Synthesis of 2-dimethylaminomethyl-cyclohexanone hydrochloride
http://orgspectroscopyint.blogspot.in/2014/09/synthesis-of-2-dimethylaminomethyl.html
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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 | ||
