Organic Chemistry I Research Paper on Pseudoephedrine
By:
Natalie Roberts
Jennifer Dargis
Nakeesha Longeley

Pseudoephedrine is a phenylethylamine which is utilized as a pharmaceutical product. It has the official IUPAC name of (1S,2S)-2-methylamino-1-phenylpropan-1-ol, and the CAS number of 90-82-4. Psuedoephedrine contains three functional groups: amine, hydroxyl, and ethyl in its ring; it also has one stereogenic carbon. The enantiomer of pseudoephedrine is ephedrine, and this substance can form two other diastereomers as well. Pseudoephedrine contains covalent bonds (both and double) and hydrogen bonds. A two-dimensional and three-dimensional structure are given below.
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[pic] Psuedoephedrine is also synthesized in various ways, sometimes with methods that add an amide to its structure in order to alter its medicinal effect. One of the most efficient techniques for synthesizing pseudoephedrine is given below:

[pic] Reagents and conditions: (i) (CH2O)n, PTSA, benzene, reflux, 1 h; (ii) 1 equiv. NaBH4, MeOH, 2 h; (iii) PhMgBr, THF, 0°C–rt, 3 h; (iv) (CH2O)n, PTSA, benzene, reflux, 1 h; (v) NaCNBH3/TMSCl, CH3CN, rt, 30 min; (vi) conc. HCl, reflux, 2 h

Pseudoephedrine is originally obtained as an alkaloid from the Oriental plant genus of Ephedra; as shown above, however, it can also be prepared artificially. The most common method of creating pseudoephedrine today is from yeast fermentation of dextrose in the presence of benzaldehyde. Typically pseudoephedrine exists as a white crystalline, odorless powder with a melting point of 182-182.5ºC. Although it is insoluble in alcohol, it is highly soluble in water and has a molecular weight of 201.70 amu.
Pseudoephedrine has a pH around 4.5-6, and the drug is generally very stable under ordinary conditions. Pseudoephedrine is commonly known as Sudafed, an over-the-counter drug that is mainly used to combat congestion. Its areas of alleviation include treatment of nasal, sinus, and Eustachian tube blockages. Normally congestion of these pathways is associated with colds or allergies. Pseudoephedrine can also be used as a treatment for priapism. The mechanism of the drug’s action is that it causes vasodilation of the blood vessels, thereby relieving the symptom. In addition, pseudoephedrine can be used to treat urinary incontinence by increasing the pressure exerted by the bladder and neck of the urethra, leading to retention of urine in the bladder. The drug also finds use as a muscle relaxant and in combination with theophylline, as a stimulant to cardiac tissue and the central nervous system. Pseudoephedrine can even be used as a protective measure against hypertension under the effects of anesthesia. Because of its ability to open air passages to the lungs, pseudoephedrine is also used in the treatment and/or prevention of bronchial asthma and the bromchiospasm associated with chronic bronchitis and emphysema. The drug is most often administered orally. In some instances, pseudoephedrine can carry side effects, though serious ones are generally rare. Possible side effects include: bloody diarrhea and abdominal pain; chest pain, confusion, dizziness, or fainting spells; hallucinations, numbness or tingling in the hands or feet; rapid or troubled breathing; seizures; and severe or persistent headaches. Some of the more common and less severe side effects may include anxiety, excessive sweating, fast/irregular heartbeat, palpitations, increased blood pressure, pain or difficulty passing urine, insomnia, tremors, and vomiting. The most mild side effects associated with pseudoephedrine are difficulty sleeping, light headaches, nausea, loss of appetite, and restlessness/nervousness. The effects of pseudoephedrine can also vary with age. Elderly patients appear more sensitive to the drug’s CNS stimulation effects (anxiety, restlessness, headache, lightheadedness, dizziness, insomnia, and psychological disturbance) and may also have reduced elimination of pseudoephedrine due to age-related declines in renal function. Children are also more likely to experience CNS-related adverse events—so much so that in January 2007, the CDC actually warned caregivers of the risk for serious injury or fatal overdose from the administration of cough and cold products to infants and children less that two years of age. This warning followed an investigation of the deaths of three infants less than six months old that were supposedly killed by the inappropriate use of these products. The symptoms preceding the deaths have not been clearly defined, and there is a lack of conclusive data describing the exact cause of death; nonetheless, the report is cause for caution. The report also estimated that 1,519 children under two years of age were treated in emergency departments during 2004-2005 for adverse effects related to cough and cold medications. On a more rare note, pseudoephedrine is also known to cause excitability in some patients, especially infants and young children. Pseudoephedrine is classified as a pregnancy category C drug. No adequate or well-controlled pregnancy studies have been done with human subjects to establish concrete information as to the drug’s effects on a fetus. Pseudoephedrine is a sympathomimetic amine, a group of compounds often associated with minor fetus malformations in certain animal species; however, human teratogenesis has not been suspected based on limited epidemiologic evidence. Nonetheless, use of pseudoephedrine during pregnancy should be avoided unless the potential benefits are known to outweigh the undefined potential risks to the fetus. Fortunately, no serious environmental effects have been observed with the taking of pseudoephedrin. Federal law, however, has made a recent effort to curb methamphetamine abuse and in doing so have precipitated alterations in pseudoephedrine sales restrictions at pharmacies. The law currently requires that products containing pseudoephedrine now be kept behind a counter or in a locked cabinet, and to further this practice, all pharmacies must maintain a written or electronic logbook of pseudoephedrine purchases. The customer must also present identification at the time of purchase. Pseudoephedrine is included as an active ingredient in many pharmaceutical products. Some of the currently marketed drugs which contain pseudoephedrine are listed below: • Panadol • NyQuil D • Contac • Codral • Sudafed • Actifed • Claritin-D (loratadine/pseudoephedrine) • Clarinex-D (desloratadine/pseudoephedrine) • Sinutab • Sinufed (pseudoephedrine HCI) • Benylin (pseudoephedrine) • Zyrtec-D (cetirizine/pseudoephedrine) • Allegra-D (fexofenadine/pseudoephedrine) • Drixoral • PediaCare (pseudoephedrine/chlorpheniramine/dextromethorphan) • Pannaz (pseudoephedrine/chlorpheniramine/methscopolamine) • Fludrex (pseudoephedrine/dextromethorphan/triprolidine) • Solpa-Sinus (pseudoephedrine/acetaminophen) • Advil Cold and Sinus (pseudoephedrine/ibuprofen) • Tylenol Sinus (pseudoephedrine/acetaminophen) • Aleve-D Cold and Sinus (pseudoephedrine HCI/naproxen sodium) References http://dictionary.reference.com/ http://chemicalland21.com/lifescience/phar/PSEUDOEPHEDRINE%20HYDROCHLORIDE.htm

http://en.wikipedia.org/wiki/Pseudoephedrine

http://www.erowid.org/archive/rhodium/chemistry/pseudoephedrine.oxazolidinone.html