Synthesis of 2-dimethylaminomethyl-cyclohexanone hydrochloride

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 mL round bottom flask 25 mL   reflux condenser reflux condenser
suction filter suction filter   suction flask suction flask
heatable magnetic stirrer with magnetic stir bar heatable magnetic stirrer with magnetic stir bar   rotary evaporator rotary evaporator
exsiccator with drying agent exsiccator with drying agent   oil bath oil 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 economy   not defined  
Yield   76 %
Target product mass   1.45 g
Sum of input masses   54 g
Mass efficiency   27 mg/g
Mass index   37 g input / g product
E factor   36 g waste / g product
Inline image 2
Inline image 3
1H-NMR: 2-Dimethylaminomethyl cyclohexanone hydrochloride
500 MHz, CDCl3
delta [ppm] mult. atoms assignment
1.35 m 1 H  
1.54 m 1 H  
1.73 m 1 H  
1.82 m 1 H  
2.05 m 1 H  
2.37 m 2 H 6-H (ring)
2.41 m 1 H  
2.67 d 3 H N-CH3
2.74 m 1 H  
2.77 d 3 H N-CH3
3.09 m 1 H N-CH2
3.57 m 1 H N-CH2
11.88 m 1 H N-H
7.26     CHCl3
Inline image 4
Inline image 5
13C-NMR: 2-Dimethylaminomethyl cyclohexanone hydrochloride
125 MHz, CDCl3
delta [ppm] assignment
24.70 C5
27.70 C3
33.88 C4
41.75 CH3
42.26 CH3
44.99 C6
46.69 C2
56.80 -CH2-N-
209.58 C1 (C=O)
76.5-77.5 CDCl3
Inline image 6
IR: 2-Dimethylaminomethyl cyclohexanone hydrochloride
[Film, T%, cm-1]
[cm-1] assignment
3068, 3020 N-H valence
2932, 2858 C-H valence
1698 C=O valence, ketone

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s