Celebrex
Treats pain, including pain caused by
arthritis in children and adults, ankylosing spondylitis or menstrual cramps.
This is a non-steroidal anti-inflammatory medicine (1).
Chemistry by Design found in Journal of
Medicinal Chemistry. The authors and departments are listed below:
Thomas
D. Penning ,* John
J. Talley ,*† Stephen
R. Bertenshaw ,† Jeffery
S. Carter ,† Paul
W. Collins , Stephen
Docter , Matthew
J. Graneto ,† Len
F. Lee ,‡ James
W. Malecha , Julie
M. Miyashiro , Roland
S. Rogers ,§ D. J.
Rogier ,† Stella
S. Yu , Gary
D. Anderson ,† Earl
G. Burton ,‡ J.
Nita Cogburn ,‡ Susan
A. Gregory ,† Carol
M. Koboldt ,‡ William
E. Perkins , Karen
Seibert ,‡ Amy
W. Veenhuizen ,† Yan
Y. Zhang ,† and Peter
C. Isakson †
Departments of Chemistry, Inflammatory
Diseases Research, and Molecular Pharmacology, Searle Research and Development (2).
There are 3 total steps to make Celebrex from 4-[(aminooxy)sulfinyl]aniline
Reagents needed for synthesis:
Step 1: HCl then NaNO2 with H2O
(-5 °c) – All these reagents are commercially available
Step 2: SnCl2 (H2O) 86%
(happens in 2 steps) – All these reagents are commercially available but SnCl2
purist commercially available solution contains at least 5% of Sn(IV) (3).
Step 3: EtOH at 75 °c
(46%)- This step is synthesized in the steps shown below (2):
Reactions learned in class:
Step 1-
The NH2 is changed into a diazonium ion N2+. This is described as the Sandmeyer reaction (4). This exact reaction has not been discussed in class before but, diazonium ions as a whole have been discussed in class before! The link below explains the Sandmeyer reaction in more detail:
The NH2 is changed into a diazonium ion N2+. This is described as the Sandmeyer reaction (4). This exact reaction has not been discussed in class before but, diazonium ions as a whole have been discussed in class before! The link below explains the Sandmeyer reaction in more detail:
http://web.mnstate.edu/jasperse/Chem365/Sandmeyer.doc.pdf
Step 2-
Is a substitution reaction of a diazonium ion. This was also discussed in class. The link below give a few examples of substitution reactions of diazonium ions (5).
Is a substitution reaction of a diazonium ion. This was also discussed in class. The link below give a few examples of substitution reactions of diazonium ions (5).
http://www.chemguide.co.uk/organicprops/aniline/propsdiazo.html
Mechanistic Explanation of step 1:
Nitrous acid (also known as nitric (III) acid)
has the formula HNO2. The phenylamine is first dissolved in
hydrochloric acid, and then a solution of sodium nitrite is added. The reaction
between the hydrochloric acid and the nitrite ions produces the nitrous acid. The
nitrite is then added to the phenylammonium chloride solution. The end product
is a solution containing benzenediazonium chloride (4). The Mechanism is shown below.
References:
1. Celecoxib. U.S. National Library of Medicine. [online] 2012,
1. Celecoxib. U.S. National Library of Medicine. [online] 2012,
http://www.nlm.nih.gov/medlineplus/druginfo/meds/a699022.html
2. Njardarson, J.T. Chemistry By Design. http://chemistrybydesign.oia.arizona.edu/app.php
2. Njardarson, J.T. Chemistry By Design. http://chemistrybydesign.oia.arizona.edu/app.php
(accessed
April 17, 2014).
3 3. Zolle, I. Technetium-99m Pharmaceuticals: Preparation and Quality Control in Nuclear
3 3. Zolle, I. Technetium-99m Pharmaceuticals: Preparation and Quality Control in Nuclear
Medicine. [online] 2007, 62-63.http://books.google.com/books?
i d=o2pPP81jWDYC&pg=PA62&lpg=PA62&dq=Is
+SnCl2+commercially+available&source=bl&ots=wX9w_6KjYd&sig=rfqDzRSVV
ZDg70DQesrrD8lEoNc&hl=en&sa=X&ei=d2dNU9TqHK238gGMxoAg&ved=0CC
YQ6AEwAA#v=onepage&q=Is%20SnCl2%20commercially%20available&f=false
4. Minnesota State University. The Sandmeyer Reaction: Substitution for an NH2 on an Aromatic
4. Minnesota State University. The Sandmeyer Reaction: Substitution for an NH2 on an Aromatic
Ring: Specialized
Information Services.
http://web.mnstate.edu/jasperse/Chem365/Sandmeyer.doc.pdf
5. Reactions of Diazonium Salts.
5. Reactions of Diazonium Salts.
http://www.chemguide.co.uk/organicprops/aniline/propsdiazo.html
(accessed April 17,
2014).