Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]([C:14]2[O:15][C:16](Br)=[CH:17][CH:18]=2)=[O:13])[CH:6]=1.[O:21]1[CH:25]=[CH:24][CH:23]=[C:22]1B(O)O>>[CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]([C:14]2[O:15][C:16]([C:22]3[O:21][CH:25]=[CH:24][CH:23]=3)=[CH:17][CH:18]=2)=[O:13])[CH:6]=1
Reactant: COC(=O)Cc1cccc(NC(=O)c2ccc(Br)o2)c1
Reactant: OB(O)c1ccco1
Product: COC(=O)Cc1cccc(NC(=O)c2ccc(-c3ccco3)o2)c1

Procedure:
Methyl ester (16) (100 mg, 0.30 mmol) was coupled to furan-2-boronic acid (37 mg, 0.33 mmol) using Method E. The crude compound was purified by column chromatography, eluting in 17% EtOAc in heptane to give the title compound.
Reaction SMILES: Br[CH:2]1[CH2:11][CH2:10][C:9]2[C:8]([O:12][CH2:13][C:14]([O:16]CC)=[O:15])=[CH:7][CH:6]=[CH:5][C:4]=2[C:3]1=O.[C:20]([NH2:28])(=[S:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[C:21]1([C:20]2[S:27][C:2]3[CH2:11][CH2:10][C:9]4[C:4](=[CH:5][CH:6]=[CH:7][C:8]=4[O:12][CH2:13][C:14]([OH:16])=[O:15])[C:3]=3[N:28]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: NC(=S)c1ccccc1
Reactant: CCOC(=O)COc1cccc2c1CCC(Br)C2=O
Product: O=C(O)COc1cccc2c1CCc1sc(-c3ccccc3)nc1-2
Yield: 27 %

Procedure:
Using ethyl [(6-bromo-5,6,7,8-tetrahydro-5-oxo-1-naphthalenyl)oxy]acetate and thiobenzamide, the procedure of Example 52 was otherwise repeated to synthesize the title compound. Yield 27%.
Reaction SMILES: [CH3:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=O.[NH3:12].O>C(O)COCCO>[CH3:1][C@:2]12[CH2:10][C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C@H:3]1[NH:12][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:9]=12
Reactant: CC1Cc2ccccc2C1=O
Reactant: N
Solvent: O
Solvent: OCCOCCO
Product: C[C@]12Cc3ccccc3[C@H]1Nc1ccccc12
Reaction time: 8 h

Procedure:
The phenylhydrazone of 2-methyl-1-indanone (1.44 g, 6.1 mmol) was heated in diethylene glycol (20 cm3) to near its reflux temperature, until ammonia started to evolve from the air condenser. Heating was continued overnight, or until the ammonia ceased to evolve. The solution was cooled, poured into an equal volume of water, and extracted into diethylether. The ethereal solution was back-extracted with 2M hydrochloric acid, which was made basic with sodium hydroxide, and re-extracted with diethylether. The extracts were evaporated and the residue was purified by column chromatography using silica eluating with 5% EtOAc petrol to yield the title compound as a colourless solid (Rf 30% EtOAc/petrol 0.8). Yield: (28%). M.p. 72° C. 1H NMR (CDCl3) δ: 1.46 (3H, s,), 3.10 (1H, d), 3.30 (1H, dd,), 4.05 (1H, s,), 4.69 (1H, s,), 6.52 (1H, dd,), 6.71 (1H, ddd,), 6.95 (1H, ddd,), 7.0-7.2 (5H, m,).
Reaction SMILES: [C:1]12([NH:11][C:12]3[CH:17]=[C:16](Cl)[N:15]=[CH:14][N:13]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH3:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]12([NH:11][C:12]3[CH:17]=[C:16]([NH:27][C:24]4[CH:25]=[CH:26][C:21]([O:20][CH3:19])=[CH:22][CH:23]=4)[N:15]=[CH:14][N:13]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2
Reactant: COc1ccc(N)cc1
Reactant: Clc1cc(NC23CC4CC(CC(C4)C2)C3)ncn1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: Cc1ccccc1
Product: COc1ccc(Nc2cc(NC34CC5CC(CC(C5)C3)C4)ncn2)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 65 %

Procedure:
100 mg of N-adamant-1-yl-6-chloropyrimidin-4-amine, 56 mg of p-anisidine, 73 mg of Na-butylate, 2.2 mg of Pd(OAc)2 and 12 mg of BINAP were taken in a screw cap vial under agron in 4 mL of dry toluene and the vial was kept in a heating block at 150° C. for 12 hours. The mixture obtained was cooled to r.t. and purification was carried out by column chromatography using PE:EtOAc 2:1. N4-Adamant-1-yl-N6-(4-methoxyphenyl)pyrimidine-4,6-diamine was obtained.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:26])[NH:11][C:12]([C:14]2[CH:25]=[CH:24][C:17]([O:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])=[CH:16][CH:15]=2)=[O:13])=[CH:5][CH:4]=1)#[N:2].N1C=CC=CC=1.[SH2:33]>C(N(CC)CC)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10](=[O:26])[NH:11][C:12]([C:14]2[CH:25]=[CH:24][C:17]([O:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])=[CH:16][CH:15]=2)=[O:13])=[CH:7][CH:8]=1)(=[S:33])[NH2:2]
Reactant: COC(=O)COc1ccc(C(=O)NC(=O)Nc2ccc(C#N)cc2)cc1
Reactant: S
Solvent: CCN(CC)CC
Solvent: c1ccncc1
Product: COC(=O)COc1ccc(C(=O)NC(=O)Nc2ccc(C(N)=S)cc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of the product of step (a) (600 mg), pyridine (56 ml) and triethylamine (8 ml) was covered with a blanket of H2S gas and stirred at ambient temperature overnight. The dark green reaction mixture was evaporated to dryness and the residue was stirred with dry ether for 1 hour. The resultant solid was collected and washed thoroughly with ether to give methyl 4-[4-(4-thiocarbamoylphenyl)allophanoyl]phenoxyacetate (593 mg) as a yellow solid; m.p. 215°-218° C. (decomposes); NMR Spectrum (DMSO-d6 +CD3CO2D) 3.73 (3H, s), 4.90 (2H, s), 7.08 (2H, d), 7.64 (2H, d), 7.98 (2H, d), 8.06 (2H, d); Mass Spectrum m/Z 388 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](Cl)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].N1C=CC=CC=1.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27]2[CH:32]=[C:31]([CH3:33])[N:30]=[C:29]([NH2:34])[N:28]=2)=[CH:22][CH:21]=1.N>O1CCOCC1>[NH2:34][C:29]1[N:28]=[C:27]([NH:26][C:23]2[CH:24]=[CH:25][C:20]([NH:19][C:8](=[O:9])[C:7]3[CH:11]=[CH:12][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)=[CH:21][CH:22]=2)[CH:32]=[C:31]([CH3:33])[N:30]=1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Reactant: Cc1cc(Nc2ccc(N)cc2)nc(N)n1
Agent: N
Solvent: C1COCCO1
Solvent: c1ccncc1
Product: Cc1cc(Nc2ccc(NC(=O)c3ccc([N+](=O)[O-])cc3)cc2)nc(N)n1
Temperature: 50 °C
Yield: 46.7 %

Procedure:
4-Nitrobenzoyl chloride (11.00 g, 0.06 mol) and dry pyridine (9.08 mL, 0.11 mol) were sequentially added to a solution of amine E3 (4.85 g, 0.02 mol) in dry dioxane (200 mL), and the resulting solution heated at ˜50° C. for 5 d. After this time, the reaction mixture was cooled to room temperature, and then basified by addition of aqueous ammonia solution. The resulting suspension was filtered through a pad of Celite to afford amide E4 as an amorphous yellow solid (3.40 g, 41%). 1H NMR [(CD3)2SO]: 2.09 [s, 3H, ArCH3], 5.87 [s, 1H, ArNHAr], 6.08 [br s, 6.08, ArNH2], 7.68 [m, 4H, ArH], 8.18 [d, J=8.80 Hz, 2H, ArH], 8.36 [d, J=8.80 Hz, 2H, ArH], 8.95 [s, 1H, ArH], 10.45 [s, 1H, ArC(O)NHAr]. LCMS (APCI+): 365 (100%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][CH2:12][C:13]2[C:14]([NH2:21])=[N:15][C:16]([S:19][CH3:20])=[N:17][CH:18]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[H-].[Na+].[C:24](N1C=CN=C1)(N1C=CN=C1)=[O:25]>CN(C)C=O>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([N:11]2[CH2:12][C:13]3[C:14](=[N:15][C:16]([S:19][CH3:20])=[N:17][CH:18]=3)[NH:21][C:24]2=[O:25])[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1
Reactant: COc1cc(NCc2cnc(SC)nc2N)cc(OC)c1
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cc(OC)cc(N2Cc3cnc(SC)nc3NC2=O)c1
Reaction time: 1 h
Yield: 59.8 %

Procedure:
Into a solution of 5.0 g (16.3 mmol) of 5-[(3,5-dimethoxy-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-ylamine in 55 mL of dimethylformamide cooled to 5° C., was added 1.63 g (40.8 mmol) of sodium hydride as a 60% mineral oil suspension. The ice bath was removed, and the reaction was stirred for 1 hour. To the reaction was then added 7.94 g (48.9 mmol) of 1,1′-carbonyldiimidazole. After stirring the mixture a further 2.5 hours, the mixture was concentrated in vacuo. The residue was partitioned between dichloromethane and a saturated solution of ammonium chloride. The dichloromethane layer was washed twice with each of saturated ammonium chloride, water, and a saturated solution of sodium chloride. The dichloromethane solution was dried over magnesium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel, eluting with chloroform/methanol (10:0.25 v/v), to give 3.24 g (60%) of the title compound.
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:12])[NH:9]2)=[N:4][CH:3]=1.[H-].[Na+].[CH2:15](I)[CH:16]=[CH2:17].O>CN(C=O)C>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:12])[N:9]2[CH2:17][CH:16]=[CH2:15])=[N:4][CH:3]=1
Reactant: O=c1ccc2ncc(F)cc2[nH]1
Reactant: C=CCI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: C=CCn1c(=O)ccc2ncc(F)cc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 63 %

Procedure:
7-Fluoro-1,5-naphthyridin-2(1H)-one (2.152 g, 13.122 mmol) was suspended in dry DMF (40 ml) under argon at 0° C., and the stirred suspension was treated with sodium hydride (1.155 g of a 60% w:w dispersion in oil, 2.2 eq.) added in portions. The suspension was allowed to warm to rt. After stirring for 30 mins at rt, the mixture was treated with allyl iodide (2.67 ml, 2.2 eq) and then stirred for a further 30 min before addition of water (100 ml). The mixture was then extracted with DCM (3×200 ml). The organic extracts were combined, dried over anhydrous magnesium sulphate, filtered and evaporated to give a residue which was purified by column chromatography on silica with a 0-10% methanol in DCM gradient to give the desired product as a light brown solid (1.683 g, 63%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])/[C:7](=[CH:10]/[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH3:19])=[CH:13][CH:12]=2)/[S:6][C:5]1=[O:20].[CH3:21][S:22](Cl)(=[O:24])=[O:23].CCN(C(C)C)C(C)C.C(OC1C=CC(/C=C2/C(=O)N(CCNC(=O)C)C(=O)S/2)=CC=1)C>>[CH2:18]([O:17][C:14]1[CH:15]=[CH:16][C:11](/[CH:10]=[C:7]2/[C:8](=[O:9])[N:4]([CH2:3][CH2:2][NH:1][S:22]([CH3:21])(=[O:24])=[O:23])[C:5](=[O:20])[S:6]/2)=[CH:12][CH:13]=1)[CH3:19]
Reactant: CS(=O)(=O)Cl
Reactant: CCOc1ccc(/C=C2\SC(=O)N(CCN)C2=O)cc1
Agent: CCOc1ccc(/C=C2\SC(=O)N(CCNC(C)=O)C2=O)cc1
Solvent: CCN(C(C)C)C(C)C
Product: CCOc1ccc(/C=C2\SC(=O)N(CCNS(C)(=O)=O)C2=O)cc1

Procedure:
The title compound 27a was prepared from compound 76 (101 mg, 0.25 mmol), methylsulfonyl chloride (21 μL, 028 mmol) and DIPEA (131 μL, 0.75 mmol) in a manner similar to that described for 25a in 96.2% (89 mg) yield as a yellow solid.
Reaction SMILES: CO.[Na].[C:4]1([CH:11]=[CH:10][CH:9]=[C:7]([OH:8])[CH:6]=1)[OH:5].[F:12][C:13]([F:29])([F:28])[C:14]1[CH:15]=[C:16]([CH:25]=[CH:26][CH:27]=1)OC1C=C(Br)C=CC=1>N1C=CC=CC=1>[F:12][C:13]([F:29])([F:28])[C:14]1[CH:27]=[C:26]([CH:25]=[CH:16][CH:15]=1)[O:5][C:4]1[CH:6]=[C:7]([OH:8])[CH:9]=[CH:10][CH:11]=1
Reactant: Oc1cccc(O)c1
Reactant: FC(F)(F)c1cccc(Oc2cccc(Br)c2)c1
Agent: [Na]
Solvent: c1ccncc1
Solvent: CO
Product: Oc1cccc(Oc2cccc(C(F)(F)F)c2)c1
Yield: 67.9 %

Procedure:
All apparatus is rigorously dried and flushed with nitrogen before use. The reaction is performed in a 500 mL 3-necked flask equipped with a mechanical stirrer, a reflux condenser topped with a nitrogen inlet tube and a stopper. The flask is charged with methanol (100 mL) and sodium (10.0 g, 0.43 mol). After all of the sodium has been consumed the methanol is distilled from the flask, and the last traces are removed by azeotropic distillation with benzene. Pyridine (250 mL) and resorcinol (35.0 g, 0.32 mol) are added to the reaction mixture, followed by 3-(3-trifluoromethyl phenoxy)bromobenzene (50.0 g, 0.22 mol) and cuprous chloride (20.0 g, 0.20 mol), and the mixture is left to stir at reflux for 24 hours. Capillary GC analysis shows that ca. 87% of the mixture is the desired monoalkylation product, the rest being dialkylation product. The mixture is cooled and filtered with the aid of ether (200 mL). The ethereal phase is washed successively with water (250 mL), 5% HCl (2×250 mL), saturated NaHCO3 (200 mL) and brine (200 mL). Then it is dried with MgSO4, and the solvents are removed on the rotary evaporator to leave 38 g of a dark oily residue. Purification is accomplished by fractional distillation in vacuo. The second fraction (distilling at 132° C. @ 1.5 mm) consisted of pure monoalkylation product (colorless oil, 25.20 g, 44.6% yield). The dialkylation product is not isolated.
Reaction SMILES: C(OC([NH:11][C@H:12]([C:24]([NH:26][C@H:27]([C:34]([NH:36][C@H:37]([CH2:42][OH:43])[CH2:38][CH:39]([CH3:41])[CH3:40])=[O:35])[CH2:28][C:29]1[N:33]=[CH:32][NH:31][CH:30]=1)=[O:25])[CH2:13][C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][CH:15]=1)=O)C1C=CC=CC=1.[BrH:44].C(O)(=O)C>C(OCC)C>[BrH:44].[BrH:44].[C:14]1([CH2:13][C@@H:12]([C:24]([NH:26][C@H:27]([C:34]([NH:36][C@H:37]([CH2:42][OH:43])[CH2:38][CH:39]([CH3:40])[CH3:41])=[O:35])[CH2:28][C:29]2[N:33]=[CH:32][NH:31][CH:30]=2)=[O:25])[NH2:11])[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][CH:15]=1
Reactant: CC(C)C[C@@H](CO)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1cccc2ccccc12)NC(=O)OCc1ccccc1
Agent: Br
Solvent: CCOCC
Solvent: CC(=O)O
Product: CC(C)C[C@@H](CO)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](N)Cc1cccc2ccccc12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To 0.59 g. (1 mmole) of N-benzyloxycarbonyl-3-(1-naphthyl)-L-alanyl-L-histidyl-L-leucinol (prepared as described in Example 9) were added 10 ml. of a 25% w/v hydrogen bromide/acetic acid solution. The mixture was stirred at room temperature for 30 minutes, after which there were added 100 ml. of anhydrous diethyl ether. The white precipitate thus formed was separated by filtration, thoroughly washed with diethyl ether and dried in a desiccator. There was obtained 0.52 g. of the desired compound as a white powdery solid, melting at 155°-159° C.; [α]24 +21.0° (C=0.5, methanol).
Reaction SMILES: [O:1]([C:8]1[C:16]([S:17](=[O:20])(=[O:19])[NH2:18])=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]=1[S:21][CH2:22][C:23]1[CH:27]=[CH:26][S:25][CH:24]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:28](SC1C=C(C=C(S(=O)(=O)N)C=1OC1C=CC=CC=1)C(O)=O)CCC>>[O:1]([C:8]1[C:16]([S:17](=[O:20])(=[O:19])[NH2:18])=[CH:15][C:11]([C:12]([O:14][CH3:28])=[O:13])=[CH:10][C:9]=1[S:21][CH2:22][C:23]1[CH:27]=[CH:26][S:25][CH:24]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NS(=O)(=O)c1cc(C(=O)O)cc(SCc2ccsc2)c1Oc1ccccc1
Reactant: CCCCSc1cc(C(=O)O)cc(S(N)(=O)=O)c1Oc1ccccc1
Product: COC(=O)c1cc(SCc2ccsc2)c(Oc2ccccc2)c(S(N)(=O)=O)c1

Procedure:
By replacing in Example 47 4-phenoxy-5-sulfamyl-3-(3-thienylmethylthio)benzoic acid for 3-n-butylthio-4-phenoxy-5-sulfamylbenzoic acid and following the procedure described, methyl 4-phenoxy-5-sulfamyl-3-(3-thienylmethylthio)benzoate is obtained with a melting point of 148°-149°C.
Reaction SMILES: [H-].[Na+].[C:3]([O:22][CH2:23][CH:24]([CH2:26][OH:27])[OH:25])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44]>CN(C)C=O>[CH2:29]([O:27][CH2:26][CH:24]([CH2:23][O:22][C:3]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)[O:25][CH2:44][CH2:43][CH2:42][CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH3:29])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44]
Reactant: OCC(O)COC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CCCCCCCCCCCCCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCCOCC(COC(c1ccccc1)(c1ccccc1)c1ccccc1)OCCCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 12 h
Yield: 68.3 %

Procedure:
1H-nmr (200 MHz, CDCl3), 3.21 (2H, m), 3.65 (2H, m), 3.85 (1H, m), 7.4 (15H, m). ##STR17## Sodium hydride (prewashed with hexane, 60% oil dispersion, 0.79 g, 32.89 mmol) was stirred in dry dimethyl formamide (50 ml) under a stream of nitrogen. 1-trityl glycerol (5.0 g, 14.95 mmol) in dry dimethyl formamide (50 ml) was added carefully. The reaction was stirred at room temperature for 30 minutes before 1-bromohexadecane (9.13 g, 29.90 mmol) was added and the reaction was stirred at room temperature under a nitrogen atmosphere for 12 hours. The reaction mixture was carefully partitioned between dichloromethane (100 ml) and water (100 ml×3). The organic layer was washed successively with saturated NaHCO3 (100 ml) and brine (100 ml), dried over sodium sulphate and evaporated to yield the crude product, which was purified by column chromatography eluting with (40-60) light petroleum: ethyl acetate (230:20). Fractions containing product were evaporated to dryness to give 1,2-dihexadecyl-3-trityl glycerol (8.00 g, 10.21 mmol) 68% yield
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]2[S:13][C:12](=[O:14])[NH:11][C:10]2=[O:15])=[CH:4][CH:3]=1.Cl[CH2:17][C:18]1[CH:19]=[C:20]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:21]=[CH:22][CH:23]=1.[H-].[Na+].O>CS(C)=O>[C:20]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:21]=[CH:22][CH:23]=[C:18]([CH2:17][O:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:8][CH:9]3[S:13][C:12](=[O:14])[NH:11][C:10]3=[O:15])=[CH:6][CH:7]=2)[CH:19]=1
Reactant: ClCc1cccc(-c2ccccc2)c1
Reactant: O=C1NC(=O)C(Cc2ccc(O)cc2)S1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: O=C1NC(=O)C(Cc2ccc(OCc3cccc(-c4ccccc4)c3)cc2)S1
Temperature: 50 °C
Reaction time: 1 h
Yield: 256.8 %

Procedure:
To a solution of 5-[(4-hydroxyphenyl)methyl]-2,4-thiazolidinedione (0.30 g, 1.3 mmol) in dimethyl sulfoxide (20 mL) were added 3-(chloromethyl)biphenyl (0.26 g, 1.3 mmol) and 60% sodium hydride (0.11 g, 2.6 mmol), and the mixture was stirred at room temperature for 1 hr and further at 50° C. for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=8:2) to give the title compound (1.3 g, yield 96%).
Reaction SMILES: [OH-].[Na+].[C:3](OC([O-])=O)([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].O1CCCC1.[CH2:19]([NH:22][CH2:23][C@H:24]([NH:26][S:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[N+:36]([O-:38])=[O:37])(=[O:29])=[O:28])[CH3:25])[CH:20]=[CH2:21]>O>[CH2:19]([N:22]([C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])[CH2:23][C@H:24]([NH:26][S:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[N+:36]([O-:38])=[O:37])(=[O:29])=[O:28])[CH3:25])[CH:20]=[CH2:21]
Reactant: CC(C)(C)OC(=O)OC(=O)[O-]
Reactant: C=CCNC[C@@H](C)NS(=O)(=O)c1ccccc1[N+](=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: C=CCN(C[C@@H](C)NS(=O)(=O)c1ccccc1[N+](=O)[O-])C(=O)OC(C)(C)C
Temperature: 25 °C
Yield: 85.6 %

Procedure:
A 2N aqueous NaOH solution (50 mL) and 6.1 g of tert-butyl dicarbonate were added to a tetrahydrofuran (100 mL) solution of 7 g of the compound obtained in Step 1, stirring at room temperature and reacted at room temperature for 6 hours. After the completion of reaction, 100 mL of water was added, followed by two extractions with 100 mL of ethyl acetate. The combined organic layer was washed with 100 mL of saturated saline and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the obtained crude product was purified by silica gel column chromatography (ethyl acetate:hexane=1:2) to obtain 8 g of the compound of interest as a yellow oil (86%).
Reaction SMILES: [Cl:1]Cl.[C:3]([C:7]1[CH:8]=[C:9]([CH:12]=[CH:13][C:14]=1[OH:15])[CH:10]=[O:11])([CH3:6])([CH3:5])[CH3:4].O>C(O)(=O)C>[C:3]([C:7]1[CH:8]=[C:9]([CH:12]=[C:13]([Cl:1])[C:14]=1[OH:15])[CH:10]=[O:11])([CH3:6])([CH3:4])[CH3:5]
Reactant: CC(C)(C)c1cc(C=O)ccc1O
Reactant: ClCl
Solvent: O
Solvent: CC(=O)O
Product: CC(C)(C)c1cc(C=O)cc(Cl)c1O

Procedure:
Chlorine gas was passed into a solution of 3-tert-butyl-4-hydroxybenzaldehyde (2.5 gm) in acetic acid (20 ml) for 1 hour. The solution was poured into water and the product collected. Recrystallisation from aqueous ethanol gave 3-tert-butyl-5-chloro-4-hydroxybenzaldehyde m.p. 123° C.