[ CAS No. 1571-85-3 ] {[proInfo.proName]}

Name: 1571-85-3|6-Nitro-2-phenyl-1H-benzo[d]imidazole|95%
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Quality Control of [ 1571-85-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 1571-85-3 ]

Product Details of [ 1571-85-3 ]

CAS No. :	1571-85-3	MDL No. :	MFCD00441943
Formula :	C₁₃H₉N₃O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FHOXCSDDMCCTPM-UHFFFAOYSA-N
M.W :	239.23	Pubchem ID :	759399
Synonyms :

Calculated chemistry of [ 1571-85-3 ]

Physicochemical Properties

Num. heavy atoms :	18
Num. arom. heavy atoms :	15
Fraction Csp3 :	0.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	70.35
TPSA :	74.5 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.58 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.43
Log Po/w (XLOGP3) :	3.07
Log Po/w (WLOGP) :	3.14
Log Po/w (MLOGP) :	2.54
Log Po/w (SILICOS-IT) :	1.33
Consensus Log Po/w :	2.3

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.74
Solubility :	0.0433 mg/ml ; 0.000181 mol/l
Class :	Soluble
Log S (Ali) :	-4.3
Solubility :	0.012 mg/ml ; 0.00005 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-4.82
Solubility :	0.00366 mg/ml ; 0.0000153 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.17

Safety of [ 1571-85-3 ]

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

Application In Synthesis of [ 1571-85-3 ]

* 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 [ 1571-85-3 ]

[ 1571-85-3 ] Synthesis Path-Downstream 1~65

1
[ 1571-85-3 ]
[ 100-44-7 ]
[ 109747-07-1 ]
[ 109747-57-1 ]

Yield	Reaction Conditions	Operation in experiment
	With iodine; sodium acetate

Reference： [1]Rao; Ratnam [Journal of the Chemical Society, 1959, p. 3087,3088]

2
[ 1571-85-3 ]
[ 74-88-4 ]
1,3-dimethyl-5-nitro-2-phenyl-benzimidazolium; iodide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With methanol at 110℃; im Rohr;

Reference： [1]Fischer,O.; Limmer [Journal fur praktische Chemie (Leipzig 1954), 1906, vol. <2> 74, p. 59]

3
[ 1571-85-3 ]
[ 1767-25-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 5h;	General procedure for the preparation of the 2-phenyl-1H-benzo[d]imidazol-5-amine derivatives 4a-4u General procedure: Method A: A suspension of 3 (5.0mmol, R=CH3, OCH3, OH, CH2CH3, CF3) and 10% Pd/C (0.13g) in methanol (30mL) was hydrogenated under normal pressure for 5h at room temperature. Filtration and evaporation gave corresponding compound 4.
85%	With hydrogenchloride; tin(II) chloride dihdyrate In ethanol; water at 80℃;
77%	With hydrogenchloride; tin(II) chloride dihdyrate In water for 2h; Reflux;

77%	With hydrogenchloride; tin(II) chloride dihdyrate In water for 2h; Reflux;	5 5-Amino-2-phenylbenzimidazole (68) (Shi et al., Bioorg. Med. Chem. 22:4735 (2014)). A mixture of 5-nitro-2-phenylbenzimidazole (67, 2.25 g, 9.43 mmol) and tin(II) dichioride dihydrate (8.18 g, 36.75) in concd HCl (30 mL) was refluxed for 2 h. The cooled reaction mixture was poured over ice-water. The mixture was basified to pH 10 and extracted into EtOAc. A solution of the crude product in hot EtOH was treated with Norit and filtered. The filtrate was diluted with water to give crystals (1.51 g, 77%): mp> 285 °C dec; ‘H NMR (400 MHz, DMSO-d6) 6 12.29 (s, 1H), 8.06 (d, J= 7.5 Hz, 2H), 7.54 -7.45 (m, 211), 7.45 -7.36 (m, lH), 7.28 (d, J 8.5 Hz, 1H), 6.68 (s, 1H), 6.53 (dd, J 8.5,2.1 Hz, 111), 4.94 (s, 2H); HPLC 98.2 area % (320 nm). Anal. Calcd for C,3H,1N30.1H2O: C, 73.98; H, 5.35; N, 19.91. Found: C, 74.13; H, 5.33; N, 19.71.
65.5%	With stannous chloride dihydrate In ethanol at 70℃; for 4h;
	With diammonium sulfide
	With tin(II) chloride dihdyrate In ethyl acetate for 12h; Reflux;	4.6. General Procedure for Synthesis of Phenol-Azo-Benzimidazole Derivatives (V-1~V-28) General procedure: A mixture of compound II-1, II-2 or II-3 (2 mmol),SnCl2·2H2O (10 mmol) in EtOAc (15 mL) was refluxed for12 h. When the reaction was complete according to TLCanalysis, the resulting reaction mixture was cooled to room temperature. Subsequently, the reaction mixture wasadjusted to pH 8-9 with saturated aq. NaHCO3 (50 mL).Then the mixture was extracted with EtOAc (2 × 150 mL).The combined organic phase was washed with brine (200mL), dried over anhydrous Na2SO4, and concentrated toafford compounds III-1, III-2 or III-3, which were useddirectly for the next step without further purification. To amixture of 5-amino-1H-benzimidazole (III-1, III-2 or III-3,2 mmol), water (5 mL) and concentrated HCl (12 mol/L,0.51 mL) at 0°C, a solution of sodium nitrite (NaNO2, 2.1mmol) in water (10 mL) was added dropwise whilemaintaining the temperature below 5°C. After stirring for 20min, a solution of diazonium chloride was prepared.Subsequently, a solution of diazonium chloride was addedgradually to a mixture of phenols (IV-1-IV-10, 2 mmol),sodium hydroxide (NaOH, 2 mmol), ethanol (15 mL) andwater (25 mL) at 0-5°C. After the addition of the abovediazonium solution, the mixture was continued to stir for 3-6h until a lot of precipitate was produced. The solid wascollected, washed with water (3×10 mL), dried and purifiedby PTLC to give the target products V-1~V-28.
	With palladium 10% on activated carbon In methanol at 20℃; for 5h;	1 10 mmol of benzoic acid, 11 mmol of 4-nitro-o-phenylenediamine and 40 g of polyphosphoric acid (PPA) were put into a reaction flask, heated and stirred at 150 ° C for 5 hours. After the reaction mixture was slightly cooled, it was slowly poured into 300 ml of ice water , With 20% NaOH aqueous solution to adjust the pH to 6, a large number of yellow solid precipitation, filtration, and water and petroleum ether were washed, vacuum drying.5 mmol of the obtained compound was added to 30 mL of methanol and stirred at room temperature until it was completely dissolved,Adding 0.13g 10% Pd / C, reaction at normal temperature and pressure for 5h, suction filtration, the filtrate of methanol spin dry, in orange red solid.1.2 mmol of the obtained compound was added to 20 mL of isopropyl alcohol with 1 mmol of 6,7-dimethoxy-4-chloroquinazoline and stirred under reflux for 5 hours. The solvent was dried and the column was separated and the developing solvent was dichloromethane : Methanol = 10: 1 to give the title compound. Yellow powder, yield: 56%

Reference： [1]Shi, Lei; Wu, Ting-Ting; Wang, Zhi; Xue, Jia-Yu; Xu, Yun-Gen [European Journal of Medicinal Chemistry, 2014, vol. 84, p. 698 - 707]
[2]Sana, Sravani; Reddy, Velma Ganga; Srinivasa Reddy; Tokala, Ramya; Kumar, Rahul; Bhargava, Suresh K.; Shankaraiah, Nagula [Bioorganic Chemistry, 2021, vol. 110]
[3]Patrick, Donald A.; Gillespie, J. Robert; McQueen, Joshua; Hulverson, Matthew A.; Ranade, Ranae M.; Creason, Sharon A.; Herbst, Zackary M.; Gelb, Michael H.; Buckner, Frederick S.; Tidwell, Richard R. [Journal of Medicinal Chemistry, 2017, vol. 60, # 3, p. 957 - 971]
[4]Current Patent Assignee: UNIVERSITY OF WASHINGTON - WO2017/127627, 2017, A1 Location in patent: Paragraph 0192
[5]Kulkarni, Ravindra G.; Laufer, Stefan A.; Chandrashekhar; Garlapati, Achaiah [Medicinal Chemistry, 2013, vol. 9, # 1, p. 91 - 99]
[6]Charlton et al. [Journal of the Chemical Society, 1951, p. 485,489, 492]
[7]Ke, Yazhen; Zhi, Xiaoyan; Yu, Xiang; Ding, Guodong; Yang, Chun; Xu, Hui [Combinatorial Chemistry and High Throughput Screening, 2014, vol. 17, # 1, p. 89 - 95]
[8]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - CN104725364, 2017, B Location in patent: Paragraph 0024

4
[ 128049-26-3 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide

Reference： [1]Fries [Justus Liebigs Annalen der Chemie, 1927, vol. 454, p. 204]

5
[ 100-52-7 ]
[ 99-56-9 ]
[ 1571-85-3 ]
[ 109747-07-1 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid

Reference： [1]Rao; Ratnam [Proceedings - Indian Academy of Sciences, Section A, 1958, # 47, p. 77,78]

6
[ 716-79-0 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
78.08%	With sulfuric acid; HNO₃ at 20℃; for 3h;	Nitration of benzimidazole Compound General procedure: Take above synthesized compound (1 g) and mixture of H2SO4 (5 mL) and HNO3 (5 mL) were taken in a beaker and stirred for 3 h at room temperature. Yellow color solid was filtered and recrystallized by ethanol with the yield of 85.00%. All the compounds (XY-1, XY-2 & XY-3) were synthesized by following the said method by using different substituted aromatic acids (XY-(a-c) respectively as given in Table 1. Thin layer chromatography was performed to assess the progression of the reaction.
38%	With sulfuric acid; HNO₃ at 35℃; for 13.25h;
	With HNO₃

Reference： [1]Mishra, Arvnabh; Narolkar, Swati; Patel, Dhaval M.; Patel, Nirmal K. [Oriental Journal of Chemistry, 2022, vol. 38, # 2, p. 432 - 438]
[2]Sugumaran; Ramanathan [Indian Journal of Heterocyclic Chemistry, 2011, vol. 21, # 1, p. 97 - 98]
[3]Huebner [Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 305]

7
[ 1076-59-1 ]
[ 99-56-9 ]
[ 1571-85-3 ]
[ 103977-08-8 ]

Yield	Reaction Conditions	Operation in experiment
50%	In acetonitrile Heating;

Reference： [1]Rao, M Hanmantha; Reddy, A Pandu Ranga; Veeranagaiah, V [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1992, vol. 31, # 2, p. 88 - 91]

8
[ 94-02-0 ]
[ 99-56-9 ]
[ 1571-85-3 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
	With Montmorillonite KSF In solid at 142℃; for 0.0666667h; Irradiation;

Reference： [1]Bougrin, Khalid; Soufiaoui, Mohamed [Tetrahedron Letters, 1995, vol. 36, # 21, p. 3683 - 3686]

9
[ 100-52-7 ]
[ 99-56-9 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sulfonated rice husk ash at 80℃; for 0.333333h; Green chemistry;	General procedure for the synthesis of benzimidazoles derivatives General procedure: 1,2-Phenylenediamine (1 mmol) was added to a mixture of RHA-SO3H (30 mg) and aldehyde (1 mmol) and the resulting mixture was stirred at 80 °C for the appropriate time in an oil bath. After completion of the reaction, as monitored by TLC (EtOAc: n-hexane 3:7), ethyl acetate (20 mL) was added and the catalyst was separated by filtration. The solvent was then removed under reduced pressure and the resulting solid product was recrystallized from ethanol, producing the pure product in good to high yields.
97%	With ammonium cerium(IV) nitrate; dihydrogen peroxide at 50℃; for 0.433333h;
96%	With Iron(III) nitrate nonahydrate; dihydrogen peroxide at 50℃; for 0.2h;

94%	With ammonium peroxydisulfate; sodium dodecyl-sulfate In water at 25℃; for 0.533333h; Micellar solution;
94%	With decylbenzenesulfonic acid; iodine In water at 20℃; for 2.5h; Green chemistry; chemoselective reaction;	General procedure for the syntheses of 2-substituted benzimidazoles General procedure: To a solutionof DBSA (0.05 mmol) in H2O (2 mL) were added an amine (0.5 mmol) andiodine (0.05 mmol). An aldehyde (0.5 mmol) was added portionwise at roomtemperature. The reaction was stirred at room temperature for several hours(see Table 3). The progress of the reaction was monitored by TLC. Thecompletion of the reaction was indicated by separation of the organic phasefrom aqueous media. The aqueous layer was decanted. The organic part wastaken in ethyl acetate, washed with saturated NaHCO3, water, brine and thendried over anhydrous Na2SO4. The organic layer was concentrated and purifiedby silica gel chromatography.
91%	With dihydrogen peroxide In ethanol at 20℃; for 0.75h; Green chemistry;
90%	With hydrogenchloride; dihydrogen peroxide; lithium chloride at 100℃; for 1.9h;
89%	With acetic acid In ethanol at 20℃; for 1h; Green chemistry;	General procedure for the synthesis of 2-substituted benzimidazoles. General procedure: The o-phenylenediamine (1.0mmol) was dissolved in EtOH 95% (10 mL), and added aldehydes (1.0 mmol), two drops of acetic acidand catalyst (2 mg) were magnetically stirred in the reaction flask at room temperature. The progress ofthe reaction was monitored by TLC using petroleum ether/EtOAc (4:1) as eluent. The reactions werestopped after 1 h. After completion of the reaction, the catalyst was separated from the reaction mixtureby filtration, the filtrate was added an equal volume of water, natural crystallization, filtration, and driedto give the products. The all products of Table 2 were confirmed from the ESI-MS, IR and 1H NMR.
89%	With bismuth (III) nitrate pentahydrate In water at 80℃; for 0.166667h; Microwave irradiation; Green chemistry;	2.1.2. General Procedure for the Synthesis of Benzimidazoles General procedure: The substrate (o-phenylenediamine, 1.0 mmol), aldehyde(1.1 mmol) and bismuth nitrate pentahydrate (24 mg, 5 mol%) were mixed together with water (1mL) in a microwave vial fitted with a magnetic stir bar.The mixture was irradiated in an automated microwave(CEM Corporation, Discover model) and the progressof the reaction was monitored by TLC. After completionof the reaction (Table 4) ethyl acetate (10 mL) wasadded to the reaction mixture and the organic layer waswashed with saturated sodium bicarbonate solution,brine and water successively. It was dried over anhydroussodium sulfate and the solvent was removed underreduced pressure. The crude mass was purifiedthrough a small silica gel column using ethyl acetate/hexanes as eluent.
89%	With sodium hydrogensulfite In water at 100℃; for 0.666667h; Green chemistry; chemoselective reaction;	General procedure for the synthesis of 2-substitutedbenzimidazole General procedure: In a round-bottomed flask (10 mL) equipped with a magnetic stirrer, a mixture of aldehyde (1.0 mmol) and NaHSO3(11.0 eq, 1.14 g) in H2O (4.0 mL) was prepared. When the mixture reached refluxing temperature, o-phenylenediamine derivatives (1.0 mmol) were added. The resulting mixture was stirred for appropriate time and monitored by HPLC (Hypersil GOLD 250 × 4.6 mm, 5 μm). After completion of the reaction, the reaction mixture was vacuum filtered after cooling to room temperature by a glass funnel. The residues were washed by water (4 mL × 2), dried in air dry oven and characterized by physical and spectral properties.
87%	With oxygen; cobalt(II) hydroxide In ethanol at 20℃; for 4h;	General procedure: To a mixture of 1,2-phenylenediamine (1.0 mmol) and aldehyde (1.2 mmol) in ethanol (3 mL) under open oxygen atmosphere, 10 mol % of the catalysts were added. The resulting mixture was stirred at room temperature for appropriate time (refPreviewPlaceHolderTable 2). After completion of the reaction, as monitored by TLC, the reaction mixture was diluted with ethanol (20 mL) and the catalyst was separated by filtration. The organic layer was concentrated under reduced pressure and the crude product was purified by silicagel column chromatography using ethyl acetate-n-hexane (1:9) as eluent to afford pure benzimidazole product. The spectral data are in full agreement with the data reported in literature.refPreviewPlaceHolder [48] , refPreviewPlaceHolder[54] and refPreviewPlaceHolder[55] Some of the compounds' spectral data are given below.
85%	With 2,3-dicyano-5,6-dichloro-p-benzoquinone In acetonitrile for 2h; Ambient temperature;
85%	With ferric hydrogen sulphate In ethanol at 20℃; for 1.25h; chemoselective reaction;
84%	With Fe₃O₄ In water at 20℃; for 10h; Green chemistry;
84%	With Fe(III) based PEG₁₀₀₀ dicationic imidazolium ionic liquid In toluene at 80℃; for 10h; Green chemistry;
84%	With dihydrogen peroxide; scandium tris(trifluoromethanesulfonate) In ethanol at 80℃; Green chemistry;	Typical experimental procedure of the preparation of products 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j,and 4k. General procedure: A mixture of o-phenylenediamine 1a (129.8 mg, 1.2 mmol),Sc(OTf)3 (73.8 mg, 0.15 mmol) and EtOH (15 mL) wre well stirred until the solid dissolved completely atreflux condition. Benzaldehyde 2b (101 μL, 1.0 mmol) and H2O2 (61 μL, 30 wt%, 2 mmol) was diluted to20 mL EtOH, and dropwised into the preprocessed mixture. After TLC showed the reaction to becomplete, the reaction mixture was cooled to rt, and then evaporated in vacuum. The product purified bycolumn chromatography (PE-EtOAc= 4:1) to give 4a (160.6 mg, 90%);
82%	With dihydrogen peroxide In methanol; water at 40℃; for 4h;
82%	With sodium metabisulfite In ethanol; water at 80℃;
81%	With air In 1,4-dioxane at 100℃; for 8h;
80%	With potassium iodide In N,N-dimethyl-formamide Microwave irradiation; Heating;
77%	With iron(III) phosphate; oxygen In neat (no solvent) at 20℃; for 0.2h;
70%	With 12-phosphotungstic heteropoly acid on graphene oxide/silica nanocomposite In water at 100℃; for 2.66667h; Green chemistry;
65%	With copper(I) iodide; oxygen In acetonitrile at 20℃; for 2h; Green chemistry;
63%	With sodium metabisulfite In N,N-dimethyl-formamide at 70℃; Microwave irradiation;
63%	With sodium disulfite Microwave irradiation;
60%	With air; cobalt ascorbic acid complex coated on titanium oxide nanoparticles In ethanol at 60℃; for 3h;	2.2.2 General Procedure for Synthesis of Benzimidazole from Benzaldehydes and o-Phenylenediamines General procedure: To a mixture of benzaldehyde (1.2mmol), 1,2-phenylenediamine(1mmol) in ethanol (0.8mL) in a glass test tube(10cm tall × 1cm diameter), was added TiO2/AA/Co nanocatalyst(0.02mol%) and the reaction mixture was heated at60°C under air and visible light conditions for the requiredtime. The reaction progress was monitored by TLC. Aftercompletion of the reaction, ethanol was added to the reactionmixture (3mL). TiO2/AA/Co nanocatalyst (solid phase) wasseparated by centrifuging followed by decantation (3 × 5mLethanol). Desired product (liquid phase) was purified by plate chromatography eluted with n-hexane/EtOAc (10/2).Assignments of products were made by 1H NMR spectraldata in comparison with authentic samples.
19.8%	With air In ethanol at 20℃; for 58h; Green chemistry;
82 %Chromat.	With 75% Fe/CeO2-ZrO2 In ethanol at 20℃; for 2h;
93 %Chromat.	Stage #1: benzaldehyde; 4-Nitrophenylene-1,2-diamine In ethanol at 20℃; for 2h; Stage #2: With dihydrogen peroxide; tetra-(n-butyl)ammonium iodide In ethanol at 20℃; for 6h;
0.3877 g	With 1-methyl-3-(propyl-3-sulfonic acid)imidazole chloride salt In water; acetonitrile at 55℃; for 5h;	General catalytic procedures General procedure: TEMPO (5 mol%), NaNO2 (8 mol%), and the IL (20 mol%)were added successively into a 5-mL round-bottom flaskthat was purged with oxygen five times. Subsequently, benzylalcohol (2 mmol) and CH3CN/H2O (10:1; 2.2 mL) wereadded in turn via a syringe. Then, the mixture was stirred at45 °C in an oil bath under atmospheric oxygen. When thebenzyl alcohol had been consumed (monitored by TLC),o-phenylenediamine (2.2 mmol) was added. The mixturewas further stirred at 55 °C under atmospheric oxygen untilcompletion of the reaction (monitored by TLC). The reactionmixture was extracted with dichloromethane(4 × 15 mL), and the combined extract was evaporatedunder vacuum. The crude product was purified by columnchromatography on silica gel to afford product 3

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[23]Reddy, P. Linga; Arundhathi; Tripathi, Mohit; Rawat, Diwan S. [RSC Advances, 2016, vol. 6, # 58, p. 53596 - 53601]
[24]Location in patent: experimental part Navarrete-Vázquez, Gabriel; Hidalgo-Figueroa, Sergio; Torres-Piedra, Mariana; Vergara-Galicia, Jorge; Rivera-Leyva, Julio Cesar; Estrada-Soto, Samuel; León-Rivera, Ismael; Aguilar-Guardarrama, Berenice; Rios-Gómez, Yolanda; Villalobos-Molina, Rafael; Ibarra-Barajas, Maximiliano [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 11, p. 3985 - 3991]
[25]Location in patent: experimental part Romero-Castro, Aurelio; Leon-Rivera, Ismael; Avila-Rojas, Laura Citlalli; Navarrete-Vazquez, Gabriel; Nieto-Rodriguez, Alejandro [Archives of Pharmacal Research, 2011, vol. 34, # 2, p. 181 - 189]
[26]Feizpour, Fahimeh; Jafarpour, Maasoumeh; Rezaeifard, Abdolreza [Catalysis Letters, 2018, vol. 148, # 1, p. 30 - 40]
[27]Chen, Guo-Feng; Shen, Hai-Dong; Jia, Hui-Ming; Zhang, Li-Yan; Kang, Hong-Yan; Qi, Qing-Qing; Chen, Bao-Hua; Cao, Jia-Li; Li, Ji-Tai [Australian Journal of Chemistry, 2013, vol. 66, # 2, p. 262 - 266]
[28]Location in patent: experimental part Behbahani, Farahnaz K.; Ziaei, Parisa; Fakhroueian, Zahra; Doragi, Neda [Monatshefte fur Chemie, 2011, vol. 142, # 9, p. 901 - 906]
[29]Location in patent: experimental part Zhu, Chenjie; Wei, Yunyang [ChemSusChem, 2011, vol. 4, # 8, p. 1082 - 1086]
[30]Geng, Zhenzhen; Zhang, Hong-Yu; Yin, Guohui; Zhang, Yuecheng; Zhao, Jiquan [Journal of Chemical Research, 2020, vol. 44, # 9-10, p. 557 - 565]

Yield	Reaction Conditions	Operation in experiment
	Red. der Nitro-Gruppe zur Amino-Gruppe (Verb.V);

Yield	Reaction Conditions	Operation in experiment
89%	With acetic acid at 20℃; for 0.166667h;	39 Example 1:2-phenylbenzimidazole: General procedure: Add 1 ml of catalytic amount of glacial acetic acid to the mortar.O-phenylenediamine 1 mmol,1.2 mmol of benzaldehyde was rapidly ground at room temperature for 10 minutes.The product was extracted with ethyl acetate and water.Concentrated under reduced pressure,The product was purified by column chromatography to give a white solid.The yield was 93%.
70%
	4-Nitro-o-phenylendiamin (I), Dibenzoylmethan (II), -Kond.(4h bei 60-70grad,HCl);

	N-Benzoyl-4-nitro-o-phenylendiamin durch Erhitzen mit Na-acetat;
	Neben 2-(4-Nitrophenyl)-5-nitrobenzimidazol aus 2-Phenylbenzimidazol in konz. H2SO4 beim Behandeln mit HNO3/konz. H2SO4;
	/BRN= 608106/, Ph-COOH, -Ggw. v. Polyphosphorsaeure;

12
[ 100-52-7 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
	With ethanol

Reference： [1]Pinnow; Wiskott [Chemische Berichte, 1899, vol. 32, p. 900]

13
[ 728-90-5 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tin; concentrated hydrochloric acid 2: fuming nitric acid

Reference： [1]Huebner [Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 305]

14
[ 98-88-4 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dimethylaniline 2: alcoholic KOH-solution
	Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / -10 - 20 °C 2: boron trifluoride diethyl etherate / 1,4-dioxane / 3 h / Reflux

Reference： [1]Fries [Justus Liebigs Annalen der Chemie, 1927, vol. 454, p. 204]
[2]Current Patent Assignee: UNIVERSITY OF WASHINGTON - WO2017/127627, 2017, A1

15
[ 99-56-9 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dimethylaniline 2: alcoholic KOH-solution
	Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / -10 - 20 °C 2: boron trifluoride diethyl etherate / 1,4-dioxane / 3 h / Reflux

Reference： [1]Fries [Justus Liebigs Annalen der Chemie, 1927, vol. 454, p. 204]
[2]Current Patent Assignee: UNIVERSITY OF WASHINGTON - WO2017/127627, 2017, A1

16
[ 1571-85-3 ]
[ 107-13-1 ]
3-(6-Nitro-2-phenyl-benzoimidazol-1-yl)-propionitrile [ No CAS ]
3-(5-nitro-2-phenyl-benzoimidazol-1-yl)-propionitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 20% 2: 18.9%	With dmap at 70℃; for 4h; Heating / reflux;	1 A mixture of 5-nitro-2-phenylbenzimidazole (1 g, 4.2 mmol), acrylonitrile (50 mL) and N,N-dimethylpiridine (25 mg) was heated at 70° C. for 4 hr.The excess of acrylonitrile was evaporated and oily residue was subjected to the flash chromatography on silica gel using hexane-ethyl acetate (75: 25 v/v) as an eluent. Structure of the regioisomers was determined using 1H NOESY studies. 0.25 g (20%) of the 6-nitro isomer and 0.23 g (18.9%) of the 5-nitro isomer were obtained.
1: 20% 2: 18.9%	With N,N-dimethylaniline at 70℃; for 4h;	1 A mixture of 5-nitro-2-phenylbenzimidazole (1 g, 4.2 mmol), acrylonitrile (50 mL) and N,N-dimethylpiridine (25 mg) was heated at 70° C. for 4 hr. The excess of acrylonitrile was evaporated and oily residue was subjected to the flash chromatography on silica gel using hexane-ethyl acetate (75:25 v/v) as an eluent. Structure of the regioisomers was determined using 1H NOESY studies. 0.25 g (20%) of the 6-nitro isomer and 0.23 g (18.9%) of the 5-nitro isomer were obtained.

Reference： [1]Current Patent Assignee: PARATEK PHARMACEUTICALS, INC. - US2003/229065, 2003, A1 Location in patent: Page 45
[2]Current Patent Assignee: PARATEK PHARMACEUTICALS, INC. - US2006/160799, 2006, A1 Location in patent: Page/Page column 62

17
[ 100-52-7 ]
[ 97-02-9 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
60%	With sodium dithionite In water; dimethyl sulfoxide at 120℃; for 4h;	4.3. General procedure for the synthesis of 2-arylbenzimidazoles 5b,d General procedure: A solution of benzaldehyde 4 (1 equiv) and 4-methoxy-2-nitrobenzenamine 2b and 2,4-dinitrobenzenamine 2d (1 equiv) in DMSO (3 mL) was treated with Na2S2O4 (3 equiv), dissolved in a small volume of water, and heated at 120 °C with stirring for 4 h. The mixture was poured into water (20 mL) and a precipitate was formed and collected by filtration, washed with water, dried, and recrystallized from ethanol.

Reference： [1]Location in patent: experimental part Batista, Rosa M.F.; Ferreira, R. Cristina M.; Raposo, M. Manuela M.; Costa, Susana P.G. [Tetrahedron, 2012, vol. 68, # 36, p. 7322 - 7330]

18
[ 99-56-9 ]
[ 1663-61-2 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
88%	With o-benzenedisulfonimide In neat (no solvent) at 20 - 25℃; for 6h; Green chemistry;

Reference： [1]Barbero, Margherita; Cadamuro, Silvano; Dughera, Stefano [ARKIVOC, 2012, vol. 2012, # 9, p. 262 - 279]

19
[ 6293-83-0 ]
[ 1670-14-0 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
86%	With copper(I) oxide; caesium carbonate; N,N`-dimethylethylenediamine; In N,N-dimethyl-formamide; at 140℃; for 16h;Inert atmosphere;	General procedure: A flask was charged with Cu2O (14 mg, 0.1 mmol), Cs2CO3 (977 mg, 3 mmol), o-haloaniline (1 mmol) and amidine hydrochloride (1.5 mmol) in 2 mL DMF under nitrogen atmosphere. The mixture was stirred at room temperature and DMEDA (20 mL, 0.2 mmol) was added via syringe. The reaction mixture was then stirred in a preheated oil bath at 140 C for 16 h, and then cooled to room temperature. The inorganic salt was filtered off and ethyl acetate, water was added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over Na2SO4, and concentrated in vacuum.The residue was purified by column chromatography on silica gelusing petroleum ether/ethyl acetate as eluent to provide the desired product.

Reference： [1]Tetrahedron,2013,vol. 69,p. 1717 - 1719

20
[ 13296-94-1 ]
[ 1670-14-0 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
56%	With copper(I) oxide; caesium carbonate; N,N`-dimethylethylenediamine In N,N-dimethyl-formamide at 140℃; for 16h; Inert atmosphere;	General experimental procedure General procedure: A flask was charged with Cu2O (14 mg, 0.1 mmol), Cs2CO3 (977 mg, 3 mmol), o-haloaniline (1 mmol) and amidine hydrochloride (1.5 mmol) in 2 mL DMF under nitrogen atmosphere. The mixture was stirred at room temperature and DMEDA (20 mL, 0.2 mmol) was added via syringe. The reaction mixture was then stirred in a preheated oil bath at 140 C for 16 h, and then cooled to room temperature. The inorganic salt was filtered off and ethyl acetate, water was added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over Na2SO4, and concentrated in vacuum.The residue was purified by column chromatography on silica gelusing petroleum ether/ethyl acetate as eluent to provide the desired product.

Reference： [1]Qu, Yanyang; Pan, Lei; Wu, Zhiqing; Zhou, Xiangge [Tetrahedron, 2013, vol. 69, # 6, p. 1717 - 1719]

21
[ 100-52-7 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium metabisulfite / ethanol; water / Cooling 2: N,N-dimethyl-formamide / 4 h / 130 °C
	Multi-step reaction with 2 steps 1: sodium metabisulfite / ethanol; water 2: N,N-dimethyl-formamide / 110 °C

Reference： [1]Kulkarni, Ravindra G.; Laufer, Stefan A.; Chandrashekhar; Garlapati, Achaiah [Medicinal Chemistry, 2013, vol. 9, # 1, p. 91 - 99]
[2]Shaukat, Awais; Mirza, Hira M.; Ansari, Amna H.; Yasinzai, Masoom; Zaidi, Sohail Z.; Dilshad, Sana; Ansari, Farzana L. [Medicinal Chemistry Research, 2013, vol. 22, # 8, p. 3606 - 3620]

22
[ 4657-12-9 ]
[ 99-56-9 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
79%	In N,N-dimethyl-formamide at 110℃;
	In N,N-dimethyl-formamide at 130℃; for 4h;

Reference： [1]Shaukat, Awais; Mirza, Hira M.; Ansari, Amna H.; Yasinzai, Masoom; Zaidi, Sohail Z.; Dilshad, Sana; Ansari, Farzana L. [Medicinal Chemistry Research, 2013, vol. 22, # 8, p. 3606 - 3620]
[2]Kulkarni, Ravindra G.; Laufer, Stefan A.; Chandrashekhar; Garlapati, Achaiah [Medicinal Chemistry, 2013, vol. 9, # 1, p. 91 - 99]

23
[ 1571-85-3 ]
[ 19250-69-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: stannous chloride dihydrate / ethanol / 4 h / 70 °C 2: triethylamine / tetrahydrofuran / 5 h / 20 °C

Reference： [1]Kulkarni, Ravindra G.; Laufer, Stefan A.; Chandrashekhar; Garlapati, Achaiah [Medicinal Chemistry, 2013, vol. 9, # 1, p. 91 - 99]

24
[ 1571-85-3 ]
[ 300384-33-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: stannous chloride dihydrate / ethanol / 4 h / 70 °C 2: triethylamine / tetrahydrofuran / 5 h / 20 °C

Reference： [1]Kulkarni, Ravindra G.; Laufer, Stefan A.; Chandrashekhar; Garlapati, Achaiah [Medicinal Chemistry, 2013, vol. 9, # 1, p. 91 - 99]

25
[ 1571-85-3 ]
[ 1440142-00-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: stannous chloride dihydrate / ethanol / 4 h / 70 °C 2: triethylamine / tetrahydrofuran / 5 h / 20 °C

Reference： [1]Kulkarni, Ravindra G.; Laufer, Stefan A.; Chandrashekhar; Garlapati, Achaiah [Medicinal Chemistry, 2013, vol. 9, # 1, p. 91 - 99]

26
[ 1571-85-3 ]
[ 1292833-61-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: stannous chloride dihydrate / ethanol / 4 h / 70 °C 2: triethylamine / tetrahydrofuran / 5 h / 20 °C

Reference： [1]Kulkarni, Ravindra G.; Laufer, Stefan A.; Chandrashekhar; Garlapati, Achaiah [Medicinal Chemistry, 2013, vol. 9, # 1, p. 91 - 99]

27
[ 100-39-0 ]
[ 99-56-9 ]
[ 1571-85-3 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium hydrogencarbonate; copper(I) bromide In dimethyl sulfoxide at 120℃; for 24h;
74%	With pyridine N-oxide at 110℃; for 2h;	General procedure for the synthesis of 2-substituted benzimidazoles General procedure: Primary alkyl bromide derivative (5 mmol), pyridine-N-oxide (12.5 mmol) and orthophenylenediamine derivative (5 mmol) are well mixed in a 25 mL round bottomed flask and placed in an oil bath on a magnetic stirrer hot plate at required temperature. The mixture was heated to selected temperature for required time (Table 2). After completion of the reaction (TLC, AcOEt-petroleum ether), the organic mixture was washed with dilute NaOH and filtered off. The filtrate was collected for recovery of pyridine. The resulting residue was recrystallized from EtOH-H2O to give the desired benzimidazole products. Pyridine was recovered from the filtrate (99.5%) by azeotropic distillation (bp. 92.6°C) and separation on sodium hydroxide. Resulting pyridine was oxidized with peracetic acid to the pyridine-N-oxide [46] which was then reused in reaction. All of the products are known compounds [47-57] and their identity was easily confirmed by comparison with authentic samples (mp, 1H-NMR, 13C-NMR).

Reference： [1]Qiu, Dezhi; Wei, Haidong; Zhou, Lihong; Zeng, Qingle [Applied Organometallic Chemistry, 2014, vol. 28, # 2, p. 109 - 112]
[2]Brătulescu, George [Synthetic Communications, 2017, vol. 47, # 8, p. 811 - 817]

28
[ 1571-85-3 ]
C₂₃H₁₆N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: tin(II) chloride dihdyrate / ethyl acetate / 12 h / Reflux 2.1: hydrogenchloride; sodium nitrite / water / 0.33 h / 0 - 5 °C 2.2: 0 - 5 °C