* 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 Chemical Research - Part S, 1996, # 2, p. 100 - 101
3
[ 67-56-1 ]
[ 54-85-3 ]
[ 2564-83-2 ]
[ 2459-09-8 ]
[ 1020092-80-1 ]
Reference:
[1] Organic and Biomolecular Chemistry, 2013, vol. 11, # 1, p. 170 - 176
[2] Organic and Biomolecular Chemistry, 2013, vol. 11, # 1, p. 170 - 176
4
[ 1570-45-2 ]
[ 54-85-3 ]
Yield
Reaction Conditions
Operation in experiment
86%
With hydrazine hydrate In ethanol at 60℃; for 1 h;
Commercially available ethyl isonicotinate was refluxed with hydrazine hydrate. for 1 hr at 60° C. and the solvent was evaporated. Trituration of this solid with diethyl ether afforded pure hydrazide 2 in 86percent yield. The treatment of hydrazide 2 with CS2 and KOH in 60 ° C. for 18 hrs produced a solid upon concentration in vacuo. It was found that this material could be easily purified by trituration with H20 followed by filtration to give thiol 3 in 78percent yield, thus avoiding chromatography over the first two steps. This operationally simple procedure afforded multi-gram quantities of 3 for subsequence focused library synthesis. Finally, diversification of the aryl ring was achieved by nucleophilic displacement reaction of thiol 3 with substituted aryl bromides in room temperature DMF using K2C03 as base.
86%
With hydrazine hydrate In ethanol at 60℃; for 1 h;
Commercially available ethyl isonicotinate was refluxed with hydrazine hydrate for 1 hr at 60° C. and the solvent was evaporated. Trituration of this solid with diethyl ether afforded pure hydrazide 2 in 86percent/o yield. The treatment of hydrazide 2 with CS2 and KOH in 60° C. for 18 hrs produced a solid upon concentration in vacuo. It was found that this material could be easily purified by trituration with H2O followed by filtration to give thiol 3 in 78percent yield, thus avoiding chromatography over the first two steps. This operationally simple procedure afforded multi-gram quantities of 3 for subsequence focused library synthesis. Finally, diversification of the aryl ring was achieved by nucleophilic displacement reaction of thiol 3 with substituted aryl bromides in room temperature DMF using K2CO3 as base.
86%
With hydrazine hydrate In ethanol for 10.25 h; Cooling with ice; Reflux
Isonicotinicacid ethyl ester 1 (1.5g, 10mmol) was dissolved in 15mL of ethanol, then under ice-cooling was slowly added dropwise with hydrazine hydrate (2g, 40mmol), after the addition was complete, it was stirred at room temperature for 15min, then heated under reflux for 10h. After completion of the reaction, ethanol was removed by rotary evaporation, poured into water, extracted with ethyl acetate, the organic phase was dried and concentrated to give the desired product 2 (1.2g, 86percent), without purification into the next step.
85%
With hydrazine hydrate In ethanol for 24 h; Reflux
Step 1: 15.12 g (0.1 mol) of ethyl pyridine-4-carboxylate and 10.00 g (0.2 mol) of hydrazine hydrate (NH 2 NH 2 · H 2 O) were added to 50 mL of ethanol, refluxed for 24 h, cooled to room temperature, and the solution was spun dry and recrystallized. The 11.62 g (0.085 mol) pyridine-4-formyl hydride was obtained in a yield of 85percent.
73%
With hydrazine hydrate In ethanol for 6 h; Reflux
To a solution of ethyl isonicotinate (1.44 g, 10 mmol) inEtOH (10 mL), 85percent hydrazine hydrate (2 mL, 35 mmol)was added dropwise. The mixture was heated under refluxfor 6 h. After the reaction was over, the mixture was cooledto room temperature, filtered, washed with cool ethyl acetate,and then dried to give white solid isonicotinyi hydrazine 2,yield (1.0 g, 73percent).
73%
With hydrazine hydrate In water for 6 h;
A mixture of ethyl isonicotinate (1.44 g, 10 mmol) and 85percent hydrazine hydrate (2 mL, 35 mmol) was heated under reflux for 6 h. The mixture was cooled to room temperature,filtered, washed with cool ethyl acetate, then dried to give white solid isonicotinohydrazide 2. Yield 1.0 g, 73percent.
12.9 g
With hydrazine hydrate In ethanol for 3 h; Reflux
General procedure: An ethanol (300 ml) suspension of salicylic acid(13.8 g; 0.1 mol) and strongly acidic ion-exchange resin,Amberlyst-15 (5 g) were stirred with refluxing for three days.Insoluble catalyst was separated by filtration, and washed withethanol (3 20 ml). Combined ethanol filtrates were mixed with hydrazine hydrate (20 ml; 20.5 g; 0.4 mol) and refluxed with slowsolvent distillation using the modified Hickman still apparatus(Scheme 3). After 3 h of refluxing, the volume of the reaction mixturewas reduced to about 50 ml and white precipitate started toform. The white suspension was cooled to room temperature andthen left at 5 C for 1 h. Insoluble product was separated by filtration,washed with ice cold ethanol, and dried on air to give pureproduct (13.2 g; 87percent).
Reference:
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2015, vol. 54B, # 10, p. 1260 - 1274
[2] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 6, p. 1532 - 1537
[3] Patent: US2015/210679, 2015, A1, . Location in patent: Paragraph 0091
[4] Patent: US2016/214969, 2016, A1, . Location in patent: Paragraph 0076-0077
[5] Patent: CN105481765, 2016, A, . Location in patent: Paragraph 0030; 0031; 0032
[6] Patent: CN104892639, 2018, B, . Location in patent: Paragraph 0052; 0053; 0054; 0066; 0067; 0068; 0069
[7] Heterocycles, 2006, vol. 68, # 8, p. 1585 - 1594
[8] Medicinal Chemistry Research, 2013, vol. 22, # 10, p. 4953 - 4963
[9] Letters in Drug Design and Discovery, 2014, vol. 11, # 9, p. 1107 - 1111
[10] Letters in Drug Design and Discovery, 2014, vol. 11, # 9, p. 1119 - 1123
[11] Monatshefte fuer Chemie, 1912, vol. 33, p. 403
[12] Acta Chimica Academiae Scientiarum Hungaricae, 1958, vol. 14, p. 197,199
[13] Chimica, 1952, vol. 7, p. 229
[14] Roczniki Chemii, 1953, vol. 27, p. 161,163[15] Chem.Abstr., 1954, p. 13688
[16] Yakugaku Zasshi, 1951, vol. 71, p. 1002[17] Chem.Abstr., 1952, p. 8120
[18] Journal of the American Pharmaceutical Association (1912-1977), 1956, vol. 45, p. 478
[19] Pharm. Ind., 1952, vol. 14, p. 366
[20] European Journal of Medicinal Chemistry, 1990, vol. 25, # 1, p. 75 - 79
[21] European Journal of Medicinal Chemistry, 2006, vol. 41, # 7, p. 841 - 846
[22] Phosphorus, Sulfur and Silicon and the Related Elements, 2006, vol. 181, # 9, p. 2079 - 2087
[23] Chemistry of Heterocyclic Compounds, 2006, vol. 42, # 2, p. 233 - 245
[24] European Journal of Medicinal Chemistry, 2009, vol. 44, # 8, p. 3340 - 3344
[25] Journal of Medicinal Chemistry, 2009, vol. 52, # 14, p. 4200 - 4209
[26] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 11, p. 4042 - 4048
[27] European Journal of Medicinal Chemistry, 2010, vol. 45, # 9, p. 3943 - 3949
[28] European Journal of Medicinal Chemistry, 2010, vol. 45, # 9, p. 3960 - 3969
[29] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2010, vol. 49, # 4, p. 526 - 531
[30] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 24, p. 7246 - 7250
[31] Medicinal Chemistry Research, 2012, vol. 21, # 7, p. 1451 - 1470
[32] Medicinal Chemistry Research, 2012, vol. 21, # 8, p. 1935 - 1952,18
[33] Medicinal Chemistry Research, 2012, vol. 21, # 8, p. 1935 - 1952
[34] Journal of the Chemical Society of Pakistan, 2018, vol. 40, # 2,
[35] Medicinal Chemistry Research, 2012, vol. 21, # 11, p. 3646 - 3655
[36] Medicinal Chemistry, 2013, vol. 9, # 1, p. 53 - 76
[37] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 8, p. 2286 - 2297
[38] European Journal of Medicinal Chemistry, 2015, vol. 102, p. 243 - 248
[39] Bioorganic Chemistry, 2018, vol. 80, p. 253 - 260
[40] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 11, p. 1097 - 1101
[41] European Journal of Medicinal Chemistry, 2014, vol. 71, p. 199 - 218
[42] Dyes and Pigments, 2014, vol. 108, p. 32 - 40
[43] Archives of Pharmacal Research, 2014, vol. 37, # 7, p. 852 - 861
[44] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 13, p. 3397 - 3407
[45] Medicinal Chemistry Research, 2015, vol. 24, # 12, p. 4166 - 4180
[46] Transition Metal Chemistry, 2015, vol. 40, # 6, p. 665 - 671
[47] Polyhedron, 2016, vol. 106, p. 138 - 143
[48] Medicinal Chemistry Research, 2016, vol. 25, # 8, p. 1666 - 1677
[49] Inorganica Chimica Acta, 2017, vol. 461, p. 301 - 315
[50] ChemMedChem, 2017, vol. 12, # 12, p. 972 - 985
[51] Patent: CN107011255, 2017, A, . Location in patent: Paragraph 0024
[52] Chemistry and Biodiversity, 2018, vol. 15, # 9,
[53] Patent: CN105085390, 2018, B, . Location in patent: Paragraph 0059-0067
5
[ 2459-09-8 ]
[ 54-85-3 ]
Yield
Reaction Conditions
Operation in experiment
94.1%
With hydrazine hydrate In ethanol at 20℃; for 3 h;
Methyl 4-picolinate (2.74 g, 20 mmol) and absolute ethanol (15 mL) were added to a 50 mL round bottom flask,Stir at room temperature until the solid dissolves completely.Slowly drip hydrated hydrazine (30mmol 100percent),A large number of needle-like white solids appeared immediately after the addition.After stirring at room temperature for 3 hours, it was filtered, rinsed with a small amount of ethanol, and dried in vacuo to give 2.58 g of white needles, yield 94.1percent,
86%
With hydrazine hydrate In ethanol at 23℃; for 16 h;
i) A solution of methyl isonicotinate (1.00 mL, 8.47 mmol) and hydrazine hydrate (1 .23 mL, 25.4 mmol) inethanol (10 mL) was stirred at RT for 16 h. Concentration and subsequent coevaporation with tolueneand DCM gave INT-28A (1.00 g, 7.31 mmol, 86percent). LCMS: caic. for [M+H]=138.07, found 138.1.
78%
With hydrazine hydrate In methanol for 5 h; Reflux
General procedure: To a solution of an appropriate methyl esters17(a–j) (1.0 mmol) in 50 mL of methanol was added 99 percenthydrazine hydrate (4.0 mmol) and the mixture was refluxedfor 5 h up to reaction completed (TLC). After completionof reaction, it was allowed to cool and the obtained solidwas washed with methanol. The crude products wererecrystallized from ethanol.
75%
With hydrazine hydrate In ethanol at 150℃; for 0.0833333 h; Microwave irradiation
[00445] To a solution of methyl isonicotinate (100 mg, 0.73 mmol) in 0.3 mL of ethanol was added hydrazine hydrate (0.35 mL, 7.29 mmol). This reaction mixture was heated in a microwave reactor for 5 min at 150°C. The reaction was allowed to cool to room temperature and diluted with 10 mL of MeOH, then concentrated. The residue was purified by column chromatography with MeOH/CH2Cl2 (1 :4) to afford 84 mg (75percent) of the title compound. XH NMR (MeOD) 58.70 (dd, J = 4.8, 1.6 Hz, 2H), 7.77 (dd, J = 4.4, 1.6 Hz, 2H). LRMS calculated for C6H7N30 (M+H)Vz: 137.05 Measured 137.1 m/z.
75%
With hydrazine hydrate In ethanol at 150℃; for 0.0833333 h; Microwave irradiation
a. PREPARATION OF ISONICOTINOHYDRAZIDE [00471] To a solution of methyl isonicotinate (100 mg, 0.73 mmol) in 0.3 mL of ethanol was added hydrazine hydrate (0.35 mL, 7.29 mmol). This reaction mixture was heated in a microwave reactor for 5 min at 150 °C. The reaction was allowed to cool to room temperature and diluted with 10 mL of MeOH, then concentrated. The residue was purified by column chromatography with MeOH/CH2Cl2 (1:4) to afford 84 mg (75percent) of the desired product. lH NMR (MeOD) δ 8.70 (dd, J = 4.8, 1.6 Hz, 2H), 7.77 (dd, J = 4.4, 1.6 Hz, 2H). LRMS calculated for C6H7N30 (M+H)Vz: 137.05 Measured 137.1 m/z.
73%
for 6 h; Reflux
Formula (II) (1.37g, 10mmol) and a concentration of 80percent by mass aqueous solution of hydrazine hydrate (2mL, 35mmol) was heated at reflux for 6h, cooled to room temperature, filter, the filter cake was washed with ethyl acetate and dried to give isoniazid as shown in formula (III) in a yield (1.0 g, 73percent).
Reference:
[1] Patent: CN104592217, 2018, B, . Location in patent: Paragraph 0049; 0050; 0051
[2] Patent: WO2015/161928, 2015, A1, . Location in patent: Page/Page column 48
[3] Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643
[4] Patent: WO2016/154471, 2016, A1, . Location in patent: Paragraph 00445
[5] Patent: WO2017/11466, 2017, A1, . Location in patent: Paragraph 00471
[6] Journal of Heterocyclic Chemistry, 2005, vol. 42, # 2, p. 259 - 264
[7] Patent: CN106699776, 2017, A, . Location in patent: Paragraph 0024-0025; 0027; 0030-0031
[8] Arzneimittel-Forschung/Drug Research, 2011, vol. 61, # 8, p. 452 - 457
[9] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 11, p. 3615 - 3621
[10] Journal of Medicinal Chemistry, 2012, vol. 55, # 9, p. 4407 - 4424
[11] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 16, p. 5185 - 5189
[12] Patent: WO2012/154403, 2012, A2, . Location in patent: Page/Page column 254-255
[13] Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 2013, vol. 115, p. 683 - 689
[14] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 12, p. 2613 - 2616
[15] New Journal of Chemistry, 2015, vol. 39, # 1, p. 453 - 460
[16] ChemMedChem, 2014, vol. 9, # 11, p. 2445 - 2448
[17] Journal of Inorganic Biochemistry, 2015, vol. 150, p. 100 - 107
[18] Journal of the Chemical Society of Pakistan, 2016, vol. 38, # 5, p. 990 - 995
[19] Chemical Biology and Drug Design, 2017, vol. 90, # 2, p. 200 - 209
[20] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 14, p. 2369 - 2374
6
[ 1453-82-3 ]
[ 55-22-1 ]
[ 54-85-3 ]
Yield
Reaction Conditions
Operation in experiment
90.4%
With hydrazine dihydrochloride In aq. phosphate buffer at 30℃; for 1 h; Enzymatic reaction
Fed-batch biotransformation was carried out in 250ml Erlenmeyer flask containing 50ml of reaction mixture with initial isonicotinamide and hydrazine–2HCl concentration of 100 and 1000mM respectively in phosphate buffer (100mM, pH 7) at 30°C and 2.0mgdcw/ml resting cells of B. smithii strain IITR6b2. Powdered isonicotinamide (0.61g) and highly concentrated solution (1ml, 5M, pH 7) of hydrazine–2HCl were fed in subsequent seven feeds at an interval of 60min to restrict the residual isonicotinamide and hydrazine–2HCl concentration above 100 and 1000mM respectively. 500μl of sample was withdrawn at every 30min during the reaction and monitored for isoniazid, isonicotinic acid and isonicotinamide concentration. Effort was made to maintain the reaction volume constant around 50ml. A control experiment was also conducted with same parameters without enzyme for any spontaneous chemical reaction
Reference:
[1] Journal of Molecular Catalysis B: Enzymatic, 2013, vol. 97, p. 67 - 73
7
[ 1453-82-3 ]
[ 54-85-3 ]
Yield
Reaction Conditions
Operation in experiment
97.34%
at 115℃; for 4 h;
[00024] 9.9918 gms of isonicotinamide was dissolved in 77.97 gms of absolute alcohol and 10.1 gms of hydrazine hydrate(100percent) was added to it. The reaction mixture was refluxed in glycerine bath for 4 hours at 115 degree Celsius; after which alcohol was distilled off and solid mass, Isonicotinic acid hydrazide (INH) was taken out in hot condition Recovered Isonicotinic acid hydrazide was 9.727 gms i.e. 97.34 wt percent and the melting point obtained was 170° C. against 169.9° C. actual.
97.34%
at 115℃; for 4 h; Heating / reflux
9.9918 gms of isonicotinamide was dissolved in 77.97 gms of absolute alcohol and 10.1 gms of hydrazine hydrate (100percent) was added to it. The reaction mixture was refluxed in glycerine bath for 4 hours at 115 degree Celsius; after which alcohol was distilled off and solid mass, Isonicotinic acid hydrazide (INH) was taken out in hot condition. Recovered Isonicotinic acid hydrazide was 9.727 gms i. e. 97.34 wtpercent and the melting point obtained was 170°C against 169. 9°C actual.
96.03%
With hydrazine In methanol at 110℃; for 4 h;
[00025] 19.3989 gins of isonicotinamide was dissolved in 39.488 gms of methyl alcohol and 14.14 gms of hydrazine hydrate (100percent) was added to it. The reaction mixture was refluxed in glycerine bath for 4 hours at 110 degree Celsius; after which alcohol was distilled off and solid mass, Isonicotinic acid hydrazide (INH) was taken out in hot condition. Recovered Isonicotinic acid hydrazide was 19.3 gms i.e. 99.49 wt percent and the melting point obtained was 169.9° C. against 170° C. actual.EXAMPLE-3 [00026] 24.99 gms of isonicotinamide was dissolved in 39.48 gms of methyl alcohol and 20.20 gms of hydrazine hydrate(100percent) was added to it. The reaction mixture was refluxed in glycerine bath for 4 hours at 110 degree Celsius; after which alcohol was distilled off and solid mass, Isonicotinic acid hydrazide(INH) was taken out in hot condition. Recovered Isonicotinic acid hydrazide was 24.0 gms i.e. 96.03 wt percent and the melting point obtained was 169.9° C. against 170° C. actual.
96.03%
With hydrazine In methanol at 110℃; for 4 h; Heating / reflux
19.3989 gms of isonicotinamide was dissolved in 39.488 gms of methyl alcohol and 14.14 gms of hydrazine hydrate (100percent) was added to it. The reaction mixture was refluxed in glycerine bath for 4 hours at 110 degree Celsius ; after which alcohol was distilled off and solid mass, Isonicotinic acid hydrazide (INH) was taken out in hot condition. Recovered Isonicotinic acid hydrazide was 19.3 gms i. e. 99.49 wtpercent and the melting point obtained was 169. 9°C against 170°C actual. Example-3 24.99 gms of isonicotinamide was dissolved in 39.48 gms of methyl alcohol and 20.20 gms of hydrazine hydrate (100percent) was added to it. The reaction mixture was refluxed in glycerine bath for 4 hours at 110 degree Celsius; after which alcohol was distilled off and solid mass, Isonicotinic acid hydrazide (INH) was taken out in hot condition. Recovered Isonicotinic acid hydrazide was 24.0 gms i. e. 96.03 wtpercent and the melting point obtained was 169. 9°C against 170°C actual.
129.3 g
With butan-2-one azine In water at 160 - 170℃; Green chemistry
The isonicotinamide with stirring into 123g,A thermometer and a reflux condenser,The upper part of the receiver is connected with a conduit to absorb ammonia gas;Open the stir,Heating to 160 ~ 170 ,After the isonicotinamide melts into liquid,Butanone with nitrogen 260g and water 90g slowly added to isonicotinamide,Control reaction temperature of 160 ~ 170 ,Will return the condenser outlet temperature control at 75 ~ 80 ,The addition of butanol at the reflux ratio R = 1 ~ 10 and the recovery of ammonia gas;Butanone with nitrogen and water drop time control in 1 ~ 2h,After the completion of the incubation reaction 30min,And then the temperature rose to 180 ° C ~ 190 ° C unreacted butanone nitrogen distillation recovery,Butanone nitrogen recovery after cooling cooling,The solid matter precipitated in the four-necked flask was filtered,washing,After drying, 129.3 g of isoniazid was obtained.
Reference:
[1] Patent: US6734309, 2004, B1, . Location in patent: Page column 2
[2] Patent: WO2004/56778, 2004, A1, . Location in patent: Page 3
[3] Patent: US6734309, 2004, B1, . Location in patent: Page column 2; 3
[4] Patent: WO2004/56778, 2004, A1, . Location in patent: Page 3
[5] Russian Journal of Physical Chemistry, 1993, vol. 67, # 5, p. 976 - 977[6] Zhurnal Fizicheskoi Khimii, 1993, vol. 67, # 5, p. 1083 - 1085
[7] Russian Journal of Physical Chemistry, 1993, vol. 67, # 5, p. 976 - 977[8] Zhurnal Fizicheskoi Khimii, 1993, vol. 67, # 5, p. 1083 - 1085
[9] Yakugaku Zasshi, 1957, vol. 77, p. 219[10] Chem.Abstr., 1957, p. 11341
[11] Patent: CN106866522, 2017, A, . Location in patent: Paragraph 0006; 0009
8
[ 13841-66-2 ]
[ 54-85-3 ]
Yield
Reaction Conditions
Operation in experiment
74.1%
With hydrazine hydrate In ethanol for 6 h; Reflux
General procedure: The obtained compounds II was dissolved with ethanol (90 mL) and hydrazine hydrate (85percent, 30 mL),then the mixture was heated to reflux for 6 h. After the reaction was completed, ethanol and the excess of hydrazine hydrate were distilled out under a reduced pressure, and a white product was left. The crude product was recrystallized from ethanol to afford white crystals III.
Reference:
[1] Pharmaceutical Chemistry Journal, 1980, vol. 14, # 3, p. 199 - 202[2] Khimiko-Farmatsevticheskii Zhurnal, 1980, vol. 14, # 3, p. 93 - 96
[3] Russian Journal of General Chemistry, 2015, vol. 85, # 3, p. 746 - 751
9
[ 55-22-1 ]
[ 54-85-3 ]
Reference:
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2010, vol. 49, # 4, p. 526 - 531
[2] Asian Journal of Chemistry, 2011, vol. 23, # 6, p. 2648 - 2652
[3] Meditsinskaya Promyshlennost SSSR, 1957, vol. 11, # 4, p. 19,20[4] Chem.Abstr., 1958, p. 7315
[5] Acta Chemica Scandinavica (1947-1973), 1957, vol. 11, p. 1787
[6] Patent: US2891067, 1957, ,
[7] Helvetica Chimica Acta, 1959, vol. 42, p. 1324,1326
[8] Journal of Pharmacy and Pharmacology, 2001, vol. 53, # 2, p. 267 - 272
[9] Phosphorus, Sulfur and Silicon and the Related Elements, 2006, vol. 181, # 9, p. 2079 - 2087
[10] European Journal of Medicinal Chemistry, 2006, vol. 41, # 7, p. 841 - 846
[11] Acta Chimica Academiae Scientiarum Hungaricae, 1958, vol. 14, p. 197,199
[12] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 1, p. 184 - 187
[13] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 21, p. 6225 - 6229
[14] Journal of Heterocyclic Chemistry, 2010, vol. 47, # 5, p. 1225 - 1229
[15] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 24, p. 7246 - 7250
[16] Arzneimittel-Forschung/Drug Research, 2011, vol. 61, # 8, p. 452 - 457
[17] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 11, p. 3615 - 3621
[18] Journal of Medicinal Chemistry, 2012, vol. 55, # 9, p. 4407 - 4424
[19] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 16, p. 5185 - 5189
[20] Medicinal Chemistry Research, 2012, vol. 21, # 7, p. 1451 - 1470
[21] Medicinal Chemistry Research, 2012, vol. 21, # 8, p. 1935 - 1952,18
[22] Medicinal Chemistry Research, 2012, vol. 21, # 8, p. 1935 - 1952
[23] Medicinal Chemistry Research, 2012, vol. 21, # 11, p. 3646 - 3655
[24] Medicinal Chemistry, 2013, vol. 9, # 1, p. 53 - 76
[25] Journal of the Brazilian Chemical Society, 2013, vol. 24, # 1, p. 115 - 120
[26] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 8, p. 2286 - 2297
[27] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 11, p. 1097 - 1101
[28] European Journal of Medicinal Chemistry, 2014, vol. 71, p. 199 - 218
[29] Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 2013, vol. 115, p. 683 - 689
[30] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2013, vol. 52, # 10, p. 1318 - 1324
[31] Dyes and Pigments, 2014, vol. 108, p. 32 - 40
[32] Archives of Pharmacal Research, 2014, vol. 37, # 7, p. 852 - 861
[33] New Journal of Chemistry, 2015, vol. 39, # 1, p. 453 - 460
[34] Letters in Drug Design and Discovery, 2014, vol. 11, # 9, p. 1107 - 1111
[35] Letters in Drug Design and Discovery, 2014, vol. 11, # 9, p. 1119 - 1123
[36] Russian Journal of General Chemistry, 2015, vol. 85, # 3, p. 746 - 751
[37] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 13, p. 3397 - 3407
[38] ChemMedChem, 2014, vol. 9, # 11, p. 2445 - 2448
[39] Medicinal Chemistry Research, 2015, vol. 24, # 12, p. 4166 - 4180
[40] Journal of Inorganic Biochemistry, 2015, vol. 150, p. 100 - 107
[41] Transition Metal Chemistry, 2015, vol. 40, # 6, p. 665 - 671
[42] RSC Advances, 2015, vol. 5, # 118, p. 97089 - 97101
[43] Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643
[44] Journal of the Chemical Society of Pakistan, 2016, vol. 38, # 5, p. 990 - 995
[45] Inorganica Chimica Acta, 2017, vol. 461, p. 301 - 315
[46] ChemMedChem, 2017, vol. 12, # 12, p. 972 - 985
[47] Patent: CN106699776, 2017, A,
[48] Patent: CN107011255, 2017, A,
[49] Acta Poloniae Pharmaceutica - Drug Research, 2018, vol. 75, # 1, p. 265 - 271
[50] Bioorganic Chemistry, 2018, vol. 80, p. 253 - 260
[51] Chemistry and Biodiversity, 2018, vol. 15, # 9,
[52] Patent: DE1116667, 1956, ,
Reference:
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2013, vol. 52, # 10, p. 1318 - 1324
[2] Patent: CN107011255, 2017, A,
13
[ 100-48-1 ]
[ 54-85-3 ]
Reference:
[1] Patent: US2830994, 1956, ,
14
[ 108-89-4 ]
[ 54-85-3 ]
Reference:
[1] Patent: CN107011255, 2017, A,
15
[ 88057-93-6 ]
[ 54-85-3 ]
[ 31599-25-4 ]
Reference:
[1] Acta Poloniae Pharmaceutica, 1993, vol. 50, # 2.3, p. 183 - 188
16
[ 17332-42-2 ]
[ 54-85-3 ]
[ 31599-25-4 ]
Reference:
[1] Acta Poloniae Pharmaceutica, 1993, vol. 50, # 2.3, p. 183 - 188
17
[ 39178-35-3 ]
[ 54-85-3 ]
Reference:
[1] Pharm. Ind., 1952, vol. 14, p. 366
18
[ 110-86-1 ]
[ 54-85-3 ]
Reference:
[1] Acta Chimica Academiae Scientiarum Hungaricae, 1958, vol. 14, p. 197,199
19
[ 536-75-4 ]
[ 54-85-3 ]
Reference:
[1] Acta Chimica Academiae Scientiarum Hungaricae, 1958, vol. 14, p. 197,199
Reference:
[1] Meditsinskaya Promyshlennost SSSR, 1957, vol. 11, # 12, p. 38[2] Chem.Abstr., 1958, p. 20151
23
[ 54-85-3 ]
[ 54-92-2 ]
Reference:
[1] Journal of the American Chemical Society, 1953, vol. 75, p. 1933,1934
[2] Journal of the American Pharmaceutical Association (1912-1977), 1953, vol. 42, p. 457,463
[3] Bulletin of the Korean Chemical Society, 2015, vol. 36, # 2, p. 628 - 635
24
[ 75-30-9 ]
[ 54-85-3 ]
[ 54-92-2 ]
Reference:
[1] Gazzetta Chimica Italiana, 1958, vol. 88, p. 393,398
25
[ 54-85-3 ]
[ 75-26-3 ]
[ 54-92-2 ]
Reference:
[1] Journal of the American Pharmaceutical Association (1912-1977), 1953, vol. 42, p. 457,463
26
[ 54-85-3 ]
[ 708-06-5 ]
[ 796-42-9 ]
Yield
Reaction Conditions
Operation in experiment
84%
for 3 h; Reflux
General procedure: H2La, H2Lb and H2Lc have been prepared by a general procedure: equimolar amounts of isonicotinohydrazide (4-pyridine carboxylic acid hydrazide) and the corresponding aldehyde, 5-bromo-2-hydroxybenzaldehyde, 2-hydroxynaphthaldehyde and 2,4-dihydroxybenzaldehyde respectively, were refluxed in ethanol for 3h and then cooled to ambient temperature. Crystals suitable for X-ray crystallography were obtained by slow evaporation of a dilute ethanolic solution of the compounds.
Reference:
[1] European Journal of Inorganic Chemistry, 2017, vol. 2017, # 6, p. 999 - 1006
[2] Polyhedron, 2014, vol. 79, p. 88 - 96
[3] Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 2006, vol. 64, # 4, p. 853 - 858
[4] Medicinal Chemistry Research, 2014, vol. 23, # 1, p. 269 - 279
[5] Journal of the American Chemical Society, 1953, vol. 75, p. 5434
[6] Journal of the American Pharmaceutical Association (1912-1977), 1954, vol. 43, p. 513,514
[7] Journal of Chemical & Engineering Data, 1988, vol. 33, # 4, p. 538 - 540
(E)-N’-(2'-ethoxybenzylidene)isonicotinohydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
81%
With acetic acid; In ethanol;Reflux;
General procedure: Nicotinic/isonicotinic hydrazides (1 mmol), substituted aromatic aldehyde (1 mmol) and glacial acetic acid (few drops) were taken in ethanol (10 mL) and refluxed for 3 h. Progress of the reaction was monitored by TLC. After the completion of the reaction,mixture was left for evaporation of solvent, and then crude product washed with dichloromethane and hexane, and dried to afford compounds 1-54.
General procedure: The desired compounds 1a-g and 2a-f were prepared by reaction between <strong>[65-22-5]pyridoxal hydrochloride</strong> (0.15 g, 0.74mmol) and the appropriate aromatic or heteroaromatic hydrazine or N-acylhydrazine (1.1 eq., 0.81mmol) in ethanol (10.0 mL). The reaction mixture was stirred for 1-48 hours at room temperature. After that, product was purified by wash-ing with cold ethanol (3.0 mL) and cold diethyl ether (3.0 mL), leading to the pure derivatives 1a-g and 2a-f as solid in 42-86% yields.
General procedure: H2La, H2Lb and H2Lc have been prepared by a general procedure: equimolar amounts of isonicotinohydrazide (4-pyridine carboxylic acid hydrazide) and the corresponding aldehyde, 5-bromo-2-hydroxybenzaldehyde, 2-hydroxynaphthaldehyde and 2,4-dihydroxybenzaldehyde respectively, were refluxed in ethanol for 3h and then cooled to ambient temperature. Crystals suitable for X-ray crystallography were obtained by slow evaporation of a dilute ethanolic solution of the compounds.
75%
In ethanol; for 4.0h;Reflux;
The ligand (E)-N?-((2-hydroxynaphthalen-1-yl)methylene)isonicotinohydrazide (H2L,Scheme 1) was synthesized by condensation of isonicotinichydrazide and 2-hydroxy-1-naphthaldehyde as reported elsewhere [28]. Isoicotinichydrazide (500 mg, 3.64 mmol)and 2-hydroxynaphthaldehyde (627 mg, 3.64 mmol) were taken in 35 mL ethanol solution and refluxed for 4 h. Upon completion of the reaction, a yellow precipitatewas obtained, which was filtered off, washed with ethanol solution and dried undervacuum. 375mg (75%). 1H-NMR (DMSO d6), 25 C, 400 MHz): (ppm) 12.51 (s, 1H, OHa),12.40 (s, 1H, NHb), 9.47 (s, 1H, NC-Hc), 8.83 (d, 2H, CHd), 8.31 (d, 1H, CHe) 7.91 (d, 1H,CHf), 7.94 (d, 1H, CHg), 7.88 (d, 2H, CHh), 7.61 (t, 1H, CHi), 7.41 (t, 1H, CHj), 7.24 (d, 1H,CHk), FT-IR (KBr, cm1): H2L, 3226s (-NH), 3029m (aromatic -CH), 1680s (>CO),1660m (>CN), 1286 (>C-O), 1186m (-C-N). Elemental analysis, Anal. Calcd(C17H13N3O2): C 70.09, H 4.50, N 14.42, found: C 70.05, H 4.60, N 14.44. ESI-MS: (m/z)292.30 [MH].
General procedure: To a solution of Isnz (1 equiv.) or VI in dry EtOH (2.5 mL) was added to the corresponding aldehyde (I, II, III, or IV, 0.9 equiv.) and a drop of glacial AcOH. The mixture was stirred until the aldehyde was consumed (checked by TLC). The solid precipitated was filtered and washed with cold EtOH.
General procedure: Ligand 1 was prepared by refluxing equimolar solution of imidazole- 2-carboxylic acid (0.112 g; 1 mM) and benzhydrazide (0.136 g; 1 mM) (HL1) in 50 mL of methanol. After 24 h, the reaction mixture was cooled to room temperature and the product formed was filtered, washed several times with water and then recrystallized from methanol to afford the desired product in pure form. Other Ligands 2-4 (HL2-HL4) were also prepared by adopting the similar procedure as in the caset of ligand, using the respective hydrazides i.e., isonicotinic acid hydrazide (0.137 g; 1 mM), furoic acid hydrazide (0.126 g; 1 mM) and thiophene-2-carboxylic acid hydrazide (0.142 g; 1 mM as summarized in Scheme 1.
General procedure: Nicotinic/isonicotinic hydrazides (1 mmol), substituted aromatic aldehyde (1 mmol) and glacial acetic acid (few drops) were taken in ethanol (10 mL) and refluxed for 3 h. Progress of the reaction was monitored by TLC. After the completion of the reaction,mixture was left for evaporation of solvent, and then crude product washed with dichloromethane and hexane, and dried to afford compounds 1-54.
General procedure: To the THF (5mL) and DMF (0.5mL) solution of 2-(Benzo[d]thiazol-2-ylthio)acetic acid (100 mg; mM) was added EDC.HCl (1.5molar equivalents) and HOBt (10mg). The reaction mixture was stirred for five minutes under nitrogen atmosphere at room temperature. Then 1.2 molar equivalents of amine (1/2) were added to the reaction mixture and the reaction mixture was continued to stir for further 12-16h. After the completion of the reaction monitored by TLC, the reaction mixture was quenched with excess of water (100mL) and extracted with ethylacetate (2×20mL). Combined organic layers were dried over anhydrous sodium sulfate and evaporated to obtain the target compound.
With triethylamine; In dimethyl sulfoxide; at 120℃; under 30003.0 Torr;Autoclave; Green chemistry;
To a 100-ml autoclave, were added aryl iodide (1.0 mmol),acylhydrazine (2.0 mmol), the catalyst (Pd: 0.78 molpercent), base(1.06 mmol) and DMSO (5.0 ml). The autoclave was flushed by CO flow and pressurized to 4.0 MPa. The reaction was performed at 120C for the given time. The reaction mixture was extracted with ethyl acetate. The carbonylation product was obtained by purifica-tion over silica column with the eluent of ethyl acetate/petroleumether (60?90C) (v/v, 2:1). In the five-run recycling test, the cata-lyst was separated by adding 30 ml mixture of petroleum ether anddiethyl ether and washed by ethyl acetate and diethyl ether afte reach testing run. The catalyst was dried vacuum and then recycled into the next batch.
General procedure: The Compound I (0.79 mmol)was dissolved in 10 mL of absolute ethanol. Then the mixture of R2-CHO (0.66 mmol), 10 mL acetic acid and 3 mL absolute ethanol was added dropwise at 70 °C. The mixture was refluxed for 5 h. The solvent was evaporated. The crude product was purified by flash chromatography (neutral Al2O3).
(E)-N'-(7-hydroxy-2,3-dihydro-1H-inden-1-ylidene)isonicotinoylhydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
66%
With acetic acid; In methanol;Reflux;
Isoniazid (0.46 g, 3.4 mmol), <strong>[6968-35-0]7-hydroxy-2,3-dihydro-1H-inden-1-one</strong> (0.5 g, 3.4 mmol) and acetic acid (0.25 mL) were dissolved in methanol (10 mL) and stirred overnight under reflux. After cooling the reaction mixture to 4 C, the resulting precipitate was collected by filtration and washed with water and methanol. The solid was suspended in toluene and was stirred for 30 min. This solution was filtered to obtain 0.37 g (66%) of the product as a yellow crystalline solid. mp 232-236 C. 1HNMR (500 MHz, DMSO-d6): delta 11.30 (s, 1H, NH), 10.15 (s, 1H, OH), 8.80-8.70 (m, 2H, Py), 7.84-7.74 (m, 2H, Py), 7.30 (dd, J=7.8,1.3 Hz, 1H, Ph), 6.89 (d, J=7.4 Hz, 1H, Ph), 6.75 (d, J=8.1 Hz, 1H, Ph), 3.13-3.00 (m, 4H, 2xCH2). 13C NMR (125 MHz, DMSO-d6): delta 167.9, 162.5, 155.5, 150.3, 150.0, 140.8, 133.1, 122.6, 122.1, 116.6, 113.0, 28.7, 28.1. Anal. Calcd. for C15H13N3O2: C, 67.40; H,4.90; N, 15.72; Found: C, 67.02; H, 5.13; N, 15.87.
The luteolin1(500mg, 1.74mmol) placed in 50ml round bottom flask, and dissolved in 20mlTHF, plus DMAP (488mg, 4mmol), After stirring for 30min at 40 solution of DCC (537mg, 2.61mmol), then stirred plus isoniazid after 30min acid (550mg, 4.5mmol) the reaction was continued at 40 for 24h.Join NH4After termination of the reaction Cl saturated solution 10ml, share THF layer, continue with CH2Cl2(10ml × 2) the aqueous layer was extracted, and the combined THF layers CH2Cl2The extract was dried over anhydrous Na2SO4Dried under reduced pressure to recover the solvent residue.The residue (10g) column chromatography through silica gel, chloroform - methanol (220: 1) to give compound4a(Yellow amorphous powder, 70mg, 14% yield)4b(Yellow amorphous powder, 60mg, 12% yield).
N'-[(3-fluoro-2-hydroxyphenyl)methylidene]pyridine-4-carbohydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
38%
In methanol; chloroform; for 1.33333h;Reflux;
General procedure: General procedure for the synthesis of the Schiff bases. The ligand,N-[[(4-(trifluoromethyl)phenyl]methylidene]pyridine-4-carbohydrazide (L1), was preparedin the following way. A 1.37 g portion (10.0 mmol) of isoniazid and 1.74 g (10.0 mmol) of4-trifluoromethylbenzaldehyde were dissolved in 40 mL of methanol-chloroform mixture (1:1 v/v).The solution was then refluxed for 80 min and then left to freely crystallise at room temperature. Afterthree days, colourless crystals suitable for X-ray structure analysis were obtained. They were filteredoff, washed with ether, and sucked dry in open air. If the crystals were of unsatisfactory quality forcrystallography, they were recrystallized from methanol-chloroform or methanol-dichloromethanemixtures. The other ligands were prepared in an analogous way.
With potassium carbonate; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere;
General procedure: In the first step mono-substituted triazine (13) was synthesized by using following procedure. A solution of triazine (12, 2mmol) and K2CO3 (4mmol) was stirred in anhydrous THF at 0C under nitrogen. Antimicrobial drugs (1-3) were then added drop-wise and the reaction mixture was allowed to warm at room temperature. The progress of the reaction was monitored by TLC. After the completion of the first step, a solution of N-Boc protected amino acids (8-10) in THF were added drop-wise. After the completion of reaction the mixture, the crude residues were purified by column chromatography using n-hexane/ethyl acetate. In the final step the di-substituted product was de-protected by using procedure described in section 4.2.
With potassium carbonate; In tetrahydrofuran;Inert atmosphere; Reflux;
In the first step mono-substituted triazine derivative was synthesized by using a solution oftriazine (5 mmol) and K2CO3 (5 mmol) was stirred in anhydrous THF at 0C under nitrogen.Isoniazid (8) solution in THF was then added drop-wise and the reaction was refluxed for 5-6hrs. The progress of the reaction was monitored by TLC. After the completion of the first step, asolution of piperazine (5 mmol) in THF were added drop-wise. After the completion of reaction,the crude residues were purified by column chromatography using n-hexane / ethyl acetate (9:1).
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In chloroform; at 0 - 20℃;
General procedure: A mixture of Boc-protected amino acid (4mmol) and HOBt (0.62g, 4mmol) in CHCl3 was stirred and cooled to 0C (ice bath). Then, antibacterial drugs (1-3) (4mmol) triethylamine (4mmol) and EDC (4mmol) were added. The mixture was allowed to warm to room temperature and stirring continued overnight. The mixture was diluted with CHCI3 and washed with 1N HC1 (thoroughly), aq. sat. NaHCO3 and NaCl solution. The organic phase was dried MgSO4 and evaporated. The crude residues were purified by column chromatography using n-hexane/ethyl acetate resulted in 71-80% yield.
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In chloroform; at 0 - 20℃;
General procedure: A mixture of Boc-protected amino acid (4mmol) and HOBt (0.62g, 4mmol) in CHCl3 was stirred and cooled to 0C (ice bath). Then, antibacterial drugs (1-3) (4mmol) triethylamine (4mmol) and EDC (4mmol) were added. The mixture was allowed to warm to room temperature and stirring continued overnight. The mixture was diluted with CHCI3 and washed with 1N HC1 (thoroughly), aq. sat. NaHCO3 and NaCl solution. The organic phase was dried MgSO4 and evaporated. The crude residues were purified by column chromatography using n-hexane/ethyl acetate resulted in 71-80% yield.
With sodium methylate; In methanol; at 25℃; for 14h;
In a 1000ml reaction flask,Add 2-chloro-4-cyanopyridine 110g,Add 660ml of methanol,Sodium methoxide 0.86g,Stirring at 25C for 2hThen add isoniazid 120g,Continue stirring at 25C for 2h,Then warm up to methanol reflux,Insulation 12hCool the reaction to room temperatureSuction filtrationLight yellow solid,That is formula 5 compounds,Yield 90%.
N'-(2-amino-5-bromopyridine-3-carbonyl)-N-isonicotinoylhydrazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84.2%
2-Amino-5-bromonicotinic acid (3.24 g, 15 mmol), HOBT (2.43 g, 18 mmol) and EDCI (3.45 g,18mmol) dissolved in DMF (30mL)N-methylmorpholine (1.5 mL, 13 mmol) was added dropwise at room temperature.Stir thoroughly for 30 min and add 4-pyridinecarboxylic acid hydrazide (2.47 g, 18 mmol).After stirring for 48h at room temperature, the reaction solution was poured into ice water.Precipitation of white solids, suction filtration,The cake was washed three times with a small amount of ethanol and vacuum dried.4.21g of an off-white solid, yield 84.2percent,
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 24h;
Isoniazid 1 (137.0mg, 1.0mmol) was mixed with N,N-diisopropylethylamine (DIPEA, 348muL, 2.0mmol) and N-succinimidyl N-methylcarbamate (258.2mg, 1.5mmol) in acetonitrile (4mL). The reaction mixture was stirred at the room temperature for 24h, formed precipitate was filtered off and recrystallised from ethyl acetate.
50 ml of methanol and 0.35 g of sodium metal were added to a 250 ml round bottom flask.After being completely dissolved,1.29 g of <strong>[2893-33-6]2,6-pyridine dicarbonitrile</strong> was added thereto, and the mixture was stirred under reflux at 80 C for 3 hours.Then add 4.11g of isoniazid to it, continue to reflux for 3h, and a large amount of precipitate formed after cooling.It was then suction filtered and rinsed with methanol.
N-(2-hydroxyphenyl)-2-(2-isonicotinoylhydrazinyl)-2-oxoacetamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
In ethanol; for 3.0h;Reflux;
General procedure: In a 100-mL round bottom flask, 0.5 g (3.06mmol) of 12a was dissolved in 30 mL of abs. ethanol at reflux temperature. Once the dissolution wascompleted, 0.42 g of INH were added and the reaction was left to stir at reflux for 3 hours (monitored by TLC).Upon cooling, a white precipitate of the title compound 8a was formed and collected by vacuum filtration. Thesame procedure was used for the synthesis of 8b,c starting from 6-chloro-<strong>[3597-63-5]2H-benzo[b][1,4]oxazine-2,3(4H)-dione</strong> 12b and 7-chloro-<strong>[3597-63-5]2H-benzo[b][1,4]oxazine-2,3(4H)-dione</strong> 12c, respectively.
(E)-N’-(4-(1,2,2-triphenylvinyl)benzylidene)isonicotinohydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In ethanol; at 80℃; for 6h;
General procedure: Benzoyl hydrazine (0.17g, 1.25mmol) and <strong>[1289218-74-1]4-(1,2,2-triphenylvinyl)benzaldehyde</strong> [13] (0.47g, 1.3mmol) were stirred at 80C for 6h in 20mL ethanol. Then cooled to room temperature, the solute was deposited. The residue was purified by suction filtering, ethanol washing and drying (0.42g, 70% yield).
((E)-N’-(3-bromo-5-chloro-2-hydroxybenzylidene)isonicotinohydrazide)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
In methanol; for 4h;Reflux;
Isonicotinic acid hydrazide (1.370 g, 10 mmol) and 3-bromo-5-chloro salicylaldehyde (2.356 g, 10 mmol) was dropped to around bottom flask having methanol (20 ml) and magnetic stir bar.Then, a Liebig condenser was connected and refluxing was carriedout along with stirring for a period of 4 h till precipitate appeared.Further, obtained precipitate was filtered and treated with methanolseveral times. Furthermore, the precipitate was also washedwith ether. The crystals of the compound were achieved by slowevaporation of the concentrated solution during a period of twoweeks. Yield 2.825 g (80%). ESI-MS Positive mode (M H) m/z353.9255, exact mass (M H) 353.9645. IR (KBr) lambdamax (cm-1):1677 (C]O), 1651 (C=N), 1553, 1447 (Aryl), 1175 (C-N). 1H NMR:7.75 (s, 1H, HC-6), 7.75 (s, 1H, HC-4), 7.85 (s, J 5.5 Hz, 1H, HC-11),7.85 (s, J 5.5 Hz, 1H, HC-12), 8.56 (s, 1H, HC-7), 8.82 (d, J 5.5 Hz,1H, HC-10), 8.82 (d, J 5.5 Hz, 1H, HC-13),12.49 (s, 1H, HO),12.75 (s,1H, HN). 13C NMR: 110.95 (C-1),153.29(C-2),123.38 (C-3),133.31 (C-4), 139.29 (C-5), 129.31 (C-6), 148.23 (C-7), 161.64 (C-8), 120.29 (C-9), 150.42 (C-10), 121.49 (C-11), 121.49 (C-12), 150.42 (C-13).
N-(7-(2-methoxynaphthalen-1-yl)-10,10-dimethyl-6,8-dioxo-8,9,10,11-tetrahydro-6H-chromeno[4,3-b]quinolin-12(7H)-yl)isonicotinamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
79%
General procedure: A mixture of isoniazid (8) (4 mmol), dimedone (2) (4 mmol) and beta-cyclodextrin (20 mol%) in 20 ml of water was placed in round-bottomed flask, and the contents were stirred at 60-65 C for 15 min. 4-Hydroxycoumarin (4) (4 mmol) and aromatic aldehydes (3a-p) (4 mmol) were then added to the reaction mixture, and the mixture was stirred at 60-65 C. The progress of the reaction was monitored by TLC using ethyl acetate-petroleum ether as eluent. After completion of the reaction, the reaction mixture was allowed to cool at room temperature. The solid separated was collected by filtration at the pump. The products were purified by crystallizing from hot ethanol.