Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][C:7]([O:8][CH2:9][CH2:10][N:11]2[CH:15]=[CH:14][N:13]=[CH:12]2)=[CH:6][CH:5]=1)([O-])=O>C(O)C.[Pd]>[N:11]1([CH2:10][CH2:9][O:8][C:7]2[CH:16]=[CH:17][C:4]([NH2:1])=[CH:5][CH:6]=2)[CH:15]=[CH:14][N:13]=[CH:12]1
Reactant: O=[N+]([O-])c1ccc(OCCn2ccnc2)cc1
Agent: [Pd]
Solvent: CCO
Product: Nc1ccc(OCCn2ccnc2)cc1
Yield: 958.8 %

Procedure:
1-(Hydroxyethyl)imidazole (5.30 g; 47.3 mmol) was dissolved in anhydrous THF (50 mL) and cooled in an ice-bath. Sodium hydride (2.08 g of a 60 wt % dispersion in oil, 52.0 mmol) was added in portions over 10 min. The ice-bath was removed, and the mixture was stirred at room temperature for 20 min. A solution of 1-fluoro-4-nitrobenzene (5.0 mL, 47.2 mmol) in anhydrous THF (10 mL) was added over 5 min and the mixture stirred for a further 1.5 hr. Water (a few mL) was cautiously added and the mixture concentrated under reduced pressure. The residue was partitioned between EA (75 mL) and water (75 mL), and the phases separated. The aqueous phase was extracted twice with EA and the combined organic layers extracted three times with 1N hydrochloric acid. The pH of these acidic extracts was then adjusted to 7 with 5N aqueous sodium hydroxide and the resulting milky solution extracted three times with EA. The combined organic extracts were washed with water and brine, then dried over magnesium sulfate and concentrated under reduced pressure to give 1-(2-(4-nitrophenoxy)-ethyl)-1H-imidazole (5.46 g) as a brown oil. A solution of 1-(2-(4-nitrophenoxy)ethyl)-1H-imidazole (5.46 g; 2.34 mmol) in ethanol (60 mL) was hydrogenated at atmospheric pressure with 10% palladium on carbon (0.40 g) at room temperature for 20 hr. The mixture was filtered through diatomaceous earth and then concentrated under reduced pressure to give 4-[2-(1H-imidazol-1-yl)ethoxy]benzenamine (4.56 g) as a white solid.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8].CC1(C)N([O])C(C)(C)CCC1.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl>[CH:2]([CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:1]
Reactant: CCOC(=O)CCCCCO
Agent: CC1(C)CCCC(C)(C)N1[O]
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: Ic1ccccc1
Product: CCOC(=O)CCCCC=O
Reaction time: 2 h

Procedure:
To a flask containing ethyl 6-hydroxyhexanoate (4.07 mL, 25.0 mmol) in CH2Cl2 (25 mL) was added TEMPO (391 mg, 2.50 mmol) followed by iodobenzene diacetate (8.86 g, 27.5 mmol). The reaction was stirred 2 hours and then diluted with CH2Cl2 (100 mL). Saturated aqueous solution of Na2S2O3 (100 mL) was added and extracted with CH2Cl2 (3×50 mL). The combined organics were washed with saturated aqueous NaHCO3 (150 mL) and brine (150 mL), dried over Na2SO4, and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (20-40% Et2O/pentanes) to provide the title compound, which was identical to the reported literature compound. (See: Taber, D. F.; Teng, D. (2002) J. Org. Chem., 67: 1607.)
Reaction SMILES: [N:1]1([C:7]([O:9][CH2:10]Cl)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Br-:12].[Li+]>C(#N)C>[N:1]1([C:7]([O:9][CH2:10][Br:12])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: [Br-]
Reactant: O=C(OCCl)N1CCOCC1
Agent: [Li+]
Solvent: CC#N
Product: O=C(OCBr)N1CCOCC1
Temperature: 90 °C
Yield: 80.2 %

Procedure:
Chloromethyl morpholine-4-carboxylate [6316] (0.3 g, 1.67 mmol, 1.0 eq) and lithium bromide (0.72 g, 8.3 mmol, 5.0 eq) was taken in acetonitrile (10 ml). The reaction was refluxed at 90° C. for 30 h. Reaction progress was monitored by TLC/1H NMR. The reaction was filtered off and filtrate was evaporated to dryness under reduced pressure to yield light brown gel, bromomethyl morpholine-4-carboxylate [6327](0.30 g, 80%)
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10](I)=[CH:11][N:12]=2)=[CH:4][CH:3]=1.[C:14]1([C:20]#[CH:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C.[Cl-].[NH4+]>[Pd+2].[Cu]I.C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([C:21]#[C:20][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:11][N:12]=2)=[CH:4][CH:3]=1
Reactant: Clc1ccc(-c2ncc(I)s2)cc1
Reactant: C#Cc1ccccc1
Agent: [Cu]I
Agent: [Pd+2]
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: CC#N
Product: Clc1ccc(-c2ncc(C#Cc3ccccc3)s2)cc1
Yield: 71.2 %

Procedure:
Under a dry nitrogen atmosphere, a stirred mixture of 0.60 gram (0.0019 mole) of 2-(4-chlorophenyl)-5-iodothiazole, 0.21 gram (0.0021 mole) of phenylacetylene, 20 ml of triethylamine, 10 ml of acetonitrile, 0.013 gram (1.0×10-5 mole) of dichlorobis(triphenylphosphine)[palladium (II), and 0.013 gram (6.5×10-5 mole) of copper (I) iodide was heated at reflux for two days. The reaction mixture was cooled, and was then poured into 100 ml of an aqueous, 10% ammonium chloride solution. This mixture was extracted with 100 ml of diethyl ether. The organic extract was washed with an aqueous, saturated ammonium chloride solution followed by two 100 ml portions of water. The washed extract was dried over anhydrous sodium sulfate and was filtered through a pad of Celite® filter aid. The filtrate was evaporated under reduced pressure leaving a residue. This residue was purified by column chromatography on silica gel, eluting with methylene chloride:n-hexane (3:1), to yield 0.4 gram of 1-[2-(4-chlorophenyl)thiazol-5-yl]-2-phenylethyne as a solid, m.p. 108°-110° C., Compound 7 of Table 1.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([CH:11]=[C:12]([Cl:14])[CH:13]=1)[C:7](OC)=[O:8])(=[O:3])[NH2:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>C1COCC1>[Cl:14][C:12]1[CH:13]=[C:4]([CH:5]=[C:6]([CH2:7][OH:8])[CH:11]=1)[C:1]([NH2:2])=[O:3]
Reactant: COC(=O)c1cc(Cl)cc(C(N)=O)c1
Agent: O=S(=O)([O-])[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: O
Solvent: C1CCOC1
Product: NC(=O)c1cc(Cl)cc(CO)c1
Reaction time: 4 h
Yield: 40.6 %

Procedure:
Step N4. To above methyl 3-carbamoyl-5-chlorobenzoate (˜9.3 mmol) in dry THF (100 mL) was added lithium aluminum hydride (1 g, 26.3 mmol) in portions. The mixture was stirred for 4 hours, then treated with sodium sulfate decahydrate (8.5 g, 26.3 mmol) for 30 min. The solid was filtered off and washed with THF for three times. The solvent was removed under vacuum and resulting residue was purified by column with DCM, then MeOH/DCM (5/95) to give 3-chloro-5-(hydroxymethyl)benzamide (13, 0.7 g, 40%).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[C:13]([CH2:15][C:16](OCC)=[O:17])[CH:12]=[CH:11][N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C.O>C1COCC1>[OH:17][CH2:16][CH2:15][C:13]1[CH:12]=[CH:11][N:10]=[C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH:14]=1
Reactant: CCOC(=O)Cc1ccnc(NC(=O)OC(C)(C)C)c1
Agent: CC(C)C[AlH]CC(C)C
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)Nc1cc(CCO)ccn1
Temperature: -69 °C
Reaction time: 0.67 h
Yield: 70.5 %

Procedure:
To a solution of ethyl 2-(2-(tert-butoxycarbonylamino)pyridin-4-yl)acetate (10) (WO 2007089512) (10.0 g, 35.7 mmol) under nitrogen in THF (100 mL), at −78° C., was added DIBAL (1M solution in THF, 71.3 mL, 71.3 mmol) over 1 hr. The reaction mixture was stirred at −78 to −60° C. for 40 min and then warmed to −15° C. over 1 hr. The solution was re-cooled to −78° C. and treated with further DIBAL (1M solution in THF, 35 mL, 35.7 mmol). The mixture was allowed to warm to −40° C. and stirred for 1 hr. Water (10 mL) was added cautiously to quench the reaction followed by MgSO4 (20 g) and the solids removed by filtration. The filtrate was concentrated to dryness under reduced pressure and the residue subjected to column chromatography (330 g), eluting with 65% EtOAc in hexanes to give tert-butyl 4-(2-hydroxyethyl)pyridin-2-ylcarbamate (11) (6.00 g, 64%) as a yellow solid: m/z 239 (M+H)+ (ES+).
Reaction SMILES: [OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.C(N(CC)CC)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>C(Cl)Cl>[CH3:21][S:22]([O:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1)(=[O:24])=[O:23]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CC[C@H](O)C1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CC[C@H](OS(C)(=O)=O)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred, 0° C. solution of (S)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate (10.4 g, 55.5 mmol) and triethylamine (15.5 mL, 0.1111 mole) in CH2Cl2 (150 mL) was added dropwise methanesulfonyl chloride (5.2 mL, 0.06665 mole). When the addition was complete, the reaction mixture was allowed to warm to room temperature, then stirred overnight. The reaction mixture was concentrated under reduced pressure to give a residue that was partitioned between ethyl acetate and saturated aqueous sodium carbonate. The organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography (100% hexane to 70:30 hexane/ethyl acetate). Fractions containing product were combined and concentrated under reduced pressure to give (S)-tert-butyl 3-(methylsulfonyloxy)pyrrolidine-1-carboxylate. 1H NMR (300 MHz, CD3OD) δ ppm 1.47 (s, 9H), 2.14-2.29 (m, 2H), 3.12 (s, 1H), 3.36-3.67 (m, 4H), 5.24-5.30 (m, 1H); MS (DCI/NH3) m/z 266 (M+H)+, 283 (M+NH4)+.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:6][CH2:5]1.C(N(CC)CC)C.[S:22](Cl)([CH3:25])(=[O:24])=[O:23]>ClCCl>[CH3:25][S:22]([O:1][CH2:2][CH2:3][C:4]1([NH:7][C:8]([O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:14])[CH2:5][CH2:6]1)(=[O:24])=[O:23]
Reactant: CC(C)(C)OC(=O)NC1(CCO)CC1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NC1(CCOS(C)(=O)=O)CC1
Temperature: -20 °C
Reaction time: 2 h
Yield: 87 %

Procedure:
To a solution of 6.472 g (32.16 mmol) of tert-butyl 1-(2-hydroxyethyl)cyclopropylcarbamate in 61 ml of anhydrous dichloromethane was added 12.79 ml (91 mmol) of anhydrous triethylamine. The resulting mixture is cooled at −20° C. Then 3.54 ml (45.66 mmol) of mesyl chloride in 11 ml of anhydrous dichloromethane was added. The resulting mixture was stirred at room temperature for 2 h. The mixture was poured into ice-water and the organic layer was washed with saturated aqueous sodium chloride, dried over sodium sulfate and evaporated. The crude product was triturated with petroleum ether and filtered to give 7.82 g of pure product as an orange solid. Mp: 88-89° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1O.[OH-].Cl[C:12]([O:14][CH3:15])=[O:13]>O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:12]([O:14][CH3:15])=[O:13]
Reactant: Oc1ccc(F)cc1Cl
Reactant: COC(=O)Cl
Agent: [OH-]
Solvent: O
Product: COC(=O)c1ccc(F)cc1Cl
Yield: 125.6 %

Procedure:
2-Chloro-4-fluorophenol (83.4 g) is added to a solution of sodum hydroxide (27.7 g) in water (450 ml), and methyl chloroformate (69.2 g) is dropwise added thereto at a temperature below 10° C. Precipitated crystals are collected by filtration and washed with water to give methyl (2-chloro-4-fluorophenyl)formate (134.8 g). M.P., 69°-71° C.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][Br:8].[Br:9][C:10]1[CH:22]=[CH:21][C:20]2[C:19]3[C:14](=[CH:15][C:16]([Br:23])=[CH:17][CH:18]=3)[CH2:13][C:12]=2[CH:11]=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.[OH-].[K+]>[Br:9][C:10]1[CH:22]=[CH:21][C:20]2[C:19]3[C:14](=[CH:15][C:16]([Br:23])=[CH:17][CH:18]=3)[C:13]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][Br:8])([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][Br:8])[C:12]=2[CH:11]=1
Reactant: BrCCCCCCBr
Reactant: Brc1ccc2c(c1)Cc1cc(Br)ccc1-2
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [K+]
Product: BrCCCCCCC1(CCCCCCBr)c2cc(Br)ccc2-c2ccc(Br)cc21
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 80 %

Procedure:
To a mixture of tetrabutylammonium bromide (300 mg, 9.3 mmol), aqueous potassium hydroxide (100 mL, 50%) and 1,6-dibromohexane (22.6 g, 92.6 mmol) was added 2,7-dibromofluorene at 75° C. After 15 minutes, the mixture was cooled down to room temperature, and extracted with CH2Cl2. The organic layer was washed with water, aqueous HCl, water and brine, dried over MgSO4, and then concentrated. Unreacted 1,6-dibromohexane was distilled off. The residue was purified by silica gel column chromatography (Hexane:CHCl3=9:1) and recrystallized from ethanol to give 2 (4.8 g, 80%) as a white solid. 1H NMR (200 MHz, CDCl3): δ 7.2-7.4 (m, 6H), 3.12 (t, 4H), 1.75 (t, 4H), 1.5 (m, 4H), 1.0 (m, 8H), 0.4 (m, 4H). 13C NMR (50 MHz, CDCl3): δ 152.3, 139.2, 130.5, 126.2, 121.7, 121.4, 55.7, 40.2, 34.1, 32.8, 29.1, 27.9, 23.6.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.OS(O)(=O)=O.[CH2:17](O)[CH3:18]>>[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([O:11][CH2:17][CH3:18])=[O:10])[CH:5]=[CH:6][CH:7]=1
Reactant: CCO
Reactant: O=C(O)Cc1cccc(Br)c1
Agent: O=S(=O)(O)O
Product: CCOC(=O)Cc1cccc(Br)c1

Procedure:
5 g of 3-bromophenylacetic acid are dissolved in 80 ml of ethanol, 3 ml of concentrated H2SO4 are added and then the mixture is heated at reflux for two hours. The ethanol is evaporated, neutralization is carried out with a saturated K2CO3 solution and then extraction is carried out with AcOEt. The organic phase is dried over MgSO4. 5.2 g of the expected compound are obtained in the liquid form.
Reaction SMILES: Cl.[Br:2][C:3]1[CH:4]=[C:5]([CH2:9][C:10]([OH:12])=[O:11])[CH:6]=[CH:7][CH:8]=1.[CH3:13][CH2:14]O>>[CH2:13]([O:11][C:10](=[O:12])[CH2:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([Br:2])[CH:4]=1)[CH3:14]
Reactant: CCO
Reactant: O=C(O)Cc1cccc(Br)c1
Agent: Cl
Product: CCOC(=O)Cc1cccc(Br)c1
Temperature: 0 °C
Reaction time: 5 h
Yield: 93.4 %

Procedure:
HCl is bubbled through a solution of 3-bromophenyl acetic acid (10.5 g, 46.5 mmol) in EtOH (70 mL) chilled at 0° C. for 5 minutes. The flask is capped and stirred at ambient temperature for 5 hours. The mixture is concentrated. The residue is taken up with water (80 mL) and extracted twice with EtOAc (70 mL). The organic extracts are combined and dried over magnesium sulfate, filtered and concentrated to afford (3-bromo-phenyl)-acetic acid ethyl ester [10.55 g, 93.4%] as an oil, which is used without further purification.
Reaction SMILES: Cl.COC(OC)CNC.[CH3:10][O:11][C:12]1[C:19]2[O:20][CH2:21][O:22][C:18]=2[CH:17]=[CH:16][C:13]=1[CH:14]=[O:15].C([BH3-])#N.[Na+].[OH-].[Na+]>C(O)C.CO>[CH3:10][O:11][C:12]1[C:19]2[O:20][CH2:21][O:22][C:18]=2[CH:17]=[CH:16][C:13]=1[CH2:14][OH:15]
Reactant: COc1c(C=O)ccc2c1OCO2
Agent: CNCC(OC)OC
Agent: Cl
Agent: [BH3-]C#N
Solvent: CO
Solvent: CCO
Product: COc1c(CO)ccc2c1OCO2
Temperature: 25 °C
Yield: 43.5 %

Procedure:
To 100 ml of methanol, were charged 0.16 ml of methanol containing 25 g of hydrochloric acid dissolved therein, 0.79 g of N-methylaminoacetaldehyde dimethylacetal, 1.0 g of 2-methoxy-3,4-methylenedioxybenzaldehyde, 0.35 g of sodium cyanoborohydride and 10 ml of ethanol and stirred in an oil bath under a nitrogen stream at 70° C. for 2 hours. After the reaction was over, the reaction mixture was cooled to room temperature and 2N NaOH aqueous solution was added thereto to make the filtrate alkaline (pH 11). The resulting mixture was then extracted with ethyl acetate. The liquid extract was analyzed by GC and LC to show, as a product, 0.88 g of 2-methoxy-3,4-methylenedioxy-N-methylbenzylamino dimethylacetal (yield 56%) and 0.44 g of 2-methoxy-3,4-methylenedioxybenzyl alcohol (yield 44%), while 2-methoxy-3,4-methylenedioxybenzaldehyde of the starting material being not recognized (conversion rate:10%). The selectivity to the desired 2-methoxy-3,4-methylenedioxy-N-methylbenzylamino dimethylacetal was 56%.
Reaction SMILES: CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.[NH2:19][C:20]1[CH:28]=[CH:27][C:23]([C:24]([OH:26])=O)=[CH:22][C:21]=1[F:29].[N:30]1([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.C(N(CC)CC)C>ClCCl>[NH2:19][C:20]1[CH:28]=[CH:27][C:23]([C:24]([N:33]2[CH2:32][CH2:31][N:30]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:35][CH2:34]2)=[O:26])=[CH:22][C:21]=1[F:29]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: Nc1ccc(C(=O)O)cc1F
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCN(C(=O)c2ccc(N)c(F)c2)CC1
Reaction time: 2 h
Yield: 100.2 %

Procedure:
1-Propanephosphonic acid cyclic anhydride (9.67 mmol, 5.76 mL, 50% solution in ethyl acetate) was added to a solution of 4-amino-3-fluorobenzoic acid (6.45 mmol, 1 g), tert-butyl piperazine-1-carboxylate (6.45 mmol, 1.2 g) and triethylamine (12.89 mmol, 1.74 mL) in dichloromethane (20 mL) and stirred for 2 hours. The reaction mixture was washed with sodium bicarbonate solution and concentrated under vacuum to give the title compound (2.09 g). MS (ESI) m/z 324.5 [M+H]+
Reaction SMILES: C([C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[C:15](C(C)(C)C)[C:14]([OH:21])=[C:13](C(C)(C)C)[CH:12]=2)[CH:8]=[C:7](C(C)(C)C)[C:6]=1[OH:30])(C)(C)C.CS(O)(=O)=O.CCCCCCCCC(C)C>C1(C)C=CC=CC=1>[C:14]1([OH:21])[CH:13]=[CH:12][C:11]([C:9]2[CH:10]=[CH:5][C:6]([OH:30])=[CH:7][CH:8]=2)=[CH:16][CH:15]=1
Reactant: CC(C)(C)c1cc(-c2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)cc(C(C)(C)C)c1O
Agent: CCCCCCCCC(C)C
Agent: CS(=O)(=O)O
Solvent: Cc1ccccc1
Product: Oc1ccc(-c2ccc(O)cc2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.2 %

Procedure:
In a three-necked flask 50 grams of 2,2′,6,6′-tetra-t-butyl-4,4′-biphenol (I) and 0.25 gm of methanesulfonic acid were mixed with a mixture of 80 ml Isopar-G (hydrocarbons C10-C1) and 20 ml of toluene. After 2 hours at 150° C., 26 grams of isobutylene is collected in a dry ice trap and the reaction cooled to room temperature and was filtered. The biphenol was dried at 130° C., giving 22.5 gram of 4,4′-biphenol (99% yield) with purity >99% were collected.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[N:15]=[N:16][N:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:18]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[C:19]1([N:17]2[CH:18]=[C:14]([C:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH:10]=3)[N:15]=[N:16]2)[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: CC(C)(C)OC(=O)N1CC=C(c2cn(-c3ccccc3)nn2)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: C1=C(c2cn(-c3ccccc3)nn2)CCNC1
Temperature: 25 °C
Reaction time: 0.58 h

Procedure:
To a solution of 1-tert-butoxycarbonyl-4-(1-phenyl-1,2,3-triazol-4-yl)-1,2,3,6-tetrahydropyridine (816 mg, 2.5 mmol) in dichloromethane (10 ml) was added trifluoroacetic acid (10 ml) and the reaction stirred at room temperature for 35 minutes. The solvent was evaporated in vacuo and the residue basfied by addition of aqueous sodium hydroxide (1M, 30 ml). Water (30 ml) was added and the mixture extracted with dichloromethane (3×30 ml). The combined organic layers were washed with saturated brine (20 ml), dried (K2CO3) and evaporated in vacuo to yield the title compound as a buff solid (486 mg, 86%). δH (CDCl3) 2.59-2.53 (2H, br s, tetrahydropyridinyl CH2), 3.14 (2H, t, J 5.7 Hz, tetrahydropyridinyl CH2), 3.56-3.58 (2H, br s, tetrahydropyridinyl CH2), 6.60 (1H, br s, tetrahydropyridinyl 5-H), 7.40-7.45 (1H, m, ArH), 7.50-7.54 (2H, m, ArH), 7.72-7.75 (2H, m, ArH), 7.84 (1H, s, triazolyl 5-H).
Reaction SMILES: [CH:1]1[C:15]2=[C:16]3[C:8]([C:9]4[C:14]2=[CH:13][CH:12]=[CH:11][CH:10]=4)=[CH:7][CH:6]=[CH:5][C:4]3=[C:3](B(O)O)[CH:2]=1.[Br:20][C:21]1[CH:22]=[C:23](I)[CH:24]=[CH:25][CH:26]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO.O.C(COC)OC>[Br:20][C:21]1[CH:22]=[C:23]([C:5]2[CH:6]=[CH:7][C:8]3[C:9]4[C:14]([C:15]5[C:16]=3[C:4]=2[CH:3]=[CH:2][CH:1]=5)=[CH:13][CH:12]=[CH:11][CH:10]=4)[CH:24]=[CH:25][CH:26]=1
Reactant: OB(O)c1ccc2c3c(cccc13)-c1ccccc1-2
Reactant: Brc1cccc(I)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Solvent: Cc1ccccc1
Product: Brc1cccc(-c2ccc3c4c(cccc24)-c2ccccc2-3)c1
Reaction time: 8 h
Yield: 70.3 %

Procedure:
18.18 g (81.3 mmol) of 3-fluorantheneboronic acid, 22.99 g (81.3 mmol) of 3-bromoiodobenzene, 4.70 g (4.10 mmol) of tetrakis(triphenylphosphine)palladium (0), 80 ml of toluene, 80 ml of dimethoxyethane and 123 g of a 2M sodium carbonate aqueous solution were combined under argon atmosphere, and the mixture was stirred for 8 hours with refluxing and heating. After finishing the reaction, water was added to the reaction mixture, and the mixture was stirred at room temperature for one hour. Methanol was added thereto, and a solid matter was obtained by filtering, and it was refined by silica gel chromatography to obtain 20.43 g (yield: 70.4%) of 3-(3-bromophenyl)fluoranthene.
Reaction SMILES: Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[CH3:10].[Li]CCCC.[C:16](=[O:18])=[O:17].O>C1(C)C=CC=CC=1>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([C:16]([OH:18])=[O:17])=[C:3]([CH3:10])[CH:4]=1)#[N:7]
Reactant: Cc1cc(C#N)ccc1Br
Reactant: O=C=O
Agent: [Li]CCCC
Solvent: O
Solvent: Cc1ccccc1
Product: Cc1cc(C#N)ccc1C(=O)O
Temperature: 25 °C
Yield: 20.4 %

Procedure:
To a solution of 4-bromo-3-methylbenzonitrile (0.48 g, 2.43 mmol) in 1 ml of toluene at −78° C. was added 1 ml of 2.6M n-BuLi in toluene followed by quenching with dry ice (0.5 g, 12.5 mmol). The reaction mixture was warmed to room temperature, then taken into water and extracted with ethyl acetate (2×15 ml). The water layer was acidified to pH 1-2 by addition of concentrated aqueous hydrochloric acid and extracted with ethyl acetate (3×15 ml). The organic layer was dried over anhydrous sodium sulfate, then filtered and concentrated to give 4-cyano-2-methylbenzoic acid (0.08 g, 20% yield). 1H-NMR (400 MHz, DMSO-d6): 13.10 (br s, 1H), 7.92 (d, 1H), 7.84 (m, 1H), 7.76 (d, 1H), 2.53 (s, 3H).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[CH:4][C:3]=1[C:9]([O:11][CH3:12])=[O:10].O.[NH2:14][NH2:15]>CO>[Cl:8][C:6]1[N:5]=[CH:4][C:3]([C:9]([O:11][CH3:12])=[O:10])=[C:2]([NH:14][NH2:15])[CH:7]=1
Reactant: COC(=O)c1cnc(Cl)cc1Cl
Reactant: NN
Solvent: O
Solvent: CO
Product: COC(=O)c1cnc(Cl)cc1NN
Reaction time: 12 h

Procedure:
205 g. of 4,6-dichloro-3-pyridinecarboxylic acid, methyl ester (1 mol.) are dissolved in 1 liter of methanol. The solution is cooled to 0° and 100 g. of hydrazine hydrate are dropped in with stirring. The solution is kept at 0° for 12 hours. The precipitated 6-chloro-4-hydrazino-3-pyridinecarboxylic acid, methyl ester is filtered off and recrystallized from methanol, yield: 175 g. (87%); m.p. 163.3°.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7](Cl)=[N:6][N:5]2[CH:11]=1.O1C[CH2:15][CH2:14][CH2:13]1.C([Mg]Br)CC.Cl>Cl[Ni](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[Cl:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH2:13][CH2:14][CH3:15])=[N:6][N:5]2[CH:11]=1
Reactant: Clc1cn2nc(Cl)ccc2n1
Reactant: C1CCOC1
Agent: Cl[Ni](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CCC[Mg]Br
Agent: Cl
Solvent: O
Product: CCCc1ccc2nc(Cl)cn2n1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
2,6-Dichloroimidazo[1,2-b]pyridazine (0.50 g, 2.66 mmol) and bis(triphenylphosphine)nickel(II) dichloride (0.17 g, 0.27 mmol) were added to tetrahydrofuran (5.0 ml) under a nitrogen stream, and a solution of n-propylmagnesium bromide in tetrahydrofuran (2 M, 1.99 ml, 3.99 mmol) was added dropwise over 10 minutes to the mixture under ice-cooling. The mixture was stirred for 10 minutes under ice-cooling, and the reaction mixture was warmed to room temperature and stirred for 4 hours at room temperature. Cold water (50 ml) was added to the reaction mixture which was then acidified with dilute hydrochloric acid, and extracted with ethyl acetate. The extracts were washed with dilute hydrochloric acid, a saturated saline, an aqueous saturated sodium bicarbonate solution and a saturated saline in this order. The resulting organic layer was dried over anhydrous magnesium sulfate, filtrated and concentrated. The concentrated residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:7) to give the title compound as white crystals. The yield was 0.21 g (40.4%).