Mental ManaEducation, Harm-Reductio

Mental Mana

Education, Harm-Reduction, and Exploration.

Tuesday, June 25, 2013

Synthesis of Amphetamine Sulfate (Adderall) from Common Ingredients

Read my prior post on Amphetamine for general information regarding the chemical.First, something to say to the federal government I'm sure are starting to watch this site. This synthesis is for study only; I am not responsible if you decide to do something as stupid as manufacture an illicit chemical (which, I probably don't need to remind you, is very veryveryveryveryvery illegal). The single day, however, I let the federal government interfere with science is the day I die. Additionally, all chemical information is from external sources (cited); I am simply consolidating it into one document to alert government officials of possible clandestine means of production for amphetamine.I cannot recommend the study of this chemical process without prior university level chemistry lab work. Unless the below looks like child's play to you, I wouldn't even consider it. Amendment I of the constitution of the United States:Congress shall make no law respecting an establishment of religion, or prohibiting the free exercise thereof; or abridging the freedom of speech, or of the press; or the right of the people peaceably to assemble, and to petition the Government for a redress of grievances.Now then, let's get started. This is a remarkably easy synthesis.From the Erowid Mirror of Rhodium:A mixture of 40 g (0.3 mole) phenylacetone, 200 ml ethanol, 200 ml 25% ammonia, 40g (1.5 mole) Al-grit and 0.3 g (1 mmol) HgCl2 is warmed with vigorous stirring until reaction takes place, after which warming is stopped immediately. Cooling should be applied if the reaction becomes too violent. When the violence of the reaction has diminished, the mixture is refluxed with vigorous stirring for about 2 hr, concentrated in vacuo to 200 ml and poured into ice water, alkalinized with 120 g KOH, and extracted with ether. The extractions are treated with 20% HCl, the resulting water layer alkalinized and extracted with 150 ml ether. The organic layer is dried over Na2SO4, the ether evaporated, and the residue distilled in vacuo. Yield: 12.5 g (30%).Preparation of amphetamine sulfate yielded 96-98% product with a purity of 99.2-99.8% (USP grade)We do, however, come into what may be a big problem. Both Phenylacetone (P2P) and Mercuric Chloride are watched chemicals by the federal government (and with all the recent controversy regarding Edward Snowden and the PRISM program, I'm sure they're watching you anyway, even if you didn't reside in the United States. Although the DEA has not released the entire watched chemical list, we can assume that some are watched (a list of currently known watched chemicalshere). We can bypass (the known) watched chemicals, but I'm sure you would still raise a few eyebrows using this synthesis. Even with the dawn of the internet and overseas shipping, there is no safe way to make illegal chemicals. Do it, and you probably will go to jail.In order to obtain P2P ( IUPAC: 1-phenylpropan-2-one; also known as phenylacetone, enzyl methyl ketone, methyl benzyl ketone, and phenyl-2-propanone) there are a plethora of possible synthesis. From the Erowid Mirror of Rhodium (2):2-Phenylpropanal can be rearranged with either mercuric chloride (HgCl2) or sulfuric acid (H2SO4) to form the isomeric phenyl-2-Propanone (P2P). 2-Phenyl-propanal (hydratropic aldehyde) is an unwatched industrial chemical which is used in the perfume industry. 2-phenylpropanal can also be made from alpha-methylstyrene.The CAS number for 2-phenyl-propanal is [93-53-8], and synonyms for it include Hydratropic aldehyde; 2-Phenylpropionaldehyde; Cumenealdehyde; alpha-methyl benzeneacetaldehyde and alpha-methyl phenylacetaldehyde. Boiling point 92-94°C/12mmHg, 222°C/760mmHg.There are other ways of performing this rearrangement, 2-phenylpropanal is isomerized to phenyl-2-propanone in up to 87% yield by passing its vapor over an iron zeolite catalyst bed at 500°C, followed by condensation of the vapors and redistilling the P2P.Even if the method below which uses mercuric chloride is higher yielding than the one using cold sulfuric acid, I would definitely reccommend the one with sulfuric acid, as it is much cheaper to use, and is not disastrous for your health or the environment. 60g of mercuric chloride contains 45 grams of mercury, enough to poison a medium-sized lake if released into the environment, and if you happen to ingest it yourself, it will accumulate in your body.It is not possible to effectively separate 2-phenylpropanal (bp 222°C/760mmHg) from phenyl-2-propanone (bp 214°C/760mmHg) through simple distillation and certainly not via vacuum distillation as the boiling points are too close. Fractional distillation could theoretically be used to separate them, but the size of the column that would have to be used makes that option impractical. A good idea for separating a mixture of the two is to oxidize the mixture with a mild oxidant which won't affect the P2P, but which will oxidize the aldehyde to 2-phenylpropionic acid. The acid can then be separated from the ketone by dissolving the mixture in a non-polar solvent and washing the solution with dilute sodium hydroxide. The P2P stays in the organic layer, which is then dried over MgSO4, the solvent removed under vacuum and the residue vacuum distilled to give pure P2P.Method A30g of 2-phenylpropanal is heated together with a mixture of 60g mercuric chloride (HgCl2, 1 eq.) and 450ml 75% ethanol in a pressure-safe sealed glass container for 4.5h at 100°C in a boiling water bath, during which time a precipitate forms. Water is added, and the solution is steam-distilled (during which operation the precipitate redissolves). The distillate is extracted with ether, dried, and the solvent is evaporated. The oily residue is then vacuum distilled with a fractionating column to collect the phenyl-2-propanone in a yield of 80% or more, bp 92-101°C at 14mmHg.When 0.1 equivalents of HgCl2 was used, only 10% phenyl-2-propanone was formed, the rest consisted of unchanged aldehyde.Method B9 g of 2-phenylpropanal is slowly added with good stirring during 35 minutes to 40ml concentrated sulfuric acid, while the temperature of the reaction mixture is kept at -16°C. After all the 2-phenylpropanal has been added, the mixture is allowed to stand at the same temperature for another 15 minutes, and then the mixture is poured onto crushed ice (100-150g is probably a suitable amount). When the ice has melted, the organics are extracted from the water phase by 3x50ml diethyl ether, the pooled organic phases dried over MgSO4, the ether distilled off and finally the residue is vacuum distilled (bp 91-96°C at 11 mmHg) to give 5.6g (62%) of phenyl-2-propanone.For the precursor to the above synthesis, we can use aplha-methylstyrene; from here. This is for the synthesis to go straight into the  Phenylacetone (phenyl-2-propanone) as well as 2-phenylpropanal.118g alpha-Methylstyrene was added to a mixture of 160g of bromine and 1200ml 15% H2SO4, and the mixture was heated at 80°C for 8h. The mixture was cooled to room temperature and the organic layer separated, and the aqueous layer extracted with benzene. The extracts and organic layer was mixed and dried over Na2SO4. The benzene was evaporated under vacuo, and the residue was vacuum distilled, and the fraction boiling at 75-85°C/8mmHg weighed 75g and was purified via its bisulfite adduct to give a product mixture boiling at 78-81°C/4 mmHg in 57% yield, consisting of 48.5% 2-phenylpropanal and 51.5% phenyl-2-propanone.Now that we have our P2P, let us get started with our Mercuric Chloride.From polymerizer87 of Sciencemadness.org:Ill start with the HgSO4 formation:Hg + 2 H2SO4 → Hg(SO4) + SO2 + 2 H2OA conical flask (Erlenmeyer) equipped with a magnetic stirbar was charged with 39.56 g of Hg and ~120 mL of H2SO4 ( I used a beaker you all know how accurate these things are). Gradually heat was applied and magnetic stirring was started. Initially the solution appeared clear with beads of Hg at the bottom of the flask. A thermometer was not used in the initial reaction, once white vapors appeared the heat was turned down to minimize acid loss. The entire reaction was stirred for 18 hours to ensure all Hg had converted to HgSO4. (note;he used concentrated sulfuric acid. If he had used dilute sulfuric acid, he would have to wait for the excess water to evaporate. Additionally, the fumes given off from this reaction will absolutely destroy your lungs, and as mercuric salts have low sublimation temperatures, they WILL give off substantial amounts of fumes. Think about it this way. In 1997 Karen Wetterhahn died from mercury poison. Who was she? She was a Ph.D professor at the Dartmouth College. She died from a few drops of dimethylmercury on top of a latex glove she was wearing and died as a result. She probably knew way, way, way more about chemistry than you or I do (definitely more about mercury than anybody I know), and still this tragedy happened. Mercury is a very volatile compound demanding the utmost respect. Ideally, highly resistant, flexible, plastic-laminate gloves with neophrene long-cuffs should be worn when working with mercury, and all work should be done under a fume hood. This may be an easy synthesis, but it is by far not a safe synthesis!) ...at ~14 hours into the reaction I looked under the flask and saw a rather large bead of Hg, So I turned up the heat and hit it pretty hard for about an hour. After turning the heat down I let it sit for another 2 hours and came back with no residual Hg left in the flask!The excess H2SO4/H2O was decanted off the HgSO4, and a previously prepared 1 L dH2O HOT was poured into the Erlenmeyer flask until the HgSO4 turned bright yellow/orange (I agree with the commentary on Erowid that the addition of hot dH2O may be decomposing the HgSO4, I'm considering taking this out) The HgSO4/dH2O/resi

Results (Indonesian) 1:

Mental ManaPendidikan, pengurangan dampak buruk, dan eksplorasi.Selasa, Juni 25, 2013Sintesis Amphetamine sulfat (Adderall) dari bahan umumRead my prior post on Amphetamine for general information regarding the chemical.First, something to say to the federal government I'm sure are starting to watch this site. This synthesis is for study only; I am not responsible if you decide to do something as stupid as manufacture an illicit chemical (which, I probably don't need to remind you, is very veryveryveryveryvery illegal). The single day, however, I let the federal government interfere with science is the day I die. Additionally, all chemical information is from external sources (cited); I am simply consolidating it into one document to alert government officials of possible clandestine means of production for amphetamine.I cannot recommend the study of this chemical process without prior university level chemistry lab work. Unless the below looks like child's play to you, I wouldn't even consider it. Amendment I of the constitution of the United States:Congress shall make no law respecting an establishment of religion, or prohibiting the free exercise thereof; or abridging the freedom of speech, or of the press; or the right of the people peaceably to assemble, and to petition the Government for a redress of grievances.Now then, let's get started. This is a remarkably easy synthesis.From the Erowid Mirror of Rhodium:A mixture of 40 g (0.3 mole) phenylacetone, 200 ml ethanol, 200 ml 25% ammonia, 40g (1.5 mole) Al-grit and 0.3 g (1 mmol) HgCl2 is warmed with vigorous stirring until reaction takes place, after which warming is stopped immediately. Cooling should be applied if the reaction becomes too violent. When the violence of the reaction has diminished, the mixture is refluxed with vigorous stirring for about 2 hr, concentrated in vacuo to 200 ml and poured into ice water, alkalinized with 120 g KOH, and extracted with ether. The extractions are treated with 20% HCl, the resulting water layer alkalinized and extracted with 150 ml ether. The organic layer is dried over Na2SO4, the ether evaporated, and the residue distilled in vacuo. Yield: 12.5 g (30%).Preparation of amphetamine sulfate yielded 96-98% product with a purity of 99.2-99.8% (USP grade)We do, however, come into what may be a big problem. Both Phenylacetone (P2P) and Mercuric Chloride are watched chemicals by the federal government (and with all the recent controversy regarding Edward Snowden and the PRISM program, I'm sure they're watching you anyway, even if you didn't reside in the United States. Although the DEA has not released the entire watched chemical list, we can assume that some are watched (a list of currently known watched chemicalshere). We can bypass (the known) watched chemicals, but I'm sure you would still raise a few eyebrows using this synthesis. Even with the dawn of the internet and overseas shipping, there is no safe way to make illegal chemicals. Do it, and you probably will go to jail.In order to obtain P2P ( IUPAC: 1-phenylpropan-2-one; also known as phenylacetone, enzyl methyl ketone, methyl benzyl ketone, and phenyl-2-propanone) there are a plethora of possible synthesis. From the Erowid Mirror of Rhodium (2):2-Phenylpropanal can be rearranged with either mercuric chloride (HgCl2) or sulfuric acid (H2SO4) to form the isomeric phenyl-2-Propanone (P2P). 2-Phenyl-propanal (hydratropic aldehyde) is an unwatched industrial chemical which is used in the perfume industry. 2-phenylpropanal can also be made from alpha-methylstyrene.The CAS number for 2-phenyl-propanal is [93-53-8], and synonyms for it include Hydratropic aldehyde; 2-Phenylpropionaldehyde; Cumenealdehyde; alpha-methyl benzeneacetaldehyde and alpha-methyl phenylacetaldehyde. Boiling point 92-94°C/12mmHg, 222°C/760mmHg.There are other ways of performing this rearrangement, 2-phenylpropanal is isomerized to phenyl-2-propanone in up to 87% yield by passing its vapor over an iron zeolite catalyst bed at 500°C, followed by condensation of the vapors and redistilling the P2P.Even if the method below which uses mercuric chloride is higher yielding than the one using cold sulfuric acid, I would definitely reccommend the one with sulfuric acid, as it is much cheaper to use, and is not disastrous for your health or the environment. 60g of mercuric chloride contains 45 grams of mercury, enough to poison a medium-sized lake if released into the environment, and if you happen to ingest it yourself, it will accumulate in your body.It is not possible to effectively separate 2-phenylpropanal (bp 222°C/760mmHg) from phenyl-2-propanone (bp 214°C/760mmHg) through simple distillation and certainly not via vacuum distillation as the boiling points are too close. Fractional distillation could theoretically be used to separate them, but the size of the column that would have to be used makes that option impractical. A good idea for separating a mixture of the two is to oxidize the mixture with a mild oxidant which won't affect the P2P, but which will oxidize the aldehyde to 2-phenylpropionic acid. The acid can then be separated from the ketone by dissolving the mixture in a non-polar solvent and washing the solution with dilute sodium hydroxide. The P2P stays in the organic layer, which is then dried over MgSO4, the solvent removed under vacuum and the residue vacuum distilled to give pure P2P.Method A30g of 2-phenylpropanal is heated together with a mixture of 60g mercuric chloride (HgCl2, 1 eq.) and 450ml 75% ethanol in a pressure-safe sealed glass container for 4.5h at 100°C in a boiling water bath, during which time a precipitate forms. Water is added, and the solution is steam-distilled (during which operation the precipitate redissolves). The distillate is extracted with ether, dried, and the solvent is evaporated. The oily residue is then vacuum distilled with a fractionating column to collect the phenyl-2-propanone in a yield of 80% or more, bp 92-101°C at 14mmHg.When 0.1 equivalents of HgCl2 was used, only 10% phenyl-2-propanone was formed, the rest consisted of unchanged aldehyde.Method B9 g of 2-phenylpropanal is slowly added with good stirring during 35 minutes to 40ml concentrated sulfuric acid, while the temperature of the reaction mixture is kept at -16°C. After all the 2-phenylpropanal has been added, the mixture is allowed to stand at the same temperature for another 15 minutes, and then the mixture is poured onto crushed ice (100-150g is probably a suitable amount). When the ice has melted, the organics are extracted from the water phase by 3x50ml diethyl ether, the pooled organic phases dried over MgSO4, the ether distilled off and finally the residue is vacuum distilled (bp 91-96°C at 11 mmHg) to give 5.6g (62%) of phenyl-2-propanone.For the precursor to the above synthesis, we can use aplha-methylstyrene; from here. This is for the synthesis to go straight into the Phenylacetone (phenyl-2-propanone) as well as 2-phenylpropanal.118g alpha-Methylstyrene was added to a mixture of 160g of bromine and 1200ml 15% H2SO4, and the mixture was heated at 80°C for 8h. The mixture was cooled to room temperature and the organic layer separated, and the aqueous layer extracted with benzene. The extracts and organic layer was mixed and dried over Na2SO4. The benzene was evaporated under vacuo, and the residue was vacuum distilled, and the fraction boiling at 75-85°C/8mmHg weighed 75g and was purified via its bisulfite adduct to give a product mixture boiling at 78-81°C/4 mmHg in 57% yield, consisting of 48.5% 2-phenylpropanal and 51.5% phenyl-2-propanone.Now that we have our P2P, let us get started with our Mercuric Chloride.From polymerizer87 of Sciencemadness.org:Ill start with the HgSO4 formation:Hg + 2 H2SO4 → Hg(SO4) + SO2 + 2 H2OA conical flask (Erlenmeyer) equipped with a magnetic stirbar was charged with 39.56 g of Hg and ~120 mL of H2SO4 ( I used a beaker you all know how accurate these things are). Gradually heat was applied and magnetic stirring was started. Initially the solution appeared clear with beads of Hg at the bottom of the flask. A thermometer was not used in the initial reaction, once white vapors appeared the heat was turned down to minimize acid loss. The entire reaction was stirred for 18 hours to ensure all Hg had converted to HgSO4. (note;he used concentrated sulfuric acid. If he had used dilute sulfuric acid, he would have to wait for the excess water to evaporate. Additionally, the fumes given off from this reaction will absolutely destroy your lungs, and as mercuric salts have low sublimation temperatures, they WILL give off substantial amounts of fumes. Think about it this way. In 1997 Karen Wetterhahn died from mercury poison. Who was she? She was a Ph.D professor at the Dartmouth College. She died from a few drops of dimethylmercury on top of a latex glove she was wearing and died as a result. She probably knew way, way, way more about chemistry than you or I do (definitely more about mercury than anybody I know), and still this tragedy happened. Mercury is a very volatile compound demanding the utmost respect. Ideally, highly resistant, flexible, plastic-laminate gloves with neophrene long-cuffs should be worn when working with mercury, and all work should be done under a fume hood. This may be an easy synthesis, but it is by far not a safe synthesis!) ...at ~14 hours into the reaction I looked under the flask and saw a rather large bead of Hg, So I turned up the heat and hit it pretty hard for about an hour. After turning the heat down I let it sit for another 2 hours and came back with no residual Hg left in the flask!The excess H2SO4/H2O was decanted off the HgSO4, and a previously prepared 1 L dH2O HOT was poured into the Erlenmeyer flask until the HgSO4 turned bright yellow/orange (I agree with the commentary on Erowid that the addition of hot dH2O may be decomposing the HgSO4, I'm considering taking this out) The HgSO4/dH2O/resi