Synthesis of AMP Sulphate. Leukart Reaction
In this topic presented the results obtained in the synthesis of AMP by using Leuckart reaction.
The general scheme of the process is shown in Scheme 1.
Scheme 1
Reagents and materials
- 16.5 g Formamide CAS 75-12-7
- 21 ml 80% Formic acid
- 16.2 ml phenyl-2-propanone (P2P)
- 50 ml petroleum ether
- 50 ml EtOH
- 100 ml HCl (14.5% 1.07 g/ml)
- 35 g NaOH in 200 ml H2O
- 14-15 ml acetone
- 3 ml H2SO4 (97-99%)
- 50-100 g sodium sulfate
- 400-500 ml DCM
- Beakers
- Flasks
- Heater
Stage 1. Formation of formyl derivative proceeds according to Scheme 2
Scheme 2
Р2P is placed into a flask. Fig 1
Fig 1
Formamide and formic acid are added to p2p Fig 2
Fig 2
A reflux condenser and a thermometer are connected to the flask. The RM is gradually heated to 160-170℃ (to the active boiling of RM) for 16-20 hours. Active ventilation of the room is necessary due to the evaporation of toxic formamide! Fig 3
Fig 3
RM is darkens Fig 4
Fig 4
Stage 2. Formyl derivative extraction
The RM is cooled to room T. 50 ml of petroleum ether is added. Fig 5
Fig 5
The mixture is transferred to a separatory funnel. The flask is additionally washed with petroleum ether. Fig 6
Fig 6
The petroleum ether is separated (upper layer). The lower layer undergoes another petroleum ether extraction. The lower layer is discarded. Fig 7
Fig 7
The petroleum ether layer is dried with sodium sulfate. Fig 8
Fig 8
Petroleum ether is distilled off Fig 9
Fig 9
Formyl derivative oil remains in the distillation flask. Fig 10
Fig 10
Stage 3. Hydrolysis of formil derivative is proceeds according to Scheme 3
Scheme 3
50 ml of EtOH and then 100 ml of hydrochloric acid are added to the resulting oil. (14.5% 1.07 g/ml) Fig 11
Fig 11
The RM mixture is boiled for 2-5 hours under a reflux condenser. Fig 12
Fig 12
The RM is cooled to room temperature. Fig 13
Fig 13
Next, the RM is transferred to a separatory funnel and washed with 2 portions (25-50 ml) of DCM. Fig 14
Fig 14
The DCM layer is separated and discarded. Fig 15
Fig 15
The separated aqueous layer contains the AMP hydrochloride Fig 16
Fig 16
Stage 4. Extraction of free base and production of amp sulfate proceeds according to Scheme 4
Scheme 4
An alkali solution of 35 g sodium hydroxide in 200 ml water is added to the aqueous layer. Fig 17
Fig 17
The solution is transferred to a separatory funnel and the amine is extracted with DCM. Fig 18
Fig 18
DCM (300 ml) is separated and dried over sodium sulfate. Fig 19
Fig 19
DCM is distilled off Fig 20
Fig 20
The free base of AMP oil remains in the distillation flask. Fig 21
Fig 21
A solution of sulfuric acid in acetone is prepared (Acetone 14-15 ml + 3-5 ml sulfuric acid 97-99%) Fig 22
Fig 22
The oil in the distillation flask is dissolved in acetone. Acetone was dried over silica gel. Fig 23
Fig 23
A solution of AMP oil in acetone is filtered through a paper filter Fig 24
Fig 24
Filtered solution of AMP in acetone Fig 25
Fig 25
A solution of sulfuric acid in acetone is added dropwise to the filtered solution of AMP in acetone with constant pH monitoring (a solution of sulfuric acid in acetone or IPA may acquire a yellow tint) Fig 26
Fig 26
Once neutral pH is reached, a thick white precipitate should form. Fig 27
Fig 27
The precipitate is filtered using a vacuum filter. Fig 28
Fig 28
The precipitate is dried on the filter. Fig 29
Fig 29
Yield is 7.3 g of AMP sulfate or 33% Fig 30
Fig 30