Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)O)[CH2:3][CH2:2]1.[BrH:18]>>[Br:18][CH2:3][CH2:2][CH:1]=[C:4]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: OC(c1ccccc1)(c1ccccc1)C1CC1
Reactant: Br
Product: BrCCC=C(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 97.3 %

Procedure:
A mixture of 26.5 g of α-cyclopropyl-α-phenylbenzenemethanol and 150 ml of 48% HBr was stirred at ambient temperature for 3 h. After addition of ice water, the mixture was extracted twice with diethyl ether, washed, dried and concentrated to obtain 33 g (97.3%) of 4-bromo-1,1-diphenyl-1-butene.
Reaction SMILES: [F:1][C:2]1([F:11])[O:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[O:3]1.[Br:12]Br>C(Cl)(Cl)(Cl)Cl.O.[Fe]>[Br:12][C:9]1[CH:8]=[CH:7][C:5]2[O:6][C:2]([F:1])([F:11])[O:3][C:4]=2[CH:10]=1
Reactant: FC1(F)Oc2ccccc2O1
Reactant: BrBr
Agent: [Fe]
Solvent: O
Solvent: ClC(Cl)(Cl)Cl
Product: FC1(F)Oc2ccc(Br)cc2O1
Temperature: 0 °C
Yield: 49.4 %

Procedure:
A mixture of 15.8 grams (0.1 mole) of 2,2-difluoro-1,3-benzodioxole in 200 mL of carbon tetrachloride was stirred, and 2.8 grams (0.05 mole) of iron powder was added. The reaction mixture was cooled to 0° C., and 5.2 mL (0.1 mole) of bromine was added during a 20 minute period. Upon completion of addition the reaction mixture was cautiously warmed to 75° C. where it was stirred for one hour and then was allowed to cool to ambient temperature where it was stirred for 18 hours. The reaction mixture was taken up in 200 mL water and stirred for 20 minutes. The organic layer was separated and washed with water and then with two portions of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was distilled under high vacuum to yield 11.7 grams of 5-bromo-2,2-difluoro-1,3-benzodioxole. The nmr spectrum was consistent with the proposed structure. The reaction was repeated several times.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([OH:8])[CH:7]=1.[CH2:12](Br)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC#N.C(OCC)(=O)C>[CH2:12]([O:8][C:6]1[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[N+:9]([O-:11])=[O:10])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: BrCc1ccccc1
Reactant: O=[N+]([O-])c1ccc(F)cc1O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: O=[N+]([O-])c1ccc(F)cc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A mixture of 5-fluoro-2-nitro-phenol (464 mg, 2.95 mmol), benzyl bromide (0.37 ml, 3.10 mmol) and cesium carbonate (1.055 g, 3.24 mmol) in MeCN (10 mL) was stirred room temperature under argon for 48 hours. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layers were combined and concentrated in vacuo to give a crude residue, which was purified by column chromatography (silica 5-25% EtOAc/hexane) to give 2-benzyloxy-4-fluoro-1-nitro-benzene.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:23]=[C:24]([CH3:26])[CH:25]=1)[O:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][C:7]=1[S:14]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)(=[O:16])=[O:15].[C:27](Cl)(=[O:30])[CH2:28][CH3:29].C(N(CC)CC)C>C(Cl)Cl>[CH3:26][C:24]1[CH:23]=[C:4]([CH:3]=[C:2]([CH3:1])[CH:25]=1)[O:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][C:7]=1[S:14]([N:17]1[CH2:22][CH2:21][N:20]([C:27](=[O:30])[CH2:28][CH3:29])[CH2:19][CH2:18]1)(=[O:16])=[O:15]
Reactant: CCC(=O)Cl
Reactant: Cc1cc(C)cc(Oc2ccc(C#N)cc2S(=O)(=O)N2CCNCC2)c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCC(=O)N1CCN(S(=O)(=O)c2cc(C#N)ccc2Oc2cc(C)cc(C)c2)CC1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a solution of compound 24 (0.102 g, 0.27 mmol) in CH2Cl2 (2 mL) was added propionyl chloride (0.035 g, 0.38 mmol) and triethylamine (0.039 g, 0.38 mmol). The reaction mixture was stirred at room temperature for 20 hrs, whereupon the starting material was consumed (TLC, 1% MeOH in CH2Cl2). The reaction mixture was concentrated in vacuo, redissolved in a minimal amount of CH2Cl2, and chromatographed over normal phase silica (MeOH/CH2Cl2). The fractions containing the desired product were combined and concentrated in vacuo to yield a white powder, which was then triturated with CH2Cl2/diisopropyl ether and vacuum filtered to yield the desired product as a powder. The powder was redissolved in CH2Cl2 and chromatographed for a second time over normal phase silica (MeOH/CH2Cl2). The fractions containing the desired product were combined and concentrated in vacuo to yield a white powder. The powder was triturated with diisopropyl ether and vacuum filtered to yield compound 57 (0.061 g, 52.1% yield, 96.6% HPLC purity). 1H NMR (500 MHz, CDCl3): 8.27 (d, J=2 Hz, 1H), 7.67 (dd, J1=9 Hz, J2=2 Hz, 1H), 6.94 (s, 1H), 6.90 (d, J=9 Hz, 1H), 6.68 (s, 2H), 3.71 (m, 2H), 3.54 (m, 2H), 3.35 (m, 4H), 2.34 (s, 6H), 2.32 (m, 2H), 1.13 (t, J=7 Hz, 3H); MS (ESI, EI+): m/z=428 (MH+).
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>C(Cl)Cl>[CH2:28]([O:27][C:25]([NH:1][CH:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1)=[O:26])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCC(N)CC1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(NC(=O)OCc2ccccc2)CC1
Yield: 96.7 %

Procedure:
To a solution of 1.2 g (6.0 mmol) 4-amino-1-t-butoxycarbonylpiperidine from Step B in 40 mL of methylene chloride was added 3.15 mL (18 mmol) of DIPEA and 1.03 mL (7.2 mmol) of benzyl chloroformate while cooled in an ice bath. After 0.5 h the reaction was quenched with aqueous sodium carbonate and extracted three times with methylene chloride. The organic layers were each washed with a portion of brine, dried over sodium sulfate, combined and concentrated. The residue was purified by FC eluting with 25% ethyl acetate in hexanes to afford 1.94 g of title compound.
Reaction SMILES: [Br:1][C:2]1[CH:13]=[CH:12][C:5]([C:6](N(OC)C)=[O:7])=[C:4]([F:14])[CH:3]=1.[CH3:15][Mg]Br.[Cl-].[NH4+]>C1COCC1>[Br:1][C:2]1[CH:13]=[CH:12][C:5]([C:6](=[O:7])[CH3:15])=[C:4]([F:14])[CH:3]=1
Reactant: CON(C)C(=O)c1ccc(Br)cc1F
Reactant: C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC(=O)c1ccc(Br)cc1F
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a mixture of 4-bromo-2-fluoro-N-methoxy-N-methylbenzamide (13 g) in THF (4.0 mL) was added dropwise methylmagnesium bromide (3M ethylether solution, 30 mL) at 0° C., and the mixture was stirred at room temperature for 3 hr. Saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound (10 g).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[CH3:9].[H-].[Na+].Cl[CH2:13][O:14][CH3:15]>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:13][O:14][CH3:15])=[CH:4][C:3]=1[CH3:9]
Reactant: COCCl
Reactant: Cc1cc(O)ccc1Br
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCOc1ccc(Br)c(C)c1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To a solution of 4-bromo-3-methylphenol (6-6) (1.0 equiv.) in DMF (0.5 M) at 0° C. was added portionwise 60% wt NaH (1.5 equiv.). The addition was controlled such that internal reaction temperature never went above 10° C. The reaction was stirred at room temperature for 45 minutes, then a solution of chloro(methoxy)methane (1.2 equiv.) in DMF (3 M) was added dropwise via additional funnel. The reaction was stirred at room temperature for 3.5 hours, and then quenched by pouring into ice. The resulting mixture was stirred at room temperature for 1 hour. Ether was added, and the two layers were separated. The aqueous layer was extracted (1×) with ether. The combined organic layers were washed with water (2×), brine, dried over MgSO4, and concentrated to give 1-bromo-4-(methoxymethoxy)-2-methylbenzene (6-7) as a colorless oil. The crude material was used in the next step without further purification.
Reaction SMILES: [N+:1]([C:4]1[C:10]([OH:11])=[CH:9][CH:8]=[CH:7][C:5]=1[OH:6])([O-])=O>C(O)C.ClCCl.[Pt](=O)=O>[NH2:1][C:4]1[C:10]([OH:11])=[CH:9][CH:8]=[CH:7][C:5]=1[OH:6]
Reactant: O=[N+]([O-])c1c(O)cccc1O
Agent: O=[Pt]=O
Solvent: ClCCl
Solvent: CCO
Product: Nc1c(O)cccc1O
Reaction time: 4 h
Yield: 95.1 %

Procedure:
A suspension of 2-nitroresorcinol (4.995 g) and platinum (IV) oxide (356 mg) in ethanol (90 ml) was hydrogenated, at room temperature, at 100 p.s.i. for 4 hours. The reaction mixture was filtered through celite, the filter cake washed with methanol (50 ml), and the combined filtrate evaporated in-vacuo to yield a brown solid. The solid was suspended in dichloromethane (100 ml) and evaporated to dryness to yield the title compound (3.83 g, 95%) as a brown solid.
Reaction SMILES: [CH2:1]([C@H:6]1[CH2:11][CH2:10][C@H:9](/[CH:12]=[CH:13]/[CH2:14][O:15][C:16]2[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][CH:17]=2)[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5].CC(C)=[O:26].OS(O)(=O)=O.O=[Cr](=O)=O.O>CC(C)=O>[CH2:1]([C@H:6]1[CH2:11][CH2:10][C@H:9](/[CH:12]=[CH:13]/[CH2:14][O:15][C:16]2[CH:17]=[CH:18][C:19]([C:20]([OH:26])=[O:21])=[CH:22][CH:23]=2)[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CC(C)=O
Reactant: CCCCC[C@H]1CC[C@H](/C=C/COc2ccc(C=O)cc2)CC1
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: O
Product: CCCCC[C@H]1CC[C@H](/C=C/COc2ccc(C(=O)O)cc2)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 4 g of 4-[(E)-3-(trans-4-pentylcyclohexyl)allyloxy]benzaldehyde (Prepared according to Example 3) in 100 ml of acetone was treated dropwise with 10 ml of Jones' reagent. The mixture was stirred at room temperature for 1 hour and then poured into 100 ml of water. The preciPitate which thereby resulted was filtered off, washed portionwise with water and dried in a vacuum. The crude product was recrystallized from ethanol and gave 2,5 g of pure 4-[(E)-3-(trans-4-pentylcyclohexyl)allyloxy]benzoic acid; m.p. 214-215° C..
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5]([C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=2)[O:6][C:7]=1[CH3:8].[C:19](=[S:22])([O-:21])[CH3:20].[K+]>CC(C)=O.[I-].[K+]>[C:19]([S:22][CH2:2][C:3]1[N:4]=[C:5]([C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=2)[O:6][C:7]=1[CH3:8])(=[O:21])[CH3:20]
Reactant: CC([O-])=S
Reactant: COC(=O)c1ccc(-c2nc(CCl)c(C)o2)cc1
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)c1ccc(-c2nc(CSC(C)=O)c(C)o2)cc1
Yield: 91.4 %

Procedure:
A solution of methyl 4-[4-(chloromethyl)-5-methyl-1,3-oxazol-2-yl]benzoate (10 g, 37.64 mmol, 1.00 equiv), potassium ethanethioate (5 g, 43.78 mmol, 1.16 equiv) and potassium iodide (300 mg, 1.81 mmol, 0.05 equiv) in acetone (160 mL) was stirred at 35° C. under nitrogen for 30 min. The product was precipitated by the addition of 250 mL water. The precipitate was collected by filtration, washed with water and dried in a vacuum oven to give 10.5 g (91%) of methyl 4-[4-[(acetylsulfanyl)methyl]-5-methyl-1,3-oxazol-2-yl]benzoate as a white solid.
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].[CH2:9]=[O:10].O.Cl>C(O)C>[C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[C:3]=1[CH:9]=[O:10])[OH:2]
Reactant: Oc1cccc(O)c1
Reactant: C=O
Agent: Cl
Solvent: O
Solvent: CCO
Product: O=Cc1c(O)cccc1O
Temperature: 25 °C
Reaction time: 0.21 h

Procedure:
Mesoporous carbons with highly ordered structure were prepared using weight ratios of 1.1 resorcinol:1.1 F127:0.48 formaldehyde:3.55-8.2 ethanol:5.1-1.67 water:0.16-0.66 HCl. In a typical synthesis, 1.1 g of resorcinol and 1.1 g of F127 were dissolved in 4.5 ml of ethanol (EtOH), and to this was added 4.5 ml of 3.0M HCl aqueous solution and 1.3 g of 37% formaldehyde (37%) was then added. After stirring for 12-13 min. at room temperature, the clear mixture turned turbid, indicating the formation of the ordered nanocomposite and a phase separation. After stirring for a total of 40 minutes, the mixture was centrifuged at 9500 rpm for 4 minutes in order to completely separate and isolate the polymer-rich gel phase. The gel was then loaded on a large Petri dish and cured at 80° C. and subsequently 150° C. for 24 hours each. Carbonization was carried out under nitrogen atmosphere at 400° C. for 2 hours at a heating rate of 1° C./min followed by further treatment at 850° C. for 3 hours at a heating rate of 5° C./min. The produced carbon material is referred to as C-ORNL-1.
Reaction SMILES: C(Cl)(Cl)=O.[C:5]1([OH:11])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Cl[C:13]([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:14]>>[C:13](=[O:14])([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[O:11][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: Oc1ccccc1
Agent: O=C(Cl)Cl
Product: O=C(Oc1ccccc1)Oc1ccccc1
Yield: 119.3 %

Procedure:
In a planar-section pot with flow spoilers, blower/stirrer and reflux condenser, 0.75 mol/h of phosgene was bubbled through 141 g (1.50 mol) of phenol in the presence of 14.1 g (10 wt. % w.r.t. phenol) of powdered H-SAPO 5. After about 2 hours reaction at 140° C., the phenol conversion was 7.1%, wherein 4.9 g of phenyl chloroformate and 8.0 g of diphenyl carbonate were formed. The selectivity to give the carbonate and phenyl chloroformate was greater than 99%.
Reaction SMILES: C(Cl)(Cl)=O.[C:5]1([OH:11])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Cl[C:13]([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:14]>[O-2].[O-2].[Ti+4]>[C:13](=[O:14])([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[O:11][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: Oc1ccccc1
Agent: [Ti+4]
Agent: O=C(Cl)Cl
Agent: [O-2]
Product: O=C(Oc1ccccc1)Oc1ccccc1
Yield: 2036 %

Procedure:
In a plane-joint jar with flow spoilers, a gas-dispersion stirrer and reflux condenser, 0.75 mol/h phosgene was continuously bubbled into 141 g (1.50 moles) of phenol at 140° C. in the presence of 14.1 g (10 wt % relative to phenol) of a powdered titanium dioxide from the Riedel de Haen company. After about 2 h reaction time, the phenol conversion was 12.5%, whereby 0.7 g phenyl chloroformate and 19.5 g diphenyl carbonate were formed. The selectivity to carbonate esters was >99%.
Reaction SMILES: [CH2:1]([CH:9]1[CH2:14][CH2:13][CH:12]([NH2:15])[CH2:11][CH2:10]1)[CH:2]1[CH2:7][CH2:6][CH:5]([NH2:8])[CH2:4][CH2:3]1.[C:16]([OH:20])(=O)[CH2:17][OH:18]>C(O)(C)C.C(O)C>[CH2:1]([CH:2]1[CH2:3][CH2:4][CH:5]([NH:8][C:16](=[O:20])[CH2:17][OH:18])[CH2:6][CH2:7]1)[CH:9]1[CH2:14][CH2:13][CH:12]([NH:15][C:17](=[O:18])[CH2:16][OH:20])[CH2:11][CH2:10]1
Reactant: O=C(O)CO
Reactant: NC1CCC(CC2CCC(N)CC2)CC1
Solvent: CCO
Solvent: CC(C)O
Product: O=C(CO)NC1CCC(CC2CCC(NC(=O)CO)CC2)CC1

Procedure:
4,4'-Methylenebis(cyclohexylamine) (56.5 g, 0.27 mole) was dissolved in hot isopropanol (500 ml) and glycolic acid (40.9 g, 0.54 mole) added portion-wise with stirring. Upon cooling, a white gummy solid separated which was isolated by decantation and redissolved in a small volume of ethanol. Crystallization produced a white crystalline, deliquescent solid; m.p. 96°-102° C. Thorough drying under vacuum increased the melting point (m.p. 149°-151° C.) and reduced the deliquescence.
Reaction SMILES: [Cl-].[Na+].[Cl:3][C:4]1[CH:30]=[CH:29][C:7]([NH:8][C:9]2[CH:17]=[C:16]([C:18]([OH:20])=O)[C:15]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)=[CH:14][C:10]=2[C:11]([OH:13])=O)=[CH:6][CH:5]=1.P(=O)(O)(O)O.CO>O>[CH:5]1[C:4]([Cl:3])=[CH:30][C:29]2[C:11]([C:10]3[C:9]([NH:8][C:7]=2[CH:6]=1)=[CH:17][C:16]1[C:18]([C:23]2[CH:24]=[C:25]([Cl:28])[CH:26]=[CH:27][C:22]=2[NH:21][C:15]=1[CH:14]=3)=[O:20])=[O:13]
Reactant: O=C(O)c1cc(Nc2ccc(Cl)cc2)c(C(=O)O)cc1Nc1ccc(Cl)cc1
Agent: O=P(O)(O)O
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: O=c1c2cc(Cl)ccc2[nH]c2cc3c(=O)c4cc(Cl)ccc4[nH]c3cc12
Temperature: 120 °C
Reaction time: 0.33 h
Yield: 94 %

Procedure:
To 300 g of polyphosphoric acid (116% phosphoric acid) heated at 80°-95° C. was added 1.0 g (17.1 mmole) of sodium chloride followed by 50 g (0.12 mole) of 2,5-di(4-chloroanilino)terephthalic acid. The mixture was heated at 110°-115° C. for five hours. After the viscous solution was cooled to 90°-95° C., the acid strength was adjusted to 110.5% by the dropwise addition of 75% phosphoric acid. The resultant melt was stirred for 20 minutes and then slowly poured into a mixture of 324 g of methanol and 36 g of water (i.e., 90% aqueous methanol) at 35° C. The temperature of the resultant slurry was allowed to rise during the addition to about 64° C., with the temperature being controlled during addition by external cooling and adjustment of melt addition rate. The slurry was heated at reflux for one hour and diluted with 280 g of water. After the resultant slurry was stirred for 30 minutes, the solid component was collected by filtration and washed with water until acid-free. The press-cake was reslurried in water, the pH was adjusted to 8.5 using aqueous sodium hydroxide, and methanol was added. The resultant slurry was heated at about 120° C. in a closed system (e.g., a pressure reactor). After the slurry was cooled to ambient temperature, the solid component was collected by filtration and washed with water until neutral. The wet cake can be oven dried or used as is for specific applications. Here, the wet cake was dried in an oven at 60° C. to give about 43 g of 2,9-dichloroquinacridone as a brilliant magenta solid.
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].[Cl:9][CH2:10][CH2:11][C:12](O)=[O:13].FC(F)(F)S(O)(=O)=O.ClCCl>O>[Cl:9][CH2:10][CH2:11][C:12]([C:6]1[CH:7]=[CH:8][C:1]([OH:2])=[CH:3][C:4]=1[OH:5])=[O:13]
Reactant: Oc1cccc(O)c1
Reactant: O=C(O)CCCl
Agent: O=S(=O)(O)C(F)(F)F
Solvent: ClCCl
Solvent: O
Product: O=C(CCCl)c1ccc(O)cc1O
Temperature: 80 °C
Yield: 74.6 %

Procedure:
To a stirred mixture of resorcinol (10 g, 91 mmol) and 3-chloropropanoic acid (9.95 g, 92 mmol) was added trifluoromethanesulfonic acid (50 g, 333 mmol) in one portion. The solution was warmed to 80° C. for 30 min, cooled to room temperature over 15 min, and poured into dichloromethane (200 mL). The resulting solution was slowly poured into water (200 mL), and the layers were separated. The aqueous layer was extracted with dichloromethane (2×100 mL), dried over anhydrous sodium sulfate, and filtered. Concentration under reduced pressure afforded 3-chloro-1-(2,4-dihydroxyphenyl)propan-1-one (13.62 g, 67.9 mmol, 74.8% yield) as an orange semi-solid. The compound was used without any further purification. LC/MS M+1=200; 1H NMR (400 MHz, CDCl3) δ ppm 12.39 (1H, s), 7.56 (1H, d, J=8.58 Hz), 7.19 (1H, s), 6.17-6.49 (1H, m), 5.23 (1H, s), 3.78-4.01 (2H, m), and 3.34 (2H, t, J=6.71 Hz).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][CH2:8][CH2:9][N:10]2C(=O)C3=CC=CC=C3C2=O)=[CH:3][CH:2]=1.O.NN>CO>[NH2:10][CH2:9][CH2:8][CH2:7][C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCc1ccncc1
Agent: NN
Solvent: CO
Solvent: O
Product: NCCCc1ccncc1
Yield: 59.7 %

Procedure:
N-[3-(4-Pyridyl)propyl]phthalimide (67.1 g, 252 mmol) was mixed with methanol (504 ml) and hydrazine monohydrate (18.3 ml, 378 mmol), and the mixture was refluxed for three hours. The reaction mixture was allowed to stand, then an insoluble matter was filtered out, and the filtrate was concentrated under reduced pressure. Chloroform (1 liter) and a 4 N aqueous sodium hydroxide solution (500 ml) were added to the residue, layers were separated, and the organic layer was dried over sodium sulfate. The organic layer was concentrated under reduced pressure and then distilled under reduced pressure to give 20.5 g (60%) of the titled compound as a colorless oily matter.
Reaction SMILES: [Br:1][C:2]1[C:3]([C:8]([OH:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.S(=O)(=O)(O)O.O.[CH3:17]O>>[CH3:17][O:9][C:8]([C:3]1[C:2]([Br:1])=[CH:7][CH:6]=[CH:5][N:4]=1)=[O:10]
Reactant: O=C(O)c1ncccc1Br
Reactant: CO
Agent: O=S(=O)(O)O
Solvent: O
Product: COC(=O)c1ncccc1Br
Yield: 42 %

Procedure:
A mixture of 5.45 g of 3-bromo-2-pyridine carboxylic acid (27.0 mmol, 1 eq.), obtained in example 3b), in 100 ml of methanol is reflux heated in the presence of 8 ml of sulfuric acid. The reaction mixture is allowed to return to ambient temperature and poured into water. It is extracted 3 times with ethyl acetate, the organic phase is dried on Na2SO4 and vacuum evaporated. 2.48 g (42%) of esterified product is obtained.
Reaction SMILES: OS(O)(=O)=O.[Br:6][C:7]1[C:8]([C:13]([OH:15])=[O:14])=[N:9][CH:10]=[CH:11][CH:12]=1.[CH3:16]O>>[CH3:16][O:14][C:13]([C:8]1[C:7]([Br:6])=[CH:12][CH:11]=[CH:10][N:9]=1)=[O:15]
Reactant: O=C(O)c1ncccc1Br
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1ncccc1Br
Temperature: 25 °C
Reaction time: 14 h

Procedure:
H2SO4 (1.2 mL, 23.4 mmol, 1.0 eq.) was added to a solution of 3-bromopyridine-2-carboxylic acid (4.7 g, 23.4 mmol, 1.0 eq.) in MeOH (50 mL). The resulting solution was stirred for 14 hours while the temperature was maintained at reflux in an oil bath. The mixture was cooled to room temperature and concentrated under vacuum. The residue was dissolved in EtOAc (50 mL) and the pH was adjusted to 10 with Na2CO3 (5 mol/L). The resulting solution was extracted with EtOAc (100 mL). The organic layer was washed with water (1×100 mL) and saturated aqueous NaCl (2×100 mL), dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with EtOAc/PE (1:20) to yield 3-bromopyridine-2-carboxylic acid methyl ester (4.0 g) as a yellow liquid.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[NH2:20])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[CH3:27][S:28](Cl)(=[O:30])=[O:29].C([O-])(O)=O.[Na+]>C(Cl)CCl>[CH3:27][S:28]([NH:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[N:11]1[CH2:10][CH2:9][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:13][CH2:12]1)(=[O:30])=[O:29]
Reactant: CS(=O)(=O)Cl
Reactant: Nc1ccccc1N1CCN(Cc2ccccc2)CC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1ccccc1N1CCN(Cc2ccccc2)CC1
Yield: 95.7 %

Procedure:
To a round-bottomed flask equipped with magnetic stirring was added 2-[4-benzylpiperazinyl]phenylamine (34 g, 127 mmol) in ClCH2CH2Cl (100 mL) and pyridine (12 mL, 140 mmol). The reaction mixture was stirred for 5 min. To the reaction was added methanesulfonyl chloride (Aldrich) (11 mL, 139 mmol), and the reaction mixture was heated at reflux for 18 h. After cooling to RT a satd soln of NaHCO3 (50 mL) was added. The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (2×50 mL). All organic fractions were combined, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to afford the sulfonamide as yellow oil (42 g). MS (ESI, pos. Ion) m/z: 346 (M+H); MS (ESI, neg. Ion) m/z: 344 (M−H). Calc'd for C18H23N3O2S: 345.15.