Disclosure of the physical properties of some amphetamines and methamphetamines NO.01

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Solubility:
-Amphetamine hydrochloride has relatively weak solubility in water and alcohol and is easy to crystallize; its sulfate is almost insoluble in ethanol and isopropyl alcohol and will still precipitate even if boiled.
-The solubility of methamphetamine hydrochloride in water and alcohol is very large, obviously much greater than that of amphetamine. Especially in water, it is difficult to crystallize. When the concentration of the solution is very high, it will appear syrupy and viscous; its sulfate will dissolve in ethanol. It has high solubility like amphetamine sulfate and cannot be directly precipitated as a solid by dropping 98% sulfuric acid into methamphetamine petroleum ether or alcohol solution. This operation of methamphetamine will produce a syrupy consistency layered.
-Whether it is amphetamine or methamphetamine, its salts are almost insoluble in alkane substances such as petroleum ether. However, for methamphetamine salts, the prerequisite for maintaining precipitation in petroleum ether is complete anhydrous dryness. If it contains moisture, the situation will completely change.
-Amphetamine hydrochloride and methamphetamine hydrochloride have certain solubility in dichloromethane and tetrahydrofuran.

Moisture content and drying method:
-Although amphetamine and methamphetamine appear to be separated from water, they actually still contain a large amount of water. Desiccant cannot be used to directly dry the methamphetamine oil separated from water, otherwise a large amount of desiccant will be required and serious operations will occur. Trouble and loss of yield because you will find that after you put in a lot of desiccant, the desiccant is still clumping. It is necessary to mix 10 times the volume of petroleum ether into amphetamine or methamphetamine to precipitate most of the water. According to visual inspection, only 200g of methamphetamine can precipitate 20~30ml of water. Use a small amount of desiccant after separation with a separatory funnel. The petroleum ether solution can be completely dried.

Incompatible materials:
-Whether it is amphetamine or methamphetamine, it is a stupid idea to use ethyl acetate or methylene chloride for dissolution, extraction, cleaning, etc. They will react with the amine and cause significant damage, even if the results are not irreversibly bad. , will also seriously affect the purity and flavor. This applies to all amine compounds. Amine does not interact with hydrocarbons such as petroleum ether, benzene, ethanol, isopropyl alcohol, and ether. Past experiments seem to show that amphetamine and methamphetamine have signs of reaction with tetrahydrofuran.

Stability:
-Amphetamine salts and methamphetamine salts are very stable in the air and almost do not deteriorate. However, amines that do not form salts are easily oxidized in the air and need to be stored with protective gas.

Liquid Chromatography:
The liquid chromatography of amphetamine and methamphetamine has better separation when using 100% tetrahydrofuran as the mobile phase. The Rf value is as follows:
-Amphetamine RF:0.4329
-Methamphetamine RF:0.6137~0.6274

Left Amphetamine Right Methamphetamine

When 100% ethanol or 100% isopropyl alcohol is used as the mobile phase, the position is similar to that of tetrahydrofuran, but it cannot effectively separate amphetamine and methamphetamine.

Chirality and medicinal efficacy:
-Weoften say that the dextrorotary forms of amphetamine and methamphetamine are more potent, but what exactly is the so-called dextrorotary form? In chemical theory, there are optical left-handed/right-handed and structural left-handed/right-handed respectively, so it is worthless to only describe left-handed/right-handed. After studying a large amount of data, we have completely confirmed that the so-called more effective dextrorotary amphetamine and dextrorotary Rotary methamphetamine, in fact, the official names are (+)S-amphetamine and (+)S-methamphetamine. They are both right-handed in optics, but left-handed in structural chemistry. ; and the less potent left-handed forms are (-)R-amphetamine and (-)R-methylamphetamine, which are optically left-handed but structurally right-handed.
-Academic research data shows that the dose-effect relationship of methamphetamine on serotonin is five times that of amphetamine. Therefore, there is a huge gap in the effectiveness of the two. Amphetamine is almost just a powerful stimulant with a simple stimulant effect. So, heating and smoking amphetamine hydrochloride will only produce a simple feeling of excitement and will not provide the expected experience of methamphetamine.

Data testing of chiral compounds is in progress. We will post the data in the comment area after the testing is completed.

Other:
After experimental verification, after we strictly reproduced the experimental content in(https://bbgate.com/threads/the-simplest-methamphetamine-synthesis-from-amphetamine.1671/), we have proven that using formaldehyde and aluminum amalgam to The scheme of methylating amphetamine to produce methamphetamine is actually not feasible. The output product looks very much like methamphetamine. It cannot directly form a solid when concentrated sulfuric acid is added dropwise to alcohol or petroleum ether. However, after TLC testing, it was found that only about 20% or even less of the amphetamine in the product was actually methylated, and it still contained as much as 70% to 80% amphetamine. This is all because the chemical balance to generate the enamine structure is very weak and aluminum The reduction of amalgam is not selective, and no cost-effective method exists to separate mixtures of amphetamine and methamphetamine. If you perform this method without data verification, you can end up with a "product" that visually looks like a crystal, but that is obviously just something with amphetamine-based ingredients. Below is the TLC data of the experimental results.

Left amphetamine, Middle cross-spot, Right reaction product

 

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I recrystallized (-)R-methylamphetamine-L-bitartrate to ensure that the ee value was as high as >99.9% and then used a polarimeter to directly characterize the optical rotation data of the pure liquid amine as follows:

Picture of recrystallized (-)R-methylamphetamine-L-bitartrate:

Pure and dry (-)R-methamphetamine(no solvent):

Pure (-)R-methamphetamine in 200mm polarimetric tube(no solvent):

Optical rotation characterization results of (-)R-methylamphetamine pure substance(The first photo is the starting scale for polarimeter calibration, and the second photo is the measurement result):

 

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I fully understood and studied the mechanism of separation of chiral isomers of methamphetamine, and optimized the complete process of chiral separation, beating, and crystallization. The yield of racemic methamphetamine base to dextromethamphetamine base reached 46%~47%, and the in-situ precipitated product during chiral separation can directly achieve the effect after recrystallization in the picture in this post, eliminating the need for recrystallization operation, and the ee value is as high as >99%; the beating process can remove excessive acid, certain The odor caused by some impurities, etc., the batch yield is >95%, and the total yield after recovery is close to 100%; the total single operation of the methamphetamine hydrochloride crystallization process takes about 2.5 hours, and an average size of 1~3mm flakes is obtained For crystals, the batch yield except the first batch is about 100%, the total yield is about 96%, and the total yield after recovery is >99%.

All process details parameters are accurately quantified and verified in practice to ensure good reproducibility.

This part of the process is classified as a trade secret by me because of its high value and will not be shared for free. If you need this, you can contact me through the forum private message channel.

Directly prepared and dried (+)S-methamphetamine hydrochloride

Beating (+)S-Methylamphetamine Hydrochloride

Crystallized (+)S-Methylamphetamine Hydrochloride Product

-From precise, highly reproducible and highly reliable process research and development work

 

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Photo of the final product of (+)S-methamphetamine produced through this process, purity>99.8%, ee>99.9%, no odor after human experience test

In addition, we found something interesting under strict experimental conditions. As a left-handed structure of the chiral isomer, the ingestion of (-)R-methamphetamine seems to cause severe skin oil overflow after about 20 minutes. Specifically The phenomenon is that the forehead, cheeks, and tip of the nose are full of oil and oil is constantly leaking out，Provides a polished and shiny appearance. This condition cannot be removed by washing with soap and other cleansers. In less than 20 minutes after washing, the amount of facial oil accumulates to the point that it can soak dry paper towels. To a certain extent, this skin oil overflow phenomenon gradually disappears after about 36 hours.

This grease overflow reaction seems to only require a very small amount of (-)R-methamphetamine residue to trigger. After our questionnaire survey, it seems that all methamphetamine hydrochloride products currently on the market have the ability to cause sebaceous overflow. Side effects, and when tested on humans using our manufactured ee>99.9% pure (+) S-methamphetamine hydrochloride without left-handed chiral residues, no signs of seborrhea were observed, and only a strong psychoactive effect occurred. Therefore, we have reason to determine that this phenomenon is entirely caused by (-)R-methamphetamine residue, a side effect that can technically be removed.

 

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This result suggests that the industry considers the feasibility of using seborrhea response as a highly accessible characterization indicator for chiral content assessment.

 

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Picture supplement
Pure and dry (+)S-methamphetamine(no solvent):

 

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I have tested DL-tartaric acid (CAS 133-37-9), D-tartaric acid (CAS 147-71-7), and L-tartaric acid (CAS 87-69- 4) Control variable method results and detailed data for all three tartaric acids. The following is a group photo of three kinds of tartaric acid separated by the controlled variable method under the forum process. The red words marked on the beaker are the types of tartaric acid used respectively. The separation process of DL-tartaric acid strictly follows the operation in(https://bbgate.com/media/d-methamphetamine-hydrochloride-synthesis-via-tartaric-acid.81/). After thorough analysis and study of this data, I optimized the version of the splitting process used today. Since these results are not freely available, I cannot disclose further details here. But I have to regretfully point out that judging from the research results, there are many problems with the splitting process in(https://bbgate.com/media/d-methamphetamine-hydrochloride-synthesis-via-tartaric-acid.81/) Problems and flaws, at least the finished product ee value it gets is not very high.
If you would like to share the process and original data, please contact me through the forum private message channel.

A group photo of the separated solid-liquid mixtures of three tartaric acids (L-tartaric acid [CAS 87-69-4] is used on the left, DL-tartaric acid [CAS 133-37-9] is used in the middle,and D-tartaric acid [CAS147-71-7] is used on the right)

The solid parts separated out by the separation of three kinds of tartaric acid (the left side comes from L-tartaric acid [CAS 87-69-4], the middle side comes from DL-tartaric acid [CAS 133-37-9], and the right side comes from D-tartaric acid [CAS147-71-7])