ChemicalBook CAS DataBase List 4,4'-METHYLENEBIS(N-METHYLANILINE)

4,4'-METHYLENEBIS(N-METHYLANILINE) synthesis

9synthesis methods

Product Name:4,4'-METHYLENEBIS(N-METHYLANILINE)
CAS Number:1807-55-2
Molecular formula:C15H18N2
Molecular Weight:226.32

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Yield:1807-55-2 543 mg

Reaction Conditions:

Stage #1: N,N'-(methylenebis(4,1-phenylene))diformamidewith lithium aluminium tetrahydride in tetrahydrofuran; for 24 h;Inert atmosphere;Reflux;
Stage #2: with Glauber's salt in tetrahydrofuran; for 1 h;Inert atmosphere;Reflux;

Steps:

Synthesis of N,N'-Dimethyl-N,N'-(methylenedi-4,1-phenylene)bis[2-(1-pyrrolidinyl)acetamide] (2g)

To a solution of 2a (793 mg, 4.0 mmol) in THF (4 mL) was added ethyl formate (937 mg, 12 mmol) at 25 °C, and the mixture was stirred at 55 °C for 48 h. Removal of the solvent under reduced pressure gave crude N,N'-(methylenedi-4,1-phenylene)bisformamide (997 mg) as a colorless solid. To a suspension of LiAlH₄ (455 mg, 12 mmol) in THF (40 mL) was added N,N'-(methylenedi-4,1-phenylene)bisformamide (997 mg) at 0 °C, and the mixture was stirred under reflux for 24 h. To the reaction mixture was added Na₂SO₄?10H₂O (6.44 g, 20 mmol) at 0 °C, and the mixture was stirred under reflux for 1 h. After the insoluble parts were filtered, the filtrate was concentrated under reduced pressure. The residue was purified by MPLC on silica gel using hexane/AcOEt (1 : 1) as eluent to give N,N'-dimethyl-4,4'-diaminodiphenylmethane (543 mg, 2.40 mmol, 60%) as pale yellow oil. To a solution of N,N'-dimethyl-4,4'-diaminodiphenylmethane (113 mg, 0.50 mmol), pyridine (95 mg, 1.20 mmol), and 4-(dimethylamino)pyridine (1 mg) in CH₂Cl₂ (10 mL) was added bromoacetyl bromide (222 mg, 1.10 mmol) at 0 °C, and the mixture was stirred at 25 °C for 3 h. The reaction mixture was poured into water (10 mL), and the organic layer was dried over Na₂SO₄, and filtered. Removal of the solvent under reduced pressure gave crude N,N'-dimethyl-N,N'-(methylenedi-4,1-phenylene)bis(2-bromoacetamide) (200 mg) as pale yellow oil. To a suspension of N,N'-dimethyl-N,N'-(methylenedi-4,1-phenylene)bis(2-bromoacetamide) (200 mg) and K₂CO₃ (276 mg, 2.0 mmol) in THF (5.0 mL) was added pyrrolidine (107 mg, 1.50 mmol) at 25 °C, and the mixture was stirred at 60 °C for 12 h. The reaction mixture was poured into water (10 mL) and extracted with CHCl₃ (10 mL). The organic layer was dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The residue was purified by MPLC on silica gel using CHCl₃/MeOH (19 : 1) as eluent to give 2g (178 mg, 0.40 mmol, 79%) as a pale yellow solid.

References:

Kimura, Tsutomu;Hosokawa-Muto, Junji;Kamatari, Yuji O.;Kuwata, Kazuo [Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,# 5,p. 1502 - 1507] Location in patent:supporting information; experimental part

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