Last Organic Blog

Our last blog assignment for Organic Chemistry was to go to Christina White’s (U. Illinois) webpage and find a publication to read and comment on. The article I chose was titled, A Sulfoxide-Promoted, Catalytic Method for the Regioselective Synthesis of Allylic Acetates from Monosubstituted Olefins via C-H Oxidation. The article states that sulfoxide ligation to Pd(II) salts is shown to selectively promote C-H oxidation opposed to Wacker oxidation chemistry and to control the regioselectivity in the C-H oxidation products. Also that using benzoquinone as the stoichiometric oxidant and 10 mol % of Pd(OAc)2 or Pd(O2CCF3)2 as the catalyst in a DMSO/AcOH (1:1) solution was found to be compatible with a wide range of functionality, which was shown in Table 2 in the article. The table shows amides, esters, and ethers that was compatible with the solution. I thought this table was useful because it talked about amides, esters and ethers that we have already learned in pervious chapters. The article also explores the potential role of sulfoxide as a ligand in promoting the palladium(II) catalyzed C-H oxidation pathway, and bis-sulfoxide palladium(II), this was shown in Table 1 of the article. These results demonstrated for the first time that sulfoxide ligation of Pd(II) salts can promote C-H acetates in useful yields, which was also shown in Table 2. Overall, I found this article very interesting and very informative. I also found that this article talked about organopalladium, which are compounds that contain a carbon-palladium bond that are prepared in situ during the course of a reaction, from another palladium regent such as Pd(OAC)₂, which was in chapter 26. Lastly, the pictures wouldn’t let me copy them, but are easily viewed in the article.

Resources:

Chen, Mark S. A Sulfoxide-Promoted, Catalytic Method for the Regioselective Synthesis of Allylic Acetates from Monosubstituted Olefins via C-H Oxidation. JACS, 2004, 126, 1346-1347. http://www.scs.illinois.edu/white/index.php?p=publications (accessed May 15, 2004)

Organic Test Question

Answer the 4 Parts to: Aldol Reaction

Use this picture of Aldol Reaction of Cyclopentanone to answer questions 1 and 2

1.      During step 3, what type of overall reaction occurs in the Aldol reaction?

(A) Acid Catalysed dehydration

(B) Acid Catalysed Aldol addition

(C) Electrophilic addition

(D) Acid catalysed enolization

Answer: (A) Acid Catalysed dehydration

2.      Which functional group is responsible for the formation of the stable conjugated enone?

Water

Hydroxy group

Acid catalyst

Carbonyl group

Answer: (D) Carbonyl group

True or False: Explain

3.      In the presence of hydroxide, either propanal or acetaldehyde serve as a nucleophile in an aldol reaction.

Answer True

4.      Either propanal or acetaldehyde can serve as an electrophile in an aldol reaction.

Answer: True

In the presence of hydroxide, each aldehyde can enolize to form a nucleophilic enolate anion. The enolate can react with an unionized aldehyde in the first step of an aldol condensation. The unionized aldehyde is an electrophile in this reaction.

Dr. Steven R. Myer’s, is currently Associate Professor of Pharmacology and Toxicology at the University of Louisville School of Medicine. Dr. Myer’s came to Campbellsville University and spoke about his research on: Smoking During Pregnancy.

Steve Myer’s states that, “cigarette smoke contains more than 4,000 chemicals, including truly nasty things like cyanide, lead, and at least 60 cancer-causing compounds.” When woman smoke during pregnancy, the toxic brew gets into there bloodstream and that’s the baby's only source of oxygen and nutrients. A shortage of oxygen can have devastating effects on the baby's growth and development. On average, smoking during pregnancy doubles the chances that a baby will be born too early or weigh less than 5 1/2 pounds at birth. Smoking also more than doubles the risk of stillbirth.

Every cigarette a women smokes increases the risks of her pregnancy. “A few cigarettes a day are safer than a whole pack, but the difference isn't as great as people would think, states Meyer’s. A smoker's body is especially sensitive to the first doses of nicotine each day, and even just one or two cigarettes will significantly tighten blood vessels. That's why even a light habit can have an outsize effect on the baby's health. On average, a pack-a-day habit during pregnancy will shave about a half-pound from a baby's birth weight. Smoking two packs a day throughout a pregnancy could make the baby a full pound or more lighter. While some women may welcome the prospect of delivering a smaller baby, stunting a baby's growth in the womb can have negative consequences that last a lifetime. Steve Myer’s also talked about, 4-Aminobiphenyl in cigarette’s, which is an amine derivative of biphenyl. It is used to manufacture azo dyes, known as a human carcinogen 4-Aminobiphenyl is shown below in Figure 1.¹

 Figure1

Molecular Formula: C₁₂H₁₁N

Molecular Weight: 169.22 g mol⁻¹

Melting Point: 52−54 °C

Boiling Point: 302 °C

Solubility in Water: practically insoluble in water, soluble in alcohol, ether and chloroform

Steve Myer’s said, studies are currently ongoing to determine the relationships between maternal and fetal metabolism. In an extension of Meyer’s studies, they are also developing the application of amniotic fluid as a biomarker of carcinogen exposure detected in the first trimester of pregnancy and developing assays for the detection of breast milk biomarkers that can be applied to women that are breast-feeding their neonates.

Overall, I think Steve Myer’s did a wonderful job on his presentation about his research on smoking during pregnancy, not only was his presentation interesting, but it was also very informative.

References:

1.      Sigma Aldrich. 2-aminbiphenyl. http://www.sigmaaldrich.com/catalog/ProductDetail.do?D7=0&N5=SEARCH_CONCAT_PNO%7CBRAND_KEY&N4=A42409%7CSIAL&N25=0&QS=ON&F=SPEC

The Hell-Volhard-Zelinsky halogenation reaction

The Hell-Volhard-Zelinsky halogenation reaction, shown in Figure 1, halogenates carboxylic acids at the α carbon.¹

Figure 1.

A carboxylic acid is first reacted with PBr₃ and Br₂. The PBr₃ replaces the OH group of the carboxylic acid with bromine, resulting in a carboxylic acid bromide. The acid bromide can then tautomerize to an enol, which will readily react with the Br₂ to brominate the molecule a second time at the α position. The first step results in a carboxylic acid bromide which is also brominated at the α position.

In a second step, the carboxylic acid may be recovered by reacting the carboxylic acid bromide with water or a weak aqueous acid. This results in the hydrolysis of the acid bromide, which is the displacement of the bromine directly bound to the carbonyl group by an OH group. (The hydrolysis is an example of a nucleophilic acyl substitution.) The final product is the original carboxylic acid brominated at the α position. This is shown in Figure 2 and Figure 3.¹³

Figure 2

Figure 3

The mechanism for the exchange between an alkanoyl bromide and a carboxylic acid is shown in Figure 4.¹ The α-bromoalkanoyl bromide has a strongly electrophilic carbonyl carbon because of the electron-withdrawing effects of the two bromides. The carboxylic acid will act as a nucleophile that the carbonyl oxygen of the carboxylic acid has a partial negative charge.¹

Figure 4


The formation of dimethylketene is an example of Hell-Volhard-Zelinsky mechanism. The starting reactant is isobutyric acid and forms propanoyl bromide using PBr_2. Dimethylketene is also been prepared by the treatment of α-bromoisobutyryl bromide with zinc and by the pyrolysis of isobutyrylphthalimide, dimethylmalonic anhydride, or α-carbomethoxy-α, β-dimethyl-β-butyrolactone. Dimethylketene dimer has been prepared by heating isobutyryl chloride with a tertiary amine. Pyrolysis of the dimer yields dimethylketene. These steps are shown in Figure 5.⁴

Figure 5

Dimethylketene

Molecular Formula: C₄H₆O

Melting point: 97⁰C

Boiling Point: 34⁰C

Resources:

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

2.      http://onlinelibrary.wiley.com/doi/10.1002/9780470638859.conrr305/abstract

3.     http://www.chemgapedia.de/vsengine/vlu/vsc/en/ch/12/oc/vlu_organik/c_acid/reaktionen_organoli_carbons.vlu/Page/vsc/en/ch/12/oc/c_acid/alfa2/alfa2.vscml.html

      4. http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv4p0348

Ethyl Butyrate

Ethyl butyrate, is an ester with the chemical formula C₆H₁₂O₂. Ethyl butyrate is soluble in propylene glycol, paraffin oil, and kerosene. Ethyl butyrate IUPAC name is Ethyl butanoate.

Molecular Formula: C₆H₁₂O₂

Melting Point: -93⁰C

Boiling Point: 121⁰C

H₂O Solubility: slighty soluble

Molecular Weight: 116.16 g/mol

Density: 0.879 g/cm³

Ethyl Butyrate is commonly used as artificial flavoring in alcoholic beverages, a solvent in perfumery products, and as a plasticizer for cellulose. In addition, Ethyl butyrate is often even added to orange juice.

Ethyl butyrate is one of the most common chemicals used in flavors and fragrances. It can be used in a variety of flavors such as, orange, cherry, pineapple, mango, guava, bubblegum, peach, apricot, fig, and plum. Industrially-speaking, it’s also one of the cheapest chemicals, which only adds to its popularity.

Ethyl butyrate can be synthesized by reacting ethanol and butyric acid. This is a condensation reaction, meaning water is produced in the reaction as a byproduct. This is shown below.

The reaction of a carboxylic acid and an alcohol yields an ester and water is eliminated.

The functional group of an ester is O=C-O. Ester formation is an equilibrium process catalyzed by an acid catalyst.

An ester is made from an alcohol and a carboxylic acid. An acid and a alcohol in ethyl butyrate is shown below.

The synthesis of ethyl 2-ethylhexanoate is an example of ethyl butanoate converted to another carboxylic acid. Here ethyl butanoate and 1-bromobutane  are reacted together to form ethyl 2-ethylhexanoate



References:

- http://www.bbc.co.uk/scotland/learning/bitesize/higher/chemistry/carbon/naming_rev4.shtml

-http://www.chemsink.com/reaction/1755986/

-http://en.wikipedia.org/wiki/Ethyl_butyrate

Grignard Reaction

In organic chemistry, we were assigned to search for a reaction that involves the use of an organolithium, organocuprate, or Grignard reagent in at least one synthetic step. The one I found was called Di-n-Butyldivinyltin and it had a Grignard reaction involved. The reaction is shown below.
 

In the first part of the reaction, the vinyl bromide is added to magnesium and tetrahydrofuran (THF) is added and a Grignard reagent was produced called vinylmagnesium bromide. In the reaction, vinylmagnesium bromide used as a Grignard reagent to produce Di-n-Butyldivinyltin. Grignard reagents are formed more rapidly in tetrahydrofuran and are an important tool in the formation of carbon-carbon bonds. Grignard reagents are strong bases, and are not compatible with good leaving groups or proton acids. However, they add to epoxides and carbonyl groups, and can be used to make other organometallic reagents by reacting with metal-halogen bonds. A Grignard reaction first involves the preparation of an organomagnesium reagent with the reaction of an alkyl bromide with magnesium metal. Its nucleophilic character allows it to react with the electrophilic carbon in a carbonyl group and forms the carbon-carbon bond. Alkynylmagnesium halides and alkynyllithium reagents are useful nucleophiles for C-C bond synthesis.

Sources:

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

-http://www.bluffton.edu/~bergerd/classes/CEM222/Handouts/organometallics.pdf

Phenylalanine

MW: 165.19

Phenylalanine (2-Amino-3-phenylpropanoic acid) has a symbol of F.⁷ Phenylalanine is a water-soluble amino acid that builds blocks for proteins in the body, which means the body needs it for health because it cannot make it. Phenylalanine is found in three forms: L-phenylalanine, which is the natural form found in proteins; D-phenylalanine, which is a mirror image of L-phenylalanine that is made in a laboratory, and DL-phenylalanine, a combination of both the forms.¹ Phenylalanine is an essential amino acid that is nonpolar because of the hydrophobic nature of the benzyl side chain.²

Amino group: (-NH₂)

Carboxylic acid group (-COOH)

Hydrogen Group (H)

The side chain in phenylalanine composed of just carbons and hydrogens atoms.








PKA Values

The equation for pKa is: pKa = -log Ka

To find the Ka, you do this:
Ka = [H+] x [X-]/[HX]

Ka is always products over reactants.³

The Pka values of phenylalanine are 2.58 and 9.24.

Isoelectric Point

For simple amino acids, in which the R group doesn't contain any titratable groups, the isoelectric point can be calculated by averaging the pK_a values for the a-carboxylic acid and a-amino groups.⁴

α -COOH pK_a is 1.8 and  α-NH₃ pK_a is 9.1

1.8 + 9.1/ 2 = 5.45

Phenylalanine isoelectric point:  5.45

IR Spectrum⁸

 

Polypeptides

  
Amino acids consists of a central carbon atom chemically bonded to one hydrogen atom (H), one carboxylic acid group (-COOH), one amino (nitrogen-containing) group (-NH₂), and one side group unique to each amino acid (R).⁹ The side group differs in shape, size, pH, and composition and gives each amino acid its identity. Peptides are amino acids linked in specific sequences to form strands of protein. One amino acid is joined to another by a peptide bond. A peptide is formed by the carboxyl group (-COOH) and bonds to an amino group (-NH₂) of another amino acid and releases water in the process. A polypeptide contains more then 10 amino acids. When two amino acids join together, the carboxyl group of one amino acid is matched with another amino acid. A condensed reaction forms a peptide bond and releases water.⁹               

This picture shows how phenylalanine and glycine are forming a peptide bond.

Citations:

1.      University of Maryland Medical Center. Phenylalanine.

http://www.umm.edu/altmed/articles/phenylalanine-000318.htm (accessed 2011)

           

2.      Phenylalanine. Encyclopedia.

http://www.absoluteastronomy.com/topics/Phenylalanine (accessed 2011)

3.      Amino Acid Structure. Phenylalanine. http://www.cem.msu.edu/~cem252/sp97/ch24/ch24aa.html (accessed 2007)

4.      Amino Acid. The Acid Base Chemistry of Amino Acids. http://chemed.chem.purdue.edu/genchem/topicreview/bp/1biochem/amino2.html (accessed 2006)

5.      Amino Acid Classification for R groups. Phenylalanine. http://mcb.berkeley.edu/courses/mcb102/discussion/Handouts/Amino%20acid%20Review%20JK.pdf

6.      Identifying Amino Acids in Protein NMR Spectra. Phenylalanine. http://hoffman.cm.utexas.edu/research/aa_h_nmr.pdf

7.      X-1A x-ray Absorption Spectra. Phenylalanine. http://xray1.physics.sunysb.edu/~micros/xas/xas.html (accessed Oct. 2, 2003)

 

8.      PhotochemCAD Spectra by Category. Phenylalanine. http://omlc.ogi.edu/spectra/PhotochemCAD/html/phenylalanine.html (accessed 1998)

9.      Nutrition. Polypeptide. http://books.google.com/books?id=46o0PzPI07YC&pg=PA208&lpg=PA208&dq=phenylalanine+polypeptide&source=bl&ots=GjuuhrOHPI&sig=nddjO-qClfNNQjCVLS3JnDNX-Yg&hl=en&ei=YISLTafVBdDUgAf14o3JDQ&sa=X&oi=book_result&ct=result&resnum=9&ved=0CF4Q6AEwCA#v=onepage&q=phenylalanine%20polypeptide&f=false (accessed 2004)