Synthesis of 2-dimethylaminomethyl-cyclohexanone hydrochloride

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EtOH, HCl

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

Equipment

	round bottom flask 25 mL			reflux condenser
	suction filter			suction flask
	heatable magnetic stirrer with magnetic stir bar			rotary evaporator
	exsiccator with drying agent			oil bath

Instruction (batch scale 100 mmol) 

Equipment 

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 

Substances 

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 

Reaction 

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 

Comments 

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

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

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

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

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