End of Semester Blog

We were asked to read and comment on a publication on Christina White's website. I chose Publication #19. It dealt with the synthesis of complex allylic esters via C-H oxidation vs C-C bond formation. Here is the picture of the reaction scheme and catalyst:

One of the most important reactions in organic synthesis is esterification. It involves coupling preoxidized carboxylic acid and alcohol fragments. Coupling usually involves stoichiometric amounts of a condensation reagent or the generation of an activated, most of the time unstable, acid derivative. Catalytic esterification methods do exist but they suffer from a limited scope, so they often require one coupling partner to be used in excess. A great advancement would be a catalytic general esterification method that oxidatively couples a hydrocarbon with a carboxylic acid.


This study introduced the first general, selective C-H oxidation method for the direct synthesis of complex allylic esters. Based on the generality and predictable selectivity of this C-H oxidation method along with the strategic advantages it enables, White and her team anticipate that it will find widespread use in complex

molecule syntheses

I enjoyed reading this publication. I found it relatively easy to understand because of everything I have learned in Organic Chemistry. There is a lot of information in the publication and many more reaction schemes to look at. I would recommend that each of you read this publication for yourselves. There is also an example of Grubb's reaction, which we just went over in class. White and her team did a great job writing this publication. It was very interesting!

Source:
http://www.scs.illinois.edu/white/pubs/pub19.pdf

Short Answer Test Question

Question:
Fill in the missing pieces of this Aldol Reaction.

Solution:
If LDA is used at low temperatures, the kinetic enolate is generated and can think react with an aldehyde. The full reaction is shown below.

Hell-Volhard-Zelinsky Halogenation

A Hell-Volhard-Zelinsky Halogenation is a reaction that halogenates carboxylic acids at the alpha carbon. This reaction takes place in the absence of a halogen carrier and is initiated by the addition of a catalytic amount of PBr3. One molar equivalent of Br2 is then added. The carboxylic OH is replaced with a bromide because of the PBr3 that was added. The result is a carboxylic acid bromide. This allows the acyl bromide to tautomerize to an enol so that it can readily react with the Br2 in order to brominate a second time at the alpha position. This reaction is named after the three German chemists. The general reaction looks like this:

I found a Hell-Volhard-Zelinsky Halogenation reaction involving cycloalkane carboxaldoxime carbamates. These compounds are useful as pesticides and have very excellent miticidal activity. These compounds are prepared by the alpha halogenation of cyclic carboxylic acids under slightly modified Hell-Volhard-Zelinsky conditions. Esterification to give the cyclic alpha halocycloalkanecarboxylic acid easter follows. The active halogen is displaced with sodium alkyl mercaptide in alcohol to produce the alkylthio ester. The hydrolysis of the ester is followed by reacting the hydrolyzed product with thionyl chloride which give the reactive acid chloride. The acid chloride is changed into the aldehyde. The aldehyde then reacts with the hydroxylamine hydrochloride in a base and gives a corresponding oxime. The oxime can be carbamoylated with the suitable reagents to form the final insecticidal agent. A picture of the synthesis follows:

Sources:

• http://en.wikipedia.org/wiki/Hell-Volhard-Zelinsky_halogenation
• http://www.google.com/patents?hl=en&lr=&vid=USPAT3721711&id=9yMuAAAAEBAJ&oi=fnd&dq=Hell-Volhard-Zelinsky+halogenation&printsec=abstract#v=onepage&q=Hell-Volhard-Zelinsky%20halogenation&f=false

Isoamyl acetate

General Information:
This ester is more commonly known as banana oil. It's formula is CH3COOCH2CH2CH(CH3)2. The molecular weight is 130.19. In the physical state it is clear and colorless with a banana-like pr pear-like odor. It's melting point is -78C and it's boiling point is 142C. Isoamyl acetate is slightly soluble in water but is very soluble in Ethyl butyrate and Isoamyl butyrate. It is used to confer banana flavor in foods. It is also used as a solvent for some varnishes and lacquers. It is also a honey bee pheromone that is used to attract large groups of honey bees to a small area. It was extensively used in the aircraft industry for stiffening and wind-proofing fabric flying surfaces. It is also used to test the effectiveness of respirators or gas masks because of its intense, pleasant odor and low toxcity.  Acetates have characteristic fruity odors. They are used as component of perfumes and flavorings. They are used as chemical intermediate to manufacture pharmaceuticals, synthetic flavorings, cleaners, and other organic compounds. 


Isoamyl actate:
This is a picture of the structure of Isoamyl acetate:

Production:
Isoamyl acetate is prepared by the acid catalyzed reaction (Fischer esterification) between isoamyl alchol and glacial acetic acid as shown in the reaction equation below. Typically, sulfuric acid is used as the catalyst. Alternately, an acidic ion exchange resin can be used as the catalyst. 

References:
http://www.chemicalland21.com/specialtychem/perchem/ISO-AMYL%20ACETATE.htm
http://en.wikipedia.org/wiki/Isoamyl_acetate

Grignard Reagent

We are discussing Grignard Reagents in class. A Grignard Reagent is an alkyl- or aryl- magnesium halide that acts as a nucleophile and attacks electrophilic carbon atoms that are present within polar bonds to yield a carbon-carbon bond. Below shows the reaction used to make 4-nonylbenzoic acid:

  

 The Grignard Reagent is used in step A. The addition of the nonylmagnesium bromide causes an immediate color change from red to black-violet. The final product of that reaction is 4-Nonylbenzoic acid methy ester. The Grignard reagent is highlighted below:

A Grignard reaction yields new C-C bonds. There were 8 new C-C bonds formed in Step A. They are highlighted below:

The group performing this experiment developed an alternative method for alkyl-(hetero)aryl- as well as aryl-heteroaryl cross coupling reactions catalyzed by iron salts. They discovered that the expensive noble metal catalysts can be replaced by cheap, air stable, commercially available and toxicaologically benign salts without any loss in efficiency. The reactions are usually carried out under "ligand free" conditions using inexpensive Grignard reagents as the preferred coupling partners. They also found due to the efficiency with which the iron catalysts activate the C-Cl bond, several functional groups are tolerated that normally would react with a Grignard reagent. Feel free to read more by clicking on the source listed below! :)

Source:
http://orgsyn.org/orgsyn/default.asp?formgroup=basenpe_form_group&dataaction=db&dbname=orgsyn

Amino Acid

Serine 

Chemical Features:

• Non-aromatic hydroxyl
• Hydrophilic due to the hydrogen bonding capacity of the hydroxyl group
• Molecular formula: C3H7NO3
• Molecular Weight: 105 g
• Appearance: white crystals or powder
• Soluble in water
• Melting point: 246 degrees Celsius

pKa Values:

• 2.21 (carboxyl)
• 9.15 (amino)

Isoelectric Point: (pH at which this amino acid carries no net electrical charge)

• 5.68

Functional Group:

• Hydroxyl

NMR Info:

• Three main peaks: Peak at 4.65, Peak at 3.75, Peak at 3.65
• Pictures can be found at: https://sharepoint.cisat.jmu.edu/isat/klevicca/Web/Amino/Serine_2001/9.htm

IR Info:

A better picture of the IR spectroscopy can be found at: http://webbook.nist.gov/cgi/cbook.cgi?Spec=C56451&Index=0&Type=IR&Large=on

Reaction Info:

• The biosynthesis of serine starts with the oxidation of 3-phosphoglycerate to 3-phosphohydroxypyruvate and NADH Reductive amination of this ketone followed by hydrolysis gives serine. Serine hydroxymethyltransferase catalyzes the reversible, simultaneous conversion of L-serine to glycine. 
• Racemic serine can be prepared from methly acrylate via several steps. It is also naturally produced when UV light illuminates simple ices such as a combination of water, methanol, hydrogen cyanide, and ammonia, suggesting that it may be easily produced in cold regions of space. 

Small Polypeptide:

References:

http://www.biology.arizona.edu/biochemistry/problem_sets/aa/serine.html

http://en.wikipedia.org/wiki/Serine

http://www.chemie.fu-berlin.de/chemistry/bio/aminoacid/serin_en.html

https://sharepoint.cisat.jmu.edu/isat/klevicca/Web/Amino/Serine_2001/9.htm

http://webbook.nist.gov/cgi/cbook.cgi?Spec=C56451&Index=0&Type=IR&Large=on

Electrophilic Aromatic Substitution from a Peer-Reviewed Journal

Aromatic compounds have multiple double bonds so the compounds cannot undergo addition reactions. Therefore, they react by electrophilic aromatic substitution reactions. The aromaticity of the ring system is preserved. I found a peer-reviewed journal through Ebsco entitled, Reaction of N,N-Dimethylaniline with N-Cyanoazoles according to Electrophilic Aromatic Substitution Pattern, that discusses an electrophilic aromatic substitution reaction. This article was found in the Russian Journal of Organic Chemistry.


N-Cyanoazoles are highly reactive organic compounds. These compounds are important intermediate products that are involved in the synthesis of numerous derivatives containing an azole ring. N-cyanoazoles are capable of acting as electrophilic reagents in elctrophlic aromatic substitution reactions because of the high polarity of the cyano group.

This journal reported on the synthesis of some imines by electrophilic aromatic substituion of hydrogen in N,N-dimethylaniline by N-cyanoimidazole,  N-cyanobenzimidazole,  N-cyano-1,2,3-benzotriazole, and N-cyano-2-methylimidazoles. These N-cyanoazoles, Ia–Id, were prepared according to certain standard procedures.

They demonstrated that the previously listed N-cyanoazoles reacted with N,N-dimethylaniline in the presence  of anhydrous aluminum bromide to give para-substituted imines in good yields (65-74%). Nitrobenzene was found to be appropriate solvent for carrying out these reaction. reactions. The high polarity and dissolving
power of nitrobenzene ensure the homogeneity of the reaction mixture. However, nitrobenzene is not involved in the reaction because of the presence of a strong electron-withdrawing nitro group in its molecule.


Here is the picture of the substitution:

Reference:
Chunaev, A. O., Stepanov, E. A., & Purygin, P. P. (2010). Reaction of N, N-dimethylaniline with N-cyanoazoles according to electrophilic aromatic substitution pattern. Russian Journal of Organic Chemistry, 46(3), 459-460. doi:10.1134/S1070428010030309