Guanidine Hydrochloride → Hydrochloric Acid

HRID 401082Notes

Reaction equation

HRID 401082 reaction equation
[C:1]1([C:7](=O)[CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:16]([O:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([N+:28]([O-:30])=[O:29])[C:26]=1[OH:27])[CH:22]=O)[CH3:17].[ClH:31].[NH2:32][C:33]([NH2:35])=[NH:34].C(NC(C)C)(C)C>C(O)C>[CH2:16]([O:18][C:19]1[CH:20]=[C:21]([CH:22]2[C:8]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[NH:35][C:33](=[NH:32])[NH:34]2)[CH:24]=[C:25]([N+:28]([O-:30])=[O:29])[C:26]=1[OH:27])[CH3:17].[ClH:31]

Participants

7

Reactant 4

HCID 5742Guanidine HydrochlorideHCID 7912DiisopropylamineHCID 99482-PhenylacetophenoneHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehyde

Product 2

HCID 313Hydrochloric AcidYield 301.2%HCID 178466038HCID 178466038, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1,2-diphenylethanone (500 mg, 2.55 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (538.5 mg, 2.55 mmol), guanidine hydrochloride (731 mg, 7.65 mmol), diisopropylamine (1.1 mL) in ethanol (5 mL) was refluxed at 80° C. for 60 h. The mixture was evaporated under reduced pressure and the residue was treated with a mixture of saturated aqueous sodium bisulfite solution (50 mL), dichloromethane (100 mL) and isopropanol (30 mL), and the resulting mixture was stirred at room temperature for 30 min. The organic layer was separated and the aqueous layer was extracted with a mixture of dichloromethane and isopropanol (3:1, 50 mL×2). The combined organic layer was dried over anhydrous sodium sulfate and purified by preparative HPLC. The product containing fractions were treated with HCl/MeOH (2 mL, 2 N) and concentrated in vacuo to give Compound 112 as an HCl salt (280 mg, yield 25.45%). 1H NMR (DMSO-d6 400 MHZ): δ 10.48 (s, 1H), 10.27 (s, 1H), 9.35 (s, 1H), 7.59 (s, 2H), 7.53 (s, 1H), 7.52-7.31 (m, 5H), 7.26 (d, J=2.0 Hz, 1H), 7.12-7.10 (m, 3H), 6.92-6.90 (m, 2H), 5.57 (d, J=3.2 Hz, 1H), 4.1-4.06 (q, J=7.2 Hz, 2H), 1.36-1.32 (t, J=7.2 Hz, 3H); MS (ESI): m/z 431.0 [M+H]+.

Workup

  1. customThe mixture was evaporated under reduced pressure
  2. additionthe residue was treated with a mixture of saturated aqueous sodium bisulfite solution (50 mL), dichloromethane (100 mL) and isopropanol (30 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with a mixture of dichloromethane and isopropanol (3:1, 50 mL×2)
  5. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  6. custompurified by preparative HPLC
  7. additionThe product containing fractions
  8. additionwere treated with HCl/MeOH (2 mL, 2 N)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bc50f798e6d64a2b8d0c6c3b088faed0
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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