Polycyclic aromatic hydrocarbon

Polycyclic Aromatic Hydrocarbon
Polycyclic aromatic hydrocarbons (PAHs, also polyaromatic hydrocarbons) are hydrocarboz—
organic compounds containing only carbon and hydrogen—that are composed of
multiple aromatic rings (organic rings in which the electrons are delocalized). Formally, the class
is further defined as lacking further branching substituents on these ring structures. Polynuclear
aromatic hydrocarbons (PNAs) are a subset of PAHs that have fused aromatic rings, that is, rings
that share one or more sides.
The simplest such chemicals arenaphthalene, having two aromatic
rings, and the three-ring compounds anthracene and phenanthrene.
PAHs are neutral, nonpolar molecules found in coal and in tar deposits. They are produced as
well by incomplete combustion of organic matter (e.g., in engines and incinerators, when
biomass burns in forest fires, etc.).
PAHs may also be abundant in the universe, and are conjectured to have formed as early as the
first couple of billion years after the Big Bang, in association with formation of new
stars and exoplanets. Some studies suggest that PAHs account for a significant percentage of
all carbon in the universe, and PAHs are discussed as possible starting materials for abiologic
syntheses of materials required by the earliest forms of life.(1)
AFM image (top) ofhexabenzocoronene, a precursor to graphene, and its standard line-angle
schematic (middle), where carbon atoms are represented by the vertices of the hexagons, and
hydrogens are inferred as projecting out at 120° angles to fill the fourth carbon valence
(bottom).(2)
Examples & structure of PAH
The tricyclic species phenanthrene and anthracene represent the starting members of the
PAHs(1). Smaller molecules, such as benzene, are not PAHs, and PAHs are not generally
considered to contain heteroatoms or carry substituents.(2)

PAHs with five or six-membered rings are most common. Those composed only of six-
membered rings are called alternant PAHs, which include benzenoid PAHs.(3)The following are
examples of PAHs that vary in the number and arrangement of their rings:
Examples of PAH compounds
Anthracene
Phenanthrene
Tetracene
Chrysene
Triphenylene

Pyrene
Pentacene
Benzo[a]pyrene
Physicochemical properties and bonding
PAHs are nonpolr and lipophilic. PAHs are insoluble in water(4). The larger members are also
poorly soluble in organic solvents as well as lipids. They are usually colorless.
Although PAHs clearly are aromatic compounds, the degree of aromaticity can be different for
each ring segment. According to Clar's rule (formulated by Erich Clar in 1964.(5).
for PAHs
theresonance structure with the largest number of disjoint aromatic п-sextets—i.e. benzene-like
moieties—is the most important for the characterization of the properties.
Phenanthrene Anthracene Chrysene

For example, in phenanthrene one Clar structure has two sextets at the extremities, while the
other resonance structure has just one central sextet; therefore in this molecule the outer rings
have greater aromatic character whereas the central ring is less aromatic and therefore more
reactive. In contrast, in anthracene the resonance structures have one sextet, which can be at any
of the three rings, and the aromaticity spreads out more evenly across the whole molecule. This
difference in number of sextets is reflecte,in the UV absorbance spectra of these two
isomers; phenanthrene has a highest wavelength absorbance around 290 nm, whileanthracene has
highest wavelength bands around 380 nm. Three Clar structures with two sextets each are
present in chrysene .Superposition of these structures reveals that the aromaticity in the outer
rings is greater (each has a sextet in two of the three Clar structures) compared to the inner rings
(each has a sextet in only one of the three).
SOME PHARMACEUTICAL IMPORTANT COMPOUND
Synthesis of Aspirin
Aspirin (acetylsalicylic acid) is a synthetic organic derived from salicylic acid. Salicylic
acid is a natural product found in the bark of the willow tree and was used by the ancient
Greeks and Native Americans, among others, to counter fever and pain. However,
salicylic acid is bitter and irritates the stomach.
A German chemist named Felix Hoffman is credited with being the first to synthesize aspirin
in 1897. Hoffman's father had severe arthritis but could not tolerate salicylic acid he was
taking for pain relief. The name given for Hoffman's new compound was A-spirin.
Apparently this comes from acetylation (A-), together with Spirin, part of the name for
Meadow-sweet (Spiraea ulmaria), a plant rich in salicylates.Friedrich Bayer, the employer of
Hoffman, patented the name and began marketing the product in 1899. It was a huge success
and sales grew rapidly. Bayer's company set up by himself, is generally reckoned to have
been the first pharmaceutical company, and the production of aspirin is generally accepted to
have laid the foundation of the modern pharmaceutical industry.In this experiment you will
synthesize aspirin (acetylsalicylic acid, C9H8O4 ), purify it, and determine the percent yield.
The purity of the product will be confirmed by qualitative analysis and by measuring its
melting point range.The reaction that is used for the synthesis is shown below. In this
reaction, an excess of acetic anhydride (C4H6O3) is added to a measured mass of salicylic
acid (C7H6O3) in the presence of a catalyst, sulfuric acid (H2SO4). The mixture is heated to
form the acetylsalicylic acid (C9H8O4) and acetic acid (C2H4O2). After the reaction takes
place, water is added to destroy the excess acetic anhydride and cause the product to
crystallize. The aspirin is then collected, purified by recrystallization, and its melting
temperature measured.(6)

Paracetamol
Paracetamol, also known as acetaminophen or APAP, is a medication used to
treat pain and fever. It is typically used for mild to moderate pain. There is poor evidence for
fever relief in children. It is often sold in combination with other ingredients such as in
many cold medications. In combination with opioid pain medication, paracetamol is used for
more severe pain such as cancer pain and after surgery. It is typically used either by mouth
or rectally but is also available intravenously.Effects last between two and four hours.
Paracetamol is generally safe at recommended doses.Serious skin rashes may rarely occur, and
too high a dose can result in liver failure. It appears to be safe during pregnancy and
when breastfeeding. In those with liver disease, it may still be used, but lower doses should be
taken. Paracetamol is classified as a mild analgesic.]
It does not have significant anti-
inflammatoryactivity and how it works is not entirely clear.(7)
Medical uses
Fever
Paracetamol is used for reducing fever in people of all ages. The World Health
Organization (WHO) recommends that paracetamol be used to treat fever in children only if their
temperature is greater than 38.5 °C (101.3 °F). The efficacy of paracetamol by itself in children
with fevers has been questioned]
and a meta-analysis showed that it is less effective
than ibuprofen.
Pain
Paracetamol is used for the relief of mild to moderate pain. The use of the intravenous form for
pain of sudden onset in people in the emergency department is supported by limited evidence.

Osteoarthritis
The American College of Rheumatology recommends paracetamol as one of several treatment
options for people with arthritis pain of the hip, hand, or knee that does not improve with
exercise and weight loss. A 2015 review, however, found it provided only a small benefit in
osteoarthritis.
Paracetamol has relatively little anti-inflammatory activity, unlike other common analgesics such
as the NSAIDs aspirin and ibuprofen, but ibuprofen and paracetamol have similar effects in the
treatment of headache. Paracetamol can relieve pain in mild arthritis, but has no effect on the
underlying inflammation, redness, and swelling of the joint. It has analgesic properties
comparable to those of aspirin, while its anti-inflammatory effects are weaker. It is better
tolerated than aspirin due to concerns with bleeding with aspirin.
Low back pain
Based on a systematic review, paracetamol is recommended by the American College of
Physicians and the American Pain Societyas a first-line treatment for low back pain. However
other systematic reviews concluded that evidence for its efficacy is lacking.[
Headaches
A joint statement of the German, Austrian, and Swiss headache societies and the German Society
of Neurology recommends the use of paracetamol in combination with caffeine as one of several
first line therapies for treatment of tension or migraine headache. In the treatment of acute
migraine, it is superior to placebo, with 39% of people experiencing pain relief at 1 hour
compared to 20% in the control group.
Postoperative pain
Paracetamol, when combined with NSAIDs, may be more effective for treating postoperative
pain than either paracetamol alone or NSAIDs alone.(8)
Synthesis
Original (Boots) method
The original method for production involves the nitration of phenol with sodium nitrate gives a
mixture of two isomers, from which the wanted 4-nitrophenol (bp 279 °C) can easily be
separated by steam distillation. In this electrophilic aromatic substitution reaction, phenol's
oxygen is strongly activating, thus the reaction requires only mild conditions as compared to
nitration of benzene itself. The nitro group is then reduced to an amine, giving 4-aminophenol.
Finally, the amine is acetylated with acetic anhydride. Industrially direct hydrogenation is used,
but in the laboratory scale sodium borohydride serves.(9)

.
Available forms
Paracetamol brand names
Tylenol 500 mg capsules
Panadol 500 mg tablets

Phenacetin
Phenacetin (or acetophenetidin) is a pain-relieving and fever-reducing drug, which was widely
used between its introduction in 1887 and the 1983 ban imposed by the FDA on its use in the
United States. Its use has declined because of its adverse effects, which include increased risk of
certain cancers and kidney damage. It is metabolized as paracetamol (acetaminophen), which
replaced it in some over-the-counter medications following the ban on phenacetin.
The first synthesis was reported in 1878 by Harmon Northrop Morse.
Phenacetin may be synthesized as an example of the Williamson ether synthesis: ethyl
iodide, paracetamol, and anhydrous potassium carbonate are refluxed in 2-butanone to give the
crude product, which is recrystallized from water(10).
BENZATHENES DERIVATIVES
Bicillin
®
C-R
(penicillin G benzathine and penicillin G procaine injectable suspension)
Bicillin C-R (penicillin G benzathine and penicillin G procaine injectable suspension) contains
equal amounts of the benzathine and procaine salts of penicillin G. It is available for deep
intramuscular injection.
Penicillin G benzathine is prepared by the reaction of dibenzylethylene diamine with two
molecules of penicillin G. It is chemically designated as (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-
(2phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid compound with
N,N’dibenzylethylenediamine (2:1), tetrahydrate. It occurs as a white, crystalline powder and is
very slightly soluble in water and sparingly soluble in alcohol. Its chemical structure is as
follows:

Penicillin G procaine, (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-
1azabicyclo[3.2.0]heptane-2-carboxylic acid compound with 2-(diethylamino)ethyl
paminobenzoate (1:1) monohydrate, is an equimolar salt of procaine and penicillin G. It occurs
as white crystals or a white, microcrystalline powder and is slightly soluble in water. Its chemical
structure is as follows:

Each disposable syringe (2 mL size) contains the equivalent of 1,200,000 units of penicillin G
comprising: the equivalent of 600,000 units of penicillin G as the benzathine salt and the
equivalent of 600,000 units of penicillin G as the procaine salt in a stabilized aqueous suspension
with sodium citrate buffer; and as w/v, approximately 0.5% lecithin, 0.55%
carboxymethylcellulose, 0.55% povidone, 0.1% methylparaben, and 0.01% propylparaben.
Bicillin C-R injectable suspension in the disposable-syringe formulation is viscous and opaque.
CLINICAL PHARMACOLOGY
General
Penicillin G benzathine and penicillin G procaine have a low solubility and, thus, the drugs are
slowly released from intramuscular injection sites. The drugs are hydrolyzed to penicillin G. This
combination of hydrolysis and slow absorption results in blood serum levels much lower but
more prolonged than other parenteral penicillins.
Intramuscular administration of 600,000 units of Bicillin C-R in adults usually produces peak
blood levels of 1.0 to 1.3 units per mL within 3 hours; this level falls to an average concentration
of 0.32 units per mL at 12 hours, 0.19 units per mL at 24 hours, and 0.03 units per mL at seven
days.
Intramuscular administration of 1,200,000 units of Bicillin C-R in adults usually produces peak
blood levels of 2.1 to 2.6 units per mL within 3 hours; this level falls to an average concentration
of 0.75 units per mL at 12 hours, 0.28 units per mL at 24 hours, and 0.04 units per mL at seven
days.
Approximately 60% of penicillin G is bound to serum protein. The drug is distributed
throughout the body tissues in widely varying amounts. Highest levels are found in the
kidneys with lesser amounts in the liver, skin, and intestines. Penicillin G penetrates into
all other tissues and the spinal fluid to a lesser degree. With normal kidney function, the
drug is excreted rapidly by tubular excretion. In neonates and young infants and in
individuals with impaired kidney function, excretion is considerably delayed.(12)
INDICATIONS AND USAGE
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Bicillin
CR and other antibacterial drugs, Bicillin C-R should be used only to treat or prevent infections
that are proven or strongly suspected to be caused by bacteria. When culture and susceptibility
information are available, they should be considered in selecting or modifying antibacterial
therapy. In the absence of such data, local epidemiology and susceptibility patterns may
contribute to the empiric selection of therapy.
This drug is indicated in the treatment of moderately severe infections due to penicillin-
Gsusceptible microorganisms that are susceptible to serum levels common to this particular
dosage .

form. Therapy should be guided by bacteriological studies (including susceptibility testing) and
by clinical response.
Bicillin C-R is indicated in the treatment of the following in adults and pediatric patients:
Moderately severe to severe infections of the upper-respiratory tract, scarlet fever, erysipelas,
and skin and soft-tissue infections due to susceptible streptococci.
NOTE: Streptococci in Groups A, C, G, H, L, and M are very sensitive to penicillin G. Other
groups, including Group D (enterococci), are resistant. Penicillin G sodium or potassium is
recommended for streptococcal infections with bacteremia.
Moderately severe pneumonia and otitis media due to susceptible Streptococcus pneumoniae.
NOTE: Severe pneumonia, empyema, bacteremia, pericarditis, meningitis, peritonitis, and
arthritis of pneumococcal etiology are better treated with penicillin G sodium or potassium
during the acute stage.
When high, sustained serum levels are required, penicillin G sodium or potassium, either IM or
IV, should be used. This drug should not be used in the treatment of venereal diseases, including
syphilis, gonorrhea, yaws, bejel, and pinta.(13)
CONTRAINDICATIONS
A previous hypersensitivity reaction to any penicillin or to procaine is a contraindication.(14)
PHENANTHRENE DERIVATIVES
 Morphine
 Codein
 Thebaine
Morphine is the most abundant opiate found in opium, the dried latex extracted by shallowly
scoring the unripe seedpods of the Papaver somniferum poppy. Morphine is generally 8–14% of
the dry weight of opium, although specially bred cultivars reach 26% or produce little morphine
at all (under 1%, perhaps down to 0.04%). The latter varieties, including the 'Przemko' and
'Norman' cultivars of the opium poppy, are used to produce two other
alkaloids, thebaine and oripavine, which are used in the manufacture of semi-synthetic and
synthetic opioids like oxycodone and etorphine and some other types of drugs. P.
bracteatum does not contain morphine or codeine, or other narcoticphenanthrene-type, alkaloids.
This species is rather a source of thebaine.Occurrence of morphine in
other Papaverales andPapaveraceae, as well as in some species of hops and mulberry trees has
not been confirmed. Morphine is produced most predominantly early in the life cycle of the
plant. Past the optimum point for extraction, various processes in the plant produce
codeine, thebaine, and in some cases negligible amounts
of hydromorphone, dihydromorphine, dihydrocodeine, tetrahydro-thebaine,
and hydrocodone (these compounds are rather synthesized from thebaine and oripavine).

In the brain of mammals, morphine is detectable in trace steady-state concentrations. The human
body also produces endorphins, which are chemically related endogenous opioid peptides that
function as neuropeptides and have similar effects as morphine.(15)
Early Syntheses of Morphine
The following section highlights two milestone achievements in morphine synthesis. In 1952,
Gates published the first total synthesis of the title alkaloid and was thus able to prove the
structure of morphine proposed by Robinson in 1925 to be correct . In addition, both enantiomers
of morphine can be accessed following the published route as Gates performed a resolution of an
advanced intermediate. Although Gates did not benefit from modern synthetic methods and
structure elucidation techniques such as NMR spectroscopy, he was able to determine the
identity of synthetic intermediates by derivatization and degradation studies of natural morphine.
Written almost 60 years ago, the original report demonstrates the amazing knowledge of
reactions, purification, and structure determination abilities of early synthetic chemists. Gates’s
full paper, as well as the earlier papers dealing with model studies, should be recommended
reading assignment for all students of organic synthesis. The very short and highly efficient
biomimetic synthesis of morphine by Rice stands out in terms of overall yield and brevity; no
subsequent contribution to this area exceeds this milestone achievement. The route follows the
biosynthetic pathway and delivers dihydrocodeinone in almost 30% overall yield. Although the
syntheses of morphine by Gates and Rice have been reviewed on several occasions , they are
included in this review as they constitute important highlights in the history of morphine research
against which all other approaches should be judged. (For clarity and better understanding, the
key transformations in featured syntheses are depicted in blue color within the schemes).(16)
Morphine biosynthesis in the opium poppy
Morphine is biosynthesized in the opium poppy from the tetrahydroisoquinoline reticuline. It is
converted into salutaridine, thebaine, and oripavine. The enzymes involved in this process are
the salutaridine synthase, salutaridine:NADPH 7-oxidoreductase and the codeinone
reductase.[73]
Researchers are attempting to reproduce the biosynthetic pathway that produces
morphine in genetically engineered yeast.]
In June 2015 the S-reticuline could be produced from
sugar and R-reticuline could be converted to morphine, but the intermediate reaction could not be
performed. In August 2015 the first complete synthesis of thebaine and hydrocodone in yeast
were reported, but the process would need to be 100,000 times more productive to be suitable for
commercial use.(17)

Medical uses
Pain
Morphine is used primarily to treat both acute and chronic severe pain. It is also used for pain
due to myocardial infarction and for labor pains. Its duration of analgesia is about three to seven
hours.
However, concerns exist that morphine may increase mortality in the setting of non ST elevation
myocardial infarction. Morphine has also traditionally been used in the treatment of acute
pulmonary edema.A 2006 review, though, found little evidence to support this practice.]
A 2016
Cochrane review concluded that morphine is effective in relieving cancer pain. Side-effects of
nausea and constipation are rarely severe enough to warrant stopping treatment.
Shortness of breath
Immediate-release morphine is beneficial in reducing the symptom of shortness of breath due to
both cancer and noncancer causes.In the setting of breathlessness at rest or on minimal exertion
from conditions such as advanced cancer or end-stage cardiorespiratory diseases, regular, low-
dose sustained-release morphine significantly reduces breathlessness safely, with its benefits
maintained over time.
Opioid use disorder
Morphine is also available as a slow-release formulation for opiate substitution therapy (OST) in
Austria, Bulgaria, and Slovenia, for addicts who cannot tolerate either methadone
or buprenorphine.(17)
References
1.Jump up^ G.P. Moss IUPAC nomenclature for fused-ring systems[full citation needed]
2.Jump up^ Fetzer, J. C. (2000). "The Chemistry and Analysis of the Large Polycyclic Aromatic
Hydrocarbons". Polycyclic Aromatic Compounds. New York: Wiley. 27 (2): 143–
162.doi:10.1080/10406630701268255. ISBN 0-471-36354-5.
3.Jump up^ Harvey, R.G. (1998). "Environmental Chemistry of PAHs". PAHs and Related
Compounds: Chemistry. The Handbook of Environmental Chemistry. Springer. pp. 1–
54. ISBN 9783540496977.
4.Jump up^ Xinliang Feng, Wojciech Pisula, and Klaus Müllen "Large polycyclic aromatic
hydrocarbons: Synthesis and discotic organization"Pure Appl. Chem.,2009, Vol. 81, No. 12, pp.
2203–2224.doi:10.1351/PAC-CON-09-07-07
5.Jump up^ Clar, E. (1964). Polycyclic Hydrocarbons. New York: Academic
Press. LCCN 63012392.6..

6.http://www.chem.latech.edu/~deddy/chem104/104Aspirin.htm
7. Jump up to:a b "International Listings for Paracetamol". Retrieved 11 January 2016.
8.Jump up^ Working Group of the Australian and New Zealand College of Anaesthetists and
Faculty of Pain Medicine (2010). Macintyre, PE; Schug, SA; Scott, DA; Visser, EJ; Walker, SM,
eds. Acute Pain Management: Scientific Evidence (PDF) (3rd ed.). Melbourne, Australia:
National Health and Medical Research Council. ISBN 9780977517459.
9.Jump up^ "Tylenol, Tylenol Infants' Drops (acetaminophen) dosing, indications, interactions,
adverse effects, and more". Medscape Reference. WebMD. Retrieved 10 May 2014.
10..Jump up^ H. N. Morse (1878). "Ueber eine neue Darstellungsmethode der
Acetylamidophenole". Berichte der deutschen chemischen Gesellschaft.
11.SHAW, E.: Transverse myelitis from injection of penicillin. Am. J. Dis. Child., 111:548,
1966.
12.KNOWLES, J.: Accidental intra-arterial injection of penicillin. Am. J. Dis. Child., 111:552,
1966.
13.DARBY, C. et al: Ischemia following an intragluteal injection of benzathine-procaine
penicillin G mixture in a one-year-old boy. Clin. Pediatrics, 12:485, 1973.
14.BROWN, L. & NELSON, A.: Postinfectious intravascular thrombosis with gangrene. Arch.
Surg.,
15. Gates M, Tschudi G (1952) The synthesis of morphine. J Am Chem Soc 74:1109–1110
16.. Gates M, Tschudi G (1956) The synthesis of morphine. J Am Chem Soc 78:1380–1393
17.www.Wikipedia.Org

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