Benzyl Bromide → 2-Benzyl-1,1,3,3-tetramethylisoindoline

HRID 1014086Notes

Reaction equation

HRID 1014086 reaction equation
C(N1C(=O)C2=CC=CC=C2C1=O)C1C=CC=CC=1.[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C1(=O)NC(=O)C2=CC=CC=C12.[K].[CH3:39][C:40]1([CH3:51])[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:42]([CH3:50])([CH3:49])[NH:41]1>CI.[Mg].C1(C)C=CC=CC=1.C(OCC)C>[CH2:19]([N:41]1[C:40]([CH3:51])([CH3:39])[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:42]1([CH3:50])[CH3:49])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

9

Reactant 4

HCID 7498Benzyl BromideHCID 75059BenzylphthalimideHCID 6410271,1,3,3-TetramethylisoindolineHCID 24194345Phthalimide potassium salt

Product 1

HCID 129238792-Benzyl-1,1,3,3-tetramethylisoindolineYield 37%

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 6328Methyl iodideSolventHCID 5462224MagnesiumSolvent

Procedure

The synthesis set up by Rizzardo and coworkers is of the greatest practical interest, and comprises the synthesis of N-benzylpthalimide from benzyl bromide and potassium phthalimide, followed by its alkylation with a Grignard reagent. In the synthesis of 1,1,3,3-tetramethylisoindoline, for example, the Grignard reagent was prepared starting from methyl iodide and magnesium using, as solvents, ethyl ether and toluene (in succession): after 4 hours at reflux, N-benzyl-1,1,3,3-tetramethylisoindoline is obtained (37% yield), which is then treated with hydrogen (4 atmospheres; room temperature) in glacial acetic acid and in the presence of palladium-based catalysts (5% on coal). After 3 hours of reaction, 1,1,3,3-tetramethylisoindoline is obtained (II, R═CH3) with a yield of 96% (P. G. Griffiths, G. Moad, E. Rizzardo, D. H. Solomon, “Australian Journal of Chemistry” 1983, 36, 397).

Sources & evidence

ORD record
ord-0c654493aa6243fdaab120a19fb94b71
Source dataset
uspto-grants-2011_07
Patent number
US07982052B2

Reaction notes

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