This document discusses ester enolates and the Claisen condensation reaction. The Claisen condensation involves the deprotonation of a 3-oxoalkanoate to form an ester enolate, which then undergoes nucleophilic addition and elimination to form a β-ketoester product. The acidic hydrogens of β-ketoesters make them readily enolizable and allow the reaction to be driven to the product. Ester enolates can undergo reactions like alkylation, Michael additions, and the Robinson annulation. Methods for synthesizing α-hydroxycarbonyls involve the use of masked alkanoyl anions like 1,3-dithiane derivatives or a
123.713A/B. Description of the Jacobsen synthesis of muconin. This is an example of total synthesis, retrosynthesis and asymmetric synthesis and shows the kind of information required in the assigment for this course.
A look at epothilone A as it includes examples of many different forms of asymmetric synthesis. Also includes a little bit about ring-closing metathesis.
The big topic of the last few years, the use of small organic molecules to catalyse enantioselective transformations. This lecture will start with proline before moving on to some of MacMillan's contributions to this field and, finally, finish with hydrogen bond catalysts and Brønsted acids.
Gives an introduction to total synthesis and why we do it (which reminds me, I must add a picture of Everest, as I think the fact that 'it is there' is the main reason for most syntheses). Then to introduce the topic with a reasonably simple synthesis, we will look at an example of the synthesis of Tamiflu.
123.713A/B. Description of the Jacobsen synthesis of muconin. This is an example of total synthesis, retrosynthesis and asymmetric synthesis and shows the kind of information required in the assigment for this course.
A look at epothilone A as it includes examples of many different forms of asymmetric synthesis. Also includes a little bit about ring-closing metathesis.
The big topic of the last few years, the use of small organic molecules to catalyse enantioselective transformations. This lecture will start with proline before moving on to some of MacMillan's contributions to this field and, finally, finish with hydrogen bond catalysts and Brønsted acids.
Gives an introduction to total synthesis and why we do it (which reminds me, I must add a picture of Everest, as I think the fact that 'it is there' is the main reason for most syntheses). Then to introduce the topic with a reasonably simple synthesis, we will look at an example of the synthesis of Tamiflu.
Use of stoichiometric amounts of a chiral source. The usual suspects will be discussed, including borane reagents (mostly pinene derivatives) and the Brown allylation.
Self explanatory really, this lecture looks at chiral auxiliaries. We will concentrate on oxazolidinones in alkylations, aldol reaction and the Diels-Alder reaction. There will be a couple examples of other auxiliaries.
An introduction to total synthesis and retrosynthesis. A quick overview of retrosynthesis followed by one of the many syntheses of (–)-stenine. This is just an overview of the fascinating world of organic synthesis, it is not intended to teach retrosynthesis or organic synthesis. For that see some of my other lecture notes.
This is the biggy, the one everyone wants to achieve. Here we will be looking at metal-based chiral catalysis. We will concentrate on bisoxazoline-based Lewis acid catalysis and then look at reductions before finishing with the ubiquitous Sharpless epoxidation and dihydroxylation.
Schmidt rearrangement, B.PHARM 4 SEM, pharmceutical organic chemSAKSHI BHATT
SCHMIDT REARRANGEMENT, A NAMING REACTION.
Mechanism of production of amines, imines, amides & nitrile from Aldehyde, ketone, tertiary alcohols, alkenes & carboxylic acid
Manufacturing of important polymers and polymer processing Bademaw Abate
This note contains synthesis of important monomers from hydrocarbons and prooduction of associated polymers which are most frequently used for textiles.
This presentation has detailed information on glycolysis. each step is explained in detail. there are certain videos which i have taken from youtube. if these videos are not viewable u can refer to shomus biology glycolysis videos. u will get a detailed info there.
lehninger 3rd edition is also very good for the structures
Happy studying :)
Use of stoichiometric amounts of a chiral source. The usual suspects will be discussed, including borane reagents (mostly pinene derivatives) and the Brown allylation.
Self explanatory really, this lecture looks at chiral auxiliaries. We will concentrate on oxazolidinones in alkylations, aldol reaction and the Diels-Alder reaction. There will be a couple examples of other auxiliaries.
An introduction to total synthesis and retrosynthesis. A quick overview of retrosynthesis followed by one of the many syntheses of (–)-stenine. This is just an overview of the fascinating world of organic synthesis, it is not intended to teach retrosynthesis or organic synthesis. For that see some of my other lecture notes.
This is the biggy, the one everyone wants to achieve. Here we will be looking at metal-based chiral catalysis. We will concentrate on bisoxazoline-based Lewis acid catalysis and then look at reductions before finishing with the ubiquitous Sharpless epoxidation and dihydroxylation.
Schmidt rearrangement, B.PHARM 4 SEM, pharmceutical organic chemSAKSHI BHATT
SCHMIDT REARRANGEMENT, A NAMING REACTION.
Mechanism of production of amines, imines, amides & nitrile from Aldehyde, ketone, tertiary alcohols, alkenes & carboxylic acid
Manufacturing of important polymers and polymer processing Bademaw Abate
This note contains synthesis of important monomers from hydrocarbons and prooduction of associated polymers which are most frequently used for textiles.
This presentation has detailed information on glycolysis. each step is explained in detail. there are certain videos which i have taken from youtube. if these videos are not viewable u can refer to shomus biology glycolysis videos. u will get a detailed info there.
lehninger 3rd edition is also very good for the structures
Happy studying :)
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Normal Labour/ Stages of Labour/ Mechanism of LabourWasim Ak
Normal labor is also termed spontaneous labor, defined as the natural physiological process through which the fetus, placenta, and membranes are expelled from the uterus through the birth canal at term (37 to 42 weeks
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
1. Chapter 23: Ester EnolatesChapter 23: Ester Enolates
and theand the
Claisen CondensationClaisen CondensationRecall theRecall the
aldolaldol
addition:addition:
Can we doCan we do
this withthis with
esterester
enolates?enolates?
2. The Claisen CondensationThe Claisen Condensation
Driven byDriven by deprotonationdeprotonation of 3-oxoalkanoate (“of 3-oxoalkanoate (“ββ–ketoester”).–ketoester”).
Step 1:Step 1: Ester Enolate FormationEster Enolate Formation
Endothermic as writtenEndothermic as written
Mechanism: Addition-EliminationMechanism: Addition-Elimination
Has to be the same or transesterification will occur
AcidicAcidic
4. Step 4:Step 4: Deprotonation of 3-OxoesterDeprotonation of 3-Oxoester
Step 5:Step 5: Protonation on Aqueous Work-upProtonation on Aqueous Work-up
ClaisenClaisen
This step drives the reaction to the product as the anion.This step drives the reaction to the product as the anion.
5. Products of Claisen condensation areProducts of Claisen condensation are alkyl 3-alkyl 3-
oxoalkanoatesoxoalkanoates (IUPAC), common name(IUPAC), common name ββ-keto--keto-
esters and, generally,esters and, generally, ββ-dicarbonyl-dicarbonyl compoundscompounds
The hydrogens between the two carbonyls areThe hydrogens between the two carbonyls are
unusuallyunusually acidicacidic: Due to inductive effect of: Due to inductive effect of
two carbonyls and resonance in the anion.two carbonyls and resonance in the anion.
6. Low pLow pKKaas mean that alkoxide or hydroxide can make the enolatess mean that alkoxide or hydroxide can make the enolates stoichiometricallystoichiometrically!!
7. 1,3-Dicarbonyl Compounds Form1,3-Dicarbonyl Compounds Form
EnolsEnols ReadilyReadily
O O
H
O O
H
65%35%
100°C
H Bonding in enol is symmetrical:H Bonding in enol is symmetrical:
oror ??
J. Am. Chem. Soc.
2006, 128, 854.
8. Acidity of Claisen product is essential to driveAcidity of Claisen product is essential to drive
the reaction. Without the acidic H, reactionthe reaction. Without the acidic H, reaction
goes in the reverse!goes in the reverse!
No goNo go, starting on the left., starting on the left. Goes from right to leftGoes from right to left, when starting with the, when starting with the
product (made by a different route, as will be seen later).product (made by a different route, as will be seen later).
MechanismMechanism of reverse Claisen condensation:of reverse Claisen condensation:
9. But:But: If one partner hasIf one partner has nono αα--hydrogenshydrogens (not(not
enolizable):enolizable):
Crossed Claisen CondensationCrossed Claisen Condensation
GivesGives mixturesmixtures of products (as in the caseof products (as in the case
of the crossed aldol addition).of the crossed aldol addition).
H O O
O O
+
1. Na+ -OCH2CH3,
CH3CH2OH
2. H+, H2O
H O
O O
80%
Ethyl 3-oxopropanoate
10. Mixed Ketone Claisen CondensationMixed Ketone Claisen Condensation
KetonesKetones areare more acidicmore acidic than esters, functionthan esters, function
asas enolateenolate partners. Their competitive aldolpartners. Their competitive aldol
additions are reversible, but Claisen is not.additions are reversible, but Claisen is not.
pKa = 19pKa = 25
This is general forThis is general for
R
O O
11. Intramolecular Claisen CondensationIntramolecular Claisen Condensation
((Dieckmann CondensationDieckmann Condensation))
Ethyl 2-oxocyclohexanecarboxylate
Mixed Claisen-Dieckmann CondensationMixed Claisen-Dieckmann Condensation
O
O
80%
O
O
O O
O O
1. Na+ -OCH2CH3,
CH3CH2OH
2. H+, H2O
O O
OO
O O
12. Use ofUse of ββ--Dicarbonyl CompoundsDicarbonyl Compounds
O O
acidicacidic
Derived enolates are relatively non-basic,Derived enolates are relatively non-basic,
but good nucleophiles:but good nucleophiles:
O O O O
1. Base
2. RX
RH
Particularly useful forParticularly useful for oxoestersoxoesters derived fromderived from
Claisen condensations, because hydrolysis leadsClaisen condensations, because hydrolysis leads
toto oxoacidsoxoacids whichwhich decarboxylatedecarboxylate..
16. Alkylation of ethyl 3-oxobutanoate (ethyl
acetoacetate), followed by ester
hydrolysis, and finally decarboxylation
gives 3-substituted or 3,3-disubstituted
methyl ketones. This is called the
acetoacetic ester synthesis.
Advantage over direct ketone enolate alkylation:Advantage over direct ketone enolate alkylation:
MuchMuch less basic enolateless basic enolate; obviates E2 for R; obviates E2 for Rsecsec..
18. Starting from diethyl propanedioate (malonic
ester) the same sequence (alkylation,
hydrolysis, decarboxylation) gives 2-alkylated
and 2,2-dialkylated acetic acids, a method
called the malonic ester synthesis.
19. Michael AdditionMichael Addition
Reaction of 3-oxo ester enolates withReaction of 3-oxo ester enolates with αα,,ββ––
unsaturated carbonyls (1,4-addition)unsaturated carbonyls (1,4-addition)
1,4-Addition is the thermodynamic process,1,4-Addition is the thermodynamic process,
1,2-addition does occur, but is reversible.1,2-addition does occur, but is reversible.
20. Robinson AnnulationRobinson Annulation
70%70%
Recall:Recall: Robinson annulationRobinson annulation is a sequence ofis a sequence of MichaelMichael
additionaddition, followed by, followed by intramolecular aldol condensationintramolecular aldol condensation
Goes via:Goes via:
Michael adductMichael adduct
21. αα-Hydroxycarbonyls-Hydroxycarbonyls
Important function in nature and in drugs. HowImportant function in nature and in drugs. How
do we make it? Ideal retrosynthesis is:do we make it? Ideal retrosynthesis is:
Alkanoyl anionAlkanoyl anion
Problem: We cannot make alkanoyl anions from aldehydes,Problem: We cannot make alkanoyl anions from aldehydes,
because bases will either deprotonate alpha to makebecause bases will either deprotonate alpha to make
enolate or add to carbonyl function as nucleophiles.enolate or add to carbonyl function as nucleophiles.
Therefore, we need to useTherefore, we need to use masked alkanoyl anions.masked alkanoyl anions.
R
OHO
R
O O
:
22. 1.1. StoichiometricStoichiometric reagents:reagents: 1,3-Dithia-1,3-Dithia-
cyclohexanecyclohexane (1,3-dithiane) anions(1,3-dithiane) anions
Dithiane is acidic because of theDithiane is acidic because of the polarizabilitypolarizability
of sulfur, stabilizes adjacent charge.of sulfur, stabilizes adjacent charge.
24. Other alkylating agents: AnotherOther alkylating agents: Another
aldehyde/ketone synthesisaldehyde/ketone synthesis
HR
O HS SH, ZnCl2
S S
R
1.
2.
Li
1. R'X
2. HgCl2
R'R
O
1.
2. HgCl2
O
R
O
OH
:
25. 2.2. CatalyticCatalytic version: Alkanal couplingversion: Alkanal coupling
usingusing thiazolium ion catalystthiazolium ion catalyst
Crucial for catalysis is:Crucial for catalysis is:
Six electrons:
Carbene
27. Drawback of the catalytic version: OnlyDrawback of the catalytic version: Only symmetricalsymmetrical coupling.coupling.
In nature: Thiamine (vitamin B1)In nature: Thiamine (vitamin B1)
A = H, ThiamineA = H, Thiamine
A = , thiamine pyrophosphateA = , thiamine pyrophosphate
Editor's Notes
Beri-beri
"A certain very troublesome affliction, which attacks men, is called by the inhabitants Beri-beri (which means sheep). I believe those, whom this same disease attacks, with their knees shaking and legs raised up, walk like sheep. It is a kind of paralysis, or rather Tremor: for it penetrates the motion and sensation of the hands and feet indeed sometimes the whole body..." Jacobus Bonitus, Java, 1630
Thiamine deficiency usually causes weight loss, cardiac abnormalities, and neuromuscular disorders. The classic thiamine deficiency syndrome in humans is beri-beri (sometimes called Kakke). Thiamine is abundant in whole grains, usually in the scutellum (the thin covering of the starchy interior endosperm), but is scarce in the endosperm. Unfortunately beri-beri is still common in parts of southeast Asia where polished rice is a staple and thiamine enrichment programs are not fully in place. Beri-beri is characterized by anorexia (loss of appetite) with subsequent weight loss, enlargement of the heart, and neuromuscular symptoms such as paresthesia (spontaneous sensations, such as itching, burning, etc.), muscle weakness, lassitude (weariness, general weakness), and foot and wrist droop. There are three main types of beri-beri: (1) dry (also neuritic, paraplegic, and pernicious) beri-beri; (2) wet (also edematous or cardiac) beri-beri; (3) and infantile (also acute) beri-beri. Dry beri-beri usually inflicts older adults and affects mainly the peripheral nerves with little cardiac involvement. It is characterized by atrophy (wasting away) and peripheral neuritis (inflammation of nerves) of the legs and paraplegia (paralysis of the lower extremities). In contrast wet beri-beri displays substantial cardiac involvement especially tachycardia (rapid heart beat) in addition to peripheral neuropathy. Edema progresses from the feet upwards to the heart causing congestive heart failure in severe cases. Infantile beri-beri is usually seen in breast-feeding infants whose mothers are thiamine deficient (but not necessarily showing signs of beri-beri). These infants are usually anoretic and often have trouble keeping the milk down. Once the disease begins it moves rapidly causing heart failure in a matter of hours.
Wernicke-Korsakoff Syndrome
Wernicke-Korsakoff Syndrome or Wernicke's encephalopathy is the thiamine deficient disease seen most often in the Western hemisphere. It mainly affects alcoholics due to three reasons: (1) the diets of alcoholics are usually poor; (2) diets rich in carbohydrates (e.g., alcohol or rice) increase the metabolic demands of thiamine; and (3) alcohol inhibits intestinal ATPase which is involved in the uptake of thiamine. Two observations suggest a genetic invovlement with Wernicke-Korsakoff Syndrome: (1) it is much higher in among Europeans than non-Europeans; and (2) transketolase (see above under " Thiamine in the Pentose Phosphate Pathway") from Wernicke-Korsakoff Syndrome patients binds TPP 10 time less strongly than normal transketolase. The symptoms of Wernicke-Korsakoff syndrome include confusion, sixth nerve damage resulting in ophthalmoplegia (paralysis of an eye motor nerve) and nystagmus (rhythmical oscillation of the eyes), psychosis, confabulation, and impaired retentive memory and cognitive function. In severe cases the patient may slip into a coma. A congenital defect in transketolase which causes a low binding affinity for TPP increases the chances of acquiring Wernicke-Korsakoff syndrome.