Clandestine Drugs - Assignment Example

Running Head: Clandestine Drugs Clandestine Drugs Name Institution CLANDESTINE DRUGS Q. What is the structure of thebaine? Thebaine (6,7,8,14-tetradehydro-4,5-epoxy-3,6-dimethoxy-17-methylmorphinan), has the structure shown above. It has the formula C19H21NO3. Thebaine has been obtained via the utilization of crystal X ray method which is conducted at low temperatures (Mahler & Stevens, 1996). Q. Identify some common licit drugs it is used to manufacture; Thebaine is utilized in the production of the drugs that follow; oxycodone, nalbuphine, buprenorphine, naloxone, oxymorphone and naltrexone (Mahler & Stevens, 1996). Q. What is the phenanthrene skeleton? Phenanthrene is a form of polycyclic aromatic hydrocarbon made up of three merged benzene rings. It is composite of anthracene and phenyl. It exists in cigarette smoke in its pure form and as such is an irritant. Phenanthrene skeleton is a sub-class of phenanthrene (Snow, 2000). It is obtained by expansion or contraction of one ring by single or double atoms, by expansion or contraction of double rings each facilitated by a single atom, by the substitution of single or double carbon atoms of a given cyclopenta (a) phenanthrene skeleton obtained from given hetero atoms, in conjunction with the aforementioned expansion or contraction. phenanthrene Q. Write a flow chart showing the steps involved in heroin manufacture and explain the chemistry involved in each step. For example I want to know things like why does morphine form a water soluble salt with Ca (OH)2 yet most of the other alkaloids do not ? Why is acid added in step 2 etc. Flow Chart After step 4, adulterants and diluents may be added by the manufacturer or by individuals further along the chain of distribution. Also, shortcuts may further be taken at various steps; 2, 3 and 4. Steps 2 and 4 are able to be eliminated altogether (Delgado, 1991). 1. Opium purification Unprocessed opium is put into a boiling water pot. The step dissolves all the opium alkaloids while the undissolved solid material is removed through filtration by the use of material for instance cheesecloth. The alkoid solution is heated to facilitate the evaporation of water leaving thick, dark paste that is allowed to dry in air. The dried alkoid solution is putty like rock and is usually around 20% more pure than any given raw material. It is then exported to heroin manufacturers. 2. Extraction of morphine Processed opium is entirely dissolved in calcium hydroxide and water, at around one-fifth of the given opium mass. The aforementioned has the effect of turning morphine, which is insoluble in given cool water into calcium morphenate which is a soluble salt. The other alkaloids available in solution do not react (Garbrecht, 1959). On the other hand, after the cooling of the mixture, the morphenate is left in solution while the chemicals settle and result into the formation of brown sludge that settles at the bottom of the container. Since codeine is water soluble some amounts of it remains in solution. Insoluble impurities that are available in calcium morphenate are filtered and passed through burlap rice sacks to be removed. The filtered solution is heated and ammonium chloride added to about a fourth of its opium mass. The solution pH is adjusted to around 8 or 9. The morphine base and codeine precipitate out of the solution after cooling. The solution is poured off through given cloth filters that leave morphine base chunks on it. The morphine chunks are squeezed dry and air dried aside. The residue is coffee colored. From this given point, production could move to step 3 directly. Ideally, crude morphine base may be further purified by its dissolution in sulfuric or hydrochloric acid leading to the formation of morphine hydrochloride. The solution is heated after the addition of activated charcoal and filtered while still hot through fine cloth. The filtration process is severally repeated and colored impurities and charcoal removed in the process. The filtrate may be sun dried leaving morphine hydrochloride behind which is a white powder upon the completion of purification. The filtrate may further be pressed into given 1 kg bricks and ultimately transferred for more processing at a given remote site. Another method is through the addition of ammonium hydroxide into morphine HCl solution that precipitates a morphine base, is filtered and consequently dried so as to form a given granular solid (Mann, 1994). 3. Conversion to heroin base Acetylation of morphine is done by the use of acetic anhydride which is a colorless liquid that is highly combustible. Morphine base or morphine hydrochloride is mixed by around three-times the weight of the morphine hydrochloride by the use of acetic anhydride and then it is gently heated at a temperature of around 85 degrees for a period of 5 hours. The time period ensures that all the morphine is dissolved. The solution that results which is constituted of water, diacetylmorphine (heroin) and acetic acid is prevented from cooling (Soine, 1986). Water is then added to the mixture obtained at around three-times of the acetic anhydride volume. The mixture is then stirred. A small quantity of chloroform is put into the mixture and allowed to sit for 20 minutes. Chloroform dissolves the colored impurities and as such settles to the pot’s bottom as a liquid that is red and greasy. The remnant water layer is poured off. Activated charcoal is put into the mixture, and as such it absorbs solid impurities which are then filtered out until solution is clear. A quantity of 2.2 kilograms sodium carbonate of morphine per kilogram were dissolved in a given amount of hot water which was added slowly until the stop of effervescence and the precipitation of a solid heroin base. Heroin base is as such filtered with fine cloth and heated till dry. The heroin base is as such granular and white powdered. Around 700 grams heroin base is manufactured from each morphine kilogram. Heroin base is further purified by the dissolution of the base into twice its mass in boiling ethyl alcohol. The solution is then filtered via a heated funnel and collected into a flask. The dissolution serves to remove the remnant amounts of sodium carbonate that is available in the base. The flask is then submerged into an ice bath. It is further transformed into a given thick white cream. The substance is then put into a refrigerator pan that has a pan that blows across it to evaporate alcohol. The paste sets after several hours. It is vacuum filtered. The emerging product is “alcohol morphine base” which is re-crystallized heroin base (Erowid, 2007). 4. Conversion to heroin hydrochloride For each heroin base kilogram, 225mL concentrated hydrochloric acid, 6.6L of ethanol and 6.6L of the ether is put out. The dissolution of the base is affected by heating it with a third of alcohol and a half of acid. It then follows that the remnant acid is added drop wise until the completion of the conversion to hydrochloride salt. On the completion of conversion, the remnant alcohol is put into the mixture and permitted to stand for around 15 minutes. When crystals begin to develop in the solution, the remnant ether is added at a go and the vessel is then covered. The mixture is nearly solid after a one hour period and is filtered and dried off. The product that is fully dried is heroin hydrochloride which is fine and white. It is then packed and shipped. Q. Ritalin is another drug commonly used in the treatment of ADHD. What is the structure of ritalin and how does it compare to amphetamine? Ritalin (methylphenidate). It has a similar backbone structure as amphetamine. However it is more complicated and as such has different results on the body than other amphetamines like methamphetamine. For instance Ritalin has a less euphoric effect than methamphetamine (Barkley, 2001). Q. Why must the benzene be anhydrous in the Friedel Crafts method above? To act as a lewis acid and as such react effectively with aluminium chloride this is an electron withdrawing compound of minimal strength. Q. You will often here of the term ‘free base’ as it applies to drugs (licit or illicit). What does the term actually mean? The term free base is in reference to the pure basic amine form that is in contrast to the salt form generated from it. The amine is more often than not a natural alkaloid product. Free base is usually utilized in pharmaceuticals and organic chemistry in the description of unprotonated amine compound form. Q. How can nitromethane be converted into methylamine? Nitromethane is converted into methylamine by the use of an alcoholic solution of methylenedioxyphenyl-2-propanone and nitromethane that is dipped into a given quantity of amalgamated aluminum that is immersed in alcohol. During the reaction, the nitromethane is first reduced to methylamine thus allowing for the Schiff base of the ketone and amine to form. Q. Pseudoephedrine as shown in Scheme 7 is drawn without stereochemistry. What is the stereochemistry of 8seudoephedrine? 4. Q. How many possible stereoisomers with the structure of pseudoephedrine exist? 2 as shown in the diagram below. (Erowid, 2007). Q. Does it matter what stereoisomer you start the synthesis with? Yes. The production of methamphetamine that is derived from methylamine and phenyl-2-propanone (P2P) gives (±)-methamphetamine, on the other hand the reduction of (+)-pseudoephedrine or (-)-ephedrine gives (+)-methamphetamine. Q. Some of the impurities that were found in heroin synthesis stemmed from the natural products in the opium. What are some of the impurities found in speed prepared using the method shown in Scheme 7? Naphthalene impurities and neutral P2P (phenyl-2-propanone). Q. How much nicotine administered intravenously would it take to kill an average (80 kg) adult? 40-60mg would kill an adult (Stapleton et al, 2006). Q. How much is in a single cigarette? Around 1mg. Q. Outline a synthetic sequence modeled on one of the methods discussed above that could be used for the production of ecstacy. Outline: -------- oil of sassafras -------> safrole ----------> isosafrole --------> MDP-2-P (extraction) | (isomerization) (synthesis) | | | V V *1. safrole + HBr *1. sodium cyanoborohydride 2. Ritter reaction *2. aluminum amalgam 3. sodium borohydride piperonal ------> beta-nitroisosafrole 4. Raney Ni catalyst (synthesis) | 5. Leukart reaction | V [numerous routes to MDA] (Dal Cason, 1990) The most prevalent route for the manufacture of MDMA, MDE (MDEA), MDA and MDOH are obtained from MDP-2-P precursor. MDP-2-P is derived from safrole which extracted from sassafras oil. Safrole is isomerized into isosafrole through the heating with KOH or NaOH. Isosafrole is oxidized into MDP-2-P. Once MDP-2-P is produced; several synthetic routes can be taken as outlined above. Sodium cyanoborohydride technique is the preferred technique Safrole + HBr route is conducive due to its simplicity Aluminum amalgam route is a useful cyanoborohydride, on the other hand it may have a high failure risk. The methods that are directly from safrole are ritter reaction which has poor yields and HBr method which produces 3,4-methylenedioxyphenyl-2-bromopropane that is converted into MDMA. Beta-nitroisosafrole route results into MDA which is as a result of the reaction of beta-nitroisosafrole with Raney Ni catalyst which is ultimately converted into MDMA (Cason, 1990). Q. Show the mechanism of the Henry reaction and compare it to a classical Aldol reaction? Aldol reaction It results in the event an aldehyde ketone or enolate reacts at its α-carbon with a carbonyl of a different molecule under acidic or basic conditions so as to yield ketone or β-hydroxy aldehyde. Mechanism Henry reaction Henry Reaction is catalyzed by a base at the C-C bond that leads to the formation of a reaction between aldehydes or ketones and nitroalkanes. It is identical to Aldol Addition and as such called Nitro Aldol Reaction. In the event that acidic protons are present (when R = H), the yields eliminate water to produce nitroalkenes. As a result, only limited base quantities can be utilized if the isolation of various β-hydroxy nitro-compounds is desired. Q. In the second part of the reaction scheme above outline a possible method that could be used for the conversion of MDA into MDMA. (Allen et al, 1987). Q. Discuss the chemistry involved in the extraction process paying particular attention to the pH involved at each stage and explain why this is done. Lysergic acid is prepared from a fungus through a series of steps in which the pH is closely regulated. The first step entails the extraction of mycelia matt through the use of acetone and 2% tartaric acid. The acetone is then removed and the basicity of the residue is ensured so as to facilitate the extraction of the solvent. The residue is composed of ergot alkaloids and lysergic acid is precipitated after the residue is acidified. The acidification results into the precipitation of crude lysergic acid. Q. Write a short essay detailing the chemistry involved with cocaine. Cocaine refers to the name given to benzoylmethyl ecgonine, which is a crystalline alkaloid obtained from coca plant. It is a stimulant. It is mostly snorted into the body. Cocaine acts as an appetite suppressant, stimulant and anesthetic. Users usually feel a 'rush' that is followed by a feeling of wellbeing and alertness. It increases dopamine levels which is a neurotransmitter that is associated with increased movement and pleasure. When the cocaine effect wears off then the user may in turn feel more depressed than before drug consumption. Q. Write a short essay detailing the chemistry involved with marijuana. The term marijuana is the name given to Cannabis sativa. Its active ingredient is THC or tetrahydrocannabinol. It may be smoked or ingested. When smoked its effects may last for between 1-3 hours while when ingested its effects may last for up to 4 hours. Marijuana accelerates heart rate, enlarges and relaxes bronchial passage. It also dilates eye blood vessels and they as such appear bloodshot. Ultimately, THC results into the increased release of dopamine that results into euphoria. References Soine W. H. (1986). Medicinal Research Reviews, 6 (1), 41-74. Garbrecht W. L. (1959). Synthesis of Amides of Lysergic Acid; Journal of Organic Chemistry, 24, 368-372. Snow O. (2000). LSD-25 &Tryptamine Synthesis, Overview & Reference Guide for Professionals. Thoth Press. Delgado J. N. et al 9th Edition (1991). Textbook of Organic Medicinal and Pharmaceutical Chemistry. New York-Lippincott. New Scientist (2002). "Ecstacy : How Dangerous is it really?" 26-33. Mann J. (1994). Chemical Aspects of Biosynthesis, Oxford Scientific Publications, OUP. Snow O. (1998). LSD-25 &Tryptamine Syntheses: Overview and Reference Guide for Professionals. Thoth Press. Erowid (2007). Chem-Compare Compare Chemical Molecules Side by Side. Vol.1.2. Retrieved 19th October 19, 2011 from http://www.erowid.org/ask/ask.php?ID=2846 Barkley, R. (2001). Medicating Kids. Interview: Frontline, PBS. Retrieved 15th October 2011 from http://www.pbs.org/wgbh/pages/frontline/shows/medicating/interviews/barkley.html Ritter (1957). Who Needs Methylamine Anyway? Chem. Abs., 51 11278. Retrieved 16th October 2011 from http://www.drugs-forum.com/chemistry/chemistry/ritter-alhg.html Mahler, C.H & Stevens, E.D (1996). Crystal Structure Communications. Vol: 52, part 2 retrieved October 18th from http://www.justice.gov/dea/concern/thebaine.html Allen, A.C et al (1987). Methamphetamine from Ephedrine: I. Chloroephedrines and Aziridines. Journal of Forensic Sciences. 32, 953-962. Retrieved 15th October 2011 from http://www.erowid.org/archive/rhodium/chemistry/meth.impurities2.html Stapleton, J.M et al (2006). Intravenous Nicotine Reduces Cerebral Glucose Metabolism: A Preliminary Study. Retrieved 15th October 2011 from http://www.nature.com/?file=/npp/journal/v28/n4/full/1300106a.html Cason, D. (1990). "An Evaluation of the Potential for Clandestine Manufacture of 3,4-Methylenedioxyamphetamine (MDA)Analogs and Homologs."Journal of Forensic Sciences. Vol 35(3):675-697. Read More