12/24/11 - Acyl Imidazolide Formation from Carboxylic Acid

    I apologize for my absence in updating this blog as I have just finished exams and I have now been frantically getting ready for Christmas while working everyday.  The reaction for this christmas eve is one that describes the synthesis of an Acid Imidazolide, which can be used in claisen like reactions due to the fact that the Imidazole acts as a good leaving group. All that is required in this reaction is to react the carboxylic acid with Carbonyl Diiamidazole (CDI), alleviating carbon dioxide and an imidazole molecule.

12/23/11 - Acyl Imidazolide Formation from Acid Chloride

   This reaction is acid imidazolide synthesis from the addition of and acid chloride to an imidazole molecule.

12/17/11 - Metal Reduction of Conjugated 2-Decalones

   As a means to regeochemically select an enolate in a decalone it is quite easy if there is a substitution at the Beta carbon.  All that is needed is a lithium solution with liquid ammonia in the presence of tert-butanol to provide protons.  These reagents create a solution of electrons which radically charge the beta position which then is pushed up to the alpha position and creating the enolate as the other negative charge is located on the oxygen, which is chelated to the lithium metal.

12/16/11 - Cyclopentadiene and Maleic anhydride

   This little snippet of a reaction was taken from an old exam for the course that I am studying for right now.  It involves a diels alder reaction between a cyclopentadiene and Maleic anhydride.  Here the diene is the cyclopentadiene (this molecule goes through diels alder reactions with itself so it is necessary to heat it above 160*C to reverse the reaction) and the dienophile as the Maleic anhydride.  This is the first step where the reaction goes as a 4π+2π endo reaction as a pericyclic reaction.  Then the second step will remove the diester as it also reduces the C=O into alcohols.  Then the final step involves turning the alkene into a 1,2-diiodine when the alkene gets halogenated, and then intramolecularly the alcohol attaches to the other point of halogenation.

12/15/11 - Sharpless Perruthenate Oxidation

   This oxidation reaction is used to turn primary or secondary alcohols into aldehydes or ketones accordingly.  The reactants involved in this reaction are the addition of (Ph3P)2RuCl2 and N-methylmorpholine-N-oxide, or also known as NMO.  What happens here is that the NMO causes the activation of the Perruthenate by oxidizing it, and then the Perruthenate continues to oxidize the alcohol which being bonded to the oxygen of the alcohol.

12/14/11 - Swern Oxidation

     Here is the second oxidation reaction, a more modern method which involves the activation of the DMSO molecule by the oxalyl chloride, which results in the addition of a chloride to the DMSO and then causes the DMSO to add to the alchohol and removing one of the alpha hydrogens.  Turning the alcohol into an aldehyde (or secondary alcohol into a ketone).

12/13/11 - Parekh-Doering Oxidation

     This oxidation reaction is used in many stereospecific molecules to make sure that the stereochemistry is not compromised during the oxidation.  This reaction is used to turn an alcohol into a ketone (secondary OH) or aldehyde (primary OH).  This technology requires the addition of DMSO with pyridine-SO3, which causes the activation of the DMSO, and triethylamine.

New Science

    This TED talk, I hope, should begin to inspire scientists and researchers into starting to think of science as a whole instead of keeping it as a personal feat.  At this day and age, with these wondrous technologies at hand, we should gain our glory from helping build this knowledge instead of sitting and being devoted to increasing the number of journal articles we have published.

12/2/11 - Creation of the Evan's Auxiliary Enolate

    This reaction works much like the selectivity within amide enolate formation, where the enolate forms in the Z formation where the R group of the enolate is eclipsed by the carbonyl.  And this reaction here causes the Evans imide to form the Z enolate selectively due to the lithium metal being an oxophilic agent to both of the carbonyls there, making sure that the bond between the N and the alpha C of the carbonyl doesn't rotate.  Now this molecule is ready to be put to use in an enolate reaction.

12/1/11 - Insertion of an Evan's Auxiliary on an enolizable carbonyl

   When performing reactions requiring specific stereochemical products (ie for biomedical purposes) it is necessary to gain these stereoisomers in very efficient ways.  One method of posing stereochemical controls is to introduce a very bulky group, adding steric interactions with the substrate and the reactant causing the reaction to add in a certain facial attack.  Over the next couple of days I will describe a certain reaction adhering to this method, and I will start here by describing how to create a stereochemically controlling reactant.  Here is the Evan's auxiliary, which adds to a acid chloride (of which we are wanting to enolize in the future) by the addition of a base (to deprotonate the Evan's auxiliary), and this case it is triethylamine.

11/30/11 - The Knoevanagel Reaction

   This reaction describes an aldol-dehydration sequence that involves the union of an aldehyde with an active methylene compound under simultaneous catalysis by a weak base and a weak acid. In this case the catalysis is by NH4OAc.  The Z groups in the picture below can be anything that induces electron withdrawing such as a carbonyl or a nitro.

11/29/11 - Silyl Enolate Thermodynamic Product

   Now that yesterday's reaction was the kinetic product of the silylation of an enolate I feel it is right to show the opposite where the thermodynamic product is formed.  The requirements for this reaction that differ from the previous one is that the base needed here must be a reversible one, which would cause all of the kinetic products to be reformed and converted to the most thermodynamically favorable product.  And that base here is HMDS, or hexamethyldisilazane.

11/28/11 - Silyl Enolate Kinetic Product

     In creating the kinetic product, that being the product with the lower energy transition state and the higher energy product, of a silyl enolate it is required that a bulky base is used to deprotonate the alpha position of the carbonyl.  In this case, the most popular base used is the Hunig's base, or otherwise known as N,N-Diisopropulethylamine, which quickly and irriversibly creates the enolate that in turn attacks a silyl triflate (here being TMS triflate).

11/27/11 - Regioselective Formation of Enolates

   In molecules of biomedical importance it is necessary to gain a regioselective basis of enolate formation, which will eventually lead to the addition of an electrophilic substitution at that point.  I apologize for the lack of pictures to describe this reaction, but I would like for you to picture in your mind a cyclohexane with a carbonyl ketone at one of the points.  On this cyclohexanone there is a substituent at the beta position, which demands a regioselective method of adding to the alpha position.  The method required is the creation of the alpha-beta unsaturation of this cyclohexanone and then the additon of lithium metal (or any other cationic metal) into the solution along with ammonia and t-BuOH.  This mixture causes the release of an electron, which ends up radicalizing the beta position on the molecule which causes the protonation at this point from the alcohol added, and this pushes the unsaturation to make the enolate on the side of substitution.

11/26/11 - Conversion of silyl enol ether enolates into Li enolates

   This is a reaction that we are currently using in our organic class (my last required course) that I am currently studying for.  I feel that I should do posts regarding the reactions I have to know for this class to help me study.  Here is a method to convert a silyl enol ether into a lithium enolate, which can then be used in enolate driven reactions.  This reaction is just performed by adding methyl lithium to the reaction which allows the methyl anion to attack the silyl group and then the oxophilic metal will replace it on the oxygen.

11/25/11 - Esterification from Carboxylic acids

    Again with the carboxylic acid chemistry, this is a reaction transforming a carboxylic acid inter an ester molecule.  The basic reaction consists of taking the desired carboxylic acid and combining it with the desired alcohol to form the ester, under conditions of heat and acid (usually sulfuric acid).  This alleviates water in this process

ROOH + R'OH ------> ROOR' + H2O

11/24/11 - Carboxylic Acid into Amide

   I figured I would continue with the carbonyl chemistry, and more specifically the carboxylic acid chemistry because it can be applied to perform so many reactions.  This is, again, a simple reaction of converting a carboxylic acid into an amide, where all that is needed is the amine (primary or secondary) or NH3 in the presence of the carboxylic acid.

RCO₂H + R'R"NH    RC(O)NR'R" + H₂O

Edit:  The addition of coupling agents in this reaction are requires, such as HATU with triethylamine and DMSO, or with T3P, triethylamine and DMF.

11/23/11 - Carboxylic Acid into Acid Chloride

    This simple reaction of converting a carboxylic acid into an acid chloride can come into much use when working with a lot of carbonyl chemistry.  The mechanism is quite simple where the carboxylic acid is introduced to sulfur dichloride oxide alleviating sulfur dioxide and hydrochloric acid, while creating the acid chloride.


RCOOH + SOCl2 ----------> RCOCl + SO2 + HCl

11/22/11 - Conversion of an Ester to an Acyl Chloride

   This here is a pretty complexed reaction to perform something simple that can be done in two steps.  But this technology saves much time and money in not having to do two steps and to separate and purify after those steps.  This involves taking the ester, and treating it with chlorosulfonic acid and phthalyl chloride while heating it in a mixture.  This reaction is limited to esters that can withstand these treatment conditions in the heat, so before the reaction the esters must be confirmed to not decompose in  these conditions.

Ref + Photo:
W.J. Middleton. J.  Org. Chem., Vol. 44,  No. 13, 1979

11/21/11 - Alcohol Dehydration

     A very simple reaction involving turning an alcohol into an alkene under an E1 elimination mechanism.  This reaction is occurring by the addition of a secondary or primary alcohol with an acid catalyst (a tertiary alcohol will not work because the mechanism requires a proton to come off from the alpha carbon.

Picture: wikipedia

11/20/11 - Hydroboration

    Today, is a simple organic reaction pertaining to the addition of borane (in THF) to an olefin (alkene).  This reaction is then worked up with hydrogen peroxide and a basic environment (usually a source of OH-) to relieve the boron from the carbon and to replace it with an alcohol group.  The mechanistic nature of this reaction calls for the borane into going anti markovnikov due to the fact that it is adopts a partial positive charge as seen below.
  
Pictures: Wikipedia

11/19/11 - Polyglycolide Resin Synthesis

 
     In a theme built upon the last post I have decided to do another reaction involving the creating of a polymer resin being formed.  This time it is the commonly known polyester resin reaction, and more specifically the polyglcolide resin.  With the simple chemical equation shown below the mechanism proceeds with the Glycolide ring opening up to produce a long chain of the ester linkages.  This reaction is induced by the presence of a catalyst, usually being that of Antimony Trioxide, and the heat to being around 195*C.  This process must be performed under a pure nitrogen atmosphere due to the fact that this can react with the oxygen in the air.

Photo: Wikipedia

11/18/11 - Polymerization of Methyl-2-Cyanacrylate

    This reaction of the day was influenced by a graceful ballerina using a fast drying glue on her point shoes making me wonder what it is she is actually putting on there.  So I looked into what the 'Jet instant glue' was made up of and it was concluded that it was a cyanacrylate based glue (which also make up the ingredients in krazy glue and many other adhesives).  So the basis of this glue is the molecule methyl-2-Cyanacrylate (seen below) and it is activated once in the presence of moisture or other nucleophilic species.  In most cases the nucleophile exists as the water molecules in the air which attack the terminal alkene group, making a carboanion, which in turn attacks another methy-2-cyanacrylate group acting as the nucleophile, producing a long, polymerized chain.
 
Picture: Wikipedia

11/17/11 - Knoevenagel Condensation

     I again apologize for the short post yesterday due to my midterm induced absence. So today I will try and include a reaction that I was absolutely stumped on last night during the test, and that being the Knoevenagel condensation reaction.  Initially, while studying, it never occurred to me that it would be necessary for me to focus on the names of reactions, which wouldn't get me anywhere in the world of chemistry, but for time restraints I ignored it.  And of course there was a question solely focused on the name of reactions.
     Well to get to the Knoevenagel condensation (image below being that of a general case).  The case is that a carbonyl compound, being either an aldehyde or a ketone, is reacted with an activated hydrogen compound having two electron withdrawing groups in the 1,3 positions making those hydrogens quite acidic.  This is done under a basic catalyzed environment to deprotonate those acidic hydrogens.  After this enolate is formed, it performs an aldol like reaction on the carbonyl compound alleviating a new alcohol group, which is soon dehydrated to form a pi bonded system.

Picture: Wikipedia

Ref:
Emil Knoevenagel (1898). "Condensation von Malonsäure mit Aromatiachen Aldehyden durch Ammoniak       und Amine". Berichte der deutschen chemischen Gesellschaft 31 (3): 2596–2619..

11/16/11 - Benzimidazole Synthesis

This fungacide molecule can be readily synthesized by reacting o-phenylenediamine with formic acid by the chemical equation C 6 H 4 (NH 2 ) 2 + HC(OCH 3 ) 3 → C 6 H 4 N(NH)CH + 3 CH 3 OH , which gives off methanol as the side product.  I appologize for such a short post today as I have my organic midterm tonight, or which I havent prepared enought, so wish me luck!! (I will most definitely need it)

11/15/11 - Leimgruber-Batcho Indole Synthesis

This annulation reaction produces the molecule Indole, which is much similar to the previous reaction Quinoline in that it is a nitrogen contaning heterocyclic molecule.  This molecule retains its importance in the pharmaceutical industry where many drugs contains this molecule and derivatives of this molecule.  It is originally contained within coal-tar, where the first synethsis was completed by heating aniline and ethylene glycol in the presence of a catalyst.  But in 1976, Leimgruber and Batcho came along to propose this very efficient synthesis of this molecule starting with o-nitrotoluenes.  In the first step the o-nitrotoluene is converted into an enamine, and then this enamine goes through a reductive cyclisation to form the Indole.


Ref:
Batcho, A. D.; Leimgruber, W. Org. Synth. 1985, 63, 214–220.

11/14/11 - Combes Quinoline Synthesis

     This annulation process involes the creation of a pyridine ring attached to a phenol ring.  The diaromatic ring system is created by reacting an unsubstituted aniline with a beta diketone molecule, following with a a ring closing dehydration using an acid to catilize the reaction.  This reaction is neat because it uses both the technology of turning a ketone into an amine and for the acid catalyzed ring closure.



Ref:
Combes, A. Bull. Chim. Soc. France 1888, 49, 89.

11/13/11 - Danheiser Annulation

     A reaction of ring making significance; this reaction is used to create a cyclopentane from a silylallene and a conjugated ketone system (α,β-unsaturated ketone).  The mechanism must be in the presence of a lewis acid in order to proceed, and in most cases TiCl2 is used along with a dichloromethane solvent.  In this particular mechanism below the α,β-unsaturated ketone is introduced to the trialkylsilylallene to produce the trialkylsilylcyclopentene molecule.

Photo: Public Domain

Ref:
"TMS-Cyclopentene Annulation: A Regiocontrolled Approach to the Synthesis of Five-Membered Rings", R. L. Danheiser, D. J. Carini, and A. Basak, J. Am. Chem. Soc. 1981, 103, 1604.

11/12/11 - Robinson Annulation

       I feel now, after creating this blog, that I should be making posts in some orderly manner, so I have decided to start off with a series of posts relating to certain reactions of Annulation processes: Those of which result in the formation of a ring after a number of reaction sequences.

       In my first of this series, I would like to make the introduction to the Robinson Annulation, an important reaction for the synthesis of biologically significant steroids.  The first step of this technology is relevant in calling it a Michael addition, where a ketone enolate is created by a base called DBU (Diazabicycloundecene - a good base that does not perform a nucleophilic addition) and it performs a 1,4-addition on a conjugated carbonyl (in this case a ketone).  The following step is an aldol reaction being instigated by adding a strong base (NaOMe) to deprotonate the alpha carbon on the newly added ketone, for it then to nucleophilically attack the C=O.  It then goes through a spontaneous dehydration elimination of the alcohol formed in that process to eleviate a conjugated system once again.

11/11/11 - Claisen Condensation

    So first off as an introduction I have decided that I will be using this blog to increase my knowledge of Chemistry by posting a reaction everyday on here (well at least attempting, we all know how good I am at not keeping up with blogs), and to educate other people in a clear way.
    In this first post I would like to look at a reaction that I have learnt in my Advanced organic Chemistry course; a reaction in which will further my understanding of the topics being taught in class.  I am not an avid organic chemist, but I do appreciate the complex notions that drives the model.  I feel that it is appropriate to attempt in explaining the reaction in a molecular model so that there can be a greater understanding of the reaction.
    This first reaction, being that of a Claisen Condensation, is one that I was studying back in September extensively in my organic chemistry class while we were analyzing carbonyl condensation reactions.  This historical reaction was published by Rainer Ludwig Claisen in 1881.
 This here is the combination of two ester molecules (where there is a central carbon with a double bond to an oxygen and single bond to an oxygen which has a single bond attached to an alkyl group) yielding a β keto ester.  There are certain requirements brought up by the mechanism stating that one of the esters must contain two deprotonable alpha hydrogens in order for one of the esters to become an ester enolate ion.  Which then in turn performs a nucleophilic attack onto the ester of the other molecule yielding a tetrahedral intermediate, which kicks out the ethoxide causing the ethoxide to deprotonate the beta keto ester.  Finally the reaction is finished with a simple acid workup to reprotonate that position.  This is just a simple case seen below, but in these synthetic mechanisms, they can be used to carry out elaborate reactions to make molecules of biological significance.

Ref:
Claisen, L., and A. Claparede. Ber. Deut. Chem. Ges., 1881, 14, 2460.

New Blog

So I have decided to make a whole new blog focusing on posting a chemical reaction a day.  the purpose of this is to educate people in the wonderful world of chemistry, while also making me learn more in the process.  I hope it is a good  experience both for me and the readers.