FGI's & Drug synthesis Flashcards
Give examples of binding interactions of functional groups?
Covalent bonds
- disulphide bond formations
Ionic bonds
- carboxylate anion and ammonium ion
Hydrogen bonds
- between protons and electronegative atoms
Van de Waals
- hydrophobic interactions between aromatic and aliphatic groups
Metal interactions
- interactions between transition metals and
electronegative atoms
- interactions between group II elements and electronegative atoms
What is the order of effectiveness of halide leaving groups?
I > Br > Cl > F
How can a hydroxyl group be converted into a chloride group?
Thionyl chloride, SOCl2
Phosphorus oxychloride, POCl3
How can a hydroxyl group be converted into a bromide group?
Tosylchloride/toluene-sulphonylchloride
Then Lithium bromide
Describe the steps to convert R-OH to R-Cl
the nucleophile attacks the delta positive S of the thionyl chloride
One pair of electrons from the double bonded oxygen goes to the oxygen and the nucleophile joins the molecule.
The lone pair of electrons now on the oxygen then returns to become a double bond forcing a chloride to leave as a leaving group
If the initial nucleotide has too many bonds after joining the electrophile then the chloride that left attacks the hydrogen on the nucleophile and the bond between the hydrogen and positive atom of the nucleophile returns to the positive atom.
How can a chloride group be converted into an iodide or fluoride group?
FINKLESTEIN REACTION
KF or KI and acetone solvent
F poor leaving group owing to stability C-F bond.
Equilibrium depends on solubility of metal salt
KCl and KBr insoluble in acetone - removed from the equilibrium.
Why is a chloride group converted to an iodide group?
Iodine is a better leaving group
This is because the stronger the acid that is formed from the leaving group, the better the leaving group. and
done has a larger atomic radius meaning it has a lower bond enthalpy, as it is longer and there are less electrostatic forces of attraction between the two positive nuclei and the shared Pair of electrons between them
Why is fluorine a poor leaving group?
The C-F bond is very stable
smaller atomic radius allowing greater forces of attraction
Why is acetone used in the Finklestein reaction?
KCl and KBr are insoluble - removed from the equilibrium as it precipitates out
How is mercaptopurine made?
Two step synthesis
- conversion R-OH to R-Cl
- conversion R-Cl to R-SH
What is a prototropic rearrangement?
Proton can move between two electronegative atoms
What is a tautomeric mixture?
Two forms of a molecule where a proton can change positions
What reagents can be used to oxidise aldehydes?
Jones’
Tollens’
What reagents can be used to reduce aldehydes?
NaBH4
LiAlH4
How can a primary alcohol be oxidised to a carboxylic acid?
Jones’ reagent
- chromic acid Cr(VI)
Jones reagent is a solution of chromium trioxide in aqueous sulfuric acid.
How does a Jones’ oxidation reaction take place?
Primary alcohol -> aldehyde -> carboxylic acid
Why is the aldehyde never isolated during a Jones’ oxidation reaction?
The oxidising agent is too strong
Why can the aldehyde be isolated during a Tollens’ oxidation reaction?
The oxidising agent is milder than Jones’ reagent
Tollens’ reagent (chemical formula Ag(NH3)2OH)
What can be used as a test for aldehydes and reducing sugars?
Tollens’ reagent
- silver mirror test
Which is one of the most powerful reducing agents?
Lithium aluminium hydride
- will reduce any functional group
- aldehyde
- ketone
- amide
- ester
Why is there low levels of chemoselectivity using lithium aluminium hydride?
Lithium aluminium hydride is extremely reactive
Why is sodium borohydride preferred as a reducing agent to lithium aluminium hydride?
Much milder
Frequently used to chemoselectively reduce aldehydes and ketones in the presence of amides
How can a nitrile be reduced to an aldehyde or an amine?
Using lithium aluminium hydride
although to an aldehyde also includes DIBAL
How can a nitro group be reduced to an amine?
Using lithium aluminium hydride
How can an azide group be reduced to an amide?
Lithium aluminium hydride
How can an oxime be reduced to an amine?
Lithium aluminium hydride
What class of drugs is fluoxetine?
Selective Serotonin Reuptake Inhibitor (SSRI)
Used to treat
- depression
- obsessive-compulsory disorder
What is the structure of fluoxetine?
Aromatic ring Chiral centre Ether link Alkyl amine Trifluromethyl group
What are the steps involved in synthesising fluoxetine?
Stereoselective Reductions - Synthesis of (S)-fluoxetine
step 1: carbonyl group converted to alcohol group
using DIP-H
step 2: R-Cl –> R-NH2
via NaI, acetone and then MeNH2
Step 3: R-OH —> R-OR’
deprotonating the alcohol so it makes a better nucleophile
Why is S-fluoxetine the predominant therapeutic isomer of the racemic mixture?
Eliminated more slowly
longer half life than R enantiomer
What is the order of reactivity for carboxylic acids and their derivatives?
Acyl halides > anhydrides»_space; esters ~ acids»_space; amides
What type of bond does procaine (Novocaine) contain?
Ester linkage
- readily hydrolysed
Why is lidocaine (Xylocaine) faster acting and longer lasting than procaine?
More stable amide bond
How many steps are there to synthesising procaine?
Four
- R-CH3 -> R-COOH. (via KmNO4)
- R-COOH -> R-COCl. (via SOCl2)
- R-COCl -> R-COOR. (weird hydroxy tertiary amine)
- R-NO2 -> R-NH2. (via H2/pd)
How can alcohols be prepared?
Alkene hydration
Reduction of carbonyls
- aldehydes
- ketones
How can ethers be prepared?
Dehydration of alcohols for symmetrical ether
Williamson synthesis for unsymmetrical ether
What type of ether is formed by the dehydration of alcohols?
Symmetrical
- the R groups are the same
What type of ether is formed by the Williamson synthesis?
Asymmetrical
describe the mechanisms for the steps in producing procaine
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