Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][C:7](=[O:16])[NH:6][C:5]=2[N:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:24][CH2:25][O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]>CN(C)C=O>[Si:27]([O:26][CH2:25][CH2:24][N:6]1[C:5]2[N:4]=[CH:3][CH:2]=[CH:1][C:11]=2[C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[CH2:8][C:7]1=[O:16])([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]
Reactant: O=C1Cc2ccccc2-c2cccnc2N1
Reactant: CC(C)(C)[Si](C)(C)OCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCCN1C(=O)Cc2ccccc2-c2cccnc21
Temperature: 40 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
Heat a mixture 5,7-dihydropyrido[2,3-d][3]benzazepin-6-one (22.5 g, 106.9 mmol) and dimethylformamide (500 mL) to 100° C. for 5 minutes. Cool to 40° C., add cesium carbonate (104.3 g, 320.1 mmol) and (2-bromoethoxy)-tert-butyldimethylsilane (29.9 mL, 138.9 mmol) and stir at ambient temperature overnight. Heat to 60° C. for approximately 2 hours, and then cool to ambient temperature. Partition the residue between ethyl acetate (1 L) and water (3 L), back extract from aqueous layer with ethyl acetate (2×500 mL), wash combined organics with brine (2×500 mL). Dry combined organics over sodium sulfate and concentrate. Purify the residue by flash chromatography, eluting with ethyl acetate:hexane (0:100 to 100:0) to give the title compound as an oil (39.4 g, 106.9 mmol, 89%). MS (m/z): 369 (M+1).
Reaction SMILES: [N+]([O-])([O-])=O.[Na+].N[C:7]1[CH:8]=[C:9]([CH:14]=[CH:15][C:16]=1[C@H:17]([NH:19][C:20](=[O:22])[CH3:21])[CH3:18])[C:10]([O:12][CH3:13])=[O:11].N1C=CC=CC=1.[FH:29]>>[C:20]([NH:19][C@@H:17]([C:16]1[CH:15]=[CH:14][C:9]([C:10]([O:12][CH3:13])=[O:11])=[CH:8][C:7]=1[F:29])[CH3:18])(=[O:22])[CH3:21]
Reactant: F
Reactant: COC(=O)c1ccc([C@@H](C)NC(C)=O)c(N)c1
Agent: O=[N+]([O-])[O-]
Agent: [Na+]
Solvent: c1ccncc1
Product: COC(=O)c1ccc([C@@H](C)NC(C)=O)c(F)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Sodium nitrate (640 mg) was added to a solution of methyl (R)-3-amino-4-(1-acetamidoethyl)benzoate (2 g) in hydrogen fluoride-pyridine (20 ml) under ice-cooling, and the mixture was stirred at room temperature for 1 hour. After the reaction, the reaction mixture was poured into ice water and extracted with chloroform. The extract was washed with water, dried and concentrated. The obtained residue was purified by silica gel column chromatography (chloroform:methanol=50:1) to give 690 mg of methyl (R)-4-(1-acetamidoethyl)-3-fluorobenzoate.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:21][CH:22]([C:26](=[O:28])[CH3:27])[C:23](=[O:25])[CH3:24])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH:29](OCC)=[O:30].Cl.[Cl-].[Na+]>O1CCCC1.CCCCCC>[C:13]([O:21][CH:22]([C:26](=[O:28])[CH3:27])[C:23](=[O:25])[CH:24]=[CH:29][OH:30])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CCOC=O
Reactant: CC(=O)C(OC(=O)c1ccccc1)C(C)=O
Agent: Cl
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(=O)C(OC(=O)c1ccccc1)C(=O)C=CO
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 109.4 %

Procedure:
Diisopropylamine (48.6 g, 480 mmol) is dissolved in 350 ml of tetrahydrofuran. At -40° C. there are added dropwise thereto 275 ml (440 mmol) of 1.6 molar butyl-lithium solution in hexane. The mixture is then cooled to -78° C. and 44.02 g (200 mmol) of 3-benzoyloxy-2,4-pentane-dione in 50 ml of tetrahydrofuran are added dropwise thereto within 30 minutes. Subsequently, 22.20 g (300 mmol) of ethyl formate are added dropwise thereto at -78° C. within 30 minutes and the mixture is stirred for 2 hours. The reaction mixture is poured into 600 ml of 1N hydrochloric acid, saturated with sodium chloride and extracted three times with 500 ml of ethyl acetate each time. The combined organic phases are dried over magnesium sulphate, concentrated on a rotary evaporator and give 54.30 g of 4-benzoyloxy-1-hydroxy-1-hexene-3,5-dione.
Reaction SMILES: [C-:1]#[N:2].[Na+].CS(C)=O.[Br:8][C:9]1[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[C:11]([CH2:17]Br)[CH:10]=1.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C>[Br:8][C:9]1[CH:10]=[C:11]([CH2:17][C:1]#[N:2])[CH:12]=[C:13]([O:15][CH3:16])[CH:14]=1
Reactant: [C-]#N
Reactant: COc1cc(Br)cc(CBr)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CS(C)=O
Product: COc1cc(Br)cc(CC#N)c1
Temperature: 40 °C
Reaction time: 0.67 h
Yield: 86.4 %

Procedure:
Sodium cyanide (3.4 g; WAKO) was added to a DMSO (100 mL) solution of Intermediate 2 (16.3 g) at room temperature and the resulting mixture was stirred at 40° C. for 1 hour and 40 minutes. Ethyl acetate (300 mL) and saturated aqueous sodium bicarbonate solution (150 mL), and water (150 mL) were added to extract the reaction mixture, the reaction mixture was washed with saturated brine (300 mL), the organic layer was dried, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Yamazen; n-hexane/ethyl acetate) to give the title compound (11.37 g).
Reaction SMILES: CS(O[CH2:6][CH2:7][CH2:8][N:9]1[C:13]2[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:12]=2[NH:11][C:10]1=[O:19])(=O)=O.[C:20]1([N:26]2[C:30]3([CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)[C:29](=[O:36])[NH:28][CH2:27]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[Na]>CN(C)C=O>[Cl:18][C:16]1[CH:15]=[CH:14][C:13]2[N:9]([CH2:8][CH2:7][CH2:6][N:33]3[CH2:32][CH2:31][C:30]4([N:26]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)[CH2:27][NH:28][C:29]4=[O:36])[CH2:35][CH2:34]3)[C:10](=[O:19])[NH:11][C:12]=2[CH:17]=1
Reactant: O=C1NCN(c2ccccc2)C12CCNCC2
Reactant: CS(=O)(=O)OCCCn1c(=O)[nH]c2cc(Cl)ccc21
Agent: [Na]
Solvent: CN(C)C=O
Product: O=C1NCN(c2ccccc2)C12CCN(CCCn1c(=O)[nH]c3cc(Cl)ccc31)CC2
Yield: 25 %

Procedure:
A mixture of 4.9 parts of 5-chloro-1,3-dihydro-2-oxo-2H-benzimidazole-1-propanol methanesulfonate, 3.7 parts of 1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one, 3.4 parts of sodium crbonate and 90 parts of N,N-dimethylformamide is stirred and heated for 1 hour at 50°-60° C. The N,N-dimethylformamide is distilled off and the residue is taken up in water. The product is extracted with 4-methyl-2-pentanone. The extract is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 10% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The residue solidifies on triturating in 4-methyl-2-pentanone. The product is filtered off and crystallized twice: first from 2-propanol and then from a mixture of N,N-dimethylformamide and water, yielding 1.8 parts (25%) of 8-[3-(5-chloro-1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)propyl]-1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one; mp. 233.7° C.
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][O:11][C:12]2[CH:19]=[CH:18][C:15]([CH:16]=O)=[CH:14][CH:13]=2)=[N:7][CH:8]=1)[CH3:2].[S:20]1[CH2:24][C:23](=[O:25])[NH:22][C:21]1=[O:26].N1CCCCC1>C(O)C>[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][O:11][C:12]2[CH:19]=[CH:18][C:15]([CH:16]=[C:24]3[S:20][C:21](=[O:26])[NH:22][C:23]3=[O:25])=[CH:14][CH:13]=2)=[N:7][CH:8]=1)[CH3:2]
Reactant: CCc1ccc(CCOc2ccc(C=O)cc2)nc1
Reactant: O=C1CSC(=O)N1
Solvent: C1CCNCC1
Solvent: CCO
Product: CCc1ccc(CCOc2ccc(C=C3SC(=O)NC3=O)cc2)nc1
Yield: 64.2 %

Procedure:
A mixture of 4-[2-(5-ethyl-2-pyridyl)ethoxy]benzaldehyde (2.40 g), 2,4-thiazolidinedione (1.66 g), ethanol (40 ml) and piperidine (0.2 ml) was heated under reflux for 8 hours. The resulting crystals were recrystallized form ethyl acetate to give 2.14 g (64%) of 5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzylidene}-2,4thiazolidinedione as colorles crystals. m.p.: 165.5°-167° C.
Reaction SMILES: O1CCO[CH:2]1[C:6]1[O:10][C:9]([CH2:11][S:12][CH2:13][CH2:14][NH:15][C:16]([NH:21][CH3:22])=[CH:17][N+:18]([O-:20])=[O:19])=[CH:8][CH:7]=1.Cl.[CH3:24][NH:25][CH3:26]>O1CCCC1.C(O)C.C(O)(=O)C>[CH3:24][N:25]([CH2:2][C:6]1[O:10][C:9]([CH2:11][S:12][CH2:13][CH2:14][NH:15][C:16]([NH:21][CH3:22])=[CH:17][N+:18]([O-:20])=[O:19])=[CH:8][CH:7]=1)[CH3:26]
Reactant: CNC(=C[N+](=O)[O-])NCCSCc1ccc(C2OCCO2)o1
Reactant: CNC
Agent: Cl
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: CCO
Product: CNC(=C[N+](=O)[O-])NCCSCc1ccc(CN(C)C)o1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To a stirred solution of N-[2-[[5-(1,3-dioxolan-2-yl)-2-furanylmethyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine (0.12 g) in tetrahydrofuran (1 ml) at room temperature was added 2 N hydrochloric acid (0.4 ml). After 20 min., a mixture of dimethylamine in ethanol (33%) (1 ml) and acetic acid (5 ml), evaporated to remove the ethanol, was added. The mixture was allowed to stand at room temperature for 20 min., then cooled in an ice bath. To the stirred solution was added sodium borohydride (0.4 g) portionwise during 5 min. After 10 min, acetic acid (1 ml) was added and the solution heated on a steam bath for 15 min. Tetrahydrofuran (30 ml) and excess of sodium carbonate were added and the mixture heated to boiling then cooled to room temperature. After 1 h, the mixture was filtered and the combined filtrate and washings evaporated in vacuo to give an oily residue which was extracted with hot ethyl acetate (25 ml). The extract was evaporated in vacuo to give an oily residue consisting of the title compound (0.06 g).
Reaction SMILES: [C:1]1([CH3:9])[CH:6]=[CH:5][C:4]([CH:7]=O)=[CH:3][CH:2]=1.Cl.[NH2:11][OH:12].C(N(CC)CC)C>O1CCCC1>[OH:12][N:11]=[CH:7][C:4]1[CH:5]=[CH:6][C:1]([CH3:9])=[CH:2][CH:3]=1
Reactant: NO
Reactant: Cc1ccc(C=O)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1ccc(C=NO)cc1
Yield: 74 %

Procedure:
To a solution of 4-tolualdehyde (600 mg, 5 mmol) in tetrahydrofuran (3 ml) was added hydroxylamine hydrochloride (700 mg, 10 mmol) and triethylamine (1.4 ml, 10 mmol). The reaction was subjected to microwave; absorbance normal; temp: 150° C.; time; 600 (s). The solid material was filtered off, and solvent removed from the filtrate under reduced pressure. The residue was purified using column chromatography (2:1 Hexanes:Ethyl Acetate) to provide (hydroxyimino)(4-methylphenyl)methane (500 mg).
Reaction SMILES: [CH3:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.Cl.[NH2:11][OH:12].C([O-])(=O)C.[Na+]>C(O)C.O.C(OC)(C)(C)C>[CH3:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[N:11][OH:12])=[CH:4][CH:3]=1
Reactant: Cc1ccc(C=O)cc1
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: COC(C)(C)C
Product: Cc1ccc(C=NO)cc1
Yield: 88.9 %

Procedure:
A solution of 4-methylbenzaldehyde (5 g), hydroxylamine hydrochloride (4.34 g) and sodium acetate (6.23 g) in ethanol and water was stirred for one hour at room temperature. After the reaction solution was diluted with t-butylmethylether, the solution was washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 4-methylbenzaldehyde oxime (5 g).
Reaction SMILES: [N+:1]([C:4]1[CH:14]=[CH:13][C:7]2[NH:8][C:9](=[O:12])[CH2:10][O:11][C:6]=2[CH:5]=1)([O-])=O>[Pd].CO.C1COCC1>[NH2:1][C:4]1[CH:14]=[CH:13][C:7]2[NH:8][C:9](=[O:12])[CH2:10][O:11][C:6]=2[CH:5]=1
Reactant: O=C1COc2cc([N+](=O)[O-])ccc2N1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: Nc1ccc2c(c1)OCC(=O)N2
Reaction time: 16 h

Procedure:
Under argon, 10% palladium on carbon (350 mg, 5% w/w) was added to a suspension of 7-nitro-3-oxo-3,4-dihydro-(2H)-1,4-benzoxazine (7 g, 39.3 mmol) in 50 ml of MeOH. The reaction mixture was hydrogenated at 40 psi for 16 hours. The reaction mixture was then diluted with THF (-200 mls) and the reaction was filtered through celite. The solvent was evaporated, leaving a brown solid as the residue. Product was recrystallized from THF/Hexane (1:5). Collected 4.2 g (72%) of a tan solid: m.p. 213-215, 'H NMR (300 M Hz, DMSO) δ 4.410 (S, 2H), 4.869 (S, 2H) 6.141 (d, 1H, J=2.44) 6.176 (dd, 1H, J=2.25, 4.69), 6.563 (d, 1H, J=8.19), 9.535 (brs, 1H); 13C NMR (300 MHz, DMSO) δ 66.9496, 102.2081, 108.1369, 116.5779; 116.8982, 144.5502, 145.4287, 164.389; Mass spectrum M+ at m/z 164
Reaction SMILES: [N]=O.ON1[C:8](=[O:9])[C:7]2=[CH:10][CH:11]=[CH:12][CH:13]=[C:6]2[C:5]1=[O:14]>C(#N)C>[CH:5](=[O:14])[C:6]1[C:7](=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH:8]=[O:9]
Reactant: O=C1c2ccccc2C(=O)N1O
Agent: [N]=O
Solvent: CC#N
Product: O=Cc1ccccc1C=O
Yield: 95 %

Procedure:
A total of 13 mmol of nitrogen monoxide was introduced into a mixture of 1 mmol of 1-hydroxyphthalan, 0.1 mmol of N-hydroxyphthalimide, and 5 ml of acetonitrile, and the resultant mixture was stirred at 60° C. for 2 hours. Isolation of products in the reaction mixture by column chromatography on a silica gel revealed that 1-hydroxyphthalane was converted, at a rate of 99%, into phthalaldehyde (yield: 95%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)=[C:6]([CH3:20])[N:5]=[CH:4][N:3]=1.Cl[CH2:22][C:23]1[O:27][C:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[CH3:20][C:6]1[N:5]=[CH:4][N:3]=[C:2]([NH:1][CH2:22][C:23]2[O:27][C:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:25][CH:24]=2)[C:7]=1[C:8]#[C:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]([F:19])([F:17])[F:18])=[CH:14][CH:15]=1
Reactant: Cc1ncnc(N)c1C#Cc1ccc(C(F)(F)F)cc1
Reactant: CCOC(=O)c1ccc(CCl)o1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: CCOC(=O)c1ccc(CNc2ncnc(C)c2C#Cc2ccc(C(F)(F)F)cc2)o1
Temperature: 70 °C
Reaction time: 4 h

Procedure:
A mixture of 4-amino-6-methyl-5-{[4-(trifluoromethyl)phenyl]ethynyl}pyrimidine (2.8 g), ethyl 5-chloromethyl-2-furancarboxylate (1.8 g), potassium carbonate (2.1 g) and toluene (60 ml) was heated while stirring at 70° C. for 4 hours. The mixture thus obtained was concentrated under reduced pressure. To the resultant residue, water was added. After extraction was performed with dichloromethane, an organic phase was dried over anhydrous sodium sulfate and evaporated. The resultant residue was purified by column chromatography to obtain a target substance (0.9 g). The target substance was subjected to e.g., proton nuclear magnetic resonance spectrometry (1H-NMR) and mass spectrometry (MS) and confirmed as the titled compound. Furthermore, MS measurement result is shown.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]#[C:5][C:6]1[S:10][C:9]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)=[CH:8][CH:7]=1.[C:16](Cl)(=O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>N1C=CC=CC=1>[CH2:16]([O:1][CH2:2][CH2:3][C:4]#[C:5][C:6]1[S:10][C:9]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)=[CH:8][CH:7]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: OCCC#Cc1ccc(-c2cccs2)s1
Reactant: O=C(Cl)c1ccccc1
Solvent: c1ccncc1
Product: C(#Cc1ccc(-c2cccs2)s1)CCOCc1ccccc1
Reaction time: 8 h

Procedure:
5-(4-Hydroxy-1-butynyl)-2,2'-bithiophene (0.8 g) was dissolved in pyridine (8 ml). Benzoyl chloride (1 ml) was added at room temperature, stirred for few minutes and kept overnight. The reaction mixture was treated as in example 21. Light yellowish crystals were then obtained and the melting point thereof was 61° C.
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[CH2:11][CH3:12])=[CH:4][CH:3]=1.[F:13][C:14]([F:26])([F:25])[O:15][C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>O.C(O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:13][C:14]([F:25])([F:26])[O:15][C:16]1[CH:21]=[CH:20][C:19]([C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[CH:7][N:8]3[CH2:11][CH3:12])=[CH:4][CH:3]=2)=[CH:18][CH:17]=1
Reactant: CCn1ccc2ccc(Br)cc21
Reactant: OB(O)c1ccc(OC(F)(F)F)cc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Solvent: CCO
Product: CCn1ccc2ccc(-c3ccc(OC(F)(F)F)cc3)cc21
Yield: 55.8 %

Procedure:
Following the procedure described in Step 2 of Example 2, 6-bromo-1-ethyl-1H-indole (0.410 g, 1.83 mmol) was reacted with 4-trifluoromethoxybenzene boronic acid (0.422 g, 2.05 mmol), using tetrakis(triphenylphosphine) palladium (0.0651 g, 0.0563 mmol), and sodium carbonate (0.792 g, 7.47 mmol) in water (3.7 mL), ethanol (1.4 mL), and toluene (8 mL). Purification by flash chromatography using hexane as an eluant yielded the title compound as a yellow oil (0.312 g, 56%). 1HNMR (300 MHz, DMSO-d6): δ7.85 (d, 2H, J=6.3 Hz), 7.8 (s, 1H), 7.65 (d, 1H, J=7.8 Hz), 7.4-7.5 (m, 3H), 7.35 (d, 1H, J=6.2 Hz), 6.45 (d, 1H J=2.3 Hz), 4.3 (q, 2H, J=7.0 Hz), and 1.4 ppm (t, 3H, J=7.0 Hz).
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1[NH2:4].Cl.Cl[CH2:12][CH2:13][NH:14][CH2:15][CH2:16]Cl.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>C(O)CCC.CCCCCC>[F:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1[N:4]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1
Reactant: ClCCNCCCl
Reactant: Nc1cc(F)ccc1F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCCCCC
Solvent: CCCCO
Product: Fc1ccc(F)c(N2CCNCC2)c1
Temperature: 25 °C
Reaction time: 48 h
Yield: 15.5 %

Procedure:
A mixture of 2,5-difluoroaniline (2.58 g, 20 mmol) and bis(2-chloroethyl)amine hydrochloride (3.96 g, 22 mmol) in butanol (10 mL) was heated at reflux for 24 hours. The mixture was cooled to room temperature, sodium carbonate (2.33 g, 22 mmol) was added, and the mixture was heated again at reflux. After 2 days, the mixture was cooled to room temperature, hexane (15 mL) and 3 N NaOH (25 mL) were added, and the resulting layers were separated. The aqueous layer was extracted with chloroform (3×25 mL) and the combined organic fractions were flashed over a column of silica gel. The silica gel was further eluted with a gradient of chloroform to chloroform/methanol (4:1). The solvent was removed from the combined fractions with Rf=0.14 [silica gel, chloroform/methanol (4:1)], giving the title compound as a yellow oil (0.606 g, 3.1 mmol, 15%). ESI-MS m/z 199 (MH+).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[OH:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[CH:14]=[C:13]([C:18](OC)=[O:19])[CH:12]=[CH:11]2.C1(C([O-])=O)C2C(=CC=CC=2)C=CC=1.Cl>O.C1COCC1>[OH:19][CH2:18][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([OH:7])[CH:17]=[CH:16]2
Reactant: COC(=O)c1ccc2cc(O)ccc2c1
Agent: Cl
Agent: O=C([O-])c1cccc2ccccc12
Agent: [Al+3]
Solvent: O
Solvent: C1CCOC1
Product: OCc1ccc2cc(O)ccc2c1
Temperature: 0 °C
Reaction time: 8 h
Yield: 86.1 %

Procedure:
To a 3-necked, 1-L round bottomed flask equipped with an overhead stirrer, digital thermometer and 500-mL constant-pressure addition funnel with a nitrogen inlet was added 11 g (0.29 mol) of lithium aluminum hydride and 200 mL of anhydrous THF. The addition funnel was charged with a solution of 40 g (0.2 mol) of methyl 6-hydroxy-2-naphthoate. The flask was cooled in ice/water and the naphthoate slowly added over 1 hour. The suspension was stirred overnight, recooled and cautiously treated with 100 mL of water. The white suspension was poured into 5% (v/v) HCl and extracted several times with ethyl acetate. The combined extracts were washed with water, dried, evaporated and the residue recrystallized in hexane/ethyl acetate to yield a total of 30 g (87%) of the title compound in three crops as beige plates, mp 179-181° C.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15]([Cl:20])=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:20][C:15]1[C:14]([N:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[CH:19][CH:18]=[CH:17][N:16]=1
Reactant: CC(C)(C)OC(=O)N1CCN(c2cccnc2Cl)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Clc1ncccc1N1CCNCC1
Yield: 110.7 %

Procedure:
Stir 4-(2-chloro-pyridin-3-yl)-piperazine-1-carboxylic acid t-butyl ester (2.00 g, 6.72 mmol) in DCM (50 mL) at room temperature, then add trifluoroacetic acid (5 mL). Stir the reaction for 2 hr. and remove solvents in vacuo, then form the free base using SCX-2® chromatography washing with methanol then eluting with around 3 M ammonia in methanol. Concentrate in vacuo to give 1-(2-chloro-pyridin-3-yl)-piperazine as a brown oil (1.47 g, 110% yield). MS (m/z): 198 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N+:10]([O-:12])=[O:11])[C:5]=1[CH3:13].[Br:15]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C1(=O)NC(=O)CC1>C(Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N+:10]([O-:12])=[O:11])[C:5]=1[CH2:13][Br:15]
Reactant: COC(=O)c1cccc([N+](=O)[O-])c1C
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Agent: O=C1CCC(=O)N1
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1cccc([N+](=O)[O-])c1CBr

Procedure:
25.55 g (130.9 mmol) of 2-methyl-3-nitrobenzoic acid methyl ester is added to 300 ml of carbon tetrachloride, and mixed with 25.6 gram (141.7 mmol) of N-bromosuccinimide and 62.8 mg of benzoyl peroxide. After seven days of refluxing, the succinimide is suctioned off after cooling, and then the filtrate is spun in until a dry state is reached. The desired compound that is incorporated in crude form into the next stage remains.
Reaction SMILES: [O-2].[Zn+2:2].[C:3]([OH:22])(=[O:21])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]/[CH:11]=[CH:12]\[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]>>[C:3]([O-:22])(=[O:21])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]/[CH:11]=[CH:12]\[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].[Zn+2:2].[C:3]([O-:22])(=[O:21])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]/[CH:11]=[CH:12]\[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: [O-2]
Agent: [Zn+2]
Product: CCCCCCCC/C=C\CCCCCCCC(=O)[O-]

Procedure:
The chemical reactivity of the ultrafine zinc oxide particles obtained in Examples 1 to 3 and Comparative Examples 1 and 2 to fatty acids was examined. Three grams of ultrafine zinc oxide particles were mixed with 27 g of oleic acid (special chemical grade available from Kanto Kagaku K.K.) at room temperature to prepare a suspension. The suspension was put in a warm air chamber maintained at a temperature of 120° C. so that zinc oxide was allowed to react with oleic acid (having a melting point of 24° C.) to form zinc oleate (having a melting point of 78° C.) and the suspension was observed whether the reaction in fact took place at a temperature of 120° C.
Reaction SMILES: [C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[OH-].[Na+:22]>O>[C:1]([O-:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[Na+:22]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCCCCC/C=C\CCCCCCCC(=O)[O-]

Procedure:
In another vessel, a basic solution of sodium oleate is prepared by pouring 15.25 g of oleic acid into 736 g of demineralised water in which have been previously dissolved 7.7 g of sodium hydroxide pellets. The pouring of oleic acid is performed in ten minutes, at room temperature and under moderate stirring.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH:10]1[CH2:14][O:13]C(C)(C)[O:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].C([O-])([O-])=O.[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Al+3]>>[CH2:1]([O:8][CH2:9][CH:10]([OH:11])[CH2:14][OH:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC1(C)OCC(COCc2ccccc2)O1
Agent: O=C([O-])[O-]
Agent: [Al+3]
Agent: [Mg+2]
Product: OCC(O)COCc1ccccc1
Temperature: 70 °C

Procedure:
Into a 1 L beaker were weighed 222 g (1.0 mol) of 4-(benzyloxymethyl)-2,2-dimethyl-1,3-dioxolane purified in Example 1-1, 250 ml of ethanol, and 400 ml of distilled water, and the whole was adjusted to pH 2 with phosphoric acid. With introduction of nitrogen thereinto, the solution was heated to 70° C. After 1.5 hours of reaction, the solution was adjusted to pH 7.0 with sodium hydroxide, the resulting salts were adsorbed onto an adsorbent “KYOWAAD 1000” (manufactured by Kyowa Chemical Industry Co., Ltd.), and the solvent was removed to obtain 3-benzyloxy-1,2-propanediol.