Serial Ligand Catalysis

Christina White of the University of Illinois’ Department of Chemistry, along with some of her colleagues, have recently published research on a serial ligand catalyst. A ligand is a group bonded to a metal, which donates electron density to (or sometimes withdraws it from) the metal.¹ Organopalladium is an example of a ligand. An organopalladium is a compound that contains a carbon-palladium bond.¹ One of the most common organopalladium ligands is palladium acetate, abbreviated Pd(OAc)₂, which is also part of both catalysts utilized in this experiment.

In the experiment an alkene was reacted with a carboxylic acid in the presence of one of two ligand catalysts. The reaction which involved the ligand catalyst also containing DMSO, produced a linear product, however, the reaction involving the polydentate sulfoxide ligand resulted in a branched allylic C-H oxidation. The team found this to be interesting and by further studying the mechanism of the branched product, they developed the concept of a serial ligand catalyst. This is 2+ different ligands binding reversibly to one metal (Pd in this case) to promote different steps for product formation in a particular catalytic cycle.²

The following is an image of the reaction and shows both catalysts:

¹ Smith, J. Organic Chemistry. 2^nd ed.; McGraw-Hill, 2008, pp 1005-1006   

²"Serial Ligand Catalysis: A Highly Selective Allylic C-H Oxidation".
M.S. Chen; N. Prabagaran; N.A. Labenz; and M.C. White.
JACS 2005, 127, 6970-6971.

Short Answer Question

Tobacco Smoking During Pregnancy

Tobacco Smoking During Pregnancy:

Biomarkers of Exposure and Relationship to Genetics

Presented by Steven R. Myers, Ph.D.

Dr. Myers of the University of Louisville’s School of Medicine gave an hour long presentation on the effects of a mother’s use of tobacco during her pregnancy. Some of the facts he gave were very surprising. There is a 30% incidence of mothers who smoke during their pregnancy; this can cause a miscarriage, premature birth, still birth, a low weight baby, Sudden Death Syndrome, or ADHD in the child, just to name a few. The IQ level of the child may be up to even 30% lower than that of a child whose mother wasn’t exposed to tobacco during her pregnancy. I found that to be not only surprising, but very sad. By either smoking or exposing herself to tobacco, a mother is practically robbing her child of potential. That seems morbidly immoral to me.

            I was aware that babies and small children who are exposed to tobacco experience health problems, but I was shocked at the numbers. From second hand smoke alone, 2 million children are seen a year for ear infections, and 530,000 see a doctor for asthma, bronchitis and pneumonia. That hit home for me. I have a cousin whose mother smoked when he was an infant. To this day, he still suffers from asthma. I saw him struggle with it when we were kids and it kills me to think that he paid the price for his mother’s awful habit.

            The way that the research team studied the effects of smoking on the mother and child was with biomarkers. A biomarker is a molecular, biochemical, or cellular alteration that is measureable in biological media such as tissues or bodily fluids. Biomarkers are chosen based on three main criteria: specificity, sensitivity, and practicality.

            Although I found the preceding information to be interesting, I particularly liked his discussion on the aromatic amines that are related to carcinogens. Some of these include aniline, 2-,3-,and 4-toluidine, and 4-aminophenyl. Benzo (a) pyrene is also a known carcinogen found in cigarettes. It is also found in the burnt part of steaks—that greatly disturbed me... I like steaks.

            One last thing that he talked about really made me think; he said that Hispanics, compared to African Americans and Caucasians, have a lower amount of the genes that rid the body of the harmful substances found in tobacco. He said that the researchers were unsure why, but I’m wondering if maybe it has something to do with natural selection?... My thought is that by looking at the three races individually, in a social aspect, it is more common to see an African American or Caucasian smoking than a Hispanic. That just makes me wonder if maybe the reason why Hispanics have less of these genes, is because they use less tobacco products. I mean if Hispanics didn’t use much tobacco, why would there be a need for their bodies to contain genes that eliminate the harmful substances found in tobacco? Just a thought…

            Overall, I enjoyed the presentation. I thought he employed great communication skills; although the topic was mostly unfamiliar with me, especially the means of experimentation, I was happy to find that his vocabulary and knowledge did not negatively influence his ability to communicate his ideas and the findings of their research.

Benzo (a) pyrene

The Hell-Volhard-Zelinsky reaction involves the halogenation of carboxylic acids at the α carbon. During the reaction, a carboxylic acid’s OH group is replaced by a bromine atom from the PBr₃ catalyst to form an acyl bromide. This compound can then form an enol via tautomerization; this allows for a second bromination to occur at the α carbon by Br₂. The following picture is the reaction scheme of this process.

  

Hydrolysis of this α-bromo acyl bromide forms an α-bromo carboxylic acid, by means of a nucleophilic acyl substitution. To speed up the reaction and to ensure that the acyl bromide intermediate is not regenerated during this step of the reaction due to lack of nucleophilic solvent, a molar equivalent of PBr₃ is used. The following mechanism is a depiction of this part of the reaction.  

An example of a Hell-Volhard-Zelinsky reaction, would be the halogenation of acetic acid at the α carbon with PBr₃. In this step, a bromine from PBr₃ would replace the hydroxy group on the acetic acid to form acetyl bromide which, after tautomerization into an enol, would be introduced to Br_2. This step of the reaction is an attack of the α carbon by Br and would produce bromoacetyl bromide which, when reacted with yet another acetic acid molecule, would form 2-bromo acetic acid and bromoacetone. If the R group was taked off of the products in the preceding picture, they would be 2-bromo acetic acid and bromoacetone.

Sources:

http://en.wikipedia.org/wiki/Hell-Volhard-Zelinsky_halogenation 

www.google.com/

Benzyl Acetate



benzyl acetate



Benzyl acetate (C₉H₁₀O₂) is the ester formed from benzyl alcohol and acetic acid. It is found naturally in many flowers such as jasmine, hyacinth, and gardenia. Due to its pleasant smell (which is peach-like), it is often used in perfumes, soaps and cosmetics. Although it possesses a fruity/ floral scent, it has a bitter taste. The clear, colorless liquid boils at approximately 210˚C, melts at -51˚C and is combustible. According to the MSDS for benzyl acetate, it is only slightly soluble in cold water, but is quite soluble in diethyl ether and acetone. The ester is commonly used as a solvent for plastics, lacquers, resins, polishes, and inks.



In order to acquire yet another carboxylic acid derivative, benzyl acetate could be reacted with NH₃ to form a  primary amide (acetamide) and an alcohol (phenyl methanol). The products are shown below.

   

acetamide





phenyl methanol



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

http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-65.pdf

http://www.sciencelab.com/xMSDS-Benzyl_Acetate-9923066

http://www.google.com/images







"Organic Syntheses"

Organometallic reagents contain a carbon atom bonded to a metal. The most commonly used metals in these reagents are lithium (organolithium reagents), copper (organocuprates), and magnesium (Grignard reagents).¹
Magnesium is a very electropositive metal, making the C-Mg bond very polar and very reactive. The following reaction (found in Organic Syntheses) describes the synthesis of 3,5-bis(trifluoromethyl)acetophenone from 3,5-bis(trifluoromethyl)bromobenzene. During this reaction, (i-PrMgCl) forms a Grignard reagent. The Grignard reagent is formed when the starting material is introduced to a magnesium atom, which is bonded to chlorine. The magnesium is then inserted into the C-Br bond, and the chlorine atom replaces the bromine. An intermediate is now formed.  The addition of acetic anhydride forms a ketone, 3,5-bis(trifluoromethyl)acetophenone, as the final product. As a result a new C-C bond has been formed between the benzene ring and the carbon atom which is bonded to the oxygen. The IUPAC name for this compound is (1-[3,5-Bis(trifluoromethyl)phenyl]-ethanone). The following is nearly an identical scheme from the report, except this scheme shows the intermediate to still contain the bromine atom and not the chlorine.

Synthesis of 3,5-bis(trifluoromethyl)acetophenone

¹Smith, J. Organic Chemistry. 2^nd ed.; McGraw-Hill, 2008, pp 739.

http://orgsyn.org/orgsyn/pdfs/v82p0115.pdf

www.google.com/images

Figure 1 Delocalization of a positive charge
over the guanidinium group of Arginine

Figure 2 Arginine Amino Acid

Arginine        

                                                        

Arginine is one of 20 naturally occurring amino acids. It removes ammonia from the body and is important in both cell division and the healing of wounds. If taken as an oral supplement, Arginine can aid as a precursor to the synthesis of nitric oxide and urea, as well as lower blood pressure. It also plays a small role in the treatments of alcoholic hepatitis, advanced cirrhosis, and erectile dysfunction. It is found in the Lysine polypeptide, which binds free sugar molecules so they can react with proteins. This provides an anti-glycation effect.

Arginine is a white crystalline powder. Its molecular weight is 174g, it melts at 235˚C, and has an isoelectric point of 10.75. Its functional groups include four amines, a guanidinium group and one carboxylic acid. Amines absorb between 3300 and 3400 cm^-1 on the IR spectrum. The C=O bond of the carboxylic acid absorbs at about 1710 cm^-1 and the O-H absorption occurs from 2500-3500 cm^-1. The pK_a value for the carboxylic acid is approximately 5. The guanidinium group has a pK_a of 12.48. The nitrogen atoms of this group delocalize a positive charge. Figure 1 shows the guanidinium group. Figure 2 is larger picture of Arginine and is a more accurate depiction of the molecule, having a hydrogen atom bound to the oxygen in the carboxyl group.

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

http://www.sciencelab.com/msds.php?msdsId=9927439

¹Smith, J. Organic Chemistry. 2^nd ed.; McGraw-Hill, 2008, pp 700, 974.

http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/proteins.htm