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Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
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USD 150+
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Structure of 698-63-5 * Storage: {[proInfo.prStorage]}
* 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.
Reference：
[1] Journal of Medicinal Chemistry, 2003, vol. 46, # 3, p. 427 - 440
2
[ 698-63-5 ]
[ 4426-72-6 ]
[ 59-87-0 ]
Reference：
[1] Australian Journal of Chemistry, 1980, vol. 33, # 3, p. 519 - 525
3
[ 698-63-5 ]
[ 21508-19-0 ]
Yield
Reaction Conditions
Operation in experiment
55%
With hydrogenchloride In water at 40℃;
The aldehyde (3.5g) and conc. HCI (20MUT) were combined and stirred overnight at 40°C. The reaction mixture was poured into cold water and extracted with ether, washed with satd. NAHCO3 AND brine, dried over anhydrous MGS04, filtered and concentrated in vacuo to give 1.76g of product (55percent)
55%
at 40℃;
The aldehyde (3.5 g) and cone. HC1 (20 ml) were combined and stirred overnight at 40 C. The reaction mixture was poured into cold water and extracted with ether, washed with satd. NaHCO3 and brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo to give 1.76 g of product (55percent)
55%
for 40 h;
The aldehyde (3.5 g) and conc. HCl (20 ml) were combined and stirred overnight at 40 C. The reaction mixture was poured into cold water and extracted with ether, washed with satd. NaHCO3 and brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo to give 1.76 g of product (55percent)
55%
With hydrogenchloride In water at 40℃;
PREPARATIVE EXAMPLE 34.1; The aldehyde (3.5g) and conc. HCI (20ml) were combined and stirred overnight at 40°C. The reaction mixture was poured into cold water and extracted with ether, washed with satd. NaHCO3 and brine, dried over anhydrous MgS04, filtered and concentrated in vacuo to give 1.76g of product (55percent)
55%
With hydrogenchloride In water at 40℃;
The aldehyde (3.5g) and conc. HCl(20ml) were combined and stirred overnight at 40°C. The reaction mixture was poured into cold water and extracted with ether, washed with satd. NaHCO3 and brine, dried over anhydrous MgS04, filtered and concentrated in vacuo to give 1.76g of product (55percent)
Reference：
[1] Chemistry - A European Journal, 2016, vol. 22, # 1, p. 129 - 133
[2] Patent: WO2004/33440, 2004, A1, . Location in patent: Page 238
[3] Patent: US2004/147559, 2004, A1, . Location in patent: Page 121
[4] Patent: US2004/106794, 2004, A1, . Location in patent: Page 122
[5] Patent: WO2005/66147, 2005, A1, . Location in patent: Page/Page column 207
[6] Patent: WO2005/68460, 2005, A1, . Location in patent: Page/Page column 202
[7] Journal of Medicinal Chemistry, 2016, vol. 59, # 7, p. 3471 - 3488
4
[ 2493-04-1 ]
[ 698-63-5 ]
Yield
Reaction Conditions
Operation in experiment
90%
With manganese(IV) oxide In dichloromethane at 20℃; for 12 h;
The compound 4 (10 g, 0.07 µM) dissolved in 150 ml dichloromethane in, adding manganese dioxide (60.9 g, 0.7 µM), stirring at room temperature 12 h, filtering, drying by anhydrous magnesium sulphate, evaporate the solvent. Vacuum distillation, to obtain compound 5 (8.9 g, orange liquid, yield 90percent).
Reference：
[1] Chemistry - A European Journal, 2010, vol. 16, # 42, p. 12718 - 12726
[2] Patent: CN108101874, 2018, A, . Location in patent: Paragraph 0006; 0017; 0020; 0023; 0026; 0028; 0031
[3] RSC Advances, 2014, vol. 4, # 25, p. 12834 - 12839
[4] Journal of the American Chemical Society, 1931, vol. 53, p. 1923
[5] Green Chemistry, 2017, vol. 19, # 5, p. 1315 - 1326
5
[ 92-55-7 ]
[ 698-63-5 ]
Yield
Reaction Conditions
Operation in experiment
89.2%
at 78 - 85℃; for 1.5 h;
100 l) was charged with 60 L of ethanol, 50 kg of 5-nitro-furfural (compound l), 20 kg (82.25 mol), and 10percent of sulfuric acid (^ (3) (4.11111, 111):Heated to 78 to 85 ° C, reacted for 1 and 5 h, concentrated under reduced pressure to remove ethanol to give a concentrate; the concentrate was dissolved in methylene chloride and washed three times with saturated sodium chloride to collect the methylene chloride layer; The crude product was purified by silica gel column chromatography (eluent PE: EA = 5: 1). The crude product was collected and the residue was purified by solidification on silica gel. Concentrated to give 5 - nitro - furfural pure product, the yield was 89.2percent.[0077] If the preparation of nitramine too Seoul, then the reaction of the product without purification separation, directly used for the preparation of Nasisi Taier.[0078] (2) Preparation of nitrofurant crude[0079] In the dark conditions, 3-amino-5-methylthiomethyl-2-oxazolidinone (compound3) 14. 7 kg (90.66 mil) in ethanol (20 L) was added to the reaction solution (60 L) of step (1) cooled to 15 to 25 ° C of 5-nitro-furfural (compound 2) After precipitation, the reaction was carried out at 20 to 25 ° C for 2 hours. The solid was filtered and the residue was filtered. The filter cake was washed with cold ethanol (5 to 10 ° C) and dried to obtain crude nitrofurant.(3) refinement of nitrofurant[0081] in the dark conditions, take nitrofurant crude 5kg, add 95percent ethanol 60L, heated to reflux, hot filter to get the filtrate; the filtrate to stand, precipitate solid, filter, filter cake with a small amount of 95percent ethanol , The solvent was removed and dried to constant weight to give a light yellow nitrofurant extract with a yield of 95percent and a total yield of 85.2percent.
88%
With sulfuric acid In water at 100℃; for 0.166667 h;
A mixture of 5-nitrofurfural diacetate(2) (10 g, 41.12 mmol) and 50 percent aqueous sulphuric acid (100mL) was heated to 100 °C for 10 min. After completion of the reaction, checked by TLC, the reaction mixture was cooled to room temperature and extracted with ethyl acetate (2 × 100 mL)and the organic layer was washed with water, brine solution and dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to obtain 5-nitrofurfural 3. Yield:5.10 g, 88 percent. m.p.: 35-36 °C.
Reference：
[1] Phosphorus, Sulfur and Silicon and the Related Elements, 2004, vol. 179, # 12, p. 2645 - 2651
[2] Molecules, 2009, vol. 14, # 10, p. 4065 - 4078
[3] Patent: CN105820145, 2016, A, . Location in patent: Paragraph 0075-0081
[4] Asian Journal of Chemistry, 2018, vol. 30, # 2, p. 312 - 316
[5] Journal of Organic Chemistry, 2018, vol. 83, # 8, p. 4427 - 4440
[6] Journal of Chemical Research, Miniprint, 1989, # 6, p. 1201 - 1218
[7] Journal of the American Chemical Society, 1930, vol. 52, p. 2550,2551
[8] Journal of the Indian Chemical Society, 1981, vol. 58, p. 217 - 219
[9] Tetrahedron Letters, 1995, vol. 36, # 11, p. 1779 - 1782
[10] Collection of Czechoslovak Chemical Communications, 1996, vol. 61, # 8, p. 1233 - 1243
[11] Patent: WO2005/14585, 2005, A1, . Location in patent: Page/Page column 18
[12] Archiv der Pharmazie, 2007, vol. 340, # 12, p. 635 - 641
[13] Patent: CN103664923, 2016, B, . Location in patent: Paragraph 0049
[14] Patent: CN104402874, 2016, B, . Location in patent: Paragraph 0067; 0071; 0072; 0073
[15] Patent: CN103755696, 2016, B, . Location in patent: Paragraph 0047
[16] Patent: CN107987069, 2018, A, . Location in patent: Paragraph 0024; 0066-0071
[17] Patent: CN108084174, 2018, A, . Location in patent: Paragraph 0068; 0069; 0070; 0073
[18] Patent: CN108383834, 2018, A, . Location in patent: Paragraph 0032; 0035; 0037; 0042; 0047
6
[ 98-01-1 ]
[ 698-63-5 ]
Yield
Reaction Conditions
Operation in experiment
78%
With Nitrogen dioxide In acetonitrile at 20℃; for 6 h;
In a reactor equipped with 5 mL of acetonitrile, 0.20 g of furfural, 0.01 g of sulfonated graphene and 0.20 mL of nitrogen dioxide were added, and the reaction was stirred at room temperature in an atmosphere of 0.1 MPa for 6 h.After the reaction was completed, nitrogen was introduced into the reaction mixture under atmospheric pressure until the nitrogen oxides completely escaped to the cold trap reaction receiver, and the catalyst was filtered out.The filtrate was washed with 5percent (m/m) aqueous sodium bicarbonate solution to near neutrality, washed with distilled water until the organic phase was neutral, and concentrated by rotary evaporation in a vacuum.The liquid chromatographic analysis was carried out using n-hexadecane as an internal standard, and the mass of 5-nitrofurfural was 0.23 g, and the yield was 78percent.
22%
at -30℃; for 2 h;
13mL of nitric acid(68percent) was added slowly to 83 ml of acetic anhydride between 15-25 °C with rapid stirring. After the addition was complete, the nitration reagent was added slowly to the solution of furan-2-carbaldehyde (1) (9.6g, 0.1mol) in acetic anhydride (100ml) cooled to -30 °C in advance. When TLC showed no starting material remained, the mixture was poured on ice water and extracted with ethyl acetate. The organic layer was dried and purified by chromatography (PE/DCM, 3/1) to give compound 2 (3.1g, 22percent).
Reference：
[1] Patent: CN108003031, 2018, A, . Location in patent: Paragraph 0037-0038
[2] Patent: EP3018125, 2016, A1, . Location in patent: Paragraph 0874-0876
[3] Journal of Medicinal Chemistry, 2016, vol. 59, # 7, p. 3471 - 3488
7
[ 13529-17-4 ]
[ 698-63-5 ]
Reference：
[1] Journal of Organic Chemistry, 2015, vol. 80, # 21, p. 10498 - 10504
8
[ 20782-91-6 ]
[ 698-63-5 ]
Reference：
[1] Angewandte Chemie - International Edition, 2018, vol. 57, # 38, p. 12494 - 12498[2] Angew. Chem., 2018, vol. 130, # 38, p. 12674 - 12678,5
9
[ 20782-90-5 ]
[ 698-63-5 ]
Reference：
[1] Collection of Czechoslovak Chemical Communications, 1980, vol. 45, # 3, p. 752 - 754
10
[ 623-17-6 ]
[ 698-63-5 ]
Reference：
[1] Journal of the American Chemical Society, 1931, vol. 53, p. 1923
[2] Patent: CN108101874, 2018, A,
11
[ 5407-68-1 ]
[ 698-63-5 ]
Reference：
[1] Journal of the American Chemical Society, 1931, vol. 53, p. 1923
[2] Patent: CN108101874, 2018, A,
12
[ 17163-15-4 ]
[ 698-63-5 ]
Reference：
[1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1989, vol. 28, # 1-11, p. 687 - 689
[2] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1989, vol. 28, # 1-11, p. 687 - 689
13
[ 5904-70-1 ]
[ 698-63-5 ]
Reference：
[1] Journal of the American Chemical Society, 1930, vol. 52, p. 2550,2551
14
[ 98-00-0 ]
[ 698-63-5 ]
Reference：
[1] Journal of Organic Chemistry, 1959, vol. 24, p. 255
[2] Patent: CN108101874, 2018, A,
15
[ 4077-58-1 ]
[ 698-63-5 ]
Reference：
[1] Journal of Organic Chemistry, 1959, vol. 24, p. 255
16
[ 20782-91-6 ]
[ 698-63-5 ]
[ 17163-18-7 ]
[ 98603-34-0 ]
Reference：
[1] Journal of Chemical Research, Miniprint, 1985, # 5, p. 1814 - 1823
17
[ 4077-62-7 ]
[ 698-63-5 ]
Reference：
[1] Journal of Organic Chemistry, 1959, vol. 24, p. 255
18
[ 499979-42-9 ]
[ 698-63-5 ]
Reference：
[1] International Journal of Chemical Kinetics, 2002, vol. 34, # 12, p. 685 - 692
19
[ 499979-43-0 ]
[ 698-63-5 ]
[ 593-77-1 ]
Reference：
[1] International Journal of Chemical Kinetics, 2002, vol. 34, # 12, p. 685 - 692
20
[ 499979-45-2 ]
[ 698-63-5 ]
[ 2211-64-5 ]
Reference：
[1] International Journal of Chemical Kinetics, 2002, vol. 34, # 12, p. 685 - 692
21
[ 156-44-5 ]
[ 698-63-5 ]
[ 62-53-3 ]
Reference：
[1] Australian Journal of Chemistry, 1980, vol. 33, # 3, p. 519 - 525
22
[ 4077-58-1 ]
[ 67-66-3 ]
[ 698-63-5 ]
Reference：
[1] Journal of Organic Chemistry, 1959, vol. 24, p. 255
23
[ 24163-39-1 ]
[ 20782-91-6 ]
[ 698-63-5 ]
[ 17163-18-7 ]
[ 98603-34-0 ]
Reference：
[1] Journal of Chemical Research, Miniprint, 1985, # 5, p. 1814 - 1823
Reference：
[1] Green Chemistry, 2018, vol. 20, # 13, p. 2973 - 2977
26
[ 698-63-5 ]
[ 67-20-9 ]
Reference：
[1] Acta Poloniae Pharmaceutica, 1959, vol. 16, p. 1,4,5[2] Chem.Abstr., 1959, p. 11760
27
[ 80-65-9 ]
[ 698-63-5 ]
[ 67-45-8 ]
Reference：
[1] Journal of the American Chemical Society, 1955, vol. 77, p. 2277,2280, 2281
28
[ 698-63-5 ]
[ 109-84-2 ]
[ 67-45-8 ]
Reference：
[1] Patent: US2742462, 1952, ,
29
[ 698-63-5 ]
[ 20782-91-6 ]
Reference：
[1] Medicinal Chemistry Research, 2013, vol. 22, # 12, p. 5940 - 5947
[2] Patent: WO2017/17631, 2017, A2,
[3] Asian Journal of Chemistry, 2018, vol. 30, # 2, p. 312 - 316
30
[ 499979-45-2 ]
[ 698-63-5 ]
[ 2211-64-5 ]
Reference：
[1] International Journal of Chemical Kinetics, 2002, vol. 34, # 12, p. 685 - 692
31
[ 698-63-5 ]
[ 5351-23-5 ]
[ 965-52-6 ]
Reference：
[1] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 14, p. 6724 - 6731
32
[ 698-63-5 ]
[ 25517-72-0 ]
[ 4936-47-4 ]
Yield
Reaction Conditions
Operation in experiment
96.9%
at 15 - 40℃; for 5 h; Large scale
Heating step 1) made of a compound represented by the formula B N - amino -5 - methylthiomethyl -2 - oxazolidinone reaction liquid, into the step 2) made of a compound represented by the formula D 5 - nitro-furfural reaction solution, to carry out dehydration condensation reaction, the control temperature is 25 °C, after dripping in 15 °C -40 °C reaction under 5h; TLC monitoring, a compound represented by the formula B N - amino -5 - methylthiomethyl -2 - oxazolidinone the reaction is complete the end of the reaction, a compound represented by the refractory fettling [...] E; 4) preparation of a compound represented by the formula E micromolecule The above-mentioned step 3) after the reaction, cooling to room temperature filtration, the filter cake is washed with methanol washing, the centrifugal spin-dry methanol, and then the cake is washed by pure water, until the washing water after PH>6; then methanol pulping for 1 time, drying after drying centrifugally refractory fettling micromolecule a compound represented by the formula E 135.9 kg.
With indium(III) chloride; sulfuric acid; orthoformic acid triethyl ester; at 78 - 85℃; for 1.5h;
100 l) was charged with 60 L of ethanol, 50 kg of 5-nitro-furfural (compound l), 20 kg (82.25 mol), and 10% of sulfuric acid (^ (3) (4.11111, 111):Heated to 78 to 85 C, reacted for 1 and 5 h, concentrated under reduced pressure to remove ethanol to give a concentrate; the concentrate was dissolved in methylene chloride and washed three times with saturated sodium chloride to collect the methylene chloride layer; The crude product was purified by silica gel column chromatography (eluent PE: EA = 5: 1). The crude product was collected and the residue was purified by solidification on silica gel. Concentrated to give 5 - nitro - furfural pure product, the yield was 89.2%.[0077] If the preparation of nitramine too Seoul, then the reaction of the product without purification separation, directly used for the preparation of Nasisi Taier.[0078] (2) Preparation of nitrofurant crude[0079] In the dark conditions, 3-amino-5-methylthiomethyl-2-oxazolidinone (compound3) 14. 7 kg (90.66 mil) in ethanol (20 L) was added to the reaction solution (60 L) of step (1) cooled to 15 to 25 C of 5-nitro-furfural (compound 2) After precipitation, the reaction was carried out at 20 to 25 C for 2 hours. The solid was filtered and the residue was filtered. The filter cake was washed with cold ethanol (5 to 10 C) and dried to obtain crude nitrofurant.(3) refinement of nitrofurant[0081] in the dark conditions, take nitrofurant crude 5kg, add 95% ethanol 60L, heated to reflux, hot filter to get the filtrate; the filtrate to stand, precipitate solid, filter, filter cake with a small amount of 95% ethanol , The solvent was removed and dried to constant weight to give a light yellow nitrofurant extract with a yield of 95% and a total yield of 85.2%.
88%
With sulfuric acid; In water; at 100℃; for 0.166667h;
A mixture of 5-nitrofurfural diacetate(2) (10 g, 41.12 mmol) and 50 % aqueous sulphuric acid (100mL) was heated to 100 C for 10 min. After completion of the reaction, checked by TLC, the reaction mixture was cooled to room temperature and extracted with ethyl acetate (2 × 100 mL)and the organic layer was washed with water, brine solution and dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to obtain 5-nitrofurfural 3. Yield:5.10 g, 88 %. m.p.: 35-36 C.
With sulfuric acid; In water; at 20 - 50℃; for 0.833333 - 0.916667h;
5-nitro-2-furancarboxaldehyde (II) A total of 86.5 g of 5-nitrofurfurylidine diacetate was added in small portions to 90 ml of sulfuric acid (73% by weight) over a period of 10 to 15 min. The mixture was stirred for 30 min at ambient temperature, 10 min at 50C, cooled to 30C, and then poured onto 150 g of crushed ice. The mixture was filtered, sucked as dry as possible on A Buchner funnel with the aid of a rubber dental dam and this afforded 51.5 g of 5-nitro-2-furancarbox- aldehyde which melted at 32-34C.
With phosphoric acid; In ethanol; water; for 1h;Reflux;
The 746 g (3.07mol) 5- nitro-2-furaldehyde diacetate 6,1500ml ethanol, 10% phosphoric acid (85% H3PO461ml + H2O936ml) solution into the reaction flask, was heated at reflux for 1h, cooled to room temperature, to give intermediate an ethanol solution 7.
With sulfuric acid; In methanol; for 1h;Reflux; Large scale;
2) preparation of a compound represented by the formula D 5 - nitro-furfural Taking 225 kg a compound represented by the formula C 5 - ethyl nitrofurfural diacetate, by adding 1000 kg dissolved in methanol, dropping 90 kg concentrated sulfuric acid, reflux reaction 1h, for cooling to room temperature, a compound represented by the refractory fettling D 5 - nitro-furfural;
With sulfuric acid; In ethanol; water;Reflux;
176 g of <strong>[92-55-7]5-nitro-2-furaldehyde diacetate</strong>, 441 ml of 95% ethanol and 352 ml of 10% sulfuric acid (35.2 g of purified water 316.8 g of sulfuric acid) were charged into a reaction flask and heated to reflux to give 5-nitrofurfural
With trifluoroacetic acid; In ethanol; at 20℃; for 10h;Darkness;
Example 6Preparation of 5-nitrofurfuralIn the 2000ml reaction flask,Added 183 g of 5-nitrofurfuraldehyde diethyl ester,Add solvent 900wt.% ethanol 900ml,Add 86 g of trifluoroacetic acid and stir at room temperature for 10 hours in the dark. After the reaction is completed, no treatment is performed.
With hydrogenchloride; In ethanol; water; for 1.5h;Reflux;
97.2 g of nitrofurfural diethyl ester, 310.0 g of ethanol and 36.0 g of hydrochloric acid were added, and the mixture was heated under reflux for 1.5 hours. After cooling, a hydrolyzed product of nitrofurfural diethyl ester was obtained, which was placed in a dropping funnel for use.
With Fe3O4 nanoparticles immobilized on zeolite-SO3H; In neat (no solvent); at 80℃; for 0.0666667h;Green chemistry;
General procedure: A mixture of aldehyde (1 mmol), 1,8-diaminonaphthalene (1 mmol), Fe3O4zeolite-SO3H (5% w/w, 0.007 g), was heated at 80 C under solvent-free conditions.Scheme 1 Synthesis of perimidine heterocycles using Fe3O4zeolite-SO3HM. Kalhor et al.1 3The reaction progress was monitored by TLC. After completion of the reaction, themixture was dissolved EtOH and the catalyst was separated by an external magnet.The pure products were obtained by adding crushed ice to filtrate.
75.1%
With zinc acetate dehydrate; In methanol; at 20℃;
A mixture of 1,8-naphthalene diamine (10 g, 63 mmol)Was dissolved in methanol (100 mL)Compound 46 (10.67 g, 75 mmol) was slowly added,In methanol (50 mL)After adding,Add zinc acetate(1.16 g, 5.3 mmol),Stirred at room temperature overnight,After completion of the reaction,Take the filter,washing,Drying, etc. to give compound 47 (13.3 g, 75.1%
Example 1General Procedure for the Synthesis of Synthesis of Aryl/heterocyclic aldehyde-2-(1,3-benzothiazol-2-yl)hydrazones (3a-p)Aryl or heterocyclic aldehydes (1 mmol) and 2-hydrazeno-benzothiazoles (1 mmol) were dissolved in ethanol (10 ml), to this resulting mixture catalytic amount of acetic acid (1 ml) was added and the mixture was stirred at 70 C. for 2 h, and the formed precipitate was collected by filtration and washed with cold methanol (3×30 mL) and chloroform (2×20 mL). The collected precipitate was recrystalysed from hot methanol affords hydrazones.5-nitro-2-furaldehyde 2-(1,3-benzothiazole-2-yl)hydrazone (3a)The compound 3a was prepared according to above described method by using 5-nitro-2-furancarboxaldehde (140 mg, 1 mmol) and 2-hydrazeno-benzothiazoles (165 mg, 1 mmol) at 70 C. for 2 h (yield 244 mg, 85%).1H NMR (DMSO-d6, 200 MHz): delta 12.3 (bs, 1H), 7.84 (m, 1H), 7.8 (s, 1H), 7.7 (d, 1H, J=3.7 Hz), 7.60 (d, 1H), 7.43 (m, 1H, J=2.9, 8.0 Hz), 7.22 (d, 1H, J=8.7 Hz), 6.90 (d, 1H, J=3.7 Hz); ESIMS: m/z 288 (M)+, 289 (M+H)+.
With potassium hydroxide; In methanol; ethanol; at 80℃;
General procedure: 4.1.3.2. Procedure B. To a warm solution of the corresponding 2-(benzo[d]thiazol-2-yl)acetonitrile (1 mmol) in absolute ethanol(8 mL) was added the corresponding aldehyde (1 mmol) and catalytic amount of 10% methanolic KOH (0.2 mmol). The reaction mixture was then stirred and heated to 80 C for 0.5-1 h, (as monitoredby TLC and LCMS for completion), the precipitate formed was collected by suction and recrystallised from ethanol to give the desired product in good yield as mentioned below. 4.1.3.16. (E)-2-(Benzo[d]thiazol-2-yl)-3-(5-nitrofuran-2-yl)acrylonitrile (14) The compound was synthesized according to the above general procedure B using 2-(benzo[d]thiazol-2-yl)acetonitrile (0.25 g, 1.44 mmol), 5-nitrofurfural (0.20 g, 1.44 mmol), alc. KOH (0.02 g, 0.29 mmol) to afford 14 (0.28 g, 65.57%) as orange coloured solid. M.p 245-247 C. H NMR (DMSO-d6): deltaH 8.26 (s, 1H), 8.15 (t, J = 7.2 Hz, 1H), 8.04 (t, J = 7.8 Hz, 1H), 7.64-7.58 (m, 3H), 6.97 (d, J = 8.0 Hz, 1H). 13C NMR (DMSO-d6): deltac 161.3, 155.9, 154.2, 153.9, 144.8, 137.6, 124.6, 123.7(2C), 122.8, 118.1, 116.5, 114.8, 113.6. ESI-MS m/z 298.3 (M+H)+. Anal. Calcd. for C14H7N3O3S; C, 56.56; H, 2.37; N, 14.13; Found: C, 56.48; H, 2.36; N, 14.12.
With oxygen;potassium hexacyanoferrate (III); In methanol; water; for 3h;Reflux;
The synthesis and testing of various related compounds are detailed below.; <strong>[698-63-5]5-Nitro-2-furaldehyde</strong> (1a, 1.0 g, 7.0 mmol) and 1,2-phenylenediamine (2a, 658 mg, 6.0 mmol) were dissolved in 15 mL of methanol. Next, an 8 mL aqueous solution of potassium ferricyanide (4.2 g, 12.6 mmol) was added and the reaction was heated to reflux for 3 hours while exposed to air. The reaction was cooled, then filtered and the filter pad was washed with ethanol. The filtrate liquor and washings were combined, concentrated in vacuo and the residue was recrystallized with EtOH:H2O (80/20) to give 1.34 g of 3a as a red-tan solid (83%) after filtration. Mp 225-226 C.; 1H NMR (300 MHz, DMSO) delta 7.91 (1H, d, J=3.9 Hz), 7.66 (2H, m), 7.48 (1H, d, J=3.7 Hz), 7.30 (2H, m); HRMS calcd. For C11H7N3O3, 230.0566 found 230.0561. LC/MS Retention time 5.55 min (>95%), FABMS 230.3 (M+1).
With methanol; sodium tetrahydroborate; at 0 - 20℃; for 1h;
To a solution 5-nitrofuran-2-carbaldehyde (794 mg,5.63 mmol) in dry methanol (10 ml), sodium borohydride (320 mg, 8.44 mmol) was added inportions at 0C. Then the reaction mixture was stirred at room temperature for another 1 h. After completion, the reaction mixture was acidified with 3 N HC1 and extracted with ethyl acetate. Organic layer was washed with brine, dried over sodium sulphate and finally solvent evaporated under vacuum to obtain the compound A. This was directly used for the next step without furtherpurification (670 mg, 83%).
81.5%
With sodium tetrahydroborate; water; In tetrahydrofuran; at 20℃; for 0.5h;
A solution of compound 2 (4.24g, 0.03 mol) in 30ml THF was stirred at room temperature. Then NaBH4 (0.3g, 0.06mol) was added in several times. When TLC showed no starting material remained, the mixture was poured into 30ml water and extracted with DCM. The organic layer was dried and removed in vacuo to give compound 3(3.5g, 81.5%).
80%
With sodium tetrahydroborate; In methanol; at 0℃; for 2.5h;Inert atmosphere;
5-Nitrofuran-2-carbaldehyde (4.00 g, 28 mmol) was dissolved in anhydrous methanol (80 mL) and cooled to 0 oC. NaBH4 (1.17 g, 31 mmol) was added to the reaction mixture, which was stirred for 2.5 h. The reaction was quenched with an HCl solution (1 M, 40 mL) and extracted with EtOAc (3 x 50 mL). The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford a crude yellow oil. Purification by flash chromatography using a prepacked 100 g silica column [solvent A: EtOAc; solvent B: hexanes; gradient: 7%A / 93%B (1 CV), 7%A / 93%B ? 60%A / 40%B (10 CV), 60%A / 40%B (2 CV); flow rate: 100 mL/min; monitored at 254 and 280 nm] afforded (5-nitrofuran-2-yl)methanol (34) (3.23 g, 22.6 mmol, 80%) as a pale yellow oil.1H NMR (600 MHz, CDCl3) delta 7.31 (1H, d, J = 3.6 Hz), 6.58 (1H, d, J = 3.6 Hz), 4.74 (2H, s), 2.09 (1H, s). 13C NMR (151 MHz, CDCl3) delta 157.37, 151.92, 112.40, 110.61, 57.45.
62.9%
With methanol; sodium tetrahydroborate; at 20℃; for 3h;Cooling with ice;
5-nitrofurfural (10 mmol, 1.41 g) was dissolved in methanol (100 ml), and sodium borohydride (15 mmol, 0.6 g) was added thereto under an ice bath condition, and the reaction was carried out at room temperature for 3 hours.Point the plate to determine the end point of the reaction, then add water (10ml) to stop the reaction, remove the solvent methanol by rotary evaporation, and extract three times with dichloromethane (25ml * 3) to obtain an oil phase. Dry over anhydrous sodium sulfate for two hours, filter and spin The solvent was distilled off to obtain a crude product, which was passed through a column with petroleum ether: ethyl acetate (4: 1) to obtain the product 2a (0.91 g, 62.9%).
46%
With sodium tetrahydroborate; In methanol; at 0℃; for 0.5h;
To a stirred solutionof 5-nitrofurfural (3) (5 g, 35.44 mmol) in methanol (100 mL), cooled to 0 C, was added sodium borohydride (1.47 g, 38.98mmol) portion-wise and continued to stirred for additional 30 min. After completion of the reaction, checked by TLC, thes olvent was concentrated under reduced pressure and theresidue was quenched with water (2 mL) and extracted with cyclopentyl methylether (4 × 25 mL). The organic layer was washed with water (2 × 30 mL), dried over Na2SO4 and evaporated to obtain (5-nitrofuran-2-yl)methanol 4. Pale yellow oil;Yield: 2.33 g, 46 %; 1 H NMR (400 MHz, CDCl3) delta 2.50 (br s,1H, OH), 4.73 (s, 2H, -CH 2 ), 6.57 (d, 1H, J = 4 Hz, H 3 -furan),7.30 (d, 1H, J = 4.0 Hz, H 4 -furan).
The aldehyde (3.5g) and conc. HCI (20MUT) were combined and stirred overnight at 40C. The reaction mixture was poured into cold water and extracted with ether, washed with satd. NAHCO3 AND brine, dried over anhydrous MGS04, filtered and concentrated in vacuo to give 1.76g of product (55%)
55%
With hydrogenchloride; at 40℃;
The aldehyde (3.5 g) and cone. HC1 (20 ml) were combined and stirred overnight at 40 C. The reaction mixture was poured into cold water and extracted with ether, washed with satd. NaHCO3 and brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo to give 1.76 g of product (55%)
55%
With hydrogenchloride; for 40h;
The aldehyde (3.5 g) and conc. HCl (20 ml) were combined and stirred overnight at 40 C. The reaction mixture was poured into cold water and extracted with ether, washed with satd. NaHCO3 and brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo to give 1.76 g of product (55%)
55%
With hydrogenchloride; In water; at 40℃;
PREPARATIVE EXAMPLE 34.1; The aldehyde (3.5g) and conc. HCI (20ml) were combined and stirred overnight at 40C. The reaction mixture was poured into cold water and extracted with ether, washed with satd. NaHCO3 and brine, dried over anhydrous MgS04, filtered and concentrated in vacuo to give 1.76g of product (55%)
55%
With hydrogenchloride; In water; at 40℃;
The aldehyde (3.5g) and conc. HCl(20ml) were combined and stirred overnight at 40C. The reaction mixture was poured into cold water and extracted with ether, washed with satd. NaHCO3 and brine, dried over anhydrous MgS04, filtered and concentrated in vacuo to give 1.76g of product (55%)
With oxygen;potassium hexacyanoferrate (III); In methanol; water; for 16h;Reflux;
The synthesis and testing of an exemplary compound (ND-7901) are detailed below.; 5-Nitro-2-furaldehyde (1a, 401 mg, 2.8 mmol) and <strong>[59649-56-8]2,3-diaminophenol</strong> (2 g, 300 mg, 2.4 mmol) were dissolved in 10 mL of methanol. Next, a 5 mL aqueous solution of potassium ferricyanide (1.7 g, 5.1 mmol) was added and the reaction was heated to reflux for 16 hours while being exposed to air. Then the reaction was cooled, filtered and the filter pad was washed with ethanol. The filtrate liquor and washings were combined and concentrated in vacuo and the residue was recrystallized from EtOH:H2O (80/20 to give 180 mg of 3g as a dark solid (26percent) after filtration. 1H NMR (300 MHz, DMSO) delta 7.90 (1H, m), 7.42 (1H, m), 7.06 (2H, m), 6.59 (1H, m); HRMS calcd. for C11H7N3O4, 246.0515 found 246.0504. LC/MS Retention time 4.73 min (>95percent), FABMS 246.4 (M+1).
2-(5-nitrofuran-2-yl)-1H-benzo[d]imidazole-5-carboxylic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88%
With oxygen;potassium hexacyanoferrate (III); In methanol; water; for 16.0h;Reflux;
5-Nitro-2-furaldehyde (1a, 306 mg, 2.1 mmol) and <strong>[603-81-6]2,3-<strong>[603-81-6]diaminobenzoic acid</strong></strong> (2e, 281 mg, 1.8 mmol) were dissolved in 10 mL of methanol. Next, a 5 mL aqueous solution of potassium ferricyanide (1.3 g, 3.8 mmol) was added and the reaction was heated to reflux for 16 hours while exposed to air. Then the reaction was cooled, filtered and the filter pad was washed with ethanol. The filtrate liquor and washings were combined and concentrated in vacuo and the residue was recrystallized from EtOH:H2O (80/20) to give 512 mg of 3e as a brown solid (88%) after filtration. 1H NMR (300 MHz, DMSO) delta 8.22 (1H, s), 7.88 (1H, d, J=3.9 Hz), 7.82 (1H, d, J=8.2 Hz), 7.63 (1H, d, J=3.9 Hz), 7.56 (1H, d, J=8.5 Hz); HRMS calcd. for C12H7N3O5, 274.0464 found 274.0446. LC/MS Retention time 3.05 min (>95%), FABMS 274.3 (M+1).
General procedure: Appropriate aldehyde (10.5 mmol) was added to the solution of <strong>[603-81-6]2,3-<strong>[603-81-6]diaminobenzoic acid</strong></strong> 6 (1.52 g, 10 mmol) in DMF (15 mL). The solution was heated to 80 C and then stirred for about 120 h. Then, the solution was cooled to room temperature. The precipitates were filtered, washed with ethanol and dried.
EXAMPLE 2 Synthesis of 2-(5-nitro-2-thienyl)-1H-benzimidazole-4-carboxylic acid 2.0 g of <strong>[603-81-6]2,3-<strong>[603-81-6]diaminobenzoic acid</strong></strong> is dissolved into 60 ml of methanol, and methanol solution of 5-nitrofurfural is added into the methanol under stirring. Then 0.5 g of cupric acetate (Cu(Ac)2.H2O) is added into the above methanol, and then to heat and reflux it; and then to filter hot solution after <strong>[603-81-6]2,3-<strong>[603-81-6]diaminobenzoic acid</strong></strong> disappears. 20% sodium sulfide aqueous solution is added into the filtrate and heat it till boiling; and then filtrate the copper sulfide deposition while it is hot; and then to evaporate the filtrate to dry, purify it through column chromatography to obtain 2-(5-nitro-2-thienyl)-1H-benzimidazole-4-carboxylic acid. The yield is about 65%.
N’-((5-nitrofuran-2-yl)methylene)benzohydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98%
With sulfuric acid; In methanol; water; acetic acid; for 1h;Reflux;
General procedure: The twenty-two substituted-benzhydrazides (1a-v) described in this study were available to be used since they were recently synthesized and reported elsewhere.35,37 An equimolar mixture of 5-nitrofuran-2-carbaldehyde (0.05 mol) and benzhydrazides (1a-v) in water, sulfuric acid, acetic acid, and methanol, (8:7:8:20 v/v) was heated under reflux during 1 h. After cooling down, the mixture was poured into cold water to give 2a-v.
86%
With sulfuric acid; acetic acid; In methanol; water; for 1h;Reflux;
General procedure: compounds were synthesized by refluxing 5-nitro-2-furaldehyde 98% (5 mmol) and hydrazides (b) (5 mmol) in water, sulfuric acid, acetic acid, and methanol (8:7:8:20 v/v) for 1 h. After cooling, the mixture was poured into cold water to precipitate, and recrystallized from acetonitrile [33].
With sulfuric acid; In methanol; water; acetic acid; for 1h;Reflux;
General procedure: The twenty-two substituted-benzhydrazides (1a-v) described in this study were available to be used since they were recently synthesized and reported elsewhere.35,37 An equimolar mixture of 5-nitrofuran-2-carbaldehyde (0.05 mol) and benzhydrazides (1a-v) in water, sulfuric acid, acetic acid, and methanol, (8:7:8:20 v/v) was heated under reflux during 1 h. After cooling down, the mixture was poured into cold water to give 2a-v.
67%
With sulfuric acid; acetic acid; In methanol; water; for 1h;Reflux;
General procedure: compounds were synthesized by refluxing 5-nitro-2-furaldehyde 98% (5 mmol) and hydrazides (b) (5 mmol) in water, sulfuric acid, acetic acid, and methanol (8:7:8:20 v/v) for 1 h. After cooling, the mixture was poured into cold water to precipitate, and recrystallized from acetonitrile [33].
(±)-(5S,7R,9S)-7,9-bis(5-nitrofuran-2-yl)-1,6,8-trioxaspiro[4.5]dec-3-en-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With trimethylsilyl trifluoromethanesulfonate; In dichloromethane; at 20℃; for 1.5h;Molecular sieve;
General procedure: To a solution of gamma-hydroxy-gamma-methylbutenolide 1 (20 mg, 0.175 mmol) and aromatic aldehyde 3a-h (1.05 mmol) in CH2Cl2 (875 muL) over 3A molecular sieves (4 pellets) was added trimethylsilyltriflate (61 muL, 0.35 mmol). The reaction stirred for 1.5 h, at which time Et3N (4 drops) was added to the reaction. The mixture was immediately loaded onto a Hexanes-wet Silica Gel column (1x18cm) and chromatographed as specified for individual reactions.
5-[1-(4-Aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (7a, 0.26 g, 1 mmol) on reacting with 5-nitro2-furaldehyde in the presence of catalytic amount of CH3COOH (3 drops) in methanol at 0 C for lOh and the obtained solid is filtered, washed with water and recrystalized in ethanol to obtain product 5-[1-(4-[(E)-1-(5-nitro-2-furyl)methylidene]aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (9a, 306 mg, 80%). 1H NMR (CDCl3, 300 MHz): delta 1.84-1.96 (m, 2H), 2.06-2.12 (m, 2H), 2.70-2.80 (m, 1H), 2.91-2.99 (m, 2H), 3.71-3.77 (m, 2H), 6.92 (d, 2H, J= 9.06 Hz), 7.14 (d, 1H, J=4.53 Hz), 7.23-7.31 (m, 2H), 7.39 (d, 1H, J= 4.53 Hz), 8.20 (s, 1H); 8.36 (bs, 1H); MS (ESI): m/z (384) (M+1)+.
80%
With acetic acid; In methanol; at 0℃; for 10h;
5-[1-(4-Aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (7a, 0.26 g, 1 mmol) on reacting with 5-nitro2-furaldehyde in the presence of catalytic amount of CH3COOH (3 drops) in methanol at 0 C. for 10 h and the obtained solid is filtered, washed with water and recrystalized in ethanol to obtain product 5-[1-(4-[(E)-1-(5-nitro -2-furyl)methylidene]aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (9a, 306 mg, 80%). 1H NMR (CDCl3, 300 MHz): delta 1.84-1.96 (m, 2H), 2.06-2.12 (m, 2H), 2.70-2.80 (m, 1H), 2.91-2.99 (m, 2H), 3.71-3.77 (m, 2H), 6.92 (d, 2H, J=9.06 Hz), 7.14 (d, 1H, J=4.53 Hz), 7.23-7.31 (m, 2H), 7.39 (d, 1H, J=4.53 Hz), 8.20 (s, 1H); 8.36 (bs, 1H); MS (ESI): m/z (384) (M+1)+.
5-[1-(4-aminophenyl)-4-piperidyl]-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7b,0.27 g, 1 mmol) on reacting with 5-nitro2-furaldehyde in the presence of catalytic amount of CH3COOH (3 drops) in methanol at 0 C for lOh and the obtained solid is filtered, washed with water and recrystalized in ethanol to obtain product 3-methyl-5-[1-(4-[(E)-1-(5-nitro-2-furyl)methylidene]aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (9b, 341 mg, 86%). 1H NMR (CDCl3, 300 MHz): delta 1.84-1.97 (m, 2H), 2.07-2.13 (m, 2H), 2.70-2.81 (m, 1H), 2.91-3.00 (m, 2H), 3.39 (s, 3H), 3.71-3.78 (m, 2H), 6.93 (d, 2H, J=9.06 Hz), 7.13 (d, 1H, J = 4.53 Hz), 7.25-7.32 (m, 2H), 7.39 (d, 1H, J = 3.77 Hz), 8.41 (s, 1H); MS (ESI): m/z (420) (M+23)+.
86%
With acetic acid; In methanol; at 0℃; for 10h;
5-[1-(4-Aminophenyl)-4-piperidyl]-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7b, 0.27 g, 1 mmol) on reacting with 5-nitro2-furaldehyde in the presence of catalytic amount of CH3COOH (3 drops) in methanol at 0 C. for 10 h and the obtained solid is filtered, washed with water and recrystalized in ethanol to obtain product 3-methyl-5-[1-(4-[(E)-1-(5-nitro-2-furyl)methylidene]aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (9b, 341 mg, 86%). 1H NMR (CDCl3, 300 MHz): delta 1.84-1.97 (m, 2H), 2.07-2.13 (m, 2H), 2.70-2.81 (m, 1H), 2.91-3.00 (m, 2H), 3.39 (s, 3H), 3.71-3.78 (m, 2H), 6.93 (d, 2H, J=9.06 Hz), 7.13 (d, 1H, J=4.53 Hz), 7.25-7.32 (m, 2H), 7.39 (d, 1H, J=3.77 Hz), 8.41 (s, 1H); MS (ESI): m/z (420) (M+23)+.
5-[1-(4-amino-2-fluorophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (7e, 0.28 g, 1 mml) on reacting with 5-nitro2-furaldehyde in the presence of catalytic amount of CH3COOH (3 drops) in methanol at 0 C for 10 h and the obtained solid is filtered, washed with water and recrystalized in ethanol to obtain product 5-[1-(2-fluoro-4-[(E)-1-(5-nitro-2-furyl)methylidene]aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (9e, 324 mg, 81%). 1H NMR(CDCl3, 300 MHz): delta 1.97-2.04 (m, 2H), 2.11-2.14 (m,2H), 2.73-2.81 (m, 1H), 2.86-2.91 (m, 2H), 3.53-3.55 (m, 2H), 6.97 (t, 1H, J= 7.84 Hz), 7.09 (t, 2H, J= 7.84 Hz), 7.16 (d, 1H, J= 2.94Hz), 7.41 (d, 1H, J= 2.94Hz), 8.37 (s, 1H), 8.73 (bs, 1H); MS (ESI): m/z (402) (M+1)+.
81%
With acetic acid; In methanol; at 0℃; for 10h;
5-[1-(4-Amino-2-fluorophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (7e, 0.28 g, 1 mml) on reacting with 5-nitro2-furaldehyde in the presence of catalytic amount of CH3COOH (3 drops) in methanol at 0 C. for 10 h and the obtained solid is filtered, washed with water and recrystalized in ethanol to obtain product 5-[1-(2-fluoro-4-[(E)-1-(5-nitro-2-furyl)methylidene]aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (9e, 324 mg, 81%). 1H NMR (CDCl3, 300 MHz): delta 1.97-2.04 (m, 2H), 2.11-2.14 (m,2H), 2.73-2.81 (m, 1H), 2.86-2.91 (m, 2H), 3.53-3.55 (m, 2H), 6.97 (t, 1H, J=7.84 Hz), 7.09 (t, 2H, J=7.84 Hz), 7.16 (d, 1H, J=2.94Hz), 7.41 (d, 1H, J=2.94Hz), 8.37 (s, 1H), 8.73 (bs, 1H); MS (ESI): m/z (402) (M+1)+.
5-[1-(4-amino-2-fluorophenyl)-4-piperidyl]-3-methyl-2,3-dihydro-1 ,3,4-oxadiazol-2-one (7f, 0.29 g, 1 mmol) on reacting with 5-nitro2-furaldehyde in the presence of catalytic amount of CH3COOH (3 drops) in methanol at 0 C for 10 h and the obtained solid is filtered, washed with water and recrystalized in ethanol to obtain product 5-[1-(2-fluoro-4-[(E)-1-(5-nitro-2-furyl)methylidenejaminophenyl)-4-piperidyl]-3 -methyl -2,3-dihydro-1,3,4-oxadiazol-2-one (9f, 352 mg, 85%). 1H NMR (CDCl3, 300 MHz): delta 1.92-2.01 (m, 2H), 2.03-2.14 (m, 2H), 2.69-2.77 (m, 1H), 2.83-2.91 (m, 2H), 3.40 (s, 3H), 3.50-3.57 (m, 2H), 6.95 (t, 1H, J= 9.06 Hz), 7.03-7.09 (m, 2H), 7.16 (d, 1H, J= 3.77 Hz), 7.40 (d, 1H, J= 3.77 Hz), 8.37 (s, 1H); MS (ESI): m/z (416) (M+1)+.
85%
With acetic acid; In methanol; at 0℃; for 10h;
5-[1-(4-Amino-2-fluorophenyl)-4-piperidyl]-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7f, 0.29 g, 1 mmol) on reacting with 5-nitro2-furaldehyde in the presence of catalytic amount of CH3COOH (3 drops) in methanol at 0 C. for 10 h and the obtained solid is filtered, washed with water and recrystalized in ethanol to obtain product 5-[1-(2-fluoro-4-[(E)-1-(5-nitro-2-furyl)methylidene]aminophenyl)-4-piperidyl]-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-one (9f, 352 mg, 85%). 1 H NMR (CDCl3, 300 MHz): delta 1.92-2.01 (m, 2H), 2.03-2.14 (m, 2H), 2.69-2.77 (m, 1H), 2.83-2.91 (m, 2H), 3.40 (s, 3H), 3.50-3.57 (m, 2H), 6.95 (t, 1H, J=9.06 Hz), 7.03-7.09 (m, 2H), 7.16 (d, 1H, J=3.77 Hz), 7.40 (d, 1H, J=3.77 Hz), 8.37 (s, 1H); MS (ESI): m/z (416) (M+1)+.
With Eu2(benzene-1,2,3,4,5,6-hexacarboxylate)(H2O)3; In acetonitrile; at 20 - 100℃; for 3h;
General procedure: General procedure for cyanosilylation of aldehydes [Eu2(MELL)(H2O)6] preheated at 100C for 1 h (10.0 mg) in ace-tonitrile (3.0 mL) at room temperature was added to the aldehyde (0.125 mmol) followed by TMSCN (0.25 mmol). The resulting solution was stirred at room temperature for 1 h prior to quenching with H2O (10.0 mL). The mixture was diluted with dichloromethane(15 mL), the organic phase was isolated, the organic extracts were dried over anhydrous Na2SO4 and the solvent was removed in vacuum. When necessary, the crude product was purified via flash column chromatography (30% ethyl acetate/hexanes as eluent) toafford the product as an oil. The conversion to the corresponding O-trimethylsilyl ethers cyanohydrins was analyzed by gas chromatography coupled with a mass spectrometer. All of thecompounds were characterized by comparison with previously reported spectral data.
Synthesis of Bd; Step 7. 4-amino-i -methyl-3-propyl- 1 H-pyrazole-5 -carboxamide (1 eq) and <strong>[698-63-5]5-Nitro-2-furaldehyde</strong> (1.1 eq) were suspended in ethanol 5 ml and the mixture heated at 60 C for 0.5 hours after conformation of forming of imine by TLC. Added CuC12 (3 eq) and the reaction mixture heated at 65 C under 02 for 0.5 hours. After completion of the reaction, the ethanol was removed under vacuum. Then workup withethyl acetate and water. Separate the organic layer and Water layer re-extracted with2x25 ml ethyl acetate. The combined organic layers are washed with brine solution,concentrated under vacuum. The residue was purified by column chromatography onsilica the desired product Bd as a yellow solid; yield 93%. ?H NMR (200 MHz CDC13):l2.87(br 1H) 7.85(br 1H), 7.74(br 1H), 4.16(s 3H), 2.8(br 2H), l.76(m 2H), 0.95(t J= 7.3Hz 3H). MASS: ESI [M + H] + 304.10; Elemental anal. calcd. for C,3H13N504C, 51.48; H, 4.32; N, 23.09; 0, 21.10; found C, 51.39; H, 4.34; N, 23.12; 0, 21.14.
90%
With dipotassium peroxodisulfate; In water; dimethyl sulfoxide; at 100℃;Sealed tube; Microwave irradiation;
General procedure: We intended to synthesize compounds based on 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one scaffold by using microwave assisted protocol (Scheme 1). In this direction we started the studies for optimization of synthesis of 5-(2-ethoxyphenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one 3a. The optimization studies were initiated by screening of different oxidizing agents as depicted in Table1, see Supplementary data using DMSO:Water in 1:1 proportion to see the conversion in desired product. Amongst all oxidants, the best result was observed with K2S2O8, in equivalence studies for catalyst, 3eq. of catalyst has given maximum yields (Table1, see Supplementary data). Therefore, all reactions were conducted using this condition after optimization of catalyst. However, oxone has also given the product 3a with minor yields. After screening of the catalyst we started study of selectivity for solvent that could affect the formation of 5-(2-ethoxyphenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one 3a. The solvent screening was carried out to find out the best conversion, the mixture of DMSO:H2O in 1:1 proportion has given the best results with excellent yields (Table2, see Supplementary data). The microwave protocols were optimized for this reaction as mentioned in Table 3, see Supplementary data; the reactions carried under different microwave Watt powers have given varied results. Wherein, entry 3(b) (Table3, see Supplementary data) was found to be the best condition for maximum conversion. A series of compounds based on 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one scaffold was synthesized using these optimized conditions, wherein, all kind of substrates with diversity around aryl ring were chosen for conversion and in all cases products obtained in good to excellent yields (Table1).
With sulfuric acid; In methanol; water; acetic acid; for 1h;Reflux;
General procedure: The twenty-two substituted-benzhydrazides (1a-v) described in this study were available to be used since they were recently synthesized and reported elsewhere.35,37 An equimolar mixture of 5-nitrofuran-2-carbaldehyde (0.05 mol) and benzhydrazides (1a-v) in water, sulfuric acid, acetic acid, and methanol, (8:7:8:20 v/v) was heated under reflux during 1 h. After cooling down, the mixture was poured into cold water to give 2a-v.
72%
With sulfuric acid; acetic acid; In methanol; water; for 1h;Reflux;
General procedure: compounds were synthesized by refluxing 5-nitro-2-furaldehyde 98% (5 mmol) and hydrazides (b) (5 mmol) in water, sulfuric acid, acetic acid, and methanol (8:7:8:20 v/v) for 1 h. After cooling, the mixture was poured into cold water to precipitate, and recrystallized from acetonitrile [33].
N-methyl-N-(6-chloro-7-methyl-1,1-dioxo-1,4,2-benzodithiazin-3-yl)hydrazine[ No CAS ]
6-chloro-7-methyl-3-[2-(5-nitrofurfurylidene)-1-methylhydrazino]-1,1-dioxo-1,4,2-benzodithiazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87%
With acetic acid; In ethanol; at 20℃; for 28h;Reflux;
General procedure: A mixture of the benzodithiazinyl hydrazine 2 (1.17 g, 4 mmol), the appropriate aryl carbaldehyde (5 mmol) and glacial acetic acid (0.5 mL, catalytic amount) in ethanol (25 mL) was stirred at room temperature for 3 h, followed at reflux for 25 h. After cooling to room temperature and standing overnight, the precipitate was filtered off, washed with ethanol (4 × 2 mL) and dried. In this manner thefollowing benzodithiazines were obtained.
N-methyl-N-(6-chloro-7-cyano-1,1-dioxo-1,4,2-benzodithiazin-3-yl)hydrazine[ No CAS ]
6-chloro-7-cyano-3-[2-(5-nitrofurfurylidene)-1-methylhydrazino]-1,1-dioxo-1,4,2-benzodithiazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With acetic acid; In 2-methoxy-ethanol; at 20℃; for 11h;Reflux;
General procedure: A mixture of N-methyl-N-(6-chloro-7-cyano-1,1-dioxo-1,4,2-benzodithiazine 4, (0.9 g, 3 mmol) andthe corresponding aryl or heteroaryl carbaldehyde (4 mmol), glacial acetic acid (0.5 mL) and 2-methoxyethanol (10 mL) was stirred at room temperature for 2 h, followed at reflux for 9 h. After cooling to room temperature and standing overnight, the precipitate was filtered off, washed with methanol (5 × 2 mL), and dried. In this manner the following benzodithiazines were obtained.
With acetic acid; In ethanol; at 80℃; for 0.166667h;Microwave irradiation;
General procedure: 2-(2-Arylidenehydrazino)-6-fluorobenzothiazoles 6a-r. General Procedure D. A mixture of compound 2 (0.0549 g, 0.0003 mol), the appropriate aromatic aldehyde (0.00033 mol) and glacial acetic acid (0.1 mL) in ethanol (5 mL) was heated under microwave (20 W) at 80 °C for 10 min. On cooling, the precipitated solid was collected by filtration, washed with water, dried and crystallized from the appropriate solvent to give the desired compounds 6a-r.
With Nitrogen dioxide; In acetonitrile; at 20℃; under 750.075 Torr; for 6h;
In a reactor equipped with 5 mL of acetonitrile, 0.20 g of furfural, 0.01 g of sulfonated graphene and 0.20 mL of nitrogen dioxide were added, and the reaction was stirred at room temperature in an atmosphere of 0.1 MPa for 6 h.After the reaction was completed, nitrogen was introduced into the reaction mixture under atmospheric pressure until the nitrogen oxides completely escaped to the cold trap reaction receiver, and the catalyst was filtered out.The filtrate was washed with 5% (m/m) aqueous sodium bicarbonate solution to near neutrality, washed with distilled water until the organic phase was neutral, and concentrated by rotary evaporation in a vacuum.The liquid chromatographic analysis was carried out using n-hexadecane as an internal standard, and the mass of 5-nitrofurfural was 0.23 g, and the yield was 78%.
22%
With nitric acid; acetic anhydride; at -30℃; for 2h;
13mL of nitric acid(68%) was added slowly to 83 ml of acetic anhydride between 15-25 C with rapid stirring. After the addition was complete, the nitration reagent was added slowly to the solution of furan-2-carbaldehyde (1) (9.6g, 0.1mol) in acetic anhydride (100ml) cooled to -30 C in advance. When TLC showed no starting material remained, the mixture was poured on ice water and extracted with ethyl acetate. The organic layer was dried and purified by chromatography (PE/DCM, 3/1) to give compound 2 (3.1g, 22%).
In the 2000ml reaction flask,To the product obtained in Example 6, 122.20 g of N-amino-5-methylthiomethyl-2-oxazolidone obtained in Example 4 was added in portions.Gradually yellow solids precipitated,After completion of the incubation 2h,After suction filtration, filter cake was rinsed with methanol and dried.The yellow solid is 204.60g,The purity of the gas phase was 99.1%, which is the product nifuratel.Calculated according to 5-nitrofurfural diethyl ester, the yield was 95.30%.
85.2%
In ethanol; at 20 - 25℃; for 2h;
was charged with 60 L of ethanol, 50 kg of 5-nitro-furfural (compound l), 20 kg (82.25 mol), and 10% of sulfuric acid (^ (3) (4.11111, 111):Heated to 78 to 85 C, reacted for 1 and 5 h, concentrated under reduced pressure to remove ethanol to give a concentrate; the concentrate was dissolved in methylene chloride and washed three times with saturated sodium chloride to collect the methylene chloride layer; The crude product was purified by silica gel column chromatography (eluent PE: EA = 5: 1). The crude product was collected and the residue was purified by solidification on silica gel. Concentrated to give 5 - nitro - furfural pure product, the yield was 89.2%.[0077] If the preparation of nitramine too Seoul, then the reaction of the product without purification separation, directly used for the preparation of Nasisi Taier.[0078] (2) Preparation of nitrofurant crude[0079] In the dark conditions, 3-amino-5-methylthiomethyl-2-oxazolidinone (compound3) 14. 7 kg (90.66 mil) in ethanol (20 L) was added to the reaction solution (60 L) of step (1) cooled to 15 to 25 C of 5-nitro-furfural (compound 2) After precipitation, the reaction was carried out at 20 to 25 C for 2 hours. The solid was filtered and the residue was filtered. The filter cake was washed with cold ethanol (5 to 10 C) and dried to obtain crude nitrofurant.(3) refinement of nitrofurant[0081] in the dark conditions, take nitrofurant crude 5kg, add 95% ethanol 60L, heated to reflux, hot filter to get the filtrate; the filtrate to stand, precipitate solid, filter, filter cake with a small amount of 95% ethanol , The solvent was removed and dried to constant weight to give a light yellow nitrofurant extract with a yield of 95% and a total yield of 85.2%.
285 g
In ethanol; at 0 - 20℃; for 2h;
Between 0 C, a solution of intermediate 7 was added aqueous ethanol three-necked flask, mechanical stirring was added dropwise a solution of Intermediate 5 in ethanol, to produce a yellow precipitate. After the addition was complete, naturally returned to room temperature, stirred 1h, place 2h, filtration, washed with water until neutral to give crude Nifuratel 348 grams. The crude product was N, N- dimethylformamide to give 285 g product was recrystallized Nifuratel 1.
at 25 - 30℃; for 2h;
N-amino-5-methylthiomethyl-2-oxazolidinone obtained in the step (3) was reacted with 5-nitrofurfural obtained in the step (4) at a molar ratio of 1: 1.1, mixing, stirring at 25 ~ 30 for 2 hours, standing, filtration, washing, drying, the nitrofurant crude; take nitrofurant crude, according to g / ml, adding 10 times the volume of ice Acetic acid, reflux, activated carbon adsorption, filter hot, the filtrate static crystallization, cooling to room temperature after filtration, the filter cake washed with ethanol to the product without red, then water, ethanol, dried and dried to nitrofurant Pure product, high performance liquid chromatography external standard method for the determination of 99.8%.
114 g
The macroporous resin adsorbing the cyclized product is placed in a 1000 ml reaction flask, and 300 ml of ethanol is added.The hydrolysis product of nitrofurfural diethyl ester was added dropwise at 8 C, and the dropping time was controlled for about 2 hours.The reaction has a large amount of yellow solids formed. After the dropwise addition was completed, the reaction was carried out at 22 C for 3 hours.After the completion of the reaction, filtration was carried out to obtain about 1.0 kg of a mixed solid of the product and the macroporous resin.The mixed solid was added to a 2000 ml four-necked flask, 800 g of acetic acid was added, and heated to 100 C. Stir at 100 C for 1 hour, filter to obtain the mother liquor, and cool to 0 C and stir for 1 hour.Recrystallization of N,N-dimethylformamide,Filtration again gave 114 g of nifuratel product.The purity of the liquid phase detection is 100%, and other indicators are superior to the pharmacopoeia standards.
Heating step 1) made of a compound represented by the formula B N - amino -5 - methylthiomethyl -2 - oxazolidinone reaction liquid, into the step 2) made of a compound represented by the formula D 5 - nitro-furfural reaction solution, to carry out dehydration condensation reaction, the control temperature is 25 °C, after dripping in 15 °C -40 °C reaction under 5h; TLC monitoring, a compound represented by the formula B N - amino -5 - methylthiomethyl -2 - oxazolidinone the reaction is complete the end of the reaction, a compound represented by the refractory fettling [...] E; 4) preparation of a compound represented by the formula E micromolecule The above-mentioned step 3) after the reaction, cooling to room temperature filtration, the filter cake is washed with methanol washing, the centrifugal spin-dry methanol, and then the cake is washed by pure water, until the washing water after PH>6; then methanol pulping for 1 time, drying after drying centrifugally refractory fettling micromolecule a compound represented by the formula E 135.9 kg.
With alumina; In neat (no solvent); at 100℃; for 0.15h;Microwave irradiation; Green chemistry;
General procedure: A mixture of the aldehyde 1 (2 mmol), the 1,3-dicarbonyl compound 2 (2 mmol), the corresponding urea derivative 3(3 mmol) and the 3D printed Al2O3 structure (0.350 g) was submitted to microwave irradiation (100 C) in coated vial. After completion of the reaction, as indicated by TLC, the mixture was cooled and the desired compound solidified. For those 1,2,3,4-tetrahydropyrimidine-5-carboxylates that not solidified, the reaction mixture was poured onto crushed ice and stirred for 5-10 min. The solid obtained was filtered under suction, washed with ice-cold water (20 mL) and then purified by column chro-matography or recrystallization from the appropriate solvent.
(2E)-3-(5-nitrofuran-2-yl)-1-[4-(piperazin-1-yl)phenyl]prop-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
42%
With sulfuric acid; In acetic acid; at 100℃;
General procedure: All the chemicals and solvents were purchased from Sigma Aldrich. The progress of all reactions was monitored on Merck KGaA precoated silica gel plates 0.25 mm (with fluorescence indicator UV254) using ethyl acetate/n-hexane as solvent system. Spots were visualized by irradiation with ultraviolet light (254 nm). Melting points (mp) were determined using open capillary method on Melting Point III Marte apparatus. Proton (1H) and (13C) NMR spectra were recorded on Bruker Avance 400 spectrometer at 400 MHz for 1H and 100 MHz for 13C using DMSO-d6 and CDCl3 as solvents referenced. Chemical shifts are given in parts per million (ppm) (delta relative to residual solvent peak for 1H and 13C). Spectra Mass was performed on a LCMS-2020 Liquid Chromatograph Mass Spectrometer Shimadzu, the column was Agilent XDB-C18, 35 muM, 21×20 nm. IR spectra were recorded on a PerkinElmer model Spectrum 400 (medium, sweep of 4000 to 400 cm-1). Synthesized compounds were ?96% pure as determined by high performance liquid chromatography (HPLC) Shimadzu with PDA detector, Nucleodur 100-5 CN-RP column 205×4.6mm, mobile phase water/0.1% TFA and acetonitrile with flow of 1mL/min. For the synthesis of 3-25, substituted acetophenones (0.5 equiv, 0.5 mmol) and nitroaromatics (0.5 equiv. 0.5 mmol) were dissolved in acetic acid (1mL) and concentrated sulfuric acid (0.05 mL) and were stirred at 100C until completion of the reaction (4-24h). The cooled mixture and the solid was washed with iced methanol (200 mL) for purification.
(1S*,2R*)-N-((5-nitrofuran-2-yl)methyl)-2-phenylcyclopropan-1-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
40%
General procedure: Trans-2-phenylcyclopropylamine hydrochloride (1.0 eq.), acetic acid (1.0eq.) and the appropriate aldehyde (0.9 eq.) were dissolved in around bottom flask in 10 mL dry DCE. The reaction mixture was stirred gently at room temperature for 2 h before sodium triacetoxyborohydride (3.0 eq.) was added in small portions to the reaction vessel. The reaction was monitored by TLC and quenched using 10 mL of an aqueous (5%) NaHCO3 solution. The organic layer was separated and the aqueous layer extracted three times with10 mL of DCE. All organic layers were combined, dried over anhydrous Na2SO4, concentrated in vacuo and purified using flash chromatography (silica gel; cyclohexane/ethyl acetate) to give the desired compound.
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