Alkylation at primary and secondary nitrogen

The Norwegian chemist Dale found that if a primary amine is reacted with a diiodo derivative of a short-chain polyethylene glycol, such as 18, then reasonable yields of the cyclic mono-aza crown ether were obtained using Na2C03 in acetonitrile, as in the formation of the [12]-N03 ligand 19.14 

Caution Carry out all procedures in a well-ventilated hood, and wear disposable vinyl or latex gloves and chemical-resistant safety goggles. 

Add benzylamine (192 g, 1.80 mol) and 1,2-bis(2-chloroethoxy)ethane (22.7 g, 0.122 mol) to a single-necked round-bottomed flask fitted with an air condenser attached to a nitrogen line. Stir the mixture for 48 h at 120 °C. 

Allow the mixture to cool to room temperature and add solid sodium hydroxide (8 g, 0.2 mol). Return the flask to 120°C and stir the mixture for 1 h. Distil off the excess benzylamine under high vacuum (0.2 mmHg at 45°C) and, when all the amine is gone, dissolve the residue in chloroform (200 mL). Wash the organic layer with water (2 x 150 mL), separate the lower organic layer, dry it over magnesium sulfate (c. 5 g, 30 min), filter and remove the solvent on a rotary evaporator. 

Remove remaining traces of solvent and benzylamine by heating the flask under vacuum (0.05 mmHg, 60°C), to leave a pale-yellow viscous oil, 39.8 g, 99%, which is /V,/V -dibenzyl-4,7-dioxa-1,10-diazadecane. Bulb to bulb distillation (Kugelrohr apparatus) at 175°C (0.2 mmHg) yields material which is sufficiently pure to be used directly in the next step. 

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