Retrosynthesis or The Disconnection approach has been discussed in this presentation. Useful Courseware for the Undergraduate and Postgraduate students of Pharmacy , and Chemical Sciences
When there are two functional groups of unequal reactivity within a molecule, the more reactive group can be made to react alone, but it may not be possible to react the less reactive functional group selectively.
A group the use of which makes possible to react a less reactive functional group selectively in presence of a more reactive group is known as protecting group.
A protecting group blocks the reactivity of a functional group by converting it into a different group which is inert to the conditions of some reaction(s) that is to be carried out as part of a synthetic route
Retrosynthesis or The Disconnection approach has been discussed in this presentation. Useful Courseware for the Undergraduate and Postgraduate students of Pharmacy , and Chemical Sciences
When there are two functional groups of unequal reactivity within a molecule, the more reactive group can be made to react alone, but it may not be possible to react the less reactive functional group selectively.
A group the use of which makes possible to react a less reactive functional group selectively in presence of a more reactive group is known as protecting group.
A protecting group blocks the reactivity of a functional group by converting it into a different group which is inert to the conditions of some reaction(s) that is to be carried out as part of a synthetic route
It is an intramolecular rearrangement reaction in which the 1,2-migration of silyl group from carbon to oxygen under basic conditions.It involves the formation of a pentacoordinate siliconintermediate.Discovered by Adrian Gibbs Brook in 1958.
more chemistry contents are available
1. pdf file on Termmate: https://www.termmate.com/rabia.aziz
2. YouTube: https://www.youtube.com/channel/UCKxWnNdskGHnZFS0h1QRTEA
3. Facebook: https://web.facebook.com/Chemist.Rabia.Aziz/
4. Blogger: https://chemistry-academy.blogspot.com/
Organic Synthesis:
The Disconnection Approach
One Group C-C Disconnection of Alcohol and Alkene
chemoselective oxidation of secondary alcohols using a ruthenium phenylendeny...VasiUddin Siddiqui
i make this presentation for my seminar project.basically it is a paper work done by Simone Manzini, César A. Urbina-Blanco, and Steven P. Nolan*EaStCHEM School of Chemistry, University of St Andrews, St Andrews, U.K. KY16 9ST ..
It is an intramolecular rearrangement reaction in which the 1,2-migration of silyl group from carbon to oxygen under basic conditions.It involves the formation of a pentacoordinate siliconintermediate.Discovered by Adrian Gibbs Brook in 1958.
more chemistry contents are available
1. pdf file on Termmate: https://www.termmate.com/rabia.aziz
2. YouTube: https://www.youtube.com/channel/UCKxWnNdskGHnZFS0h1QRTEA
3. Facebook: https://web.facebook.com/Chemist.Rabia.Aziz/
4. Blogger: https://chemistry-academy.blogspot.com/
Organic Synthesis:
The Disconnection Approach
One Group C-C Disconnection of Alcohol and Alkene
chemoselective oxidation of secondary alcohols using a ruthenium phenylendeny...VasiUddin Siddiqui
i make this presentation for my seminar project.basically it is a paper work done by Simone Manzini, César A. Urbina-Blanco, and Steven P. Nolan*EaStCHEM School of Chemistry, University of St Andrews, St Andrews, U.K. KY16 9ST ..
Synthesis, Characterization and Antibacterial Activity of New Complexes of So...IOSR Journals
Complexes of some lanthanide picrates (Ln3+ = Pr3+, Nd3+ and Dy3+) with benzo-18-crown-6 and 221-cryptand were synthesized and characterized by elemental analysis, FTIR, and UV-Visible. Spectrophotometric methods, thermal analysis (TGA & DTG), melting point, magnetic susceptibility and molar conductance. Also an in-vitro study on gram positive (Staphylococcus aureus) and gram negative bacteria (Escherichia coli, Salmonella and pseudomonas aeruginosa) was performed and the results were compared to those of the broad spectrum antibiotic Chloramphinicol. The benzo-18-crown-6 complexes have the general formula of [Ln.L.(Pic)2]Pic.nH2O , where; (Ln3+ = Pr3+, Nd3+, and Dy3+) , (L = Benzo-18-crown-6) , (Pic = Picrate anion) , (n = 1-2). In these complexes two picrate anions are coordinated to the metal ion through the phenolic oxygen and oxygen of the ortho nitro group, thus, the metal ions in these complexes have a coordination number of (10). The complexes of 221-cryptand have the general formula of [Ln.L.(Pic)]Pic2.nH2O where; (Ln3+ = Pr3+, Nd3+, and Dy3+), (L = 221-cryptand), (Pic = Picrate anion), (n = 1,2 or 7). In these complexes one picrate anion is coordinated to the metal ion, also through the phenolic oxygen and the oxygen from the ortho nitro group, thus the metal ions in the cryptand complexes have a coordination number of (9).
It contains introduction, homogeneous, heterogenous, transition metal, organometallic, enzymatic and phase transfer catalysis part with certain aspect of greener approach.
It cover approximately all topic according to M.pharm Organic chemistry syllabus, not in advance but for general and basic purpose of understanding.
Green Chemistry Catalysts for Transfer Hydrogenation Reactions: Synthesis, ch...Karam Idrees
The poster that I presented at the 253rd American Chemical Society National Meeting and Exposition in San Francisco,
CA. It highlights some of my research at Millersville University under the mentorship of Dr. Edward Rajaseelan.
PEGylated magnetic nanoparticles (PEG@Fe3O4) as cost effectivealternative for...Pawan Kumar
An efficient, cost effective and environmental friendly PEGylated magnetic nanoparticle catalyzed oxida-tive cyanation via CH activation of tertiary amines to corresponding -aminonitriles using hydrogenperoxide as oxidant and sodium cyanide as cyanide source is described. The synthesized nanocatalyst waseasily recovered with the help of external magnet and was successfully reused for several runs withoutany significant loss in catalytic activity.
PEGylated magnetic nanoparticles (PEG@Fe3O4) as cost effectivealternative for...Pawan Kumar
tAn efficient, cost effective and environmental friendly PEGylated magnetic nanoparticle catalyzed oxida-tive cyanation via CH activation of tertiary amines to corresponding -aminonitriles using hydrogenperoxide as oxidant and sodium cyanide as cyanide source is described. The synthesized nanocatalyst waseasily recovered with the help of external magnet and was successfully reused for several runs withoutany significant loss in catalytic activity.
Chelating ion exchange and antimicrobial studiesIJECSJournal
The Copolymer (p-HBTF-I) was synthesized by condensation of p-hydroxybenzoicacid and thiosemicarbazide with formaldehyde in the presence of 2M HCL as a catalyst at 126 ± 2 0C for 5 hrs. with molar proportion of reactants. The copolymer (p-HBTF-I) was characterized by elemental analysis, FT-IR, UV-Visible 1H-NMR Spectroscopy. The chelating ion-exchange property of this polymer was studied for five metal ions viz. Cu (II), Ni (II), Co (II), Zn (II), and Pb (II) ions. The chelating ion-exchange study was carried out over a wide range of pH, shaking time and in mediaof various ionic strengths. The copolymer possesses antimicrobial activity for certain bacteria such as B. Subtilis, ,E.Coli, S. Typhi .
Azomethine Metal Chelates as an Efficient Catalyst for Oxidation of Organic C...CrimsonPublishersACSR
Azomethine ligands and their metal chelates are flexible compounds synthesized from the condensation
of an amino compound with carbonyl compounds and extensively used for industrial purposes and also
show a broad range of biological efficiencies including antibacterial, antifungal, antiviral, antimalarial,
antiproliferative, anti-inflammatory, anticancer, anti-HIV, anthelminthic and antipyretic properties.
Azomethine metal chelates show excellent catalytic activity in diversity reactions. Over the past few
years, there have been many reports on their applications in homogeneous and heterogeneous catalysis.
The high thermal and moisture stabilities of many azomethine metal chelates were useful attributes for
their application as catalysts in reactions involving at high temperatures. Recent researches in oxidation
catalysis have focused on how to employ the metal-catalyzed oxidation of organic substrates. This review
concerns with the current developments for the oxidations of organic compounds.
1,4- Addition of copper acetylides to unsaturated ketonesSaibalendu Sarkar
TMSI promoted 1,4-addition of Copper acetylides to unsaturated aldehydes and ketones.This ppt is totally based on a paper published in Journal of American Chemical Society. The ppt is more about the analysis of the paper
1. Asymmetric Organocatalysis:
Introduction:
Organocatalysis uses small organic molecules predominantly composed of C, H, O, N, S and P to
accelerate chemical reactions. The advantages of organocatalysts include their lack of sensitivity to
moisture and oxygen, their ready availability, low cost, and low toxicity, which confer a huge direct
benefit in the production of pharmaceutical intermediates when compared with (transition) metal
catalysts.
“Organocatalysis is the field wherein small organic molecules efficiently and selectively
catalyze organic transformations”. David W. C. MacMillan
“Organocatalysis is the catalysis of a reaction with an organic small molecule. By
accepted
convention, organic small molecule means a molecule without a metal, and not a
macromolecule like protein, nucleic acid, or polymer”. K.N. Houk
“Organocatalysis is catalytic reactions mediated by small organic molecule in absence of
metals or metal ions”.
Thiourea Organocatalysis:
Thiourea organocatalysis describes the utilization of properly designed derivatives of
urea and - preferably – thiourea to accelerate and stereochemically control organic
transformations through predominantly double hydrogen- bonding interactions with the
respective substrate(s) (non-covalent organocatalysis). The scope of these small-molecule H-
bond donors termed (thio)urea organocatalysts covers both non-stereoselective and
stereoselective applications in organic synthesis (asymmetric organocatalysis). In nature non-
covalent interactions such as hydrogen bonding ("partial protonation") play a crucial role in
enzyme catalysis that is characterized by selective substrate recognition (molecular
recognition), substrate activation, and enormous acceleration and stereocontrol of organic
transformations. Based on the pioneering examinations by Kelly, Etter, Jorgensen, Hine,
Curran, Goubel, and De Mendoza on hydrogen bonding interactions of small, metal-free
compounds with electron-rich binding sites; Schreiner and co-workers performed series of
theoretical and experimental systematic investigations towards the hydrogen-bonding ability
of various thiourea derivatives. In simple Diels-Alder reaction, it acts like weak Bronsted
acid catalysts, but operate through explicit double hydrogen bonding instead of covalent
(strong) binding known from traditional metal-ion mediated catalysis.
2. Advantage of T hiourea Catalyst:
1. Relatively simple and inexpensive;
2. Non-toxic and metal free derivatives;
3. No inert atmosphere is necessary to handle and tolerant to water;
4. Thiourea derivatives are stable and can be stored for several months at room
temperature;
5. Thiourea based catalysts can be recovered from reaction mixture and used repeatedly;
6. The small amount of catalyst is enough to catalyse a reaction cycle.
History ab out O rganocatalysis:
First the organocatalytic reaction without any metal is discovered by German Chemist Justus von
Liebig, in 1859. This discovery is the beginning of an epoch of organocatalysis. In modern organic
chemistry, the use of metal containing catalyst is less appropriate because of their hazardous
properties. It is also be noted that the transition metal catalysts are less stable, moisture sensitive,
more toxic, expensive as compared to non-metal based organocatalysts. Transition metals build up the
biological system. Some metals are required in our body but can be toxic in large amount. So,
handling and use of metal catalysts have to be done carefully otherwise metals can entire in our body
with food, water, by absorption through the skin etc.
To solve this problem use and preparation of organocatalyst without any
metal is proposed. Some organocatalyst gives the racemic product of a reaction. But resolution is very
difficult to separate two enantiomers. To solve this problem people used asymmetric organocatalysts.
Today many chemists of the whole world isolate naturally occurring compounds
(like proline) and draw as promising organocatalysts in the different directions of asymmetric
organocatalysis.
Use of Thiourea Catalyst:
Primary amine thiourea catalysts have wide application in organic synthesis. It is used to get highly
enantioselective product of a reaction. Primary amine-thioureas based on tert-butyl esters of α-amino
acids are the most efficient organocatalysts for “difficult” Michael reactions. The catalyst based on
(S)-di-tert-butyl aspartate and (1R,2R)-diphenylethylenediamine gives the product of a reaction
between aryl methyl ketones and nitroolefins in excellent yields and enantioselectivities. Bi-functional
praimary amine thiourea catalyst is used for reduction of a ketone to get highly enantioselective
product. For example,
3. The above type of reaction gives highly enantioenriched product.
Example:
Synthesis of Primary Amine Thiourea Catalyst:
[(S)-2-(3-((1R,2R)-2-amino-1,2-diphenylethyl)thioureido)-N-benzyl-3,3-
dimethylbutanamide(3):
Scheme-1 (Boc Protection of Tertiary Leucine):
ReactionScheme:
HO
NH2
O
1.Sodium Carbonate
2.BOC-Anhydride
Dichloromethane, Water
HO
N
H
O
O
O
Compounds: (S)-tertiary leucine, sodium carbonate, BOC-anhydride.
O O O
O O
BOC-Anhydride:
4. Solvent: THF for BOC-anhydride, water for amino acid.
Procedure: Amino acid (1 eqv.) is dissolved in required amount of water and then THF is mixed .
The solution is cooled to zero degree, sodium carbonate and BOC-anhydride is added sequentially to
this cooled solution. After some time the reaction mixture is stirred to room temperature to overnight.
Observation: The progress of the reaction is observed, by checking TLC(ninhydrin test). After
running the TLC , it gives only one spot of starting material ,does not give any spot of reaction
mixture that indicates the reaction is completed.
WorkTo Be Done: After complete of the reaction , reaction mixture is acidified by 10%
HCL(acidity is maintained at pH=2) and worked up using ethylacetate. Organic part is washed with
brine,dried over sodium sulphate and concentrated in rotavapor and BOC-protected amino acid is
collected as a solid.
Identification: To confirm the BOC protection IR and proton NMR has been taken. IR gave the
characteristic peak at 1717 cm-1 (ester). NMR gives two charrecteristic peaks of tertiary group.
Yield: 95%
Scheme-2 (Formation Of Amide Bond, Using Benzyl Amine):
Reaction Scheme:
Compounds: Benzyl amine, N-BOC-L-tert-leucene,1-(3-dimethylaminopropyl)-3-
ethylcarbodiimide hydrochloride (EDC), 1-hydroxybenzotriazole hydrate (HOBT),N,N-
diisopropylethylamine (DIPEA).
Solvent: Dichloromethane.
NH2 HO
N
H
O
O
O
1.EDC
2.HOBT
3.DIPEA
Dichloromethane, 23 degree, 6 hr
H
N
N
H
O
O
O
EDC:
N N C N HCL
HOBT:
N
N
N
OH 3.DIPEA:
, ,
N
5. Procedure: N-BOC-L-tert-leucine (1 eqv.), EDC (1.1 eqv.), HOBT (1.1 eqv.) are taken in a dry
round flask with a magnetic stir bar. The mixture is dried in vaccuam and nitrogen atmosphere done.
The round bottom is covered with a septum. The mixture is disssolved in dichloromethane solvent and
the colorless solution is stirred at room temperature. Then benzyl amine (1.1 eqv.) and DIPEA (1.1
eqv.) is added sequentially to the clear solution , the reaction mixture is stirred at room temperature
for minimum 6 hr.
Observation: The progress of the reaction is observed by checking TLC. After running the TLC
plate in 10% ethyl acetate in hexane gives three spot of reaction mixture which are above the given
spot and Benzyl amine , HOBT gives the spot at the same given position. All spots are UV as well as
Iodine active. The spots of reaction mixture indicats that the reaction is completed.
Workto Be Done: After complete the reaction, reaction mixture is poured into a separating funnel
To work up. 1(M) HCL is added to the mixture and organic part is separated,then aqueous phase is
extracted with dichloromethane. Organic phase are combined, washed sequentially with sodium-bi-
carbonate(sat.) and brine, then dried over sodium sulphate. Dried organic part is concentrated in
rotavapor to collect the amide as a white solid. Then coloumn has been done to separate pure amide
using 8% ethylacetate in hexane.
Identification: To identify the amide bond NMR has been taken and gives the charrecteristic peak of
amide proton and also gives the peak of benzene ring protons.
Yield: 82.06%
Scheme-3(Deprotection of BOC):
ReactionScheme:
Compounds: BOC-protected amide,4(M)HCL.
Solvent: 1,4-dioxane
Procedure: 4(M)HCL in 1,4-dioxane(9 eqv.) is added in BOC-protected amide and a magnetic bar is
entered into the round bottom flusk. The solution is stirred for half an hour at room temperature.
H
N
N
H
O
O
O
4(M) HCL
1,4-Dioxane
H
N
NH2.HCl
O
6. Observation: The progress of the reaction is observed by checking TLC. After running the TLC in
10% ethylacetate in hexane it gives one spot of the authentic and another one i.e. reaction mixture
gives one spot at the given position. As the BOC-protected amide is less polar than the amine salt, so
amide gives the spot which is above the reaction mixture, all spots are both UV and Iodine active.
That indicates the reaction is completed.
WorkSo Far: After complete the reaction the reaction mixture is evaporated under reduce pressure
.The residue is dried in high vacuo and got a yellow salt of BOC-deprotected amine.
Identification: BOC-deprotection is confirmed by TLC cheacking.
Scheme-4 (Preperation Of Isothiocyanate):
1.Thiophosgene Derivative[Cs(Oph)Cl] Method:
ReactionScheme:
Compounds: amide salt, saturated sodium-bi-carbonate, thiophosgene derivative [CS(Oph)Cl].
Solvent: dichloromethane.
Procedure: Amide salt is dissolved in dichloromethane then saturated sodium-bi-carbonate is added
.The reaction mixture is stirred at zero degree temperature to get clear solution. Sodium-bi-carbonate
is added to neutralise the salt to get free amine which react with thiophosgene derivative. CS(Oph)Cl
(1.05 eqv.) is added to the cooled solution and reaction mixture is stirred for 20 min. at zero degree.
Then it stirred at room temperature for half an hour.
Observation: After stirred the reaction mixture become two phase one is light orange organic phase
and another is aqueous phase. The progress of the reaction is observed by checking TLC. After
running TLC in 30% ethylacetate in hexane reaction mixture gives spot, [CS(Oph)Cl] gives three spot
and salt gives one spot .All spots are both UV and Iodine active. Complete of the reaction is checked
from TLC.
Work So Far: Reaction mixture is poured into a separating funnel to separate organic phase.
Organic phase is separated and aqueous phase is extracted with DCM . Organic phase are combined,
H
N
NH3Cl
O
PhO Cl
S,
Na2CO3, DCM
0 - 23 degree
No Reaction
7. washed with brine, dried over sodium sulphate. The dried phase is concentrated under reduced
pressure and got the yellow color crude product. The spot is separated by coloumn cromatography
method using 15% ethylacetate in hexane. The upper spot is collected (less polar than salt) and
evaporated to get the product. It is dried in high vac.
Identification: NMR has been taken but it does not give the charrecteristics peak of isothiocyanate.
Conclusion: The reaction is failed.
2. Carbon-Di-Sulphide Method:
ReactionScheme:
Compounds: Amide salt, carbon di sulphide, triethyl amine.
Solvent: Absolute ethanol.
Procedure: The amide salt is dissolved in absolute ethanol. The solution is stirred to get clear
solution and then carbon di sulphide (10 eqv.) ,triethyl amine (10 eqv.) is added to the solution
sequentially. In that case one more equv. triethyl amine is added as the reaction is done using amide
salt
Observation: No precipitation is formed that concludes the reaction does not happen.
3. Thiophosgene Method:
ReactionScheme:
Compounds: Amide salt, saturated sodium bi carbonate, thiophosgene
H
N
NH3Cl
O
Na2CO3, DCM
S
Cl Cl
0-23 degree,
H
N
NCS
O
H
N
NH3Cl
O
Absolute Ethanol
tri- ethyl amine
CS2
No PPT
8. Solvent: DCM
Procedure: .Amide salt is dissolved in dichloromethane (10eqv.) and the solution is stirred. In
stirred solution saturated sodium bi carbonate (10 eqv.) is added. The resulting solution is stirred at
zero degree temperature in an ice bath. In the clear colorless solution thiophosgene (1.05 eqv.) is
added via syringe and the resulting light orange biphasic mixture is stirred at zero degree about 20
minutes. Then the mixture is stirred at room temperature for half an hour.
Observation: The progress of the reaction is observed by checking TLC. After running TLC in
10% ethylacetate the reaction mixture gives only one spot and also the salt gives one spot. Now as the
isothiocyanate is less polar than the amine salt, it gives the spot above the amine salt spot. This
indicates that the reaction is completed.
Work to Be Done: The biphasic reaction mixture is poured into a separating funnel and the organic
phase is separated from mixture. The aqueous phase is extracted with DCM. Then the organic phase
are combined, washed with brine, dried over sodium sulphate. The dried organic part is filtered out
and concentrated under reduced pressure to get yellow color product. Then coloumn is done to
remove color impurity using 8% ethylacetate in hexane. After coloumn it has been shown that the spot
of the isothiocyanate break into two spot with very small difference in Rf vallue.
Identification: NMR and IR is taken to charrecterise the product. NMR gives the charrecteristic
peak of isothiocyanate.
Yield: 81.87%
Scheme-5(Preparation Of Catalyst):
ReactionScheme:
Comoound: Isothiocyanate,(R,R)-1,2-cyclohexyldiamine.
Solvent:DCM.
H
N
N
O
C
S DCM
NH2
NH2
H
N
N
H
O
N
H
S
H2N
9. Procedure: A clear solution is obtained after stirring a solution of Isothyocyanate in DCM.Then a
portion of (R,R)- 1,2-cyclohexyldiamine is added in that clear solution . Then the solution is stirred by
overnight.
Observation: The progress of the reaction is observed by checking the TLC.
Workto be done:The reaction mixture is evaporate to obtain a yellow crude product.
Conclusion:
Fromisothiocyanate we cansynthesise huge numberof catalyst.Which can be usedin different
type of reactiontoget highly enantioselective product.