Birch reduction of ephedrine.
and nuclear magnetic resonance (NMR) tests.
Birch reduction of ephedrine Formation of a New, Versatile Intermediate for Organic Synthesis Gury Zvilichovsky* and Isra Gbara-Haj-Yahia Department of Organic Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel [email protected] Received February 16, 2004 Abstract: The reduction of (-)-ephedrine by lithium in liquid ammonia resulted Birch reduction that uses sodium hydroxide and ammonium nitrate to produce ammonia gas in situ that can strip lithium of electrons and use them to reduce pseudoephedrine to MA (Figure 1); 1. Compounds that exhibit reac- Birch. Mar 1, 2025 · The Birch reduction usually reduces the aromatic ring, but in this case it eliminates the hydroxy group of ephedrine to give methamphetamine. 101 The major products are usually the 1,4-dihydro derivatives in accord with ESR evidence, which shows that a trimethylsilyl group stabilizes aromatic radical anions. il Received February 16, 2004 Abstract: The reduction of (-)-ephedrine by lithium in Aug 6, 2004 · The reduction of (-)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine. The ozonolysis of this group was A deep royal blue color was noted as the lithium metal dissolved in the condensed ammonia. PROCEDURE 1: A mixture of 80. Birch Chemistry Department, Australian National University, Canberra ACT 0020, Australia Abstract: The unique availability of substituted cyclohaa-I, 4and 1,Edienes notably enol ethers, from Birch reduction of benzenes, permits many novel synthetic reactions of general utitility. 73 grams/mole. The ephedrine freebase MUST BE DRIED before using in a birch reduction as ephedrine forms a hydrate (ephedrine. One common method- of illicit methamphetamine manufacture utilizes an alkali metal, typically lithium, and liquid ammonia to chemically reduce ephedrine or pseudoephedrine to form methamphetamine. I thought this article would be good for the identification of 1-(1,4-cyclohexadien-1-yl)-N-methyl-2-pr opanamin e (2) which is the product resulting from "overreduction" of (pseudo)ephedrine under Birch conditions. The use of Mar 2, 2007 · The reduction of (-)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine, a potentially versatile intermediate for further synthetic transformations. Forensic Scientist Jun 1, 2020 · The One Pot method is a variation of the Birch reduction method, which utilizes ammonia and an alkali metal to reduce pseudoephedrine or ephedrine to MA. Soc. In this process, lithium serves as an electron source with ammonia as a solvent that allows the electrons to reduce the hydroxyl group of ephedrine to form methamphetamine. , 1-(1,4-cyclohexadienyl)-2-methylaminopropane (CMP). 2 (VI)) is a reduction reac tion of ephedrine/psedoephedrine using excess alkali m etal e. 1/2 H2O). Apr 1, 2007 · Details of the production process (reduction of ephedrine) and its similarity with the synthesis of "Vint, " and the similarity of the plants effects suggest that the final injectable solution Jan 1, 2020 · Birch/Nazi route (Fig. Chem. Previous studies show that as the reduction progresses, ephedrine is consumed while the aziridines (cis- and trans-1,2-dimethyl-3-phenylaziridine) evolve. Apr 8, 2021 · This undergraduate dissertation project was designed to enhance organic and analytical chemistry skills of final year forensic science students. It provides steric control is one of the most This undergraduate dissertation project was designed to enhance organic and analytical chemistry skills of final year forensic science students. The use of Jan 1, 2005 · Structural determination of the principal byproduct of the lithium-ammonia reduction method of methamphetamine manufacture. J. The Li-amine gets 88% 2,5 dihydroisoproplylbenzene. Emde incorrectly cites Ogata 6 as producing (+)-methamphetamine in 1919 by heating (-)-ephedrine or (+)-pseudoephedrine with HI and yellow phosphorus. This forms a STABLE Imine which can be extracted and reduced in a Birch reaction, just use one more equivalent of Lithium then with a plain ephedrine reduction. org During a typical reduction of (pseudo)ephedrine, only the hydroxyl group is reduced, producing methamphetamine. The reduction of (−)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine. Reduction With Palladium/Barium Sulfate--Bromo or Chloro Ephedrine Reduced to Methamphetamine: Apr 11, 2023 · 8-Phenylmenthol esters of salicylic acid derivatives undergo efficient Birch reduction and in situ diastereoselective alkylations to afford methoxycyclohexadienes bearing new quaternary stereogenic centers. , 1-(1,4cyclohexadienyl)-2-methylaminopropane (CMP). Propose a mechanism, similar to that for the Birch reduction, to explain this unusual course of the reaction. The mixture is then allowed to stand until the ammonia has evaporated. The resulting 1,4-cyclohexadienyl group is a potentially versatile intermediate for further synthetic I plan on using the modified birch reduction on a small amount of Ephedrine and I would like some of you more experienced people to look over my procedure and give me feedback on it before I attempt it. Jun 1, 2020 · The One Pot method is a variation of the Birch reduction method, which utilizes ammonia and an alkali metal to reduce pseudoephedrine or ephedrine to MA. The reaction conditions are alcohol-free, ammonia-free, and achieve excellent yields and high selectivities at room temperature. Birch Reduction of (-)-Ephedrine. Nagai Method. In addition to the reduction of the aromatic ring, the hydroxy group was reduced as well. 2 The most common strategy employes HI (Nagai route) or Birch reduction. Compounds that exhibit reac- Birch Reduction of (-)-Ephedrine. Ely,DC. 8 One Supporting: 2, Mentioning: 7 - The reduction of (-)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine. Jul 8, 2004 · The reduction of (−)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine. In recent years, a modification of the Birch reduction referred to as “shake and bake” has become the method of choice for illicit methamphetamine synthesis . The reaction of sodium Dec 1, 1990 · The illicit manufacture of methamphetamine from ephedrine via reduction with hydriodic acid and red phosphorus is discussed. P2P. … Dec 10, 2019 · methylamine), Red-P (reduction of ephedrine using red phosphorus and hydroiodic acid) or the Birch reduction method. , lithium/s odium in liquid ammonia to form 1-(1 ʹ ,4 ʹ -cyclohexadienyl)- Oct 17, 2019 · Birch Reduction of Electron-Rich and Electron-Poor Aromatic Molecules – Examples and Mechanisms. . The ozonolysis of this group was Nov 2, 2012 · A Birch‐type reduction enabled the reductive removal of the β‐hydroxy group from (2S)‐2‐amino‐3‐hydroxy‐2‐methyl‐3‐phenylpropanoic acid to generate enantiopure L‐α‐methyl Hydrogenolysis of ephedrine or phenylpropanolamine (here hydrogenolysis is defined as reduction of C-X) is not a result of reduction of the benzylic carbon-OH bond. And a special for carl: Dexamphetamine can be prepared directly from l-PAC by the BIRCH if B+enzylamine is used for the amination. See full list on erowid. McGrath,1990 A suspected clandestine methamphetamine laboratory was seized in Vacaville California Ephedrine a precursor for the manufacture of methamphetamine was discovered at the site This has been achieved via a chiral protonation approach using easily accessible chiral acids, such as ephedrine and oxazolidinones, to quench enolates formed during the partial reduction process. , 2005). 5g ephedrine sulfate added to clean dry 2 liter bottle -45g calcium ammonium nitrate added to bottle Feb 9, 2023 · reduction conditions, the classic Birch reduction using a group 1 or 2 metal dissolved in ammonia remains the most widely used method. The use of an ester-based auxiliary is a designed improvement over the use of prolinol-derived amides, which are expensive and often very difficult to cleave. This strategy can be fur-ther broken down into two distinct catego-ries. The Comba t Methamphetamine Epidemic Act (2005) had a very fundamental Jan 1, 2005 · Abstract. Photoredox May 17, 2021 · Production method hazards There are four methods of producing methamphetamine—P2P, red phosphorus, Nazi/Birch reduction and one-pot. The Birch Reduction is a process for converting benzene (and its aromatic relatives) to 1,4-cyclohexadiene using sodium (or lithium) as a reducing agent in liquid ammonia as solvent (boiling point: –33°C) in the presence of an alcohol such as ethanol, methanol or t-butanol. Mar 2, 2007 · The reduction of (-)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine, a potentially versatile intermediate for further synthetic transformations. Jun 1, 2020 · Birch/Nazi route (Fig. The presence of an anion-stabilizing group on the substrate arene usually a carboxylic acid derivative drives the regiochemical control of the Birch reduction and generally Those interested in the catalytic reduction of ephedrine and related compounds may find the following references useful; review of foreign language references and foreign patents is limited to the Chemical Abstract citations. Ephedrine HCl, molecular weight MW = 201. The principal chemicals are ephedrine or pseudoephedrine, anhydrous ammonia, and sodium or lithium metal. The principal chemicals are phenyl-2 The Birch reduction in organic synthesis Arthur J. The realistic figure for HI/red mix is only usually 50 % realistically, and lengthy steam distillation is always needed to separate the leftover Pseudoephedrine from the product. This method is often referred to as the lithium-ammonia reduction method or the Birch reduction method. Person, Ph. Birch reduction-methylation of 15 gave 19 with a diastereoselectivity of >35:1 The configurations of ephedrine were determined by reduction of the chloro- and bromoephedrines by Emde 4 and Schmidt 5 using various reduction methods not including the HI/red P method. NOTE:This method (Li-amine) still can over reduce as show by this example, but it illustrates how sucessfully the aromatic competes for the electron with the water. Birch reduction of 6 and 10 gave enantiomerically related lactam enolates that were alkylated with methyl iodide, allyl bromide, benzyl bromide, p-benzyloxybenzyl bromide, and p-methoxybenzyl bromide to give 7a-7e, 11a, and 11b with diastereoselectivities > 20:1. Thus, this synthesis is largely non-stereoselective. The principal methods used are the Nagai method, Birch's reduction or the semplifyed shake'n'bake. Apr 8, 2021 · The Birch reduction is a reaction commonly taught in the second-year undergraduate organic curriculum that involves the reduction of an aromatic compound to an alicyclic product using sodium metal KEYWORDS: Methamphetamine, 1-(1',4'-Cyclohexadienyl)-2-methylaminopropane, Ephedrine, Pseudoephedrine, Birch Reduction, Potassium Permanganate, Forensic Chemistry Introduction One of the primary methods of clandestine methamphetamine synthesis is the reduction of ephedrine or The reduction of (−)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine. The actual moiety reduced is C-X, where X refers to the halogen 3-5,17-19,39,54 , sulfate 6 , phosphate 7 or perchlorate 8 esters ( Fig 1 ). If the starting material is not pure then other materials can undergo reduction as well. with stirring. Nov 29, 2018 · KEYWORDS: Methamphetamine, 1-(1′,4′-Cyclohexadienyl)-2-methylaminopropane, Ephedrine, Pseudoephedrine, Birch Reduction, Potassium Permanganate, Forensic Chemistry Introduction One of the primary methods of clandestine methamphetamine synthesis is the reduction of ephedrine or pseudoephedrine utilizing an alkali metal such as lithium or Mentioning: 3 - This undergraduate dissertation project was designed to enhance organic and analytical chemistry skills of final year forensic science students. The resulting 1,4-cyclohexadienyl group is a potentially versatile i … Sep 1, 2004 · The reduction of (-)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine. The Birch reduction of pyrilamine was conducted using two methods, and the unknown products were distinguished via GC screen, GC-MS, and NMR analyses. At a distance of less than 2 m from the cook, which was the distance at which all of the one-pot samples were collected during this study, Red-P cooks had a mean concentration of 100 900 ng/100 cm 2; Birch reduction cooks had a mean concentration of 25 200 ng/100 cm 2, and the one-pot cooks had a mean concentration of 26. The l-ephedrine was added dropwise to the lithium ammonia solution over a period of approximately 10 min. The resulting 1,4-cyclohexadienyl group is a potentially versatile intermediate for further synthetic transformations. Google Scholar Dec 1, 1990 · Even though the HI/red P ephedrine reduction method is relatively new (1982) in clandestine laboratories, the method has been known for many years and has been used to reduce carbonyl groups, nitriles, halides, and alcohols [2,3]. Birch reduction of aryltrialkylsilanes by lithium–liquid ammonia–ethanol at −70 °C has been studied systematically and a typical conversion is indicated in Scheme 38. The ozonolysis This undergraduate dissertation project was designed to enhance organic and analytical chemistry skills of final year forensic science students. The Birch reduction in organic synthesis Arthur J. ac. 2 (VI)) is a reduction reaction of ephedrine/psedoephedrine using excess alkali metal e. Also known as the Nazi method, the Birch method typically yields ounce quantities of high quality d-methamphetamine and typically is used by independent producers. Previous work available in the scientific literature reported only one route specific impurity using ephedrine hydrochloride as the starting material. Feb 27, 2022 · Birch reduction: this proceeds via a dissolving metal reduction of ephedrine or pseudoephedrine in the presence of ammonia. We would like to show you a description here but the site won’t allow us. The reaction involves mixing the ephedrine or pseudoephedrine with anhydrous ammonia gas and either sodium or lithium metal. 2), which can be observed forming during a reaction. 4 The Birch reduction. The stereochemistry, mechanism, synthetic impurities, and analysis of clandestine methamphetamine samples are addressed. The water on the hydrated ephedrine will react with the Li and diminish the mole ratio of Li. Birch reductions traditionally employ alkali metals dissolved in ammonia to produce a solvated electron for the reduction of unactivated arenes such as benzene (Ered < −3. Birch reduction-methylation of 15 gave 19 with a diastereoselectivity of >35:1 Match case Limit results 1 per page. The birch reduction with sodium gets 92% 2,5 dihydroisopropylbenzene. React l-PAC with Benzylamine 1/1. Ephedrine Freebase, molecular weight MW = 165. 23 grams/mole. Phenyl-2-propanone. An increasing number of the clandestine methamphetamine laboratories (currently roughly estimated at 20%) use a procedure known as a dissolving metal reduction, Birch reduction, or in the popular literature as the "Nazi" method, of ephedrine or pseudoephedrine commonly extracted from over-the-counter medications. With excess alkali metal, and in the presence of an additional proton source [1-8], the aromatic ring is additionally reduced to form a cyclohexadiene (Figure 1). , lithium/sodium in liquid ammonia to form 1-(1ʹ,4ʹ-cyclohexadienyl)-2-methylaminopropane (CMP) [54], notated as (S)–N-Methyl-1-(1,4-cyclohexadienyl)-2-propanamine [66]. Formation of a New, Versatile Intermediate for Organic Synthesis Gury Zvilichovsky and Isra The Birch reduction in organic synthesis Arthur J. 50 ng/100 cm 2. 42 V vs SCE). these reactions take place within a single reaction vessel, giving it the name of the one-pot method. D. Unlike the Birch reduction method, which utilizes liquid anhydrous ammonia to release electrons from an alkali metal, the One Pot method generates ammonia gas in situ. It involves the red phosphorus and Hydroiodic acid. The Birch reduction was instrumental to the discovery of the birth control pills and many other drugs. and nuclear magnetic resonance (NMR) tests. 7 . This undergraduate dissertation project was designed to enhance organic and analytical chemistry skills of final year forensic science students. Benskeser Reduction:reduction of arenes using Li in 1ºamines, ethylenediamine, or a mix of 1º and 2ºamines; more powerful than Birch conditions can lead to reduction beyond dihydro stage and mixture of products Catalytic Hydrogenation: procedes far past Birch reduction Organic Reactions, 1992, 42, 1 Not Discussed in this group meeting: 4. In addition to the reduction of the aromatic ring, the One common method of illicit methamphetamine manufacture utilizes an alkali metal, typically lithium, and liquid ammonia to chemically reduce ephedrine or pseudoephedrine to form methamphetamine. The impurity is the most commonly encountered MA impurity prepared The Birch reduction technique (“Nazi” method) used ephedrine or pseudoephedrine, lithium, and anhydrous ammonia, and the “cold” method used ephedrine or pseudoephedrine, red phosphorus, and iodine crystals (Bianchi et al. g. Since these conditions are similar to a classical Birch reduction in which sodium, ammonia, and an alcohol are used to reduce aromatic rings to form cyclohexadienes, the This undergraduate dissertation project was designed to enhance organic and analytical chemistry skills of final year forensic science students. Jul 7, 2009 · Alkali metals in silica gel (the Na2K-SG(I) reagent) cleanly effect Birch reductions of substrates with at least two or more aromatic rings. Aug 1, 2004 · Europe PMC is an archive of life sciences journal literature. Three of these methods are distinctly different. The use of this synthetic C07D213/60 — Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a Feb 1, 2005 · Birch reduction of (-)-ephedrine Formation of a new, versatile intermediate for organic synthesis [PubMed] Additional information and reprint requests: Eric C. Anyway, back to the drawing board. If the starting material is not pure then other materials can undergo reduction The reduction [1] of aromatic substrates with alkali metal, alcohol in liquid ammonia, known as “Birch reduction”, has greatly increased the utility of benzenoid compounds in alicyclic synthesis [2]. 1. The reactions are summarized in Fig. When all of the l-ephedrine had been added, ammonium chloride was added slowly to the solution. Ephedrine Methamphetamine Jan 10, 2013 · Although the chemistry involved in the Birch reduction of ephedrine or pseudoephedrine is somewhat exotic, there is only one major contaminant in the final product reported; 1-(1,4-cyclohexadienyl)-2-methylaminopropane (structure D1) [8]. Lithium Ammonia Reduction Ephedrine Methamphetamine Lithium-Ammonia Reduction of Ephedrine to Methamphetamine RA. A modified Birch reaction method was employed to synthesize amphetamine from ephedrine and detect the most known byproduct of clandestine manufacture of amphetamines, e. The reduction of isopropylbenzene. Birch/Nazi route (Fig. The reduction of (-)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine. Alternatively, enzyme desymmetrisation of symmetrical diol compounds formed from the partial reduction products of substituted pyrroles is also reported. Jan 1, 2014 · However, reduction of the aminoketone with sodium amalgam gives a mixture of (±)-ψ-ephedrine (which predominates slightly) and (±)-ephedrine. Forensic Scientist C07D213/60 — Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a Feb 1, 2005 · Birch reduction of (-)-ephedrine Formation of a new, versatile intermediate for organic synthesis [PubMed] Additional information and reprint requests: Eric C. Ephedrine Methamphetamine The Birch reduction usually reduces the aromatic ring, but in this case, it eliminates the hydroxy group of ephedrine to give methamphetamine. 7 grams (0. The use of this synthetic This undergraduate dissertation project was designed to enhance organic and analytical chemistry skills of final year forensic science students. While the hydroxyl group of ephedrine is more reactive than the aromatic ring, excess A deep royal blue color was noted as the lithium metal dissolved in the condensed ammonia. It has had a less profound effect on heterocyclic synthesis [3]. Reduction of ephedrine to methamphetamine is well documented in the literature. Jan 1, 2014 · Birch, A. Jul 14, 2020 · The Birch reduction is a powerful synthetic methodology that uses solvated electrons to convert inert arenes to 1,4-cyclohexadienes—valuable intermediates for building molecular complexity. Jan 28, 2022 · Abstract: The reduction of (-)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine. Although the chemistry involved in the Birch reduction of ephedrine or pseudoephedrine is somewhat exotic, there is only one major contaminant in the final product reported; 1-(1,4-cyclohexadienyl)-2-methylaminopropane (structure D1) [8]. Reaction 1 resulted in the loss of the pyridine ring of pyrilamine; the product from reaction two has yet to be determined. 102 A significant exception is p-trimethylsilyltoluene Nov 30, 2012 · This paper focuses on the determination of route specific impurities produced when methylamphetamine is synthesised using the Birch reduction. The impurity is the most commonly encountered MA impurity Aug 2, 2024 · Language Joined Aug 14, 2023 Messages 49 Solutions 1 Reaction score 44 Points 18 Deals 3 This undergraduate dissertation project was designed to enhance organic and analytical chemistry skills of final year forensic science students. 2 molar ratio. 1944, 430–436. Nov 30, 2012 · This paper focuses on the determination of route specific impurities produced when methylamphetamine is synthesised using the Birch reduction. The "birch" reaction is attractive because of the high yields, it produces compared to the other mass production methods. This method usually starts with (−)-pseudoephedrine containing decongestants. Ephedrine is iodinated by Hydroiodic acid to form The reduction of (-)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine. The ozonolysis of this group was Ephedrine Hydriodic acid (liquid) Hydrogen iodide (gas) Hypophosphorous acid Iodine (tincture) Pseudoephedrine Red phosphorous Anhydrous ammonia Coleman fuel Ephedrine Lithium metal Pseudoephedrine Sodium metal P2P: Red Phosphorus: Birch Reduction: Carbon dioxide Formic acid Lead Mercury Potentially flammable extraction process sludges Reduction of Ephedrine HCl to Methamphetamine. 20. of a suitable reducing agent, the reduction of ephedrine/pseudoephedrine can not take place, Scheme 2. Formation of a New, Versatile Intermediate for Organic Synthesis Gury Zvilichovsky* and Isra Gbara-Haj-Yahia Department of Organic Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel gury@vms. The Birch reduction usually reduces the aromatic ring, but in this case, it eliminates the hydroxy group of ephedrine to give methamphetamine. Birch, Reduction, Pyrilamine The Birch reduction usually reduces the aromatic ring (Section 17-14C), but in this case it eliminates the hydroxy group of ephedrine to give methamphetamine. 4 mole) of EPHEDRINE HCl, 20 grams of red phosphorus and 170 mls of 57% hydriodic acid is refluxed for 25 hours. The first is a stoichiometric approach that uses a compound capable of undergoing a finite number of one-electron reduction processes. The reaction of sodium Mar 2, 2007 · As discussed previously, the reduction of ephedrine by hydriodic acid generates a number of intermediates and byproducts (Fig. Arthur Birch (1915–1995), an Australian, developed the “Birch reduction” at Oxford University during WWII in Robert Robinson’s laboratory. Over time a Oct 12, 2013 · N-methyl-1-phenylpropan-2-amine 's production begin with either Phenyl-2-Propanone (P2P) or with ephedrine or pseudoephedrine. , lithium/sodium in liquid ammonia to form 1-(1ʹ,4ʹ-cyclohexadienyl)-2-methylaminopropane (CMP) , notated as (S)–N-Methyl-1-(1,4-cyclohexadienyl)-2-propanamine . Thanks in advance! The procedure: -1. huji. cwkxeufbwzwqokdxnfpzjlgzdflicspvhakstfzekhbibonikllubjvurtuxerirkqegkjs