Synthesis of A Sulphate via Oxime Reduction (Report 2)โ
Previously, a synthesis via aluminum amalgam was carried out with a low yield of the target amine
http://bbzzzsvqcrqtki6umym6itiixfhn...amine-synthesis-via-p2p-oxime-reduction.8562/
The experiments were carried out according to the methods in the articles
Ronald L. Foreman, Frederick P. Siecel, And Robert C. Mrtek Synthesis of Deuterio-l-amphetamine, d1 Sulfate. Journal of Pharmaceutical Sciences, 1969, Vol.58, No. 2, pp. 189-192
James W. Wilson Synthesis of dl-Amphetamine Sulfate Labeled with C14. Journal of the American Pharmaceutical Association, Sci. Ed., 1950, vol. 39, pp. 687-688
The process proceeds according to Scheme 1
Scheme 1โ
Starting reagents and materials
- 22 g ั2ัโ
- 12 g Hydroxylamine hydrochloride + 120 ml H2Oโ
- 88 ml 4N NaOH
- 12 ml GAA
- 1000 ml DCM
- 50-100 g Na2SO4
- 100-110 g CaCl2 + 200 ml H2O
- 70-100 ml 15-20% NaOH
- 9 g NaBH4
- 150 ml THF
- 100 ml IPA
- 5 ml H2SO4
- H2O
- Marquis reagent
- Flasks
- Beakers
- Funnels
- Termometer
- Stirrer
- Heate
- Paper filter
- pH-indicator strips
22 p2p with 12 ะณ hydroxylamine hydrochloride in 120-125 ml of water stir at 30-40โ. Fig 0โ
Fig 0โ
Solution of NaOH (88 ml 4N) is added within 70 minutes. Fig 1โ
Fig 1โ
โ
After 70 min, GAA (12 ml) is added to the RM Fig 2โ
Fig 2โ
The pH of the RM should be neutral. Fig 3โ
Fig 3โ
Oxime is extracted with DCM Fig 4โ
Fig 4โ
When exposed to air, the DCM layer turns green. Fig 5โ
Fig 5โ
The DCM layer is washed with a saturated solution of calcium chloride (100-110 g in 200 ml of water) Fig 6โ
Fig 6โ
The DCM layer is dried with sodium sulfate. Fig 7
Fig 7โ
Dried layer of DCM Fig 8
Fig 8โ
DCM is distilled off Fig 9
Fig 9โ
After distillation of DCM, orange oil remains Fig 10
Fig 10โ
50 ml of THF is added to the oil Fig 11
Fig 11โ
9 g of sodium borohydride are placed in a dry flask. Fig 12
Fig 12โ
100 ml of THF is added to the NaBH4 Fig 13
Fig 13โ
The oxime solution is added to the NaBH4 in small portions while stirring. Fig 14
Fig 14โ
The mixture is stirred for 20 hours Fig 15
Fig 15โ
RM is transferred to a large 1000 ml beaker Fig 16
Fig 16โ
200 ml of water is added to the RM Fig 17
Fig 17โ
A solution of 15-20% NaOH is prepared Fig 18
Fig 18โ
70 ml of the prepared solution of 15-20% NaOH is added to the RM Fig 19
Fig 19โ
The RM is transferred to a separatory funnel and 200-250 ml of DCM is added. The mixture is mixed well. In case of poor separation, portions of water and DCM are added alternately. Fig 20
Fig 20โ
Extraction is carried out 2-3 times. The DCM layer is collected (total volume 600 ml) Fig 21
Fig 21โ
DCM is dried with sodium sulfate Fig 22
Fig 22โ
The dried DCM is transferred to a distillation flask. Fig 23
Fig 23โ
The DCM is distilled off. A yellow oil with an amine smell remains in the flask. Fig 24
Fig 24โ
Oil sample tested with Marquis reagent (1 ml 37% formalin + 3-5 ml H2SO4 103%) Fig 25
Fig 25โ
A solution of H2SO4 in IPA is prepared. (10 ml of IPA is dried overnight over SiO2) 5 ml of H2SO4 is added to it, the resulting volume of solution is 50 ml Fig 26
Fig 26โ
To the obtained oil, after distillation of DCM, 25-40 ml of anhydrous IPA (dried over SiO2) is added. Fig 27
Fig 27โ
The resulting solution is poured into a beaker. Fig 28
Fig 28โ
The resulting solution is filtered through a paper filter. Fig 29
Fig 29โ
The amine solution in IPA should have an alkaline pH. The sulfuric acid solution in IPA should have an acidic pH. Fig 30
Fig 30โ
A solution of sulfuric acid is added dropwise to the amine solution in the IPA until a neutral pH is achieved. Fig 31
Fig 31โ
The resulting yield was less than 1g. Fig 32
Fig 32โ