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

HRID 1014086
Notes
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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
ParticipantsProcedureSources & evidenceReaction notes

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 1140
Toluene
Solvent
HCID 3283Diethyl EtherSolvent
HCID 6328Methyl iodideSolvent
HCID 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
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07982052B2

Reaction notes

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On this pageParticipantsProcedureSources & evidenceReaction notes