Michael Reaction

For blog assignment #9, Dr. Mullins explained that we would need to find and work out a problem that deals with anything within chapters 24 and 26.  After reading through both chapters I decided to pick a problem on something that I've had difficulty with trying to understand the concept.  So I decided to work out a problem that involves the Michael reaction from chapter 24.  A Michael reaction involves two carbonyl compounds: the enolate of one carbonyl compound and an alpha, beta-unsaturated carbonyl compound.  The Michael reaction is when the conjugate addition (1,4-addition) of a resonance-stabilized enolate to the beta carbon of an alpha, beta-unsaturated carbonyl system.  In this Michael reaction, the enolate acts as the nucleophile and attacks the beta carbon, which is the key step to this mechanism. The Michael reaction always forms a new carbon-carbon bond on the beta carbon of the Michael acceptor.  The question is below:

Draw the product formed from a Michael reaction with the given starting materials using ^-OEt, EtOH.

In step 1, the enolate is formed by a base, ^-OEt, removing an acidic proton between the two carbonyl groups.  The oxygen atom from the base attacks the hydrogen and the pair of electrons and a negative charge are given to the alpha carbon on the enolate.  This lone pair of electrons and negative charge on this carbon are eventually used as a nucleophile in step 2.  The following reaction depicts step 1 in this Michael reaction:

In step 2, the nucleophilic attack of the enolate to the beta carbon of the alpha, beta-unsaturated carbonyl compound takes place.   After this nucleophilic attack occurs, a new carbon-carbon bond is formed and a stabilized enolate is formed.  Also, after the nucleophilic attack of the enolate on the beta carbon occurs, the electron pair of the double bond and a negative charge are given to the alpha carbon on this compound.  The following reaction depicts step 2 in this reaction:

In step 3, the lone pair and negative charge of the alpha carbon on the compound protonate and attack the hydrogen atom from EtOH.  With this protonation if the enolate and a new carbon-hydrogen bond is formed.  The following step in this reaction depicts step 3:

The Michael reaction involves first the formation of the enolate then the nucleophilic attack at the beta carbon and then protonation.  With these steps being taken correctly the end product should end as such:

I would like to say that I think this was the best idea for a blog yet because we can find something in these chapters that we dont understand then research it and construct a problem over it.  The Michael reaction was a difficult reaction to understand, however after constructing a question and working it out I feel a lot more confident with this reaction.


Sources


1)  Organic Chemistry. Janice Gorzynski Smith. 2nd edition

Extra Credit Seminar

  On April 15, 2011 there was a seminar about tobacco smoking during pregnancy and the effects and results of smoking while pregnant.  The seminar was titled, "Biomarkers of exposure and relationship to genetics" and the speaker was Dr. Steven R. Myers.  Dr. Myers is the associate professor for the Department of Pharmacology and Toxicology at the University of Louisville School of Medicine.
  Dr. Myers started his seminar talking about smoking while pregnant and the things that can happen to the baby as a resultant of this situation.  The main problem with smoking while pregnant is that the baby gets less food and oxygen if a woman smokes while pregnant than if a woman doesn't smoke while pregnant.  He also explained the risks that come with smoking while being pregnant and here are a few listed:
   - Stillborn baby
   - Premature birth
   - Miscarriage
   - Sudden Infant Death Syndrome (SIDS)
   - Low birth-weight babies

  He then went into talking about tobacoo and the chemical make-up and the many types of diseases that occur from smoking.  Tobacco is composed of 4,000 chemicals and cause multiple types of cancers including lip, esophagus, pancreas, lung and kidney cancer.  Many respiratory diseases that can also occur are tuberculosis, pnuemonia, influenza, bronchitis and asthma.  Other health consequences that occur are:
   - a 60% increase in risk of developing lower respiratory illness
   - impaired lung function
   - increase of frequency of middle ear infections

  Dr. Myers then discussed the biomarker aspect to the tobacco and why someone would want to study it.  A biomarker is a molecular, biochemical, or cellular alterations that are measurable in biological media, such as human tissues, cells or fluids.  He then explained that the reasoning for someone studying biomarkers are to find the many chemicals, mutagens and carcinogens found in tobacco.  There are three criteria that must be met for a biomarker to be useful and they are:
   1. Specificity
        - direct result of chemical or contaminent
   2. Sensitivity
        - earliest detectable change
   3. Practicality
        - cheaper way to get answer

Dr. Myers was a very informative speaker and I really enjoyed the seminar and being able to speak with him after the seminar.  During the seminar he talked about a compound that is found in tobacco smoke and it is called 4-aminobiphenol.  The structure is below

Hell-Volhard-Zelinsky reaction

The Hell-Volhard-Zelinsky involves the halogenation of carboxylic acids at the alpha carbon of the carbonyl group.  The basic reaction reacts as such:

The first step in the mechanism of this reaction involves the substitution of a bromide on the hydroxyl(OH) group of the carboxylic acid.  The catalyst PBr3 causes this bromide to replace the OH group which causes the formation of the carboxylic acid bromide.  The present acyl bromide is then tautomerized to form an enol which reacts with the Br2 which creates the second placement of a bromide on the compound.  The following depicts the mechanism of this reaction:

An example of a synthesis where this Hell-Volhard-Zelinsky mechanism is used is in the formation of dimethylketene.  In this synthesis the starting reactant is isobutyric acid which then reacts with PBr2 to form the product of propanoyl bromide or a-bromoisobutyryl bromide.  This product is then reacted with zinc and some heat and results in the overall final product of dimethylketene.  The Hell-Volhard-Zelinsky mechanism is used in the first step of the reaction.  The steps in this reaction are:

The Hell-Volhard-Zelinsky reaction of a halogenation of carboxylic acids at the alpha carbon is named after three chemists.  Their names are Carl Magnus von Hell ( German chemist), Jacob Volhard (German chemist) and Nikolay Zelinsky who was a Russian chemist.  This reaction is being discussed in the Organic Chemistry 2 class at Campbellsville University.


Sources:
1.  "Hell-Volhard-Zelinsky Halogenation." Wikipedia, the Free Encyclopedia. Web. 21 Apr. 2011. http://en.wikipedia.org/wiki/Hell-Volhard-Zelinsky_halogenation.
2.  Organic Syntheses Website. Web. 21 Apr. 2011. http://orgsyn.org/orgsyn/default.asp?formgroup=basenpe_form_group.

Methyl trans-Cinnamate

Methyl trans-cinnamate is the methyl ester of cinnamic acid.  Methyl trans-cinnamate gives off the appearance of a white to light yellow fused crystalline mass with a strong, aromatic odor.  It is found naturally in a variety of plants and fruits, most specifically strawberries.  It is mostly used in the fragrant and flavor industries as an agent for perfumes and such.  The structure for methyl trans-cinnamate is:

The properties of Methyl trans-cinnamate:
   - Melting Point: 260-262°C
   - Boiling Point: 34-38°C
   - Water Solubility: Insoluble
   - Molecular Weight: 162.19 g/mol
   - Linear Formula: C6H5CH=CHCO2CH3
   - IUPAC name: Methyl (E)-3-Phenylprop-2-enoate

The carboxylic acid the ester is derived from is:

An example of one reaction where methyl trans-cinnamate is converted to another derivative:

Sources:

1. "Methyl Cinnamate." Chemical Book. Web. 9 Apr. 2011. http://www.chemicalbook.com/ChemicalProductProperty_EN_CB5206328.htm.
2.  Methyl Cinnamate." Wikipedia, the Free Encyclopedia. Web. 9 Apr. 2011. http://en.wikipedia.org/wiki/Methyl_cinnamate.
3.  "Cinnamic Acid | RM.com ®." Magick, Wicca, Paganism and Other Esoteric Knowledge | RM.com ®. Web. 9 Apr. 2011. http://www.realmagick.com/cinnamic-acid/.

Methyltriisopropoxytitanium

Methyltriisopropoxytitanium is the product of the reaction of titanium tetraisopropoxide in ether and of titanium tetrachloride.  Methyllithium in ether is then added to the cooled reactants to produce the final product, Methyltriiopropoxytitanium.  The IUPAC name for this final product is methyltitanium triisopropoxide.  The newly formed carbon-carbon bonds is the methyl group located on the titanium ion. 

The reaction scheme for this reaction is listed below for A. :

1

In a reaction involving an organolithium reagent the organometallic compound has a bond between a carbon and a lithium atom.  Since lithium is very electronegative, the charge of the overall bond is placed on the carbon atom which creates a carbanion.  For this reaction, A, the only step of the reaction involves the organolithium reagent acting on the titanium atom and forming the newly bonded Ti-C bond.  The first reactant for the reaction is an organotitanium compound. This product of Methyltriiospropoxytitanium is extremely flammable liquid and vapor and can cause severe eye and skin irritation.  The target organs for this compound are the respiratory system and eyes.  This overall reaction of Methyltriisopropoxytitanium involves an organolithium reagent which alters the overall product.  2

Source

1. "Organic Syntheses Prep." Organic Syntheses Website. Web. 03 Apr. 2011. http://orgsyn.org/orgsyn/prep.asp?prep=v81p0014.

2. MSDS Methyltitanium(IV) Triisopropoxide, 1M Solution in THF CAS 18006-13-8 MSDS Methyltris(isopropoxy)titanium(IV)." MSDS & Custom Synthesis Organic Synthesis Bio-Synthesis Suppliers. HBCChem. Web. 03 Apr. 2011. http://www.chemcas.org/drug/analytical/cas/18006-13-8.asp.