Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([CH3:4])=[CH2:3].[CH2:7]1[O:10][CH:8]1[CH3:9].CN(CCO)C.C1(C=CC(O)=CC=1)O>>[C:1]([O:6][CH2:7][CH:8]([OH:10])[CH3:9])(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: C=C(C)C(=O)O
Reactant: CC1CO1
Agent: CN(C)CCO
Agent: Oc1ccc(O)cc1
Product: C=C(C)C(=O)OCC(C)O
Reaction time: 8 h

Procedure:
2-hydroxypropyl methacrylate was prepared in the same apparatus and under the same reaction conditions as described in Example 5 by reacting, hourly, a mixture of 930 g methacrylic acid, 830 g proplyene oxide, 28.8 g N,N-dimethylaminoethanol, 9.3 g i-amyl nitrite and 0.93 g hydroquinone at a temperature of 100° C. After 8 hours of continuous operation, the reactor was free of polymer.
Reaction SMILES: OS(O)(=O)=O.[NH2:6][C:7]1[CH:8]=[C:9]([OH:16])[C:10](=[CH:14][CH:15]=1)[C:11]([OH:13])=[O:12].[CH3:17]O>>[NH2:6][C:7]1[CH:8]=[C:9]([OH:16])[C:10](=[CH:14][CH:15]=1)[C:11]([O:13][CH3:17])=[O:12]
Reactant: Nc1ccc(C(=O)O)c(O)c1
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccc(N)cc1O
Yield: 88 %

Procedure:
Absolute methanol (100 mL) and fresh concentrated H2SO4 are carefully combined in a 250 mL round botton flask with continuous stirring (exothermic). 4-Aminosalicylic acid (10.0 grams, 65.4 mmol) is added to produce a dark solution, which is heated under reflux for 6 hours. The product is allowed to cool and then concentrated on a rotary evaporator to approximately half the original volume. At this point a solid precipitate appears. The concentrate is poured into 400 mL of water, and the resulting suspension titrated to approximately pH 3, by stepwise addition of 5N NaOH (to pH 6.5), followed by solid Na2CO3, with evolution of CO2 gas. The concentrate was chilled on ice, and the resulting precipitate collected by filtration. The filtrate is washed with cold water, and then dried in vacuo over NaOH pellets, to afford 9.6 grams (88% yield) of methyl 4-aminosalicylate, a pale lavendar powder (m.p. 115°-117° C.). The structure was confirmed by 1H NMR spectrometry in d6 -acetone.
Reaction SMILES: [CH:1]12[O:7][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6]2.[CH3:8][NH:9][CH3:10].C1COCC1>CO>[CH3:8][N:9]([CH3:10])[C@@H:1]1[CH2:6][CH2:5][CH2:4][CH2:3][C@H:2]1[OH:7]
Reactant: C1CCC2OC2C1
Reactant: CNC
Solvent: C1CCOC1
Solvent: CO
Product: CN(C)[C@@H]1CCCC[C@H]1O
Temperature: 0 °C
Reaction time: 4 h

Procedure:
To a solution of cyclohexene oxide (3.64 mL, 36.0 mmol) in 30 mL of dry methanol was added dropwise 2.0 M dimethylamine in THF (15.0 mL, 30.0 mmol). The reaction mixture was stirred at 0° C. for 4 h. The solution was then warmed to room temperature and stirred for 18 h. The reaction mixture was then concentrated under reduced pressure to afford 1.11 g (26% crude yield) of the crude product which was used in the following reaction without purification.
Reaction SMILES: Cl.[CH3:2][N:3]([CH3:10])[CH2:4][CH2:5][C:6](OC)=[O:7].O.[NH2:12][NH2:13]>CO>[CH3:2][N:3]([CH3:10])[CH2:4][CH2:5][C:6]([NH:12][NH2:13])=[O:7]
Reactant: COC(=O)CCN(C)C
Reactant: NN
Agent: Cl
Solvent: O
Solvent: CO
Product: CN(C)CCC(=O)NN
Temperature: 70 °C
Reaction time: 3 h
Yield: 65 %

Procedure:
To a solution of methyl 3-(dimethylamino)propanoate hydrochloride (compound 142.6, 2.00 g, 15.3 mmol, 1.00 equiv) in methanol (40 mL) was added hydrazine hydrate (6 mL, 6.00 equiv). The reaction mixture was stirred at 70° C. for 3 h. The mixture was concentrated in vacuo and then dissolved in 50 mL of H2O and washed with 2×10 mL of ethyl acetate. The aqueous layers were combined and concentrated in vacuo to afford 1.30 g (65%) of 3-(dimethylamino)propanehydrazide as a colorless oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:9])=[N:7][CH:8]=1.[OH:10]O.O>C(O)(=O)C.[O-2].[O-2].[Mn+4]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:9])=[N+:7]([O-:10])[CH:8]=1
Reactant: OO
Reactant: COc1ccc(C)nc1
Agent: [Mn+4]
Agent: [O-2]
Solvent: O
Solvent: CC(=O)O
Product: COc1ccc(C)[n+]([O-])c1
Reaction time: 8 h

Procedure:
A solution consisting of 5-methoxy-2-methylpyridine (12.3 g.) and 30% hydrogen peroxide (12 ml.) dissolved in glacial acetic acid (50 ml) was heated in a steam bath for a period of 12 hours and then allowed to stand overnight (~16 hours) at room temperature (~25° C.). Water (5 ml.) was next added to the mixture, followed by manganese dioxide until effervescence ceased. The resulting mixture was then filtered and the recovered filtrate was subsequently evaporated under reduced pressure to afford crude 5-methoxy-2-methylpyridine-N-oxide (yield, 13.5 g.) as the residual oil.
Reaction SMILES: [OH:1][N:2]1[C:7]([CH3:9])([CH3:8])[CH2:6][CH2:5][CH2:4][C:3]1([CH3:11])[CH3:10].N(OC(C)(C)C)=O.N[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>[Cu](Cl)Cl.C(#N)C>[O:1]([N:2]1[C:7]([CH3:9])([CH3:8])[CH2:6][CH2:5][CH2:4][C:3]1([CH3:11])[CH3:10])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: Nc1ccccc1
Reactant: CC1(C)CCCC(C)(C)N1O
Agent: Cl[Cu]Cl
Agent: CC(C)(C)ON=O
Solvent: CC#N
Product: CC1(C)CCCC(C)(C)N1Oc1ccccc1
Yield: 72 %

Procedure:
The procedure of Example 1 is repeated using 3.9 g (25 mmol) of 1-oxyl-2,2,6,6-tetramethylpiperidine, and 7.84 g (76 mmol) of tert-butyl nitrite, 24 mg (0.25 mmol) of copper(II) chloride, 120 mL of acetonitrile and 4.65 g (50 mmol) of aniline at 65° C. The crude product is purified by vacuum flash chromatography (heptane) to give 4.2 g of the title compound as a colorless oil in a 72.4% yield.
Reaction SMILES: [H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1.CN(C)C=O.[Br:17][CH2:18][CH2:19][CH2:20]Br>O>[Br:17][CH2:18][CH2:19][CH2:20][N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1
Reactant: c1ccc2[nH]ccc2c1
Reactant: BrCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: BrCCCn1ccc2ccccc21
Temperature: 25 °C
Reaction time: 20 h
Yield: 25 %

Procedure:
To sodium hydride (0.9 g, 30 mmol, 80% oil dispersion) and indole (2.81 g, 24 mmoles) was added anhydrous dimethylformamide (50 mL). The resultant mixture was stirred at room temperature under argon for 1 h. Then neat 1,3-dibromopropane (7.3 mL, 72 mmol) was added and the reaction mixture was stirred at room temperature for 20 h. The reaction mixture was poured into water (120 mL) and the resultant slurry was extracted with diethyl ether (3×100 mL). After the organic extracts were combined and concentrated in vacuo, the crude material was purified by dry column chromatography (350 mL funnel filled with Silica 10–40μ, Sigma cat. S-6628) using as eluent a mixture of ethyl acetate and hexanes (1:49 v/v, containing 0.2% v/v isopropylamine) to yield 1.43 g of N-(3-bromopropyl)indole.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:13]=[CH:12][C:6]([CH:7]=[CH:8][C:9](O)=[O:10])=[CH:5][CH:4]=1.S(Cl)([Cl:16])=O.[C:18]([O:21][CH2:22][CH3:23])(=[O:20])[CH3:19]>>[CH3:1][O:2][C:3]1[CH:13]=[CH:12][C:6]([CH:7]=[CH:8][C:9]([Cl:16])=[O:10])=[CH:5][CH:4]=1.[C:18]([O:21][CH2:22][CH3:23])(=[O:20])[CH3:19]
Reactant: COc1ccc(C=CC(=O)O)cc1
Reactant: O=S(Cl)Cl
Solvent: CCOC(C)=O
Product: COc1ccc(C=CC(=O)Cl)cc1
Yield: 387.6 %

Procedure:
In a 100-mL three-neck flask, 3.1 g of 4-methoxycinnamic acid and 14.0 g of ethyl acetate were placed to give a suspension. The suspension was combined with 2.2 g of thionyl chloride (1.05 times the mole of 4-methoxycinnamic acid) added dropwise while maintaining the reactor inside temperature at 65° C. to 70° C. After the dropwise addition, a reaction was performed until the conversion from 4-methoxycinnamic acid reached 99% or more. After completion of reaction, 6.1 g of ethyl acetate was distilled off together with unreacted thionyl chloride and an acidic gas at 60° C. under reduced pressure. After the concentration, the resulting mixture was combined with ethyl acetate in an amount equal to the distilled-off amount and yielded 19.2 g of a 4-methoxycinnamoyl chloride/ethyl acetate solution (3).
Reaction SMILES: [C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.S(Cl)([Cl:12])=O.C(C1C=CC(OCCCCO)=CC=1)(C)(C)C>ClCCl>[C:1]([Cl:12])(=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1cccnc1
Agent: CC(C)(C)c1ccc(OCCCCO)cc1
Solvent: ClCCl
Product: O=C(Cl)c1cccnc1

Procedure:
Nicotinoyl chloride was prepared by treating 100 g (0.81 mole) of nicotinic acid with 280 ml of thionyl chloride at reflux for two hours. The excess thionyl chloride was removed in vacuo and the crystalline acid chloride hydrochloride was suspended in 500 ml of dichloromethane. To the stirred mixture was added 66 g (0.30 mole) of 4-p-t-butylphenoxy-1-butanol dissolved in 400 ml of dichloromethane. After forty-eight hours the mixture was washed with one liter of saturated sodium bicarbonate. The dichloromethane solution was dried over magnesium sulfate and evaporated to a syrupy residue. The material was chromatographed on 1 kg of silica gel with elution by dichloromethane-methanol, 96:4, to afford 43.8 g (45%) of the nicotinate ester as an oil. The hydrobromide salt was prepared by treatment of a solution of 43.8 g in 800 ml of ethyl acetate with 30 ml of 4.5N hydrogen bromide in ether. The precipitate was collected, washed with pentane and dried, m.p. 132°-133° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5](O)=[CH:6][CH:7]=[N:8]2.CCN(C(C)C)C(C)C.O=P(Cl)(Cl)[Cl:27]>C1(C)C=CC=CC=1>[Cl:27][C:5]1[C:4]2[C:9](=[CH:10][C:11]([O:13][CH3:14])=[CH:12][C:3]=2[O:2][CH3:1])[N:8]=[CH:7][CH:6]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COc1cc(OC)c2c(O)ccnc2c1
Solvent: Cc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(OC)c2c(Cl)ccnc2c1

Procedure:
To a mixture of crude 5,7-dimethoxyquinolin-4-ol (5.36 g, 26 mmol) and Hunig's Base (9.1 ml, 52 mmol) in toluene, was added POCl3 (29 ml, 313 mmol). The mixture was refluxed for 5 h. Excess POCl3 was removed under reduced pressure and azeotroped with toluene. The resultant gum was treated with sat. NaHCO3 until no gas generated. The mixture was extracted with EtOAc, the organic extracts were combined and washed with sodium bicarbonate and solvent removed under reduced pressure. The crude product was purified via column chromatography on silica gel (RediSep 120 g column, gradient elution with 0-50% EtOAc/DCM) to afford 4-chloro-5,7-dimethoxyquinoline as a yellow solid. MS Found m/z=[M+H]+. 224.2 Calc'd for C11H10ClN: 223.7.
Reaction SMILES: [OH:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH2:13](Cl)[C:14](=[CH2:16])[CH3:15].C(=O)([O-])[O-].[K+].[K+].Cl>CC(C)=O.CN(C)C1C=CC=CC=1>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:11][C:12]=1[CH2:15][C:14](=[CH2:13])[CH3:16]
Reactant: CCOC(=O)c1ccc(O)cc1
Reactant: C=C(C)CCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)c1ccccc1
Solvent: CC(C)=O
Product: C=C(C)Cc1cc(C(=O)OCC)ccc1O
Yield: 89.3 %

Procedure:
Ethyl 4-hydroxybenzoate (50.0 g), methallyl chloride (32.6 g) and potassium carbonate (45.6 g) were refluxed with heating in acetone (150 ml) for 40 hours. The reaction mixture was filtrated and the filtrate was concentrated under a vacuum. The residue, after toluene (150 ml) was added thereto, was washed with 2% sodium hydroxide aqueous solution and water successively. The extract was dried over sodium sulfate anhydride and then concentrated under a vacuum, thereby yielding an oily compound. This compound was dissolved in N,N-dimethylaniline (80 ml) and refluxed with heating for about 10 hours. While being cooled with ice, the reaction mixture was acidified with concentrated hydrochloric acid and then extracted with toluene. The extract was extracted with 10% sodium hydroxide aqueous solution. The water layer was acidified with concentrated hydrochloric acid and then extracted with toluene. The extract was washed with water, dried over sodium sulfate anhydride and then concentrated under a vacuum, thereby yielding 59.2 g of ethyl 4-hydroxy-3-methallylbenzoate.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[CH:21][C:5]([C:6]([C:8]2[N:12]([CH3:13])[C:11]([CH:14]([CH3:20])[C:15]([O:17]CC)=[O:16])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.[OH-].[Na+].C(O)C>O>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([C:6]([C:8]2[N:12]([CH3:13])[C:11]([CH:14]([CH3:20])[C:15]([OH:17])=[O:16])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1
Reactant: CCOC(=O)C(C)c1ccc(C(=O)c2ccc(Cl)cc2)n1C
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CC(C(=O)O)c1ccc(C(=O)c2ccc(Cl)cc2)n1C

Procedure:
A solution of 4.05 g. (0.0126 mole) of ethyl 5-(p-chlorobenzoyl)-α-methyl-1-methylpyrrole-2-acetate, 15 ml. of 1N sodium hydroxide solution and 2 ml. of ethanol is refluxed for 30 minutes. The solution is cooled, diluted with water and filtered. The filtrate is acidified with dilute hydrochloric acid. The precipitated solid is collected and recrystallized from methanol-water to give a white crystalline solid, 5-(p-chlorobenzoyl)-α-methyl-1-methylpyrrole-2-acetic acid, m.p. 135-136° C. Analysis: Calcd. for C15H14ClNO3 : C, 61.76; H, 4.83; N, 4.82% Found: C, 61.68: H, 4.86; N, 4.89%
Reaction SMILES: [CH:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.NC1C(C)=CC=CN=1.N[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O)(=O)C1C=CC=CC=1.C=CCCCC.C1(C)C=CC=CC=1>>[C:1]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)(=[O:8])[CH2:22][CH2:23][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: Nc1ccccc1
Reactant: O=Cc1ccccc1
Agent: Cc1cccnc1N
Agent: O=C(O)c1ccccc1
Solvent: Cc1ccccc1
Solvent: C=CCCCC
Product: CCCCCCC(=O)c1ccccc1
Reaction time: 0.04 h

Procedure:
Under the same reaction procedure and conditions as in Example 1 (benzaldehyde 0.5 mmol, 2-amino-3-picoline 0.1mmol, aniline 0.3 mmol, bezoic acid 0.03 mmol, 1-hexene 2.5 mmol, toluene 0.87 mmol), the mixture in a 500 ml pressure reactor was stirred at normal temperature for 2-3 minutes and then combined with Rh(PPh3)3Cl 1 0.01 mmol. While the reactor was stopped with a stopper, the reactants were stirred at various temperatures (70-130° C.) as shown in the following table 10 for 1 hour. After completion of the reaction, gas chromatography was conducted to determine the yields of heptanophenone, products according to various temperatures and the results are given in Table 10, below.
Reaction SMILES: O.[NH2:2][NH2:3].Cl[C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][N:6]=1>C(O)C>[NH:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][N:6]=1)[NH2:3]
Reactant: O=C(O)c1ccc(Cl)nc1
Reactant: NN
Solvent: CCO
Solvent: O
Product: NNc1ccc(C(=O)O)cn1
Yield: 71 %

Procedure:
Hydrazine monohydrate (101 g) was added to a solution of 6-chloronicotinic acid (20 g) in ethanol (20 ml) at room temperature and stirred under reflux. After completion of the reaction, the solvent was evaporated, ethanol was added and the solid was collected by filtration to give 6-hydrazinonicotinic acid (13.8 g).
Reaction SMILES: [NH:1]1[CH:8]=[CH:7][C:5](=[O:6])[NH:4][C:2]1=[S:3].[OH-].[Na+].O.[CH3:12]I>C(O)C>[CH3:12][S:3][C:2]1[NH:4][C:5](=[O:6])[CH:7]=[CH:8][N:1]=1
Reactant: O=c1cc[nH]c(=S)[nH]1
Reactant: CI
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CSc1nccc(=O)[nH]1
Temperature: 30 °C
Yield: 42.2 %

Procedure:
A mixture of 12.8 g (99.9 mmol) of 2-thiouracil and 4.3 g (108 mmol) of sodium hydroxide was placed in 500 ml Erlenmeyer flask, and dissolved on the oil bath with a minimum amount of water. Twice the volume of 99% ethanol was then added, the solution cooled to 30° C., and 6.3 ml (99.9 mmol) of methyl iodide added. The solution was heated to 60° C. for 20 min, then cooled to room temp. The precipitate was filtered off, and, after acidifying the filtrate with acetic acid, the excess solvent was removed in vacuo. The combined precipitates were thoroughly washed with water and recrystallized from ethanol to give 6.0 g (47%) of product.
Reaction SMILES: ClCCl.[CH2:4]([C@H:6]1[O:8][CH2:7]1)[Cl:5].[C:9]1([OH:15])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(OC)(C)(C)C.CS(O)(=O)=O>[Cl:5][CH2:4][C@@H:6]([OH:8])[CH2:7][O:15][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: Oc1ccccc1
Reactant: ClC[C@@H]1CO1
Agent: CS(=O)(=O)O
Solvent: COC(C)(C)C
Solvent: ClCCl
Product: O[C@H](CCl)COc1ccccc1
Reaction time: 1 h
Yield: 122 %

Procedure:
To a mixture of N′,N′-disalicylidene ethylenediaminatocobalt(II) (138 mg, 0.425 mmol) and dichloromethane (10 ml) was added methanesulfonic acid (3 μl, 0.510 mmol) and the reaction system was stirred for 1 hour while being filled with air. The reaction solution was evaporated to dryness under reduced pressure to give a crude blackish (dark) brown cobalt (III) complex. Thereto was added tert-butylmethyl ether (4 ml) to disperse the crude cobalt (III) complex and then thereto were added (S)-epichlorohydrin (2.00 ml, 25.5 mmol, optical purity 99% e.e.) and phenol (2.00 g, 21.3 mmol) in order. The mixture was stirred for 24 hours under nitrogen atmosphere at room temperature. After the reaction, the reaction mixture was diluted with tert-butylmethyl ether (20 ml), the solution was washed with a 6% aqueous sodium hydroxide solution (10 ml) and a saturated sodium chloride solution (10 ml) in order, and the organic layer was condensed under reduced pressure to give crude (S)-1-chloro-3-phenoxy-2-propanol (4.85 g). This crude compound (4.85 g) was dissolved in isopropanol (10 ml) and thereto was added a 24% aqueous sodium hydroxide solution (4.50 g, 25.5 mmol) under ice-cooling. The mixture was stirred for 1 hour at room temperature. After the reaction, the reaction mixture was diluted with tert-butylmethyl ether (50 ml) and the solution was washed with water (20 ml), a saturated aqueous ammonium solution (20 ml) and a saturated aqueous sodium chloride solution (20 ml) in order. The organic layer was condensed under reduced pressure to give crude (R)-glycidylphenyl ether (3.24 g). Quantitative analysis by gas chromatography and optical purity measurement by HLPC were conducted on the compound. As a result the subject compound, (R)-glycidylphenyl ether (3.07 g, 96.1%) was produced with optical purity at. 99% e.e.
Reaction SMILES: [CH3:1][N:2]1[C:6](=O)[CH:5]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[NH:3]1.P(Cl)(Cl)([Cl:16])=O>>[Cl:16][C:6]1[N:2]([CH3:1])[N:3]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:5]=1
Reactant: Cn1[nH]c(-c2ccccc2)cc1=O
Reactant: O=P(Cl)(Cl)Cl
Product: Cn1nc(-c2ccccc2)cc1Cl
Temperature: 0 °C
Reaction time: 8 h
Yield: 96.8 %

Procedure:
2-Methyl-5-phenylpyrazol-3-one (7.9 g, 0.0429 mol) is added to phosphorus oxychloride (15.3 g). The mixture is stirred at 120°C to 135°C for 8 hours, then poured into ice water, made alkaline and extracted with methylene chloride. The solution is evaporated in vacuo at 90°C to yield 8.0 g (93.8%) of an oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2(O)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:17]3[CH:22]=[CH:21][C:20]4[O:23][CH2:24][O:25][C:19]=4[CH:18]=3)=[C:9]2[C:26]([O:28]CC)=[O:27])=[CH:4][CH:3]=1.C1OC2C=CC(C3C4C(=CC=CC=4)C(=O)C=3C(OCC)=O)=CC=2O1.FC1C=CC([Mg]Br)=CC=1>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]([C:17]3[CH:22]=[CH:21][C:20]4[O:23][CH2:24][O:25][C:19]=4[CH:18]=3)[CH:9]2[C:26]([OH:28])=[O:27])=[CH:4][CH:3]=1
Reactant: CCOC(=O)C1=C(c2ccc3c(c2)OCO3)c2ccccc2C1(O)c1ccc(F)cc1
Agent: CCOC(=O)C1=C(c2ccc3c(c2)OCO3)c2ccccc2C1=O
Agent: Fc1ccc([Mg]Br)cc1
Solvent: C1CCOC1
Product: O=C(O)C1C(c2ccc(F)cc2)c2ccccc2C1c1ccc2c(c1)OCO2
Reaction time: 0.75 h
Yield: 35 %

Procedure:
Ethyl (1RS)-1-(4-Fluorophenyl)-1-hydroxy-3-(3,4-methylenedioxyphenyl)indene-2-carboxylate. To a solution of ethyl 3-(3,4-methylenedioxyphenyl)-1-oxoindene-2-carboxylate (100 mg, 0.31 mmol) in THF (5 ml) under an argon atmosphere at 0° C. was added a solution of freshly prepared 4-fluorophenyl magnesium bromide (0.62 mmol). After stirring for 45 min, the mixture was partitioned between 3M HCl and EtOAc. The organic extract was washed successively with H2O, 5% aqueous NaHCO3 and saturated aqueous NaCl. The solvent was removed in vacuo, and the residue was purified by flash chromatography, eluting with 15% EtOAc/ hexanes to afford the title compound (45 mg, 35%).
Reaction SMILES: [CH2:1]=[CH2:2].[C:3]1([CH3:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>>[CH2:1]([C:6]1[CH:7]=[CH:8][C:3]([CH3:9])=[CH:4][CH:5]=1)[CH3:2]
Reactant: C=C
Reactant: Cc1ccccc1
Product: CCc1ccc(C)cc1

Procedure:
The catalyst samples as described in Examples 4 and 5 were also tested for activity and selectivity in the vapor phase alkylation of toluene with ethylene to produce p-ethyl toluene. At a WHSV of 1.0-1.2g toluene/gm catalyst/hr and a toluene:ethylene molar ratio of 2.5-2.8:1.0 the liquid product was collected over an 8-16 hour period for each of the reaction temperatures 400° C. and
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14](=[O:29])[CH2:15][CH:16]([CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:17]([O:19]C)=[O:18])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl[C:31]1[S:32][C:33]2[CH:39]=[C:38]([Cl:40])[CH:37]=[CH:36][C:34]=2[N:35]=1.S1C2C=CC=CC=2N=C1NC1C=CC(C2C=CC(C(=O)CC(C)(C)C(O)=O)=CC=2)=CC=1>>[Cl:40][C:38]1[CH:37]=[CH:36][C:34]2[N:35]=[C:31]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([C:8]4[CH:13]=[CH:12][C:11]([C:14](=[O:29])[CH2:15][CH:16]([CH2:21][CH2:22][C:23]5[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=5)[C:17]([OH:19])=[O:18])=[CH:10][CH:9]=4)=[CH:6][CH:7]=3)[S:32][C:33]=2[CH:39]=1
Reactant: COC(=O)C(CCc1ccccc1)CC(=O)c1ccc(-c2ccc(N)cc2)cc1
Reactant: Clc1ccc2nc(Cl)sc2c1
Agent: CC(C)(CC(=O)c1ccc(-c2ccc(Nc3nc4ccccc4s3)cc2)cc1)C(=O)O
Product: O=C(CC(CCc1ccccc1)C(=O)O)c1ccc(-c2ccc(Nc3nc4ccc(Cl)cc4s3)cc2)cc1
Yield: 24.7 %

Procedure:
This compound was prepared from methyl 4-(4′-amino-1,1′-biphenyl-4-yl)-4-oxo-2-(2-phenylethyl)butanoate (78 mg, 0.20 mmol), 2,6-dichloro-1,3-benzothiazole (61.6 mg, 0.30 mmol) in a similar manner to the method described for 4-[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoic acid, providing 26.7 mg (25%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 10.80 (br s, 1H), 7.75-8.05 (m, 9H), 7.60 (d, 1H), 7.10-7.40 (m, 6H), 3.50 (q, 1H), 3.10 (m, 1H), 2.85 (m, 1H), 2.65 (m, 2H), 1.80 (m, 2H). LC-MS m/z 541.3 (MH+), ret. time 4.07 min.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=[O:9])=[N:6][CH:7]=1.O=S(Cl)Cl.[CH2:15](O)[CH3:16]>>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][CH2:15][CH3:16])=[O:9])=[N:6][CH:7]=1
Reactant: Nc1ccc(C(=O)O)nc1
Reactant: CCO
Solvent: O=S(Cl)Cl
Product: CCOC(=O)c1ccc(N)cn1
Temperature: 25 °C
Yield: 75 %

Procedure:
To a solution of 5-aminopicolinic acid (110; 8.4 g, 60.8 mmol) in ethanol (100 mL) was added SOCl2 (14.5 g, 120 mmol) at 0° C. The mixture was stirred under reflux for 12 h. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure. Enough saturated aqueous Na2CO3 solution was added to adjust pH=9. The resulting mixture was filtered and the solids were dried under reduced pressure to afford ethyl 5-aminopicolinate 111 (7.5 g, 75%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:14][C:8]2[N:9]=[CH:10][N:11]=[C:12](Cl)[C:7]=2[C:6]=1[CH3:15])=[O:4].[O:16]1[CH2:21][CH2:20][CH:19]([O:22][C:23]2[C:28]([NH2:29])=[CH:27][CH:26]=[CH:25][N:24]=2)[CH2:18][CH2:17]1>>[CH3:1][O:2][C:3]([C:5]1[S:14][C:8]2[N:9]=[CH:10][N:11]=[C:12]([NH:29][C:28]3[C:23]([O:22][CH:19]4[CH2:20][CH2:21][O:16][CH2:17][CH2:18]4)=[N:24][CH:25]=[CH:26][CH:27]=3)[C:7]=2[C:6]=1[CH3:15])=[O:4]
Reactant: Nc1cccnc1OC1CCOCC1
Reactant: COC(=O)c1sc2ncnc(Cl)c2c1C
Product: COC(=O)c1sc2ncnc(Nc3cccnc3OC3CCOCC3)c2c1C

Procedure:
Prepared analogously to 1.1 from 4-chloro-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester and 2-(tetrahydro-pyran-4-yloxy)-pyridin-3-ylamine.