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

Aromaticity

(Speaking to my 15 year old brother)

Benzene is the easiest compound to use when trying to explain aromaticity. Benzene is a six carbon ring with alternating double bonds (3 π bonds).

http://t3.gstatic.com/images?q=tbn:ANd9GcRRetZejfNY9WM7hYn6fyz182OUkKJkkfDg_xul20bIXsJ_j6tq

 This is a picture of Benzene. Each point of the ring represents a carbon atom. The three extra lines you see represent double bonds, also called π bonds. A chemical bond is simply and attraction between two atoms. A double bond simply means there are two bonds between the atoms and the electrons are shared.

Aromaticity describes the special stability that Benzene has because of the structure. Since Benzene is considered Aromatic is follows Huckel’s rule. This criteria is as follows:

The molecule must cyclic which means there is a ring of atoms. It is easy to tell that the atoms are placed in a ring by drawing a circle around the molecule.

The molecule must be planar which means that all atoms in the molecule must lie in the same plane.

3.      The molecule has to be completely conjugated which means there has to a p orbital on very atom. A p orbital explains the wave-like behavior of the electrons. Below is a picture of the Benzene molecule drawn with a p orbital on each atom.

http://t0.gstatic.com/images?q=tbn:ANd9GcTG76fwSOJElip2ZUQnjt5sfALo5XjhLfkVtHsQnUTwUsl_DnkFyA

 And finally, the molecule must contain 4n+2 π electrons. This confirms that the molecule is stable because all the bonding orbitals are filled with paired electrons. You can count the number of π electrons a molecule has and set this equation equal to that number. If n is equal to 0 or any other positive number the rule has been met.  A π electron resides in a π bond. 3 π bonds = 6 π electrons because there are 2 π electrons in each double bond. Here is an example of how to confirm this rule applies using Benzene.

4n + 2 = 6

4n = 4

n = 1

Since n is a positive integer, the rule is confirmed. 

Sample Question Not Seen On Test

I anticipated a problem on determining the number or protons giving rise to an NMR signal. The example listed in chapter 14 on page 505 is a good example of this type of problem. The problem and solution are listed below.

Question:
A compound of molecular formula C9H10O2 gives the following integrated 1H NMR spectrum. How many protons give rise to each signal?

(The spectrum is shown in the book on page 505 at the bottom of the page.)

Answer:
Step 1: Determine the number of integration units per proton by dividing the total number of integration units by the total number of protons.

• Total number of integration units: 54+23+33=110 units
• Total number of protons = 10
• Divide: 110 units/10 protons = 11 units per proton

Step 2: Determine the number of protons giving rise to each signal.

• To determine the number of H atoms giving rise to each signal, divide each integration value by the answer of Step 1 and round to the nearest whole number. 

                      Solution: Signal A - 54/11 = 4.9 = 5 H
                                    Signal B - 23/11 = 2.1 = 2 H
                                    Signal C - 33/11 = 3H

The area under an NMR signal is proportional to the number or absorbing protons. The height of each step is proportional to the area under the peak, which is in turn proportional to the number of absorbing protons. Knowing the molecular formula of a compound and integration values from its 1H NMR spectrum gives the actual number of protons responsible for a particular signal.

M+2 Peak

My muddiest point to date in Organic Chemistry deals with M+2 Peak. I understand what it is but I am a little unsure of how it works. I turned to the internet to better understand this concept.
            The M+2 peak in mass spectrum is found if the chlorine or bromine is present. The two molecular ion peaks (M+ and M+2) each contain one chlorine atom. The chlorine can either be ³⁵Cl and ³⁷Cl. ³⁵Cl isotope has a formula mass of 78 and ³⁷Cl has a formula mass of 80. A ratio of 3:1 describes the peak heights. This tells us that chlorine contains 3 times as much of the ³⁵Cl isotope as the ³⁷Cl one. Therefore, there will be 3 times more molecules that contain the lighter isotope than the heavier one.
            Compounds that contain bromine have a different ratio. They have a 1:1 ratio. Bromine has two different isotopes as well, ⁷⁹Br and ⁸¹Br. If there are two lines in a molecular region with a gap of 2 m/z units and are of almost equal heights, a bromine atom is present in the molecule.
            After reading the information on this website I feel that I better understand the M+2 peak. I have put the link at the bottom of the blog if you would like to go check the website out for yourself!


http://www.chemguide.co.uk/analysis/masspec/mplus2.html