Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:3]2[C:8]([CH:9]=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[C:16]1(B(O)O)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C>[C:16]1([C:2]2[C:3]3[C:8]([CH:9]=[C:10]4[C:15]=2[CH:14]=[CH:13][CH:12]=[CH:11]4)=[CH:7][CH:6]=[CH:5][CH:4]=3)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Brc1c2ccccc2cc2ccccc12
Reactant: OB(O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: c1ccc(-c2c3ccccc3cc3ccccc23)cc1
Yield: 91.2 %

Procedure:
An amount of 15.14 g (58.9 mmol) of 9-bromoanthracene, 7.2 g (59 mmol) of phenylboronic acid, and 1 g of tetrakis triphenylphosphine palladium as catalysis were dissolved in a mixed solvent of 100 ml of toluene and 25 ml of ethanol. Then, 50 ml of 2M sodium carbonate solution was added to the mixed solvent and allowed to react at 90° C. for 12 hours. After the reaction was completed, the organic layer was separated and purified by column chromatography to obtain 13.65 g (53.7 mmol) of 9-phenylanthracene. The yield was 91.2%.
Reaction SMILES: [C:1]([C:6]1[N:7]=[CH:8][C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH:18]=1)=[CH:15][CH:14]=[CH:13][CH:12]=3)(OCC)=[O:2].[BH4-].[Na+].O>C1COCC1>[OH:2][CH2:1][C:6]1[N:7]=[CH:8][C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH:18]=1)=[CH:15][CH:14]=[CH:13][CH:12]=3
Reactant: CCOC(=O)c1cc2c(cn1)[nH]c1ccccc12
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: OCc1cc2c(cn1)[nH]c1ccccc12
Temperature: 25 °C
Reaction time: 12 h
Yield: 84.1 %

Procedure:
3.5 grams (15 mmol) of 3-carboethoxy-β-carboline were suspended in 300 ml THF, 2.7 grams (75 mmol) sodium borohydride were added and the mixture was stirred at room temperature for 12 hours. The mixture was then cooled, 50 ml water were added and the resulting mixture was stirred overnight. The solvent was evaporated under reduced pressure and water (300 ml) was again added. The aqueous suspension was extracted with dichloromethane, followed by ethylacetate, the organic extracts were combined, and the solvent was evaporated under reduced pressure. The remaining residue was purified by column chromatography on silica gel, using and a 9:1 mixture of ethylacetate and methanol as eluent, to give 3-(hydroxymethyl)-β-carboline (2.5 grams, 81% yield).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[N:6][CH:7]=1.S(Cl)(Cl)=O.[CH3:16]O>>[CH3:16][O:10][C:9](=[O:11])[CH2:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=1
Reactant: CO
Reactant: O=C(O)Cc1cncc(Br)c1
Solvent: O=S(Cl)Cl
Product: COC(=O)Cc1cncc(Br)c1
Temperature: 25 °C

Procedure:
To a solution of (5-bromo-pyridin-3-yl)-acetic acid (4.2 g, 20 mmol) in methanol (50 mL) was added thionyl chloride (4.4 mL, 60 mmol) slowly at 0° C. After the addition, the reaction mixture was warmed up and heated to reflux temperature for 2 hours. After cooling back to room temperature, the reaction mixture was concentrated in vacuo and the residue was re-dissolved in EtOAc (250 mL) and washed with aq. NaHCO3 solution and brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give a crude product (4.6 g, quant.) as light yellow solid. MS: 230.1 & 232.0 (M+H+).
Reaction SMILES: O=C[C@@H:3]([C@H:5]([C@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[OH-:13].[K+:14]>>[O:13]=[C:3]([O-:4])[C@H:5]([C@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6].[K+:14]
Reactant: [OH-]
Reactant: O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO
Agent: [K+]
Product: O=C([O-])[C@@H](O)[C@@H](O)[C@H](O)CO

Procedure:
The multi-step synthesis from D-galactose comprises oxidizing the D-galactose in KOH solution to open the pyranose ring and form potassium D-lyxonate, subjecting the latter compound to alcoholic solution under acid conditions to provide furanose ring closure and form the D-lyxono-1,4-lactone, and then introducing a protecting group at C-2 and C-3 by reaction with ketone in the presence of a dehydrating agent. Use of acetone as the ketone in the latter step gives the compound 2,3-0-isopropylidene-D-lyxono-1,4-lactone. From that point on the multi-step system includes the general reaction steps of the above short synthesis.
Reaction SMILES: S(Cl)([Cl:3])=O.[Cl:5][C:6]1[N:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8](O)=[O:9]>CN(C=O)C.ClCCl>[Cl:5][C:6]1[N:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([Cl:3])=[O:9]
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1cccnc1Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)c1cccnc1Cl

Procedure:
Thionyl chloride (2.48 ml, 10 eq) and DMF (2 drops) were added to a solution of 2-chloronicotinic acid (535 mg, 3.4 mmol) in dichloromethane (3 ml). The mixture was heated at reflux overnight then concentrated in vacuo and azeotroped with toluene (2×5 ml) to give 2-chloronicotinoyl chloride as a yellow oil. A solution of this acid chloride in dichloromethane (5 ml) was added dropwise to a solution of Intermediate 5 (750 mg, 2.69 mmol) and NMM (355 μl, 1.2 eq) in dichloromethane (15 ml) at 00. Dimethylaminopyridine (catalytic) was added and the mixture stirred at room temperature for 2 h. The mixture was then concentrated in vacuo. The residue was dissolved in ethyl acetate (50 ml) and washed with aqueous NaHCO3 (2×50 ml). The organic phase was dried (MgSO4) and concentrated in vacuo, to give the title compound. δH (CDCl3) 10.55 (1H, s), 8.51 (1H, m), 8.05 (1H, m), 7.67 (1H, m), 7.57 (3H, m), 7.2 (2H, m), 4.24 (1H, m), 3.62 (3H, s), 3.08 (2H, m), 1.03 (9H, s); m/z (ESI, 70V) 418 (M++H).
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]([CH3:24])[C:11](=[O:23])[N:12]([CH3:22])[C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[CH:5][CH:4]=1.B(Br)(Br)Br>C(Cl)Cl>[OH:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:10]([CH3:24])[C:11](=[O:23])[N:12]([CH3:22])[C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[CH:7][CH:8]=1
Reactant: COc1ccc(-c2c(-c3ccc(OC)cc3)n(C)c(=O)n2C)cc1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: COc1ccc(-c2c(-c3ccc(O)cc3)n(C)c(=O)n2C)cc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 0.1 %

Procedure:
To a stirred −40° C. solution of 4,5-bis(4-methoxyphenyl)-1,3-dimethyl-1H-imidazol-2(3H)-one (0.6 g, 1.84 mmol) in DCM (10 mL), BBr3 (0.7 mL, 7.38 mmol) was added dropwise and the reaction mixture was then stirred for 48 h at RT, quenched with 6 N HCl and washed with water. The combined organic layers were then dried over Na2SO4, filtered and then concentrated in vacuo to afford 4-(4-hydroxyphenyl)-5-(4-methoxyphenyl)-1,3-dimethyl-1H-imidazol-2(3H)-one (0.38 mg, 66%) as a solid.
Reaction SMILES: [CH3:1][C:2]([O:5][C:6]([N:8]1[C@H:11]([C:12]([OH:14])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].OS(O)(=O)=O.[NH3:20]>CO>[C:2]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C@H:11]1[C:12](=[O:14])[NH2:20])=[O:7])([CH3:4])([CH3:3])[CH3:1]
Reactant: N
Reactant: CC(C)(C)OC(=O)N1CC[C@H]1C(=O)O
Agent: O=S(=O)(O)O
Solvent: CO
Product: CC(C)(C)OC(=O)N1CC[C@H]1C(N)=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 92 %

Procedure:
A mixture of 1-Boc-L-azetidine-2-carboxylic acid (10 g), conc. H2SO4 (1 mL) in dry MeOH (200 mL) was stirred at RT for 2 h. The reaction mixture was then concentrated in vacuo, the residue was diluted with EA, basified with sat. NaHCO3 solution. The organic extract was washed with water, dried (MgSO4), filtered and concentrated to yield the crude methyl ester as a yellow oil (11 g, 102%). This crude ester was dissolved in dry MeOH (200 mL) and treated with 7M ammonia solution in MeOH (100 mL). The resulting white suspension was stirred at RT for 72 h and filtered off. The filtrate was concentrated in vacuo to give the title compound as a white solid (8.5 g, 92%).
Reaction SMILES: [C:1]([NH:8][C@H:9]([C:12]([OH:14])=[O:13])[CH2:10]O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>C1COCC1>[CH3:7][C:4]([O:3][C:1]([NH:8][C@@H:9]1[C:12](=[O:13])[O:14][CH2:10]1)=[O:2])([CH3:5])[CH3:6]
Reactant: CC(C)(C)OC(=O)N[C@@H](CO)C(=O)O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N[C@H]1COC1=O
Temperature: -45 °C
Reaction time: 0.5 h
Yield: 56.4 %

Procedure:
Methyl azodicarboxylate-derivatized resin (6.55 g, 4.0 meq) was swollen briefly (15 min) in dry THF (100 mL). The stirred suspension of beads was cooled to -45° C. and BOC-L-serine (473.5 mg, 2.30 mmol) was added. To this mixture at -45° C. was added a solution of triphenylphosphine (1.06 g, 4.0 mmol) in THF (5 mL) dropwise over 10 min. The suspension was stirred 30 min at -45° C., allowed to warm slowly to 0° C. over 1 h, and stirred 2 h further. H2O (36μL) was added as a precautionary quench and the resin was filtered and washed with THF (2 ×100 mL) and CH3CN (100 mL). The filtrate and washings were pooled and concentrated in vacuo at 35° C. The residue was flash chromatographed (35% EtOAc/hexane) to yield 242.7 mg (56%) of BOC-L-serine β-lactone: mp 119.5-120.5° C (dec); [α]25 -26.7 (±0.2)°(c 1.0, CH3CN); IR [Fluorolube (trademark) mull](CH2Cl2 cast) 3358 (s), 1836 (s), 1678 (vs), 1532 (s), 1291 (m), 1104 (s) cm-1 ; ε1847 cm-1 (0.1 mm KBr, THF or CH3CN) 0.34 mL mg-1 mm-1, 64 M-1 ; mm-1 ; 1H NMR (200 MHz, CD2Cl2) δ5.53 (br s, 1H, NH), 5.05 (dd, 1H, 8, 6 Hz, CH), 4.47 (~d, 2H, 6 Hz, CH2O), 1.47 (s, 9H, tert-Bu); 13C NMR (50.32 MHz, CD2Cl2) ≃170.0 (s), 155.1 (s), 81.5 (s), 66.6 (t), 59.9 (d), 28.2 (q); Anal. Calc. for C8H13NO4 : C, 51.33; H, 7.00; N, 7.48. Found: C, 51.04; H, 6.97; N, 7.42; EI--MS: 188.0929 (MH+, 188.0923 calcd.); CI--MS (NH3) 205 (M+NH+), 392 (2M+NH4+).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[N:11][C:10]=1[C:20]([O:22]CC)=[O:21])=[O:7])([CH3:4])([CH3:3])[CH3:2].O[Li].O.Cl>CO.O>[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[N:11][C:10]=1[C:20]([OH:22])=[O:21])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)c1nc(-c2ccccc2)sc1NC(=O)OC(C)(C)C
Agent: Cl
Agent: [Li]O
Solvent: CO
Solvent: O
Product: CC(C)(C)OC(=O)Nc1sc(-c2ccccc2)nc1C(=O)O
Temperature: 52.5 °C
Yield: 68.7 %

Procedure:
To a solution of compound ethyl 5-(tert-butoxycarbonylamino)-2-phenylthiazole-4-carboxylate (348 mg, 1 mmol) in MeOH/H2O (10 mL, 1:1) was added LiOH.H2O (20 mg, 5 mmol). The reaction mixture was heated at 50-55° C. until starting material disappeared from TLC. It was cooled at about 0-4° C. and conc. HCl added dropwise until pH of about 5. The resulted mixture was then extracted with DCM (3×20 mL). Combined organic layers were washed with brine (2×20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (50:1 DCM:MeOH) to give the 5-(tert-butoxycarbonylamino)-2-phenylthiazole-4-carboxylic acid (0.22 g, 68%) as white solid: 1H-NMR (CDCl3, 500 MHz) δ (ppm): 9.69 (s, 1H), 7.89-7.91 (m, 2H), 7.46-7.47 (m, 3H), 1.57 (s, 9H); MS (ESI) m/z: 321 [M+H+]
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][C:3]=1[N+:18]([O-:20])=[O:19].[CH2:21]([NH2:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1COCC1>[CH2:21]([NH:28][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][C:3]=1[N+:18]([O-:20])=[O:19])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CN1CCN(S(=O)(=O)c2ccc(Cl)c([N+](=O)[O-])c2)CC1
Reactant: NCc1ccccc1
Solvent: C1CCOC1
Product: CN1CCN(S(=O)(=O)c2ccc(NCc3ccccc3)c([N+](=O)[O-])c2)CC1
Yield: 86.5 %

Procedure:
1-(4-Chloro-3-nitro-benzenesulphonyl)-4-methyl-piperazine (0.50 g, 1.57 mmol) and benzylamine (0.502 g, 4.70 mmol) were dissolved in THF (10 ml) and heated at reflux for 3 h. The reaction mixture was then reduced in vacuo and partitioned between ethyl acetate and water. The organics were washed with brine, dried (MgSO4) and reduced in vacuo, and the resultant residue purified by column chromatography eluting with 0-10% methanol in ethyl acetate to give benzyl-[4-(4-methyl-piperazine-1-sulphonyl)-2-nitro-phenyl]-amine as a yellow solid (0.53 g, 86%). (LC/MS: Rt 2.21, [M+H]+ 391.05).
Reaction SMILES: [I:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(=O)(=O)(O)O.[OH-].[Na+].[CH3:19]O>>[I:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([O:6][CH3:19])=[O:5]
Reactant: CO
Reactant: Cc1ccc(I)c(C(=O)O)c1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: COC(=O)c1cc(C)ccc1I
Temperature: 16 °C
Yield: 98 %

Procedure:
A visually clean 100 L flask equipped with a mechanical stirrer thermocouple and water chilled condenser was charged with MeOH (50 L). 2-iodo-5-methylbenzoic acid (5.85 kg, 22.32 mol) was then added while stirring. Concentrated sulfuric acid (0.595 L, 11.16 mol) was then added portion-wise which caused an increase in temperature from 17° C. to 22° C. This mixture was gradually brought to an internal temperature of 64.6° C. and aged overnight (˜18 h). The next morning the reaction had reached >98% conversion by HPLC. The flask was cooled to 16° C. by placing in an ice bath and 850 mL of 10 N NaOH (0.98 equiv.) was added slowly (over 10 minutes) while monitoring the pH. After the addition the pH was 5-6 (caution: bringing pH over 9 can result in saponification during the work-up). The solution was then concentrated to about 16 L and this suspension was transferred to a 100 L extractor. The flask was rinsed with 8 L of IPAc and 4 L of water which were also transferred to the extractor. 32 L of IPAc were added along with 10 L of 5 w % NaHCO3 and 10 L of 15 w % Brine. The layers were cut and the aqueous layers were back-extracted with 20 L of IPAc. The organic layers were then combined and washed with 10 L of 15 w % Brine. The organic layers were collected to provide B-1 (6.055 kg, 2193 mol, 98% yield) in 98.3% purity. 1H NMR (500 MHz, CDCl3, 293K, TMS): 7.84 (1 H, d, =8.07 Hz), 7.62 (1 H, d, J=2.14 Hz), 6.97 (1 H, dd, J=8.08, 2.14 Hz), 3.97-3.86 (3 H, m), 2.33 (3 H, s).
Reaction SMILES: [NH2:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:19][CH:20]1[O:22][CH2:21]1>CCOC(C)=O>[N+:9]([C:5]1[CH:4]=[N:3][C:2]2[NH:1][CH:20]([CH2:21][OH:22])[CH2:19][O:8][C:7]=2[CH:6]=1)([O-:11])=[O:10]
Reactant: BrCC1CO1
Reactant: Nc1ncc([N+](=O)[O-])cc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: O=[N+]([O-])c1cnc2c(c1)OCC(CO)N2
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 49 %

Procedure:
Into a 75 mL sealed tube were combined 2-amino-3-hydroxy-5-nitropyridine (0.138 g, 0.000890 mol), N,N-dimethylfonnamide (4.1 mL) and potassium carbonate (0.39 g, 0.0028 mol). The mixture was allowed to stir at room temperature for 10 minutes then 1-bromo-2,3-epoxypropane (0.12 g, 0.00089 mol) was added in one portion. The flask was sealed, then heated to 110° C. and stirred overnight. After allowing to cool, the mixture was concentrated under vacuum to give a crude solid which was dissolved in EtOAc (75 mL), washed with water and brine, then dried (Na2SO4), filtered and concentrated under vacuum to leave a crude residue. The residue was purified by column chromatography on silica gel using MeOH/CH2Cl2 (0-10% gradient) as eluent to give a solid (0.092 g, 46%). LC-MS 1.92 min. M/Z=212.0 (M+1). 1H NMR (d6-DMSO) δ 8.8 (d, 1 H), 7.8 (d, 1 H), 5.1 (t, 1H),4.2 (m, 1 H), 4.0 (m, 1H), 3.62 (m, 1H), 3.45 (m, 1H), 3.21 (m, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][CH3:10])=[CH:4][CH:3]=1.Cl.[NH2:13][OH:14].[OH-].[Na+].Cl>O.C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[N:13][OH:14])[CH2:9][CH3:10])=[CH:4][CH:3]=1
Reactant: CCC(=O)c1ccc(Cl)cc1
Reactant: NO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCC(=NO)c1ccc(Cl)cc1

Procedure:
33.6 g of p-chloropropiophenone was mixed with 200 ml of ethanol and 40 ml of water. 24 g of hydroxylamine hydrochloride was added. 44 g of solid sodium hydroxide was added over a 10-minute period to the stirred mixture at room temperature. The mixture was heated to 80°, then refluxed for 80 minutes. The mixture was cooled and poured into cold dilute hydrochloric acid. The resulting mixture was filtered. The solid product was dissolved in methylene chloride; the solution was dried (MgSO4) and stripped of solvent. Recrystallization of the solid product from hexane gave 1-(4-chlorophenyl)-1-propanone oxime (4A), m.p.: 56°-57.5°.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[Li]CCCC.CN([CH:18]=[O:19])C>>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:18]=[O:19]
Reactant: c1ccc2scnc2c1
Reactant: CN(C)C=O
Agent: [Li]CCCC
Product: O=Cc1nc2ccccc2s1
Reaction time: 1 h

Procedure:
To a solution of benzo[d]thiazole (1 g, 7 mmol) in DMF (10 mL) was added n-BuLi (8.4 mL, 21 mmol) over 15 min at −78° C. and the mixture was stirred at this temperature for 1 hour. The reaction was quenched with water, extracted with EtOAc and dried over anhydrous sodium sulfate. The solution was then concentrated under vacuum to give benzo[d]thiazole-2-carbaldehyde as a light yellow solid (500 mg).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.C([Li])CCC.CN([CH:18]=[O:19])C>C1COCC1.CCCCCC>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:18]=[O:19]
Reactant: c1ccc2scnc2c1
Reactant: CN(C)C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: O=Cc1nc2ccccc2s1
Reaction time: 0.33 h

Procedure:
To a stirred solution of benzothiazole (3.28 ml) in anydrous THF (40 ml), at −78°, under a nitrogen atmosphere, butyllithium (2.0 ml of a 1.6M solution in hexane) was added dropwise. After 0.33 h, a solution of DMF (7 ml) in anydrous THF (20 ml) was added dropwise and the reaction mixture was allowed to rise to 0° over 1 h. The reaction was quenched by pouring the mixture into water (100 ml) and extracted with EE (2×150 ml). The organic layer was washed with brine, dried and the solvent evaporated under reduced pressure. The crude residue was purified by flash chromatography (eluting with CH-EA in gradient from 95:5 to 8:2), and crystallized from PE to give the title compound as a yellow solid (1.88 g). M.p. 76-77°
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=O.CO.[CH3:12][NH2:13]>C(Cl)Cl.CO>[CH3:12][NH:13][CH2:5][C:4]1[CH:7]=[CH:8][CH:9]=[C:2]([OH:1])[CH:3]=1
Reactant: O=Cc1cccc(O)c1
Reactant: CN
Solvent: CO
Solvent: ClCCl
Product: CNCc1cccc(O)c1
Yield: 79 %

Procedure:
10.0 g of 3-hydroxybenzaldehyde and 9.55 g of a 40% methanol solution of methylamine were mixed, and then the solvent was evaporated. The resulting Schiff base was dissolved in 50 ml of ethanol, and with stirring under ice cooling, 10.0 g of sodium borohydride was added The mixture was stirred overnight at room temperature. The solvent was evaporated under reduced pressure, and the residue was extracted with ethyl acetate and a saturated aqueous sodium chloride solution. The organic layer was separated, and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography [Wakogel C-100, 100 g; eluting solvent: methylene chloride/methanol=10/1→5/1to give 8.88 g (yield 79%) of N-methyl-3-hydroxybenzylamine as pale yellow crystals having a melting point of 138° to 140° C.
Reaction SMILES: [CH3:1][C:2]1[C:3](=O)[CH:4]=[C:5]([CH3:10])[C:6](=[O:9])[C:7]=1[CH3:8].C(O)C.Cl.[NH2:16][OH:17].Cl>O>[CH3:1][C:2]1[C:3](=[N:16][OH:17])[CH:4]=[C:5]([CH3:10])[C:6](=[O:9])[C:7]=1[CH3:8]
Reactant: NO
Reactant: CC1=CC(=O)C(C)=C(C)C1=O
Agent: Cl
Solvent: O
Solvent: CCO
Product: CC1=CC(=NO)C(C)=C(C)C1=O
Temperature: 60 °C
Reaction time: 0.17 h

Procedure:
To a solution of 2,3,5-trimethyl-1,4-benzoquinone (70 g, 0.51 mol) of hot ethanol (200 mL) was added a warm solution of hydroxylamine hydrochloride (35 g, 0.50 mol) and conc. hydrochloric acid (5 mL) in water (100 mL). The resulting red solution was stirred for 10 min at 60° C., stoppered and allowed to cool overnight in a refrigerator. The bright yellow precipitate was collected by vacuum filtration and dried to yield 63.9 g (83% yield) of crude product. Recrystallization from 50% aq. ethanol afforded the product as a yellow solid, mp 175° C. (dec.) (lit.: Smith, L. I.; Schubert, W. M. J. Am. Chem. Soc. 1948, 70, 2656; mp 182° C.). Spectral data: 1H NMR (CD3SOCD3): δ 1.90 (s, 3H), 1.93 (s, 3H), 2.30 (s, 3H), 7.55 (s, 1H), 12.95 (s, 1H, exchangeable with D2O); 13C NMR (CD3COCD3): δ 11.49, 12.94, 16.09, 120.53, 132.77, 137.39, 140.72, 149.04, 186.13.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][C:21]2[CH:26]=[CH:25][C:24](/[CH:27]=[CH:28]/[C:29]3[CH:34]=[CH:33][C:32]([N:35](C(OC(C)(C)C)=O)[CH3:36])=[CH:31][CH:30]=3)=[CH:23][CH:22]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][C:21]2[CH:26]=[CH:25][C:24](/[CH:27]=[CH:28]/[C:29]3[CH:34]=[CH:33][C:32]([NH:35][CH3:36])=[CH:31][CH:30]=3)=[CH:23][CH:22]=2)(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)OCCOCCOCCOc2ccc(/C=C/c3ccc(N(C)C(=O)OC(C)(C)C)cc3)cc2)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CNc1ccc(/C=C/c2ccc(OCCOCCOCCOS(=O)(=O)c3ccc(C)cc3)cc2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 50.2 %

Procedure:
200 mg 2-[2-(2-{4-[(E)-2-{4-[(tert-butoxycarbonyl)(methyl)amino]phenyl}-vinyl]phenoxy}ethoxy)ethoxy]ethyl 4-methylbenzenesulfonate (2c) were dissolved in 2.5 mL dichloromethane. 250 μL trifluoroacetic acid were added and the mixture was stirred for 4 h at room temperature. The solvent was removed under reduced pressure. The crude product was dissolved in dichlormethane (5 mL) and washed with sodium carbonate solution (10%, 2×2 mL). The organic layer was dried over sodium sulfate, the solvent was removed under reduced pressure and the residue was purified by flash chromatography (silica, 12-100% ethyl acetate in hexane). 84 mg 2d were obtained as light red solid.
Reaction SMILES: [C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[OH-:9].[Na+]>>[C:1]([OH:8])(=[O:7])[C@H:2]([CH2:3][C:4]([OH:6])=[O:5])[OH:9]
Reactant: [OH-]
Reactant: O=C(O)/C=C/C(=O)O
Agent: [Na+]
Product: O=C(O)C[C@H](O)C(=O)O

Procedure:
For the purpose of examination as to fumarase activity, the bacterial cells were suspended in 100 ml of a 1.0 M aqueous solution of fumaric acid having a pH adjusted to 7.0 by NaOH and were reacted at 45° C. for 2 hours and the L-malic acid thereby formed was reacted with 2,7-naphthalenediol in the presence of sulfuric acid. The amount of the L-malic acid was determined by the color which it had developed. The amount of the succinic acid which had been formed was determined by high pressure liquid chromatography.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.Br[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:22]([O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH3:11]
Reactant: CCCCCCCCCCCCBr
Reactant: O=Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCOc1ccc(C=O)cc1
Temperature: 65 °C
Reaction time: 18 h
Yield: 99.8 %

Procedure:
4-Hydroxybenzaldehyde (673 mg, 5.5 mmol), 1-bromododecane (1.25 g, 5 mmol) and potassium carbonate (859 mg, 6.22 mmol) were added to dimethylformamide (3 ml), and they were stirred at 65° C. for 18 hours. After the completion of the reaction followed by the extraction with ethyl acetate, 4-dodecyloxybenzaldehyde (yield: 1.45 g, 99%) was obtained in the form of white crystals.