Synthesis of Amphetamine Sulphate via Oxime Reduction (Report 2)

[GhostChemist]

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​