General method for nucleophilic aromatic substitution of aryl fluorides and chlorides with dimethylamine using hydroxide-assisted decomposition of N,N-dimethylforamide

Abstract

A practical and convenient procedure for the nucleophilic aromatic substitution of aryl fluorides and chlorides with dimethylamine was developed using a hydroxide assisted, thermal decomposition of N,N-dimethylforamide. These conditions are tolerant of nitro, nitrile, aldehyde, ketone, and amide groups but will undergo acyl substitution to form amides for methyl esters and acyl chlorides. Isolated yields of the products range from 44 – 98%, with the majority being greater than 70% for seventeen examples.

Stabilising fleeting intermediates of stilbene photocyclization with amino-borane functionalisation: the rare isolation of persistent dihydrophenanthrenes and their [1,5] H-shift isomers

“…All starting materials were purchased from Energy Chemical. (Pyridin-2-ylmethyl)triphenylphosphonium chloride, 9 2-metho-xybenzyltriphenylphosphonium chloride, 10 benzylphosphonium bromide, 11 2-thienylmethyltriphenylphosphonium chloride, 12 3-thienylmethyltriphenylphosphonium bromide, 13 2-dimesityl-borylbenzaldehyde, 22 2-bromo-4-(dimethylamino)benzalde-hyde, 23 and 5-bromo-2-(dimethylamino)benzaldehyde 24 were synthesized according to procedures reported in literature. The starting materials for E -8a and E -9a ( BO1′ and BO1m , respectively) were prepared according to procedures outlined in the ESI.…”

Rapid synthesis of pomalidomide-conjugates for the development of protein degrader libraries

“…DMF has actually been used as a source of dimethylamine for other SNAr reactions in the literature, but typically at elevated temperatures (> 90 °C), and in the presence of ammonia or hydroxide. 30,34,35 Since there was evidence that DMF was not acting purely as a solvent under our conditions, we wanted to examine other commonly used solvents in an attempt to optimise this reaction. Solvent optimisation began with a screen using both primary (4) and secondary (5) model amines that utilised similar functionality to typical protein degrader linkers (Table 1).…”

Synthesis of Rhodamines and Rosamines Using 3,6-Difluoroxanthone as a Common Intermediate

“…Reaction conditions involved mixing 1 with 20 equiv of amine at temperatures of 150 °C (cyclic amines) or 200 °C (acyclic amines) in a sealed vessel. In most of our examples, amines were used neat in the reaction effectively carrying out solvolysis; however, for the synthesis of 9 and 13 , dimethylamine was generated via KOH decomposition of dimethylformamide (DMF) (for 9 ) , and azetidine hydrochloride was deprotonated prior to use in dimethyl sulfoxide (DMSO) (for 13 ). We employed two different types of pressure vessel systems: a traditional thick-walled glass pressure vessel heated in a silicone oil bath and a polytetrafluoroethylene (PTFE)-lined stainless steel tank reactor (heated in an explosion-proof convection oven).…”