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Saturday, 6 September 2014

Synthesis of 2-dimethylaminomethyl-cyclohexanone hydrochloride

Cyclohexanone+Paraformaldehyde+Dimethylammonium chloride
reacts to
2-Dimethylaminomethyl cyclohexanone hydrochloride

Synthesis of 2-dimethylaminomethyl-cyclohexanone hydrochloride

Reaction type:reaction of the carbonyl group in aldehydes, Mannich reaction
Substance classes:ketone, aldehyde, amine
Techniques:heating under reflux, stirring with magnetic stir bar, evaporating with rotary evaporator, filtering, recrystallizing, heating with oil bath
Degree of difficulty:Easy


round bottom flask 25 mLround bottom flask 25 mLreflux condenserreflux condenser
suction filtersuction filtersuction flasksuction flask
heatable magnetic stirrer with magnetic stir barheatable magnetic stirrer with magnetic stir barrotary evaporatorrotary evaporator
exsiccator with drying agentexsiccator with drying agentoil bathoil bath

Operating scheme

Inline image 1

Instruction (batch scale 100 mmol) 
100 mL round bottom flask, reflux condenser, Buechner funnel (Ø 5.5 cm), suction flask, 
heatable magnetic stirrer, magnetic stir bar, rotary evaporator, desiccator, oil bath 
cyclohexanone (bp 156 °C) 9.82 g (10.3 mL, 100 mmol) 
paraformaldehyde (mp 120-170 °C) 3.60 g (120 mmol) 
dimethylammonium chloride 8.16 g (100 mmol) 
hydrochloric acid (conc.) 0.4 mL 
ethanol (bp 78 °C) 64 mL 
acetone (bp 56 °C) 180 mL 

9.82 g (10.3 mL, 100 mmol) cyclohexanone, 3.60 g (120 mmol) paraformaldehyde, 8.16 g 
(100 mmol) dimethylammonium chloride and 4 mL ethanol are filled in a 100 mL round 
bottom flask with reflux condenser and magnetic stir bar. 0.4 mL conc. hydrochloric acid are 
added and the mixture is heated under stirring for 4 hours under reflux. 
Work up 
The hot solution is filtered in a round-bottom flask and the solvent is evaporated at the rotary 
evaporator. The residue is dissolved in 20 mL ethanol under heating. At room temperature 
70 mL acetone are added to the solution. For complete crystallization the solution is stored 
over night in the freezer compartment. The crystallized crude product is sucked off over a 
Buechner funnel (Ø = 5.5 cm) and dried in the desiccator over silica gel. 
Crude yield: 15.6 g; mp 149-150 °C 
For further purification the crude product is again dissolved in about 40 mL ethanol under 
reflux and at room temperature 110 mL acetone are added. The crystallization is completed in 
the freezer compartment. The product is sucked off and dried in the desiccator. 
Yield: 14.7 g (76.7 mmol, 77%,); mp 156-157 °C 
To verify a complete crystallization, the mother liquor is stored in the freezer compartment. 
No product should crystallize any further.

Simple evaluation indices

Atom economynot defined
Target product mass1.45g
Sum of input masses54g
Mass efficiency27mg/g
Mass index37g input / g product
E factor36g waste / g product


Inline image 2

Inline image 3

1H-NMR: 2-Dimethylaminomethyl cyclohexanone hydrochloride
500 MHz, CDCl3
delta [ppm]mult.atomsassignment
1.35m1 H
1.54m1 H
1.73m1 H
1.82m1 H
2.05m1 H
2.37m2 H6-H (ring)
2.41m1 H
2.67d3 HN-CH3
2.74m1 H
2.77d3 HN-CH3
3.09m1 HN-CH2
3.57m1 HN-CH2
11.88m1 HN-H


Inline image 4
Inline image 5

13C-NMR: 2-Dimethylaminomethyl cyclohexanone hydrochloride
125 MHz, CDCl3
delta [ppm]assignment
209.58C1 (C=O)


Inline image 6

IR: 2-Dimethylaminomethyl cyclohexanone hydrochloride
[Film, T%, cm-1]
3068, 3020N-H valence
2932, 2858C-H valence
1698C=O valence, ketone

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