Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I-].[Na+].[C:3]([NH:6][CH2:7][CH2:8][NH:9][C:10]1[N:15]=[C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:13]=[C:12]([NH:22][C:23](=[O:26])[CH2:24]Cl)[CH:11]=1)(=[O:5])[CH3:4].[Cl:27][C:28]1[CH:40]=[CH:39][CH:38]=[CH:37][C:29]=1[O:30][CH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.CCN(C(C)C)C(C)C>C1COCC1.C(#N)C>[C:3]([NH:6][CH2:7][CH2:8][NH:9][C:10]1[N:15]=[C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:13]=[C:12]([NH:22][C:23](=[O:26])[CH2:24][N:34]2[CH2:33][CH2:32][CH:31]([O:30][C:29]3[CH:37]=[CH:38][CH:39]=[CH:40][C:28]=3[Cl:27])[CH2:36][CH2:35]2)[CH:11]=1)(=[O:5])[CH3:4]
Reactant: CC(=O)NCCNc1cc(NC(=O)CCl)nc(-c2ccccc2)n1
Reactant: Clc1ccccc1OC1CCNCC1
Agent: [I-]
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Solvent: CC#N
Product: CC(=O)NCCNc1cc(NC(=O)CN2CCC(Oc3ccccc3Cl)CC2)nc(-c2ccccc2)n1

Procedure:
Sodium iodide (19 mg; 0.13 mmol) was added to a solution of chloroacetamide 6 (40 mg; 0.12 mmol), piperidine 7.6 (31 mg; 0.15 mmol) and DIPEA (30 μL; 0.17 mmol) in 3:1 acetonitrile:THF (2 mL). After 22 h the reaction was filtered through a short plug of silica gel with THF as a wash. The solution was concentrated in vacuo then purified on silica gel (20 mL) with 10:1 EtOAc:i-PrOH yielding a hard white foam (59.2 mg; 98%). LC (method B) tR=12.9 min; 1H NMR (200 MHz, CDCl3) δ 9.51 (s, 1H), 8.37 (m, 2H), 7.47 (m, 3H), 7.38 (m, 1H), 7.31-7.14 (m, 2H), 7.02-6.86 (m, 2H), 6.72 (brs, 1H), 5.69 (brt, J=5.6 Hz, 1H), 4.48 (m, 1H), 3.67 (m, 2H), 3.53 (m, 2H), 3.19 (s, 2H), 2.90 (m, 2H), 2.56 (m, 2H), 2.20-2.00 (m, 4H), 1.86 (s, 3H). ESIMS 523.0/525.0 (100/42) [MH+], 262 (58), 198 (75).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].[OH-].[K+].[O:17]1[CH2:22][CH2:21][CH:20]([CH2:23][OH:24])[CH2:19][CH2:18]1>CS(C)=O>[O:17]1[CH2:22][CH2:21][CH:20]([CH2:23][O:24][C:2]2[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][C:3]=2[C:11]([F:14])([F:13])[F:12])[CH2:19][CH2:18]1
Reactant: OCC1CCOCC1
Reactant: O=C(O)c1ccc(C(F)(F)F)c(Cl)n1
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Product: O=C(O)c1ccc(C(F)(F)F)c(OCC2CCOCC2)n1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 86.4 %

Procedure:
6-Chloro-5-(trifluoromethyl)picolinic acid (330 mg, 1.46 mmol) and powdered potassium hydroxide (328 mg, 5.85 mmol) were dissolved in DMSO (9 mL). The solution was stirred for 15 min. at ambient temperature. (Tetrahydro-2H-pyran-4-yl)methanol (170 mg, 170 μL, 1.46 mmol; CAN 14774-37-9) was added. The mixture was stirred for 1 d at ambient temp., poured onto ice water/brine/1N HCl (75 mL) and extracted with EtOAc (2×150 mL). The combined extracts were washed with ice water/brine (75 mL), dried over Na2SO4. The solvent was removed under reduced pressure to give the title compound as a grey solid (385 mg, 86%) which was used in the next step without further purification. MS: 304.0 [M−H]−.
Reaction SMILES: [CH3:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][CH:5]=[C:4]([CH3:11])[C:3]=1[Br:12]>C(O)(=O)C.C(O)C.[Fe]>[CH3:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[C:4]([CH3:11])[C:3]=1[Br:12]
Reactant: Cc1ccc([N+](=O)[O-])c(C)c1Br
Agent: [Fe]
Solvent: CCO
Solvent: CC(=O)O
Product: Cc1ccc(N)c(C)c1Br

Procedure:
2,6-Dimethyl-3-nitrobromo benzene (5.7 g, 0.025 mol) was dissolved in acetic acid (60 mL) and ethanol (60 mL). To this was added iron powder (5.6 g, 0.01 mol) in small portions and after the addition, it was refluxed for 2-3 h under nitrogen. An additional 2.8 g of iron powder was added and again refluxed for another 2 h. The mixture was filtered through celite and concentrated in vacuo. The residue was neutralized with sodium carbonate solution and repeatedly extracted (×3) with boiling ethyl acetate (50 mL each). Ethyl acetate was concentrated after drying over sodium sulfate to give a brown solid which was purified by chromatography on silica gel using 4% ethyl acetate in hexane to give a pale yellow solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][N:17]3[C:21]4[CH2:22][CH2:23][CH2:24][N:25]([CH3:29])[S:26](=[O:28])(=[O:27])[C:20]=4[CH:19]=[CH:18]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl.[NH2:31][OH:32].C([O-])(=O)C.[Na+]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][CH2:16][N:17]3[C:21]4[C:22](=[N:31][OH:32])[CH2:23][CH2:24][N:25]([CH3:29])[S:26](=[O:28])(=[O:27])[C:20]=4[CH:19]=[CH:18]3)[CH2:12][CH2:13]2)=[CH:6][CH:7]=1
Reactant: CN1CCCc2c(ccn2CCCN2CCN(c3ccc(F)cc3)CC2)S1(=O)=O
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CN1CCC(=NO)c2c(ccn2CCCN2CCN(c3ccc(F)cc3)CC2)S1(=O)=O
Yield: 66.2 %

Procedure:
A suspension of 174 mg (0.4 mmol) of Compound 26, 56 mg (0.8 mmol) of hydroxylamine hydrochloride and 66 mg (0.8 mmol) of sodium acetate in 20 ml of methanol was refluxed for 17 hours. Post-treatment and purification were conducted in a similar manner as in Example 20, whereby 119 mg of the title compound were obtained (yield: 66%).
Reaction SMILES: C1(O[C:8](=[O:22])[NH:9][C:10]2[C:11]([O:20][CH3:21])=[N:12][C:13]([CH3:19])=[C:14]([CH:16]([CH3:18])[CH3:17])[CH:15]=2)C=CC=CC=1.[Cl:23][C:24]1[CH:25]=[C:26]([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH:27]=[CH:28][CH:29]=1>>[CH:16]([C:14]1[CH:15]=[C:10]([NH:9][C:8]([N:33]2[CH2:32][CH2:31][N:30]([C:26]3[CH:27]=[CH:28][CH:29]=[C:24]([Cl:23])[CH:25]=3)[CH2:35][CH2:34]2)=[O:22])[C:11]([O:20][CH3:21])=[N:12][C:13]=1[CH3:19])([CH3:17])[CH3:18]
Reactant: Clc1cccc(N2CCNCC2)c1
Reactant: COc1nc(C)c(C(C)C)cc1NC(=O)Oc1ccccc1
Product: COc1nc(C)c(C(C)C)cc1NC(=O)N1CCN(c2cccc(Cl)c2)CC1
Yield: 63 %

Procedure:
Phenyl-N-(5-isopropyl-2-methoxy-6-methylpyridine-3-yl)carbamate and 1-(3-chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound.
Reaction SMILES: N1C=CN=C1.[Br:6][C:7]1[CH:8]=[C:9]([CH:12]=[C:13]([Br:15])[CH:14]=1)[CH2:10][OH:11].[Si:16](Cl)([C:29]([CH3:32])([CH3:31])[CH3:30])([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C=O)C.C(OCC)(=O)C>[C:29]([Si:16]([O:11][CH2:10][C:9]1[CH:8]=[C:7]([Br:6])[CH:14]=[C:13]([Br:15])[CH:12]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)([CH3:32])([CH3:30])[CH3:31]
Reactant: OCc1cc(Br)cc(Br)c1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](OCc1cc(Br)cc(Br)c1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Yield: 94.4 %

Procedure:
With stirring, imidazole (1.1 g, 16.0 mmol) is added to a solution of 3,5-dibromobenzyl alcohol (2.8 g, 10.5 mmol) in absolute DMF (20 ml), and the mixture is cooled to 0° C. tert-Butyldiphenylsilyl chloride (3.3 ml, 17.8 mmol) is added dropwise to the reaction solution, which is then stirred at 0° C. for 2 h. The mixture is then warmed to RT and stirred for another 2 h. The reaction mixture is diluted with ethyl acetate (20 ml) and extracted with a semisaturated aqueous NH4Cl solution (20 ml). The organic phase is dried over MgSO4, filtered off and concentrated under reduced pressure. Further purification is carried out by chromatography [PE/EA (99:1)] on a silica gel column. This gives the title compound (5.0 g) as a colorless solid. TLC, silica gel (glass plates), [petroleum ether/ethyl acetate (99:1)], Rf=0.8.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[C:11]1[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([Cl:20])[CH:18]=3)[NH:13][C:12]1=[O:21])[O:6][CH2:5]2.C(N(CC)C(C)C)(C)C.[C:31](Cl)(=[O:33])[CH3:32]>C1COCC1>[Cl:20][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12](=[O:21])[C:11]2=[C:7]1[C:8]2[C:4](=[CH:3][C:2]([NH:1][C:31](=[O:33])[CH3:32])=[CH:10][CH:9]=2)[CH2:5][O:6]1
Reactant: Nc1ccc2c(c1)COC2=C1C(=O)Nc2ccc(Cl)cc21
Reactant: CC(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)Nc1ccc2c(c1)COC2=C1C(=O)Nc2ccc(Cl)cc21
Temperature: 25 °C
Reaction time: 3 h
Yield: 86.8 %

Procedure:
To a solution of 3-(5-Amino-3H-isobenzofuran-1-ylidene)-5-chloro-1,3-dihydro-indol-2-one (56.5 mg, 0.189 mmol) and N,N-diisopropylethylamine (98.8 μL, 0.567 mmol) in 2.5 mL THF was added acetyl chloride (13.4 μL, 0.189 mmol). After stirring at room temperature for 3 h, the mixture was concentrated in vacuo and the solid triturated with MeOH. Filtering the mixture and rinsing with MeOH and hexanes/EtOAc (7:3) afforded the title compound (55.9 mg, 87%) as a yellow solid.
Reaction SMILES: [CH3:1][NH2:2].[CH2:3]([O:7][C:8]1[C:13]([CH:14]=O)=[CH:12][C:11]([C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)=[C:10]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[N:9]=1)[CH2:4][CH2:5][CH3:6].Cl>CO>[CH2:3]([O:7][C:8]1[C:13]([CH2:14][NH:2][CH3:1])=[CH:12][C:11]([C:16]2[CH:17]=[CH:18][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][CH:21]=2)=[C:10]([C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)[N:9]=1)[CH2:4][CH2:5][CH3:6]
Reactant: CCCCOc1nc(-c2ccc(F)cc2)c(-c2ccc(S(C)(=O)=O)cc2)cc1C=O
Reactant: CN
Agent: Cl
Solvent: CO
Product: CCCCOc1nc(-c2ccc(F)cc2)c(-c2ccc(S(C)(=O)=O)cc2)cc1CNC
Reaction time: 4 h

Procedure:
Methylamine (2.0M in methanol, 1 ml) was added to a stirring mixture of 2-butoxy-6-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]pyridine-3-carboxaldehyde [Example 30] (150 mg, 0.35 mMol) and molecular sieves (3A, 1.0 g) in 50 ml methanol. After stirring for 4 hours, the mixture was cooled by an ice bath and 5 ml 5% HCl was added. The mixture was concentrated to an oil containing the molecular sieves. Water (50 ml) and 5 ml 5% NaHCO3 were added and the product was extracted into ethyl acetate (2×50 ml). The ethyl acetate extracts were combined, dried over Na2SO4, filtered and concentrated to a solid. The titled material was purified by silica gel chromatography to give a solid: m.p. (DSC) 113.98° C. Anal. Calc'd. C24H27N2O3SF: C, 65.14; H. 6.15; N, 6.33. Found: C, 64.81; H, 6.15; N, 6.17.
Reaction SMILES: [F:1][C:2]([F:36])([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][N:30]=1)[C:3]1[N:12]=[C:11]([NH:13][C:14]2[CH:18]=[C:17]([CH3:19])[N:16](C(OC(C)(C)C)=O)[N:15]=2)[C:10]2[C:5](=[CH:6][C:7]([O:27][CH3:28])=[CH:8][CH:9]=2)[N:4]=1.C(O)(C(F)(F)F)=O.C(Cl)Cl>>[F:36][C:2]([F:1])([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][N:30]=1)[C:3]1[N:12]=[C:11]([NH:13][C:14]2[CH:18]=[C:17]([CH3:19])[NH:16][N:15]=2)[C:10]2[C:5](=[CH:6][C:7]([O:27][CH3:28])=[CH:8][CH:9]=2)[N:4]=1
Reactant: COc1ccc2c(Nc3cc(C)n(C(=O)OC(C)(C)C)n3)nc(C(F)(F)c3ccc(F)cn3)nc2c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc2c(Nc3cc(C)[nH]n3)nc(C(F)(F)c3ccc(F)cn3)nc2c1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 41.2 %

Procedure:
To tert-Butyl 3-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazolin-4-ylamino)-5-methyl-1H-pyrazole-1-carboxylate (100 mg, 0.20 mmol) was added 20% TFA/DCM, and the mixture was stirred at rt for 2.5 h. The mixture was concentrated and the residue was purified by preparative reverse-phase HPLC (TFA as a modifier). The fractions containing the desired product were neutralized with saturated aq NaHCO3 and extracted with EtOAc (100 mL). The organic layer was separated, washed with brine (2×10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxy-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine as an off-white solid (33 mg, 41%). 1H NMR (250 MHz, DMSO-d6) δ 12.10 (s, 1H), 10.54 (s, 1H), 8.67 (d, J=2.0 Hz, 1H), 8.59 (d, J=8.16 Hz, 1H), 7.97-8.06 (m, 2H), 7.22-7.28 (m, 2H), 5.97 (s, 1H), 3.93 (s, 3H), 2.17 (s, 3H). LCMS (ESI) m/z 401 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[C:10]2[C:5](=[CH:6][C:7]([N+:15]([O-:17])=[O:16])=[C:8]([NH:11]C(=O)C)[CH:9]=2)[NH:4][C:3]1=[O:18].Cl[CH2:21][C:22]1[O:23][CH:24]=[CH:25][N:26]=1.C([O-])([O-])=O.[K+].[K+].C1CCN2C(=NCCC2)CC1>CO>[NH2:11][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][C:7]=1[N+:15]([O-:17])=[O:16])[N:4]([CH2:21][C:22]1[O:23][CH:24]=[CH:25][N:26]=1)[C:3](=[O:18])[C:2]2([CH3:1])[CH3:19]
Reactant: CC(=O)Nc1cc2c(cc1[N+](=O)[O-])NC(=O)C2(C)C
Reactant: ClCc1ncco1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: C1CCC2=NCCCN2CC1
Product: CC1(C)C(=O)N(Cc2ncco2)c2cc([N+](=O)[O-])c(N)cc21
Yield: 94.9 %

Procedure:
Analogously to general procedure (I) N-(3,3-dimethyl-6-nitro-2-oxo-2,3-dihydro-1H-indol-5-yl)-acetamide (1 g) is alkylated using 2-chloromethyl-oxazole (0.47 g; 4 mmol) and K2CO3 (1.1 g; 7.96 mmol) at RT for 18 h. After aqueous work-up the crude material (1.30 g) is de-acetylated in MeOH (30 ml) using DBU (280 μl) at reflux. After aqueous work-up 5-amino-3,3-dimethyl-6-nitro-1-oxazol-2-ylmethyl-1,3-dihydro-indol-2-one (1.09 g) is obtained and used without further purification.
Reaction SMILES: [Si]([O:8][C@H:9]1[C@H:16]2[N:12](/[C:13](=[N:21]/[C:22]3[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[C:24]([Cl:30])[C:23]=3[CH3:31])/[O:14][C@H:15]2[C:17]([F:20])([F:19])[F:18])[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.O[C@H]1[C@@H]2N(/C(=N/C3C=CC(C#N)=C(Cl)C=3C)/OC2)CC1>>[OH:8][C@H:9]1[C@@H:16]2[N:12](/[C:13](=[N:21]/[C:22]3[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[C:24]([Cl:30])[C:23]=3[CH3:31])/[O:14][C@H:15]2[C:17]([F:18])([F:20])[F:19])[CH2:11][CH2:10]1
Reactant: Cc1c(/N=C2\O[C@@H](C(F)(F)F)[C@H]3[C@H](O[Si](C)(C)C(C)(C)C)CCN23)ccc(C#N)c1Cl
Agent: Cc1c(/N=C2\OC[C@@H]3[C@H](O)CCN23)ccc(C#N)c1Cl
Product: Cc1c(/N=C2\O[C@@H](C(F)(F)F)[C@@H]3[C@H](O)CCN23)ccc(C#N)c1Cl

Procedure:
The title compound was prepared from compound 8A following a procedure analogous to that found in Example 1 in the preparation of compound 1J. MS: m/z 360 [M+H]+
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.[C:17]([OH:25])(=[O:24])[C:18]([CH2:20][C:21](O)=[O:22])=[CH2:19]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([N:16]3[C:21](=[O:22])[CH2:20][CH:18]([C:17]([OH:25])=[O:24])[CH2:19]3)=[CH:14][CH:15]=2)=[CH:6][CH:7]=1
Reactant: Nc1ccc(CCc2ccc(F)cc2)cc1
Reactant: C=C(CC(=O)O)C(=O)O
Product: O=C(O)C1CC(=O)N(c2ccc(CCc3ccc(F)cc3)cc2)C1

Procedure:
In an analogous manner to that described in Example 36 c), the reaction of 4-[2-(4-fluoro-phenyl)-ethyl]-phenylamine with itaconic acid yields the (RS)-1-{4-[2-(4-fluoro-phenyl)-ethyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid as a white solid; MS: m/e=326 (M−H)+.
Reaction SMILES: [C:1]1([C:11](=[O:26])[CH2:12][C:13]([O:15][C:16]([CH3:25])([CH2:19][CH2:20][CH:21]=[C:22]([CH3:24])[CH3:23])[CH:17]=[CH2:18])=[O:14])C2C(=CC=CC=2)C=CC=1.CC(O)(CCC=C(C)C)C=C.C=C1OC(=O)C1>>[O:26]=[C:11]([CH3:1])[CH2:12][C:13]([O:15][C:16]([CH3:25])([CH2:19][CH2:20][CH:21]=[C:22]([CH3:24])[CH3:23])[CH:17]=[CH2:18])=[O:14]
Reactant: C=CC(C)(CCC=C(C)C)OC(=O)CC(=O)c1cccc2ccccc12
Agent: C=C1CC(=O)O1
Agent: C=CC(C)(O)CCC=C(C)C
Product: C=CC(C)(CCC=C(C)C)OC(=O)CC(C)=O

Procedure:
The pro-accord 3,7-dimethyl-1,6-octadien-3-yl 3-(naphthyl)-3-oxo-propionate, which is a β-ketoester pro-accord, is prepared by treating 3,7-dimethyl-1,6-octadien-3-ol (linalool), which is a fragrance raw material according to the present invention, with diketene under suitable conditions to form intermediate 3,7-dimethyl-1,6-octadien-3-yl 3-oxo-butyrate, which is subsequently treated with 2-naphthoyl chloride to yield the pro-accord. 3,7-Dimethyl-1,6-octadien-3-yl 3-(β-naphthyl)-3-oxo-propionate when exposed to suitable conditions (e.g., exposure to nascent moisture) breaks down to release a mixture of linalool and methyl β-naphthyl ketone, both of which are fragrance raw materials as defined herein.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11]2[N:16]=[C:15]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)[CH:14]=[CH:13][N:12]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].ClC1C=CC=C(C(OO)=[O:31])C=1>C(Cl)Cl>[N+:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11]2[N:16]=[C:15]([C:17]3[CH:18]=[N+:19]([O-:31])[CH:20]=[CH:21][CH:22]=3)[CH:14]=[CH:13][N:12]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cccc(Nc2nccc(-c3cccnc3)n2)c1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: O=[N+]([O-])c1cccc(Nc2nccc(-c3ccc[n+]([O-])c3)n2)c1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
200 mg (0.68 mmol) of N-(3-nitrophenyl)-4-(3-pyridyl)-2-pyrimidine-amine are suspended in 5 ml of methylene chloride, and 225 mg (0.71 mmol) of 3-chloroperbenzoic acid are added. After 2 hours a further 10 ml of methylene chloride are added. The suspension is stirred for a further 20 hours at room temperature. Filtration and flash chromatography of the residue (methylene chloride:methanol:25% aqueous ammonia solution=90:10:1) yield N-(3-nitro-phenyl)-4-(N-oxido-3-pyridyl)-2-pyrimidine-amine; Rf =0.4 (methylene chloride:methanol:25% aqueous ammonia solution=90: 10:1), m.p. 252°-258°.
Reaction SMILES: CC(C)([O-])C.[K+].[C:7]1(=[N:14][OH:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.Cl[C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=1.O>CN(C=O)C>[N+:23]([C:20]1[CH:21]=[CH:22][C:17]([O:15][N:14]=[C:7]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)=[CH:18][CH:19]=1)([O-:25])=[O:24]
Reactant: O=[N+]([O-])c1ccc(Cl)cc1
Reactant: ON=C1CCCCCC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc(ON=C2CCCCCC2)cc1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 80.6 %

Procedure:
Potassium t-butoxide (19 g, 1600 mmol) was added in portions to a cooled (2° C.) solution of cycloheptanone oxime (19 g, 150 mmol) in DMF (150 mL). The cooled reaction mixture was stirred for 40 minutes and then 1-chloro-4-nitrobenzene (25 g, 160 mmol) in DMF (50 mL) was added over 5 minutes. The reaction mixture was stirred at ˜10° C. for 30 minutes and then allowed to warm to room temperature and stirred for an additional 2 hours, and then stood at ambient temperature for 16 hours. The reaction mixture poured into water (1600 mL) with stirring. The mixture was stirred for an additional 20 minutes and then allowed to stand at room temperature for 5 hours. The precipitate was collected by filtration and washed with water. Recrystallization of the crude material from hexane provided cycloheptanone O-(4-nitro-phenyl)-oxime (30 g). Cycloheptanone O-(4-nitro-phenyl)-oxime (12 g, 50 mmol) was dissolved in warm isopropanol (120 mL) and 12 N hydrochloric acid (17 mL) was added. The reaction mixture was heated to reflux for 4 hours and then cooled in an ice bath. The solid was collected by filtration, washed with water and cold isopropanol, and dried in an oven to give 2-nitro-7,8,9,10-tetrahydro-6H-benzo[b]-cyclohepta[d]furan (7.8 g, 34 mmol). A mixture of 2-nitro-7,8,9,10-tetrahydro-6H-benzo[b]-cyclohepta[d]furan (5.8 g, 25 mmol) and Raney nickel (-5.6 g wet weight) in ethanol (270 mL) was hydrogenated at 50 PSI on a Parr shaker overnight. The mixture was filtered through Celite® and the filtrate was concentrated. The crude solid was purified by flash column chromatography (gradient elution with 15-25% ethyl acetate-hexanes) to give 7,8,9,10-tetrahydro-6H-benzo[b]-cyclohepta[d]furan-2-ylamine (4.6 g). Mp 98-99° C.
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([CH:24]=[CH:25][CH:26]=1)[CH2:11]C1(C([O-])=O)C(C=C(Cl)Cl)C1(C)C)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(Cl)=CC1C(C(O)=[O:34])C1(C)C>>[O:1]([C:8]1[CH:9]=[C:10]([CH:24]=[CH:25][CH:26]=1)[CH2:11][OH:34])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC1(C)C(C=C(Cl)Cl)C1C(=O)O
Reactant: CC1(C)C(C=C(Cl)Cl)C1(Cc1cccc(Oc2ccccc2)c1)C(=O)[O-]
Product: OCc1cccc(Oc2ccccc2)c1

Procedure:
A process according to claim 1 for the preparation of 3-phenoxybenzyl-[3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropanecarboxylate], which comprises reacting 3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropanecarboxylic acid with dimethylchloromethylydene-ammonium chloride and further reacting dimethyl-[3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarbonyloxy]-methylydene-ammonium chloride obtained with 3-phenoxybenzyl alcohol in the presence of said organic base.
Reaction SMILES: [CH:1]1([NH2:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>CS(O)(=O)=O.C1(C)C=CC=CC=1>[C:1]1([NH:7][C:4]2[CH:5]=[CH:6][C:1]([NH:7][CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:2][CH:3]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NC1CCCCC1
Agent: CS(=O)(=O)O
Solvent: Cc1ccccc1
Product: c1ccc(Nc2ccc(NC3CCCCC3)cc2)cc1
Reaction time: 1.5 h

Procedure:
Into a three neck 500 ml flask equipped with a thermometer, stirrer, Dean Stark trap and condenser was charged 18.4 grams of N-phenylquinoneimine, 150 ml toluene, 19.9 cyclohexylamine and 5 drops methanesulfonic acid. The reaction was conducted at 110° C. for 1.5 hours after which time the product was washed with 200 ml water containing 10 grams of Na2S2O4. The product was decanted, filtered and stripped at a pot temperature of 100° C. at 4 mm Hg. 27 grams of N-phenyl-N'-cyclohexyl-p-phenylenediamine were recovered.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:19]([O:20][CH3:21])=[CH:18][CH:17]=[CH:16][C:4]=1[CH:5]=[CH:6][C:7]1[S:8][C:9]2[NH:10][CH2:11][CH2:12][CH2:13][C:14]=2[N:15]=1.[CH3:22][S:23](Cl)(=[O:25])=[O:24].C(=O)(O)[O-].[Na+]>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[C:19]([O:20][CH3:21])=[CH:18][CH:17]=[CH:16][C:4]=1[CH:5]=[CH:6][C:7]1[S:8][C:9]2[N:10]([S:23]([CH3:22])(=[O:25])=[O:24])[CH2:11][CH2:12][CH2:13][C:14]=2[N:15]=1
Reactant: CS(=O)(=O)Cl
Reactant: COc1cccc(C=Cc2nc3c(s2)NCCC3)c1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Product: COc1cccc(C=Cc2nc3c(s2)N(S(C)(=O)=O)CCC3)c1OC
Temperature: 25 °C
Reaction time: 3 h
Yield: 86.8 %

Procedure:
To a solution of 2-(2,3-dimethoxystyryl)-4,5,6,7-tetrahydrothiazolo[5,4-b]pyridine (1.0 g, 3.3 mmole) in pyridine (10 ml) was added dropwise methanesulfonyl chloride (0.45 g, 3.97 mmole) with ice-cooling. The reaction mixture was heated with stirring at room temperature for 3 hours and then a sodium bicarbonate solution was added to the mixture which was extracted with a chloroform-methanol mixed solvent. The extract was dried over magnesium sulfate and concentrated. The residue was purified by flash column chromatography and recrystallized from hexane-ethyl acetate to obtain the title compound (1.09 g, yield: 92.7%).
Reaction SMILES: [CH3:1][CH:2]([CH3:6])[CH2:3][CH2:4]Br.[N:7]([N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)=[O:8].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C)C=O>[CH3:1][CH:2]([CH3:6])[CH2:3][CH2:4][N:12]1[CH2:13][CH2:14][N:9]([N:7]=[O:8])[CH2:10][CH2:11]1
Reactant: O=NN1CCNCC1
Reactant: CC(C)CCBr
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)CCN1CCN(N=O)CC1

Procedure:
A mixture of 3-methyl-1-bromo-butane (3.94 g.), N-nitroso-piperazine (3 g.), anhydrous potassium carbonate (3.6 g.) and a small crystal of potassium iodide in dimethyl formamide was heated at 100° for 2 hours. Solvent was removed under reduced pressure and the residue dissolved in ether and water. The ether extract was separated, dried and evaporated to give an oil which was adsorbed on silica gel. Elution with ethyl acetate gave N-(3-methylbutyl)-N'-nitroso piperazine, further purified by dissolving in dilute acid, washing the acid extract with ether, basifying the acid extract and re-extracting with ether. The yield of colourless oil was 3 g (62%).