Synthesis of A Sulphate via Oxime Reduction (Report 2)
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 1
Starting reagents and materials
- 22 g р2р
- 12 g Hydroxylamine hydrochloride + 120 ml H2O
- 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 г hydroxylamine hydrochloride in 120-125 ml of water stir at 30-40℃. Fig 0
Fig 0
Solution of NaOH (88 ml 4N) is added within 70 minutes. Fig 1
Fig 1
After 70 min, GAA (12 ml) is added to the RM Fig 2
Fig 2
The pH of the RM should be neutral. Fig 3
Fig 3
Oxime is extracted with DCM Fig 4
Fig 4
When exposed to air, the DCM layer turns green. Fig 5
Fig 5
The DCM layer is washed with a saturated solution of calcium chloride (100-110 g in 200 ml of water) Fig 6
Fig 6
The DCM layer is dried with sodium sulfate. Fig 7
Fig 7
Dried layer of DCM Fig 8
Fig 8
DCM is distilled off Fig 9
Fig 9
After distillation of DCM, orange oil remains Fig 10
Fig 10
50 ml of THF is added to the oil Fig 11
Fig 11
9 g of sodium borohydride are placed in a dry flask. Fig 12
Fig 12
100 ml of THF is added to the NaBH4 Fig 13
Fig 13
The oxime solution is added to the NaBH4 in small portions while stirring. Fig 14
Fig 14
The mixture is stirred for 20 hours Fig 15
Fig 15
RM is transferred to a large 1000 ml beaker Fig 16
Fig 16
200 ml of water is added to the RM Fig 17
Fig 17
A solution of 15-20% NaOH is prepared Fig 18
Fig 18
70 ml of the prepared solution of 15-20% NaOH is added to the RM Fig 19
Fig 19
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 20
Extraction is carried out 2-3 times. The DCM layer is collected (total volume 600 ml) Fig 21
Fig 21
DCM is dried with sodium sulfate Fig 22
Fig 22
The dried DCM is transferred to a distillation flask. Fig 23
Fig 23
The DCM is distilled off. A yellow oil with an amine smell remains in the flask. Fig 24
Fig 24
Oil sample tested with Marquis reagent (1 ml 37% formalin + 3-5 ml H2SO4 103%) Fig 25
Fig 25
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 26
To the obtained oil, after distillation of DCM, 25-40 ml of anhydrous IPA (dried over SiO2) is added. Fig 27
Fig 27
The resulting solution is poured into a beaker. Fig 28
Fig 28
The resulting solution is filtered through a paper filter. Fig 29
Fig 29
The amine solution in IPA should have an alkaline pH. The sulfuric acid solution in IPA should have an acidic pH. Fig 30
Fig 30
A solution of sulfuric acid is added dropwise to the amine solution in the IPA until a neutral pH is achieved. Fig 31
Fig 31
The resulting yield was less than 1g. Fig 32
Fig 32