Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:55])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([OH:50])[CH:46]([O:51][CH2:52][CH2:53][CH3:54])[CH2:45]2)[CH:7]([CH3:56])[CH2:6][CH2:5][C:4]1=[O:57])[CH3:2].C(N(C(C)C)CC)(C)C.[N+:67]([C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][C:71]=1[S:76](Cl)(=[O:78])=[O:77])([O-:69])=[O:68]>C(Cl)Cl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:55])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([O:50][S:76]([C:71]3[CH:72]=[CH:73][CH:74]=[CH:75][C:70]=3[N+:67]([O-:69])=[O:68])(=[O:77])=[O:78])[CH:46]([O:51][CH2:52][CH2:53][CH3:54])[CH2:45]2)[CH:7]([CH3:56])[CH2:6][CH2:5][C:4]1=[O:57])[CH3:2]
Reactant: CCCOC1CC(C=C(C)C2OC(=O)C3CCCCN3C(=O)C(=O)C3(O)OC(C(OC)CC(C)CC(C)=CC(CC)C(=O)CCC2C)C(OC)CC3C)CCC1O
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCCOC1CC(C=C(C)C2OC(=O)C3CCCCN3C(=O)C(=O)C3(O)OC(C(OC)CC(C)CC(C)=CC(CC)C(=O)CCC2C)C(OC)CC3C)CCC1OS(=O)(=O)c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 16 h
Yield: 69.4 %

Procedure:
To a solution of 17-ethyl-1-hydroxy-12-[2'-(4"-hydroxy-3"-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (130 mg) in dry methylene chloride (1.75 ml) was added an excess of diisopropylethyl amine (67 μl) and o-nitrophenylsulfonyl chloride (72 mg) followed by addition of 4-dimethylaminopyridine (47 mg). The mixture was stirred at room temperature for 16 hours at which time it was diluted with ethyl acetate, extracted from half-saturated sodium bicarbonate solution and washed with brine. The combined organics were dried over magnesium sulfate and the concentrate purified by flash chromatography on silica gel (ethyl acetate: hexane (1:2)+1% methanol to give the title compound (111 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([NH:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[CH:5]3)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]
Reactant: Nc1ccc2[nH]ccc2c1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N1CCC(Nc2ccc3[nH]ccc3c2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 125.6 %

Procedure:
5-Aminoindole (100 mg, 0.757 mmol) was dissolved in acetonitrile (2 mL), and the solution was added with 1-(tert-butoxycarbonyl)-4-piperidinone (181 mg, 0.908 mmol), acetic acid (0.870 mL, 15.2 mmol) and sodium triacetoxyborohydride (160 mg, 0.755 mmol) little by little, followed by stirring at room temperature for 1 hour. The reaction mixture was added with water and sodium carbonate to adjust the pH to 9. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated to obtain 5-[1-(tert-butoxycarbonyl)-4-piperidylamino]indole (300 mg).
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].S(=O)(=O)(O)O.[CH2:17](O)[CH3:18]>>[OH:1][C:2]1[C:3]([CH3:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([O:7][CH2:17][CH3:18])=[O:6]
Reactant: Cc1c(O)cccc1C(=O)O
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1cccc(O)c1C
Temperature: 25 °C
Yield: 95 %

Procedure:
To a solution of 3-hydroxy-2-methylbenzoic acid (1.00 g, 6.57 mmol) in ethanol (10 mL) was added sulfuric acid (0.16 g, 1.64 mmol), and the mixture was heated under reflux for 12 hours. The reaction solution was cooled to room temperature, and one half of the solvent was concentrated under reduced pressure. Then, water (30 mL) was added thereto, and the mixture was neutralized with sodium carbonate. The mixture was extracted with diethyl ether, and the organic layer was washed with water, and then concentrated under reduced pressure. To the resulting residue was added hexane and crystallized to give the title compound (1.12 g, yield 95%).
Reaction SMILES: Cl.[NH2:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:13][CH2:12][C@@H:11]([NH:14][C:15](=[O:17])[CH3:16])[CH2:10]2)=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.N1(/[C:32](/[NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[N:33]\[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])C=CC=N1>C1COCC1>[C:44]([O:43][C:42](=[O:48])[NH:41]/[C:32](/[NH:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:13][CH2:12][C@@H:11]([NH:14][C:15](=[O:17])[CH3:16])[CH2:10]2)=[CH:7][CH:8]=1)=[N:33]/[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:47])([CH3:45])[CH3:46]
Reactant: CC(=O)N[C@@H]1CCN(c2ccc(N)cc2)C1
Reactant: CC(C)(C)OC(=O)/N=C(/NC(=O)OC(C)(C)C)n1cccn1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)N[C@@H]1CCN(c2ccc(N/C(=N\C(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)cc2)C1
Yield: 69.8 %

Procedure:
N-[(3R)-1-(4-aminophenyl)pyrrolidin-3-yl]acetamide mono hydrochloride (Method 43; 2.47 g, 9.67 mmol) and Hunigs base (2.02 ml, 1.16 mmol) were reacted with di-tert-butyl [(Z)-1H-pyrazol-1-ylmethylylidene]biscarbamate (2.95 g, 9.5 mmol) in THF (50 ml) at room temperature for 72 hours. After evaporation under reduced pressure, chromatography on silica gel with EtOAc/isohexane (50:50 to 100) gave the title compound as a yellow oil (3.06 g, 69%). NMR: 1.39 (s, 9H), 1.52 (s, 9H), 1.81 (s, 3H), 1.82-1.93 (m, 1H), 2.11-2.24 (m, 1H), 3.00-3.08 (m, 1H), 3.21-3.51 (m, 3H), 4.29-4.40 (m, 1H), 6.50 (d, 2H), 7.29 (d, 2H), 8.12 (d, 1H), 9.74 (s, 1H), 11.49 (s, 1H); m/z 462.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([O:14][C:15](=[O:17])[CH3:16])[CH:13]=1)[C:8](O)=[O:9])(=[O:3])[CH3:2].S(Cl)([Cl:20])=O>CN(C)C=O.C1(C)C=CC=CC=1>[C:1]([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([O:14][C:15](=[O:17])[CH3:16])[CH:13]=1)[C:8]([Cl:20])=[O:9])(=[O:3])[CH3:2]
Reactant: CC(=O)Oc1cc(OC(C)=O)cc(C(=O)O)c1
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: CC(=O)Oc1cc(OC(C)=O)cc(C(=O)Cl)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 95.5 %

Procedure:
To a mixture of 3,5-diacetoxybenzoic acid (8.00 g, 33.59 mmol) and dimethylformamide (5 drops) in toluene was added freshly distilled thionylchloride (16 mL). The mixture was stirred for 15 min under nitrogen atmosphere at ambient temperature. Then it was refluxed for 2 h at 80° C. in a hot water bath. The excess thionyl chloride was evaporated in vacuo and toluene was added. Insoluble yellow solid was discarded. Toluene was evaporated in vacuo and gave 3,5-diacetoxybenzoyl chloride (8.23 g, 95.5%), which can be recrystallized from hexane. Data are: 1H NMR (CDCl3, 300 MHz) δ 7.75 (d, 2H), 7.29 (t, 1H), 2.34 (s, 6H); 13C NMR (CDCl3, 75 MHz) δ 168.8, 167.0, 151.4, 135.3, 122.8, 122.0, 21.2; mp=89.5-91° C.; HRMS (EI+) found 256.0130 M+, calcd 256.0139 for C11H9O5Cl; Anal. Calcd for C11H9O5Cl: C, 51.48; H, 3.53. Found: C, 51.60; H, 3.68.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][OH:10])[CH:5]=[N:6][C:7]=1[Cl:8].C[N+]1([O-])CCOCC1>C(Cl)Cl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[O:10])[CH:5]=[N:6][C:7]=1[Cl:8]
Reactant: OCc1cnc(Cl)c(Cl)c1
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Solvent: ClCCl
Product: O=Cc1cnc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 22.3 %

Procedure:
To a solution of (5,6-dichloro-3-pyridinyl)methanol (200 mg) in DCM, molecular sieves (3 Å) (55 mg) and 4-methyl-morpholine-N-oxide (198 mg) was added and stirred at room temperature for 10 minutes. Then tetra-n-propylammonium perruthenate (VII) (38 mg) was added and stirred overnight. The reaction mixture was filtered and the solvent was evaporated to dryness under vacuum. The residue obtained was purified by chromatography column on silica gel using a mixture of EtOAc/hexane as eluent to give 44 mg (22%) of the title compound.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[N:8][CH:9]=1)([O-])=O.C(=O)([O-])[O-].[Na+].[Na+].N>Cl>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[N:8][CH:9]=1
Reactant: O=[N+]([O-])c1ccc(Oc2ccccc2)nc1
Agent: Cl
Agent: N
Agent: O=C([O-])[O-]
Product: Nc1ccc(Oc2ccccc2)nc1
Temperature: 20 °C
Reaction time: 16 h
Yield: 70 %

Procedure:
5-Nitro-2-phenoxypyridine (0.5 9, 2.3 mmol) was added portion wise to a solution of stannous chloride (2.6 g, 12 mmol) dissolved in concentrated hydrochloric acid (10 mL) at a temperature of 0-5° C. The reaction mixture was then stirred at 20° C. for 16 hours. Sodium carbonate (5 g) and aqueous ammonia (50 mL) was added. The mixture was extracted with ethyl acetate (2×50 mL) and the combined organic phases were washed with water (2×40 mL), dried (MgSO4), and concentrated in vacuo to give 0.3 g of 5-amino-2-phenoxypyridine.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([CH3:14])[CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl.[CH3:30][NH:31][O:32][CH3:33]>CN(C=O)C.C(Cl)Cl>[CH3:33][O:32][N:31]([CH3:30])[C:11](=[O:13])[CH2:10][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH3:14]
Reactant: C[C@H](CC(=O)O)NC(=O)OC(C)(C)C
Reactant: CNOC
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CON(C)C(=O)C[C@@H](C)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 47.7 %

Procedure:
To a solution of (R)-3-(tert-butoxycarbonylamino)butanoic acid (4.30 g, 21.16 mmol) in DMF (20 mL) and DCM (20.00 mL) was added EDC (4.46 g, 23.27 mmol) and HOBt (4.21 g, 27.5 mmol). The mixture was stirred at rt for 15 min, then N,O-dimethylhydroxylamine hydrochloride (3.10 g, 31.7 mmol) was added, followed by TEA (5.90 mL, 42.3 mmol) dropwise. The resulting light yellow suspension was stirred at rt for 7 hr. The reaction was quenched with addition of water (100 mL). The mixture was extracted with EtOAc (2×). The combined EtOAc extracts were washed with water (2×), 0.3 M aqueous KHSO4, saturated aqueous NaHCO3 (2×), saturated aqueous NaCl (2×), dried over Na2SO4, filtered and concentrated to give (R)-tert-butyl 4-(methoxy(methyl)amino)-4-oxobutan-2-ylcarbamate (2.48 g, 10.1 mmol, 47.6% yield) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 5.32 (s, 1H), 4.14-3.96 (m, 1H), 3.68 (s, 3H), 3.18 (s, 3H), 2.71 (dd, J=15.6, 4.6 Hz, 1H), 2.61-2.49 (m, 1H), 1.41 (d, J=17.2 Hz, 9H), 1.24 (d, J=6.7 Hz, 3H).
Reaction SMILES: CC(C(N=NC1C(C(O)=O)=CC=CC=1)C(N[C:8]1[CH:13]=[CH:12][C:11]2[NH:14][C:15]([NH:17][C:10]=2[CH:9]=1)=[O:16])=O)=O.C1C(N=NC2C(=O)N(C3C=CC(S([O-])(=O)=O)=CC=3)N=C2C([O-])=O)=CC=C(S([O-])(=O)=O)C=1.[Na+].[Na+].[Na+].N>O>[N:14]1[C:15](=[O:16])[N:17]=[C:10]2[CH:9]=[CH:8][CH:13]=[CH:12][C:11]=12
Reactant: CC(=O)C(N=Nc1ccccc1C(=O)O)C(=O)Nc1ccc2[nH]c(=O)[nH]c2c1
Agent: N
Agent: O=C([O-])C1=NN(c2ccc(S(=O)(=O)[O-])cc2)C(=O)C1N=Nc1ccc(S(=O)(=O)[O-])cc1
Agent: [Na+]
Solvent: O
Product: O=C1N=c2ccccc2=N1
Reaction time: 5 h

Procedure:
20 g of C.I. pigment yellow 151 having an average primary particle diameter of 80 nm (in which the content of metal ions having a valence of at least 2 was 270 ppm), 4 g of a commercially available dye C.I. acid yellow 23 and 110 g of deionized water were mixed, aqueous ammonia was added so as to adjust the pH of a mixture liquid to 9.0, and the mixture liquid was dispersed with a paint shaker in the presence of zirconia beads as media for approximately 5 hours, to obtain a water-based pigment dispersion. The obtained water-based pigment dispersion was diluted so as to have a concentration of 3% by weight, and the diluted water-based pigment dispersion was dropped to NO.2 filter paper, to show bleeding of the dye.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]1[CH:14]=[CH:13][CH2:12][O:11]1)([O-])=O.[N+](C1C=CC=CC=1C1CC=CO1)([O-])=O.CCN(CC)CC>[Pd].CO>[O:11]1[CH2:12][CH2:13][CH2:14][CH:10]1[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[NH2:1]
Reactant: O=[N+]([O-])c1ccccc1C1C=CCO1
Agent: [Pd]
Agent: O=[N+]([O-])c1ccccc1C1CC=CO1
Solvent: CCN(CC)CC
Solvent: CO
Product: Nc1ccccc1C1CCCO1
Yield: 84 %

Procedure:
5% Palladium on carbon (16.3 g, 50% wet, 3.83 mmol, Aldrich 330116) was placed in a Parr bottle under nitrogen, followed by MeOH (100 mL, JT-Baker 909333). The crude mixture of 2-(2-nitrophenyl)-2,5-dihydrofuran and 2-(2-nitrophenyl)-2,3-dihydrofuran (3a & 3b) (163 g) dissolved in MeOH (389 mL) was added to the Parr bottle, followed by NEt3 (237.6 mL, 1.705 mol, Sigma-Aldrich 471283). The bottle was placed on a Parr shaker and saturated with H2. 30 psi H2 was added and the bottle was shaken until starting material was completely consumed (LCMS and NMR showed complete reaction). The reaction mixture was purged with nitrogen, filtered through Celite™ and rinsed with EtOAc. The filtrate was concentrated on a rotary evaporator giving a brown oil. The reaction was repeated three more times on the same scale and the batches were combined for purification. The crude product was vacuum distilled (ca. 15 torr) collecting the distillate at 108-129° C. to give (4) as a clear faint yellow oil (427.9 g, average yield was 84%; 98% GCMS purity). LCMS (C18 column eluting with 10-90% CH3CN/water gradient over 5 minutes with formic acid modifier) M+1: 163.95 (1.46 min). 1H NMR (300 MHz, CDCl3) δ 7.15-7.04 (m, 2H), 6.77-6.62 (m, 2H), 4.85-4.77 (m, 1H), 4.18 (s, 2H), 4.12-4.02 (m, 1H), 3.94-3.85 (m, 1H), 2.25-1.95 (m, 4H) ppm.
Reaction SMILES: [CH2:1]([N:3]([CH2:13][CH3:14])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-])=O)=[CH:6][N:5]=1)[CH3:2].[Sn](Cl)Cl>C(OCC)C.Cl>[NH2:10][C:7]1[CH:8]=[CH:9][C:4]([N:3]([CH2:13][CH3:14])[CH2:1][CH3:2])=[N:5][CH:6]=1
Reactant: CCN(CC)c1ccc([N+](=O)[O-])cn1
Agent: Cl
Agent: Cl[Sn]Cl
Solvent: CCOCC
Product: CCN(CC)c1ccc(N)cn1
Yield: 191.5 %

Procedure:
Following procedures similar to those disclosed in Artland, et al., J. Heterocyclic Chem., Vol. 14, 129-134 (1977), the reaction of 10.0 g (0.0512 mole) of 2-diethylamino-5-nitropyridine with 147.0 g (0.659 mole) of tin (II) chloride dehydrate in diethyl ether and concentrated hydrochloric acid produced a residue. This reaction was repeated, and the residues were combined, giving a total of 20 g. The combined residue was purified by column chromatography on silica gel, eluting with acetone to yield 16.2 g of 5-amino-2-diethylaminopyridine as an oil. The nmr spectrum was consistent with the proposed structure.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=O.C([BH3-])#N.[Na+].C[Si](Cl)(C)C>>[CH2:6]1[C:7]2[CH:8]=[CH:9][CH:10]=[C:2]([OH:1])[C:3]=2[CH2:4][CH2:5]1
Reactant: O=C1CCc2c(O)cccc21
Agent: C[Si](C)(C)Cl
Agent: [BH3-]C#N
Agent: [Na+]
Product: Oc1cccc2c1CCC2

Procedure:
4-Hydroxy-2,3-dihydro-1H-inden-1-one (W. Liu et al., Org. Lett. 2007, 9, 2915-2918) was reduced with sodium cyanoborohydride/trimethylsilyl chloride to provide 2,3-dihydro-1H-inden-4-ol. This was chlorinated with N-chlorosuccinimide to generate 7-chloro-2,3-dihydro-1H-inden-4-ol.
Reaction SMILES: [C:1]([O:8]CC)(=O)[C:2]([O:4][CH2:5][CH3:6])=[O:3].O.[NH2:12][NH2:13]>C(O)C>[NH:12]([C:1](=[O:8])[C:2]([O:4][CH2:5][CH3:6])=[O:3])[NH2:13]
Reactant: CCOC(=O)C(=O)OCC
Reactant: NN
Solvent: O
Solvent: CCO
Product: CCOC(=O)C(=O)NN
Temperature: 80 °C
Reaction time: 3 h
Yield: 88.5 %

Procedure:
To a round-bottom flask was added a solution of diethyl oxalate (10.0 g, 68.4 mmol, 1.00 equiv) in ethanol (100 mL). Hydrazine hydrate (2.75 g, 85.8 mmol, 1.00 equiv) was added and the resulting mixture was stirred for 3 h at 80° C. After cooling to ambient temperature, the solids were removed via filtration and the filtrate was concentrated in vacuo to yield 8.00 g (80%) of the title compound as a colorless oil.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[N:4][C:5]2[CH:6]([C:12]([NH2:14])=O)[CH2:7][CH2:8][CH2:9][C:10]=2[CH:11]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=S>N1C=CC=CC=1>[C:12]([CH:6]1[C:5]2[N:4]=[CH:3][C:2]([CH3:1])=[CH:11][C:10]=2[CH2:9][CH2:8][CH2:7]1)#[N:14]
Reactant: Cc1cnc2c(c1)CCCC2C(N)=O
Agent: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: c1ccncc1
Product: Cc1cnc2c(c1)CCCC2C#N
Reaction time: 3 h
Yield: 52.2 %

Procedure:
3-Methyl-5,6,7,8-tetrahydroquinoline-8-carboxamide (3.6g.) in pyridine (54 ml.) was treated with P2S5 (7.56 g.) and the mixture heated at reflux with stirring for 3 hours. The solvent was removed under reduced pressure and the residue cooled in ice-water then made basic with 10% NaOH. The basic solution was extracted with chloroform (3 times) and the combined extracts extracted with 2NHCl (twice). The combined acid extracts were basified with solid sodium carbonate and extracted into chloroform (3 times). The combined chloroform extracts were washed with brine dried (MgSO4) and evaporated to give the title compound 1.7 g. This was converted to the hydrochloride by dissolving in ether and adding ethereal HCl. An oily residue was formed from which the supernatent liquid was decanted. The residue was triturated twice with dry ether and the remaining solid recrystallised from isopropyl alcohol giving the hydrochloride of the title compound m.p. 189° C.
Reaction SMILES: [CH2:1]([NH2:6])[CH2:2][CH2:3][CH2:4][CH3:5].[CH:7](=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>CO>[CH:7](=[N:6][CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CCCCCN
Reactant: O=Cc1ccccc1
Solvent: CO
Product: CCCCCN=Cc1ccccc1

Procedure:
100 g (1.15 mol) N-pentylamine was added to 200 ml methanol at a temperature of 22° C. 121.8 g (1.15 mol) benzaldehyde was added. The mixture was refluxed and subsequently, methanol was distilled off. The residual N-benzylidene-N-pentylamine 199.8 g (99.4%) was used in the next step.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([O:8][CH3:9])[CH:5]=[CH:6][CH:7]=1.[Li]CCCC.CN([CH:18]=[O:19])C.OS(O)(=O)=O>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[C:3]=1[CH:18]=[O:19]
Reactant: CN(C)C=O
Reactant: COc1cccc(F)c1
Agent: O=S(=O)(O)O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COc1cccc(F)c1C=O
Temperature: -78 °C
Reaction time: 1 h
Yield: 55 %

Procedure:
The solution of 3-Fluoro anisole (2.2 g, 17.44 mmol) in anhydrous THF (40 ml) under a nitrogen atmosphere was cooled to −78° C., and then n-BuLi (1.6 M, 19.18 mmol) was slowly added thereto. The reaction mixture was stirred at −78° C. for 1 hour, slowly added with DMF (1.6 ml, 20.93 mmol), and then stirred for 1 hour. After the termination of the reaction, the resulting reaction solution was added with dilute H2SO4, extracted two times with ethyl acetate, washed with brine, dried over MgSO4, and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=6:1), thus obtaining the title compound as a white solid (1.48 g, 9.6 mmol, 55%).
Reaction SMILES: [CH3:1][N+:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[CH:10][N+:11]([CH3:14])=[CH:12][CH:13]=2)=[CH:6][CH:7]=1.[Cl:15]Cl.[S:17]([S:20]([O-:22])=[O:21])([O-:19])=[O:18].[Na+].[Na+].[OH-].[Na+].S(S([O-])=O)([O-])=O>O>[S:17]([S:20]([O-:22])=[O:21])([O-:19])=[O:18].[CH3:14][N+:11]1[CH:10]=[CH:9][C:8]([C:5]2[CH:4]=[CH:3][N+:2]([CH3:1])=[CH:7][CH:6]=2)=[CH:13][CH:12]=1.[Cl-:15].[Cl-:15]
Reactant: ClCl
Agent: C[n+]1ccc(-c2cc[n+](C)cc2)cc1
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Product: [Cl-]

Procedure:
The solubility rate and the paraquat-Cl2 analysis were determined as follows. A hydrosulfite solution is prepared from 5.00 g sodium hydrosulfite, 2.00 g sodium hydroxide, and 93.00 g DI water. 1.00 g of dry product is dissolved in 999.0 g STW water and 1 ml samples are taken at 1, 2, 5, and 10 minutes. 1 ml sample is added to 98.0 g STW water and mixed. Then 1 ml hydrosulfite solution is added and mixed. Absorbance is read at 394 nm using a Pye Unicam Spectrophotometer SP1750. Absorbance of the test sample is matched with absorbance on control graph to give % Paraquat dichloride.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([OH:13])[CH:7]=[CH:6]2.CN(C)C=O.[Br:19]N1C(=O)CCC1=O>O>[Br:19][C:9]1[C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2)[CH:6]=[CH:7][C:8]=1[OH:13]
Reactant: O=C1CCC(=O)N1Br
Reactant: COc1ccc2cc(O)ccc2c1
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc2c(Br)c(O)ccc2c1
Reaction time: 0.75 h
Yield: 87.8 %

Procedure:
Add 6-methoxynaphthalene-2-ol (20 g, 114.8 mmol) to dimethylformamide (DMF, 250 mL) at ambient temperature followed by N-bromosuccinimide (NBS, 21.5 g, 120 mmol) over a 30 minute period. After 45 minutes, dilute with water (800 mL), collect and dry the precipitate to provide 25.5 g (87%) of 1-bromo-6-methoxy-naphthalen-2-ol.
Reaction SMILES: [O-2].[Zn+2:2].N.[CH2:4]([O:8][CH2:9][CH2:10][OH:11])[CH2:5][CH2:6][CH3:7]>[Cl-].C[N+](C)(CCCCCCCCCCCCCCCCCC)CCC[Si](OC)(OC)OC>[CH2:4]([O:8][CH2:9][CH2:10][OH:11])[CH2:5][CH2:6][CH3:7].[Zn:2]
Reactant: [Zn+2]
Agent: CCCCCCCCCCCCCCCCCC[N+](C)(C)CCC[Si](OC)(OC)OC
Agent: N
Agent: [Cl-]
Solvent: CCCCOCCO
Product: [Zn]

Procedure:
The reaction product of 0.81 g. of zinc oxide, 9.91 g. of dimethyl-n-octadecyl [3(trimethoxysilyl)propyl] ammonium chloride, 10.0 g. of 28% aqueous ammonia in 100 g. of 2-n-butoxyethanol, after overnight agitation, was diluted with 15.0 g. of additional 2-n-butoxyethanol and gave a clear, homogeneous solution of a zinc ammine siliconate with an Si/Zn ratio of 2.0/1.0. Upon air drying, the solution gave a non-tacky coating which was firm, soft, water-repellent and water-insoluble, but swollen by toluene.
Reaction SMILES: [CH3:1][N:2]([C:16]1[CH:17]=[CH:18][C:19]([C:22]([NH:24][C@H:25]([C:31]([OH:33])=[O:32])[CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[O:23])=[CH:20][CH:21]=1)[CH2:3][C:4]1[CH:5]=[N:6][C:7]2[N:13]=[C:12]([NH2:14])[N:11]=[C:10]([NH2:15])[C:8]=2[N:9]=1.C([O-])(=O)C.[Zn+2:38].C([O-])(=O)C>CO>[Zn:38].[CH3:1][N:2]([C:16]1[CH:17]=[CH:18][C:19]([C:22]([NH:24][C@H:25]([C:31]([OH:33])=[O:32])[CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[O:23])=[CH:20][CH:21]=1)[CH2:3][C:4]1[CH:5]=[N:6][C:7]2[N:13]=[C:12]([NH2:14])[N:11]=[C:10]([NH2:15])[C:8]=2[N:9]=1
Reactant: [Zn+2]
Agent: CC(=O)[O-]
Agent: CN(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1
Solvent: CO
Product: [Zn]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A zinc salt of methotrexate was prepared as follows. Methotrexate (3.0 g, 0.0066 moles) was dissolved in 600 ml methanol at room temperature with rapid stirring. A solution of zinc acetate (0.6 g, 0.0033 moles) in 2 ml methanol was added dropwise to the methotrexate solution. Immediate precipitation (flocculent) was observed. The mixture was stirred for one hour at room temperature. The mixture was then concentrated in a rotating evaporator (roto-vap) at 40° C. The residue obtained (3.2 g) was dried under high vacuum. (C20H22N8O5)2Zn, MW 974.29; percent zinc: 6.46 (found), 6.71 (theoretical).
Reaction SMILES: [NH2:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][C:4]([OH:6])=[O:5].C[O-].[Na+].O.O.C([O-])(=O)C.[Zn+2:19].C([O-])(=O)C>CO>[Zn:19].[NH2:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][C:4]([OH:6])=[O:5]
Reactant: [Zn+2]
Agent: CC(=O)[O-]
Agent: C[O-]
Agent: N[C@@H](CC(=O)O)C(=O)O
Solvent: CO
Solvent: O
Product: [Zn]

Procedure:
L-aspartic acid (2.00 g, 15.0 mmol) was added to an MeOH solution of NaOMe (prepared with Na: 0.69 g, MeOH: 50 ml) at 0° C. and stirred. An MeOH solution (30 ml) of zinc acetate dihydrate (3.30 g) was then gradually dropwise added thereto at room temperature. After stirring for 2 hours at that same temperature, the precipitated crystal (in suspension) was recovered by filtration, washed with water, air dried, and then dried under a reduced pressure (5 mmHg, 80° C.).