Green chemistry General procedure: In a round-bottomed flask, a mixture of nitrile (1 mmol) and sodium azide (1.2 mmol) in the presence of 40 mg of Fe3O4*SBTU*Ni(II) was stirred at 120 °C in PEG for an appropriate time (monitored by TLC). Then, the reaction mixture was cooled down to room temperature. After magnetic separation of catalyst, HCl (4 N, 10 mL) was added to the filtrate and the product extracted with ethyl acetate (2 × 10 mL). The organic layer was washed with water several times, dried with anhydrous Na2SO4 and concentrated to give the crude solid crystalline product.
87% With sodium azide; (1,10-phenanthroline)bis(triphenylphosphine)copper(I) nitrate In water; isopropyl alcohol at 65℃; for 0.25 h; Inert atmosphere; Microwave irradiation; Green chemistry General procedure: In a round-bottomed flask, a mixture of organic nitrile 1 (1.0 equiv) and NaN3 (1.5 equiv) was added to 5 ml solution of H2O-IPA (1:1) containing 10 molpercent [Cu(phen)(PPh3)2]NO3 as catalyst under N2 atmosphere. The reaction mixture was irradiated under microwave heating at 245 W for 15–25 min at 65°C. Reaction progress was monitored by thin-layer chromatography (TLC). After reaction completion, the mixture was filtered to remove the catalyst. The filtrate was acidified with 5 N HCl (20 ml) to neutralize the product, extracted with ethyl acetate (2 9 10 ml). The combined organic layer was dried over anhydrous MgSO4. The combined filtrate was subjected to evaporation to obtain the crude compound, which was purified over silica gel column (60–120 mesh) using 50 percent ethyl acetate in hexane as eluent to obtain corresponding 5-substituted 1H-tetrazoles 2 as product.
86% With sodium azide In methanol; N,N-dimethyl-formamide at 20 - 100℃; for 7 h; General procedure: A mixture of benzonitrile (1 mmol), sodium azide (2 mmol), Ln(OTf)3-SiO2 (2008 mg) and DMF/MeOH (4:1, 5 mL) in a pressure vial was initially stirred at room temperature. After 30 min, the temperature of the reaction mixture was raised to 100 °C and stirred for another 7 h. After consumption of 1a (as indicated by TLC), the catalyst was separated by filtration and the filtrate was treated with ethyl acetate (15 mL). The organic layer was washed with 4 N HCl (20 mL). The resultant organic layer was separated and the aqueous layer was extracted with ethyl acetate (15 mL). The combined organic layer was washed with water (2 × 10 mL), dried over anhydrous sodium sulfate and concentrated to afford white crystalline solid.5-Phenyl-1H-tetrazole(3a)IR (KBr, cm−1): 3331, 2907, 2850, 2611, 1607, 1485, 1433, 1050, 828, 742. 1H NMR (300 MHz, CDCl3): 8.04–8.007 (m, 1H), 7.611–7.574 (m, 2H). 13C NMR (75 MHz, CDCl3): 156.03, 131.19, 129.08, 126.805, 123.924. MS: m/z = 146 [M]+.
82% With trimethylsilylazide; di(n-butyl)tin oxide In 1,4-dioxane at 150℃; for 0.833333 h; Microwave irradiation General procedure: Dibutyltin oxide (0.33 mmol, 82 mg, 0.2 equiv), andtrimethylsilyl azide (3.33 mmol, 383 mg, 2 equiv) were added to a solution of 3-bromobenzonitrile (300mg, 1.67 mmol, 1 equiv) in anhydrous 1,4-dioxane (2 mL/mmol). The reaction mixture was subjectedto microwave irradiation in a tightly sealed microwave vessel for 50 min at 150 0C, then cooled to roomtemperature. The solvent was removed under reduced pressure. The residue was dissolved in diethylether (10 mL and extracted with 2 M aq. NaOH (3 x 10 mL). The aqueous layer was acidified with 4 Maq. HCl to pH 1 and extracted with ethyl acetate (4 x 10 mL). The organic extract was washed withbrine (10 mL), dried over MgSO4, and evaporated under reduced pressure to give the intermediatetetrazole(1.45 mmol, 326 mg, 86percent) as a white solid.
79% With sodium azide; lead(II) chloride In N,N-dimethyl-formamide at 120℃; for 8 h; Inert atmosphere General procedure: Benzonitrile (103 mg, 1 mmol) and sodium azide (97.5 mg, 1.5 mmol) were dissolved in 2 ml of dry DMF in a 25 ml round bottom flask. PbCl2 (27.8 mg, 0.1 mmol, 10 mol percent) was added to the reaction mixture and stirred at 120 °C for 8 h under nitrogen. After completion of the reaction (as monitored by TLC), the reaction mixture was cooled to room temperature and 10 ml of ice water was added followed by addition of 3 N HCl until the reaction mixture became strongly acidic (pH 2-3). The reaction mixture was extracted three times with 20 ml ethyl acetate. The organic layer was washed with brine solution and dried over anhydrous sodium sulfate, and was evaporated under reduced pressure to give a white solid product of 5-phenyl 1H-tetrazole with 81percent yield.
79% With sodium azide In N,N-dimethyl-formamide at 120℃; for 16 h; General procedure: In a round-bottom flask, 0.2 g benzonitrile (2 mmol) and0.4 g sodium azide (6 mmol), were added to 10 mL DMF.To this mixture, 20 mg of functionalized KIT-6 was addedand the reaction mixture was refluxed. The progress ofreaction was monitored by TLC (75:25 ethyl acetate/nhexane).After completion of the reaction, the reactionmixture was cooled and filtered. The solid materials werewashed three times with acetone and then with the water.The catalyst was collected and dried to activation for nextrun. The product was obtained by acidification of solutionwith hydrochloric acid (5 mL, 6 M). The precipitate wasfiltered and recrystallized from a water/ethanol mixture toget pure product as a white powder, yield: 88percent.
78% With sodium azide; silver nitrate In N,N-dimethyl-formamide at 20 - 120℃; for 5 h; General procedure: Sodiumazide (0.378 g, 0.046 mmol) was added to a solution of AgNO3 (5 mg, 10 mmol)in DMF (5 ml) and reaction mixture was stirred for 5 min, to this stirredsolution benzonitrile 1a (0.4 ml, 0.033 mmol) was added dropwise over theperiod of 1 min at room temperature and stirring continued for 10 min at thesame temperature and then heated at 120 C for 5 h. After consumption of 1a,the reaction mixture was cooled to room temperature and chilled by addingcrushed ice into the reaction mixture followed by addition of 2 N HCl tillreaction mixture reached the pH 2. The reaction mixture was then extractedwith ethyl acetate. The organic layer was dried with anhydrous Na2SO4, andconcentrated to obtain tetrazole 2a in 83percent yield as an off white solid (268 mg).
72% With sodium azide; tetra(n-butyl)ammonium hydrogensulfate In water at 85℃; for 9 h; Green chemistry General procedure: General Procedure for Preparation of Tetrazoles in Water(Method II). TBAHS (0.25 mmol) was added to a mixture of nitrile (1 mmol), sodium azide (1.5 mmol), and 2 mL H2O in around-bottomed flask. The reaction mixture was heated to 85 °C. After completion of the reaction (as monitored by TLC), the crude reaction mixture was transferred into a separatory funnel, to which was added 1 N HCl (15 mL) extracted by ethylacetate (EtOAc, 10 mL × 5). The combined organic layers were washed with H2O and dried over anhydrous sodium sulfate, and were evaporated under reduced pressure to give pure 5-substituted-1H-tetrazole.
70% With sodium azide; ammonium chloride In N,N-dimethyl-formamide for 24 h; Reflux General procedure: In a typical procedure, 5-aryl-1H-tetrazoles (1–24) were synthesized by adding aryl nitriles (1 eq.), sodium azide (1.2 eq.), and ammonium chloride (1 eq.) in solvent, the mixture was refluxed for 24 h. Progress of the reaction was monitored by thin layer chromatography. After completion of the reaction, 2.5 mL of 2M NaOH was added and the solution was stirred for half an hour. The reaction mixture was concentrated on reduced pressure, and dissolved in water. 3M HCl was added to the reaction mixture until precipitates formed. The precipitates were filtered and washed with distilled water. The yields of title compounds were found to be moderate to high.
67% With sodium azide In N,N-dimethyl-formamide for 24 h; Sealed tube; Green chemistry General procedure: The benzonitrile derivatives (2 mmol), sodium azide (3.2 mmol), and DMF (2 mL) were mixed in a sealed tube, then 30 mg of catalyst MSS-SO3H (or catalyst MSS-SO3Zn) was added into the tube, which was heated for 24 h under 140 C. After 24 hours’ reaction,the catalyst was separated by magnetic force, and the solution was poured into water.The liquid was acidified to pH 1, then ethyl acetate was added to extract the tetrazoles. Carefully evaporating the solvent under reduced pressure, we got the isolated tetrazoles. A sample for characterization was purified on a flash silica column.
54% With sodium azide; scandium tris(trifluoromethanesulfonate) In water; isopropyl alcohol at 160℃; for 1 h; Microwave irradiation; Sealed tube General procedure: Synthesis of 5-(4-chlorophenyl)-1H-tetrazole (2c) was achieved as follows: 4-chlorobenzonitrile 1c (274 mg, 2 mmol), NaN3 (260 mg, 4 mmol), Sc(OTf)3(197 mg, 0.4 mmol), and 8mL of a 3:1 isopropanol=water mixture were added to a30-mL Pyrex microwave vessel and capped. The microwave vessel was then placedin a Milestone Start Synth microwave reactor. The reaction was magnetically stirredand heated for 1 h at 160 C. The reaction was monitored by thin-layer chromatography(TLC) using an ether=hexane mixture (typically 50=50) for development.The reaction mixture was then diluted with saturated aqueous sodium bicarbonate(20 mL) and washed with ethyl acetate (215mL). The aqueous sodium bicarbonatelayer was cooled with ice and acidified to a pH of 2 or less with concentratedhydrochloric acid, which was added dropwise. The precipitate formed was extractedwith ethyl acetate (315 mL). The combined organic layers were dried with anhydroussodium sulfate and decanted into a tared round-bottom flask. The organiclayer was concentrated under reduced pressure by rotary evaporation at 40 C andthen under high vacuum. The tetrazole product was recrystallized from ethyl acetateand hexane. All reagents mentioned were not unpurified.

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