Organic Chemistry II Subscribe with Bloglines class wiki class vodcast

Wednesday, July 27, 2005

Production of ketone from an alcohol: an unwanted side product




The above reaction shows an epimeric steroid alcohol being converted by a catalyst of ruthenium and aluminum oxide to a racemic mixture of 17-estradiol 3-methyl ether and a ketone. The racemic mixture is formed by converting the beta version of the ether, where the hydroxyl group is on the top of the ring, to the alpha version of the ether, where the hydroxyl group is underneath the ring. The reaction is stopped when the amount of alpha ether is roughly equivalent to the amount of beta ether. In the notation used, the wavy line between the hydroxyl group and the ether shows that the hydroxyl group can be in either the front or the back of the molecule.

However, a ketone can be produced instead of the alpha ether when the alcohol is oxidized. Because the purpose of the reaction is to racemize the ether, this ketone is an unwanted side product. To prevent oxidation, toluene at 100 C is used as a solvent. The chemical properties of toluene slow the formation of the ketone so that at temperatures around 100 C, the yield of the racemic mixture is about 54%. Any ketone that does form can be separated from the ether by flash chromatography. This reaction is a good way to racemize the ether efficiently and inexpensively; it was traditionally synthesized at a much higher cost.


For the full text of the article describing this process, see this report.

Sunday, July 24, 2005

ChemSketch Demo

Here is a 3 minute Flash screencast that Yana made to help with the use of ChemSketch in your blog assignment. If you know how to do something well please consider doing a brief screencast like this. You can download Camtasia here.

Even if something seems simple to you, it may not be for everyone. A good way to know if a screencast it useful is to notice recurring errors made by student in their blog assignment.

Examples:
-how to find a reaction in the literature
-how to use CiteULike
-how to post to Blogger
-how to resize pictures
-how to link to a reference without pasting the entire url in the post text
-how to tell if a reference is suitable
etc.

Saturday, July 23, 2005

Second deadline over

All of the grades for the second blog assignment deadline are now posted and cannot be changed. A few comments:
1) Most of you are now using CiteULike properly so there are now plenty of examples other students can look at to see how it should be done.
2) It would be nice if you could tag all your articles with "orgo" so that all the articles of the class could be tracked with an RSS feed.
3) Many of you are giving a lot more than what I am asking for an running into some trouble in the process. All I want is one single reaction with nice readable molecules drawn from ChemSketch (or by hand as a last resort) with an arrow and reagent on the arrow. It will be easiest for you to pick a reaction that we covered in class because you won't have to explain it in as much detail.
4) If you want to give me more information that is fine but make sure that you support your statements with a link to a document with primary data (like experimental results) or to a document where the information trail continues on to primary data. For example, "progesterone reduces the risk of cancer" should be clickable to an article where the actual study has this as a conclusion OR to an article that has a similar statement with a link to primary data. References lumped at the end of your post are not good enough. Articles that you link to with general references at the bottom are also not usable. Unfortunately this means that a lot of government public health sites or company websites are not suitable for references. Your opinions and your speculations don't have to be supported by a reference. Try to post well before the next deadline so I can help you get this right.

Friday, July 22, 2005

Synthesis of Lupinine Esters from Betulonic Acid Chloride




The reaction shown above outlines the synthesis of the lupinine ester. These esters have been studied for their biological properties. Found mainly in plants there is heavy research being done on them for their antiviral, antitumor and hepatoprotective activity. In some cases lupinine esters can exhibit local anesthetic properties.

The reaction shows how you would synthesize a lupinine ester from betulonic acid chloride with lupinine. Side conditions for this reaction include the presence of triethylamine and must be performed in dry CCl4.

CiteULike Reference

Production of Hydrogen by means of hydrogenation of ethanol

Along with the growing interest in Fuel Cell powered cars comes the need for higher production methods of Hydrogen, both in bulk form and in-car conversions (for fuels such as methanol and ethanol to be converted to hydrogen on board). Previous methods of converting Ethanol to hydrogen was by means of high-temperature steam reformation (at temperatures in excess of 600° C) to produce Hydrogen gas and CO.

This journal describes a special method of low-temperature dehydrogenation of ethanol over special Raney catalyst with Cu added to it. The first step produces one mole each of hydrogen gas and acetaldehyde (per mole of ethanol). This is followed by the decarbonylation of acetaldehyde to form methanol and CO. The whole reaction undergoes a water-gas shift to net one mole each of Methane and Carbon dioxide and two moles of Hydrogen.



Compared to high temperature reformation methods, which produces 6 moles of hydrogen per mole of ethanol, this reaction doesn't seem as fuel efficient, though the authors were confident, that with an internal combustion engine on-board that uses the methane produced as fuel, the total output energy would be equal.

Citeulike Link

Thursday, July 21, 2005

Catalytic Hydrogenation of an Acid




















This reaction is an example of the catalytic hydrogenation of an acid in an ionic liquid similar to the reagents sodium metal/liquid ammonia discussed in lecture. This particular reaction has sorbic acid and hydrogen gas reacting with a ruthenium catalyst and a biphasic 1-butyl-3-methyl imidazolium hexafluorophosphate (bmimPF6)/methyl tert-butyl ether (MTBE) system to create cis-hex-3-enoic acid. The above reaction occurs with ~85% selectivity. The author of this paper was examining enantioselective hydrogenation in ionic liquids because this mechanism could provide a means for facile recycling of metal complexes of expensive chiral ligands. The author also studies some hydrogenation reactions that lead to the precursor of the antiinflammatory drug ibuprofen, the active ingredient in Advil.

For the full text click here.

Preparation of Progesterone from Cholesterol



This is what I understand happens, following the process of production of progesterone, described on page 894, second column.
In the first two steps cholesterol is brominated in benzene, and oxidized in a solvent with acid permanganate(aq). In the last step the product is again debrominated using zinc dust.

The strong oxidizing agent potassium permanganate is used, as well as sulfuric acid. The article below describes the process of production of progesterone from cholesterol.
Progesterone has numerous physiological effects. Although primarily associated with the reproductive system, progesterone has multiple effects outside of it. This steroid hormone can act as an antiinflamatory agent, reducing the immune response; it can also assist in thyroid hormone action and bone building. Progesterone appears to prevent endometrial cancer (cancer involving the uterine lining) as well as breast cancer (1).

Article link

Wednesday, July 20, 2005

Williamson Synthesis of Ethers


The above reaction is an example of a Williamson synthesis of an ether. It is one the earlier steps in the reaction mechanism resulting in the octaethylene glycol derivative of 1,1,1,3,5,5,5-heptamethyltrisiloxane. Such an initial Williamson synthesis reaction had to be carried out so that later steps in the reaction—that is, ones involving material types not readily accessible—could successfully yield the derivative product. The resultant glycol derivative is an example of a defined surfactant. This particular journal article focused on the correlation between surfactant constituents and the effect on properties such as spreading performance.
The Williamson synthesis involves an SN2 reaction in which a halogen, sulfonyl, or sulfate group is replaced by an alkoxide ion, which can itself be prepared by a reaction of the alcohol with an active metal such as sodium or its hydride (i.e. NaH). The resultant alkoxide salt then reacts with the alkyl halide (must be primary) to produce an ether via the SN2 mechanism.
Other examples of Williamson synthesis of ethers can be found in this same reaction mechanism used to produce the surfactant. Article Link.

Tuesday, July 19, 2005

Lucas Reagant


The reaction seen above is an example of a substitution nucleophilic 1 reaction. The mild reaction conditions and high yields makes the Lucas reaction a convient way to be utilized in the industrial-scale preparation of alkyl chlorides from aliphatic alcohols. However, the wide use of the Lucas reagent in industrial settings is limited due to the cost of ZnCl2. This reaction proceeds rapidly and is needed for the fast demand and industrial use of menthyl chloride. A description of the reaction is shown here.

Monday, July 18, 2005

Methanol Synthesis and Dehydration Combined in a Single-Stage DME Synthesis Process


Dimethyl ether (DME) is a multipurpose clean fuel and chemical feedstock that can be produced from a wide variety of of sources and has a number of important applications. About 10,000 tons of DME are manufactured each year for uses in cosmetics and aerosal paint propellants. Its new use as a clean fuel source is gaining attention and research, as it contains no sulfur or nitrogen compounds, has a very low toxicity, and is not corrosive to metals. It can be stored and transported as a liquid at low temperatures

A single-stage, liquid phase synthesis process for DME in a slurry phase reactor system is efficient and facilatates heat removal. The combination of methanol synthesis and methanol dehydration reversible reactions in a single step is thermodynamically more favorable. The liquid phase operation allows for better heat management and higher yields of DME.

The first pictured reaction shows the methanol synthesized from carbon dioxide and it is combined with the second pictured reaction into the last pictured reaction, in which the synthesized methanol is dehydrated to produce DME.

See here for the CiteULike with the reactions and here for another journal article about DME. In addition, the catalytic synthesis of methanol is covered in Ch.10 of Wade and DME itself is discussed in Ch.14.

Saturday, July 16, 2005

A simple one-pot synthesis of β-alkoxy alcohols from alkenes


The main protocol for the synthesis of β-alkoxy alcohols is the alcoholysis of 1,2-epoxides. To synthesize epoxides, we can use oxone in the presence of transition metal complexes, or cyclodextrines, or via the formation of dioxiranes.

An application of this type of reaction is the synthesis of β-methoxy alcohols. It is done by the one-pot reaction of alkenes with oxone in methanol without any other catalyst.

Note: Oxone (2KHSO5·KHSO4·K2SO4) is the registered trademark from Du Pont.

General reaction and some examples are shown above.

For reference, please click on http://www.citeulike.org/user/hongan1985/article/258103

Chap 9 UT map ready for testing

We have quiz 9 in Unreal Tournament 2004 map format available for testing. If you have UT2004 just download the map and textures here.

I'll make these maps available on the network shortly but for now you have to download and play on your computer.

You can play with or without bots (or other players). So if you just want to calmly explore select no bots and don't play on the network.

If you don't have UT2004 but still want to play let me know and we can make arrangements.

Please report any errors or problems as comments on the Edufrag blog on the post of the map you are playing.

This is an example of a student assignment done as a map instead of a blog post.

Friday, July 15, 2005

Creating Amphetamines by Tosylation of Alcohols




The picture above shows a few of the steps in the creation of amphetamines. In these steps, tosyl chloride is added to (2,5-dimethoxyl-4-methylphenyl)-2-propanol to create the tosylate. After this step, the reaction can proceed in one of two ways. If the chirality of the amphetamine is not important, ammonia is added to the tosylate to give 2,5-dimethoxy-4-methylamphetamine. This reaction has an 80% yield, but has a racemic mixture of products because it is thought to be an SN1 reaction. If the chirality is important, the tosylate is converted into an azide with sodium azide, then hydrogenated using a paladium catalyst to form 2,5-dimethoxy-4-methylamphetamine. Forming the amphetamine using this method gives a final yield of about 77%. The chirality of the original alcohol is inverted by the tosylation, so reacting an (S)-alcohol with the tosyl-azide-hydrogen sequence would give an (R)-amphetamine, and vice versa.

For the full text of the article describing this process, see this report.

Saturday, July 09, 2005

Tests

Dr. Bradley,
When are the dates for the test 1 and 2 and the final test date?

Avik

First deadline grades

The first deadline for the blog assignment has now past. Everyone who posted has been graded. There is nothing you can now do to improve your grade on the first assignment. Learn from your mistakes and the mistakes of other students by reading my comments on all the posts to make the next deadline in 2 weeks.

One general comment: use a specific reaction of a specific compound that you find in the article. Avoid drawing general structure with R groups.

Friday, July 08, 2005

The dioxygenase-catalysed formation of vicinal cis-diols
























This is an example of the reaction of an epoxide ring reacting with water and and enzyme (epoxide hydrolase) to create a vicinal diol. The paper displays experiments with several different compounds and the role of mono- and di-oxygenase enzymes in arene
metabolism. The paper also displays a variety of intermediary or alternative pathways the the substrates can take to generate different, but useful products. The primary focus is on the impressive ability of bacterial oxygenases to catalyse the cisdihydroxylation
of a diverse range of arenes and alkenes to yield a single enantiomer.

Full Text

or

CiteULink Reference

Addition of Grignard Reagents to Ketones


------------------------


This is an example of the reaction of a ketone with a Grignard reagent, which gives a tertiary alcohol. The paper presents a study of several different idol-3-ones reacting with Grignard reagents. Idol-3-ones are potentially useful intermediates in the synthesis of alkaloids and pharmaceutical agents.
Going one step further: due to the lack of stability in the tertiary alcohol, a rearrangement is observed on the alcohol molecule, creating a gain in resonance stabilization in the final molecule. The study examined a variety of conditions under which the rearrangement occurred, in order to recognize the most efficient one. It was determined that the rearrangement took place with great facility under acidic or basic conditions or was thermally induced.

full text

or
CiteULike Quick Reference

Blog Picture Suggestions

Two things that I did to help add clarity to my images was:
1) In Flikr, before you obtain the URL click on the image which is bigger than the one that shows up in your album and then go to properties to obtain the URL. This image is larger to when Blogger formats it, the picture is more clear.
2) To make the picture even more clear: go into "Edit HTML" of your blog post when you edit it. Then find the line for your image that will look like this:

"http://photos18.flickr.com/22901961_b9fc681f83.jpg?v=0">="DISPLAY: block; MARGIN: 0px auto 10px; WIDTH: 320px; CURSOR: hand; TEXT-ALIGN: center" alt="" src="http://photos18.flickr.com/22901961_b9fc681f83.jpg?v=0" border="0" /

and delete the text in pink (width) from the HTML code. This will make the image a little more clear. If your image is too large though, it will extend out into the navigation on the right so make sure when you delete width that your image doesn't do that.

repeating mistakes

Before you post take a look at the comments I made on all of the other students' posts. I see the same errors coming up in the last few posts. In order to get full marks you must:
1) make sure your molecules and reagents are big enough to view easily from http://chem242.blogspot.com. See the first few examples that I graded "full marks" to see how big is big enough
2) you must use CiteULike
3) ALL of the reference info needs to be present in CiteULike (authors, journal name, year, page, volume, title, abstract)
4) the single step reaction that you have in your scheme MUST be in the article you are citing

I will shortly stop giving this feedback repeatedly and just grade it accordingly at each deadline.

If any student has tips (especially for making molecules the proper size in Chemsketch) it would be great if you could record a 1-2 minute screencast of it. Just download the trial version of Camtasia, save as an avi and I'll give you instructions to upload.

Synthesis of Ethylene Oxide as a fumigant


This shows the synthesis of ethlyene oxide which can be used as a fumigant for foods, textiles, soils and for sterilizing biomedical instruments. It readily diffuses through materials without damanging them. Its antibacterial effect is probably due to its ability to alkylate critical cellular enzymes.



Heres a link

Tutoring

The Drexel Learning Center is offering tutoring for organic chemistry students this term. If you find this to be useful share your experience here.

Thursday, July 07, 2005

Nitroglycerine synthesis


This is a nitrate ester made by esterification. In this process, glycerols reacts with Nitric Acid under a catalyst of Sulphuric Acid at 300oC to yield an ester complex of glyceryl trinitrate otherwise known as nitroglycerine, and three water molecules. In this process, there has been formation of an ester bond (COO). This production is very crucial for medical purposes. Nitroglycerine is used to relieve angina, a condition when the heart isn’t receiving much oxygen. Also, Nitroglycerine was used in a study with yohimbine/l-arginine combination to see the treatment of erectile dysfunction in males. The metrics used in this study were the male’s systolic and diastolic blood pressures. This study created a correlation between the effects of erectile dysfunction with the inadvertent cause of coronary artery disease. Intravenous Nitroglycerine was used to help in the study with the chemical compositions with arginine. Here is a reference for this article on its uses.

anti-Markovnikov hydration of an Alkyne


This is en example of what we learned in class, the Markovnikov hydration of n-propyne (a terminal Alkyne) that produces a Ketone. Using ACS publications, i found an article that describes an ideal anti-Markovnikov hydration of the same compound, to produce an Aldehyde instead.



To induce this reaction, the catalyst cyclopentadienylruthenium is used in a 2-Propanol solvent at 100 deg C, with yields over 99% for this reaction, other Alkynes bearing over 90% for the most part.

full article

The Role of Phosphate Esters in Biochemistry (DNA and Cellular Processes)



The backbone of deoxyribonucleic acid (DNA) is composed of nucleic acids, which are made up of ribofuranoside units strung together by phosphate esters. These phosphodiester bonds (two ester bonds) create the DNA backbone.

This simple ChemSketch shows the linking of nucleotides in DNA via phosphate ester groups:


Phosphate esters are created when phosphoric acid and an alcohol combine. Here is an example with methanol (alcohol), which can form three esters based on how many moles of methanol are used:

In addition to its role in the backbone of DNA, phosphate groups play a biochemical role in ribosome-substrate interactions and the regulation of cellular processes. The regulation of their formation on key body proteins regulates these processes, and malfunctions in their regulation can result in cancer, diabetes, and even obesity.
Phosphate groups also play a major part in the bending of the DNA backbone, due to the repulsion of the negative charges. Other experimentation concerning the role of phosphate ester groups includes looking at their electrostatic contribution to the free energy of the bent DNA backbone as well as the synthesis of heparin-immobilized polyetherurethanes, whose side groups have hydrolysable ester groups (heparin being a synthetic anti-coagulent).

Here is reference one and reference two and reference three from CiteULink.

In addition, Chapter 11 and Chapter 23 from Wade provide substantial information on this topic.

Question about blog assignment

Hi Dr Bradley,

I've already fixed my post and uploaded the images.

I did not delete any comments that you made. On Wednesday after I posted the assignment, I checked the blog many times on the day and made some changes. But I still saw "No comments". I actually never delete any comments.

Do I need to correct anything else from my assignment? Do I need to redo it?

Thank you!

Blog Aassignment Help

For those of you having a hard time finding a primary source with reactions I found a great E-journal database through the Drexel Library that I used in my blog posts.

Just follow the link bellow and log in with your Drexel ID to access the journal data base. Once at the site, go to the tab that says "search the journals." I used the "search journals" part to type in keywords such as reagents used, compound names, and you can even search by picking a drug of interest and seeing if there is an article on how it synthesized. The articles come in full text and I like using the HTML version because its easier to navigate and see the images.

http://pubs.acs.org.ezproxy.library.drexel.edu/

Lindlar's Catalyst


The above is one of the final reactions in the synthesis of an enantiospecifically labeled fatty acid. It involves a reduction with Lindlar's Catalyst in the presence of deuterium, an isotope of hydrogen. Lindlar's Catalyst (powdered barium sulfate coated with Pd, poisoned with quinoline) converts an alkyne to a cis-alkene, as seen in the reaction above. The article I looked at focused on pheromone biosynthesis in S. isatideus and the role stereochemistry played. Article Link.

Pinacol Rearrangement

The pinacol rearrangement is essentially a dehydration reaction of an alcohol, specifically a diol. The following is an example of a pinacol rearrangement in which the (R,R)-diol (TBDMS is tert-butyldimethylsilyl) was allowed to react with 2,2 dimethylpropane (2,2-DMP) in the presence of boron trifluoride etherate at room temperature. This particular reaction was done in order to attain the acetone derivative.

Interestingly, instead of retaining its chirality, the product of the pinacol arrangement actually resulted in a racemic mixture. Subsequent derivatives of this product eventually yield benzophenone (hydroxyphenstatin), which, biologically, is a potent antitumor and antimitotic agent. Accordingly, hydroxyphenstatin has also been proven to inhibit tubulin assembly. Article Link.

Wednesday, July 06, 2005

Synthesis of ester derivatives of salicylic acid and diflunisal

Let's look at some chemical structures:
One problem occurs with aspirin is that it has a destructive effect on the blood vessel walls and inhibit the synthesis of prostacyclin. To resolve this problem, we can use potential anti-platelet agents including the O-acyl esters which are synthesized from salicylic acid and diflunisal. Those agents work by acylation of cyclooxygenase and have a higher extraction than aspirin. That makes them yield a greater selectivity in their effect on platelet inhibition relative to prostacyclin inhibition on vessel walls.

The actual reaction is shown on the top.

For reference, please click on http://www.citeulike.org/user/hongan1985/article/246557

Tuesday, July 05, 2005

More blog assignment info

1) For a reminder of how to use Chemsketch, Flickr and Blogger to do your assignment review this tutorial. There seems to be a problem with the ChemSketch version on the Drexel server so use the link to the free version of ChemSketch in that post.

2) You may not copy reactions or text from articles.

3) Pick one simple reaction that we covered and only draw that.

4) You may use ChemSketch or drawing on a tablet PC or drawing on paper and scanning the reaction if you have to but in the long run ChemSketch will come in very handy so might as well learn it now.

5) After uploading make sure that the pic is not too wide, as it will distort the right hand frame of the blog.

Quiz Ch. 10: Questions 3 & 9

3) Is cyclopentene glycol named that way because it comes from a cyclopentene that has been reacted to produce a vicinal diol?

9) CH3 MgBr + CH3CO2CH3 yield 2-methyl-2-propanol. But wouldn't an excess (xs) of CH3 MgBr yield CH4 and CH3COCH3 because the excess CH3 MgBr would react with the formed hydroxyl group on 2-methyl-2-propanol???

Monday, July 04, 2005

Esterification: The Synthesis of Aspirin (ASA)



The most common medical ester is aspirin (ASA; acetyl salicylic acid). Other drugs such as Worm Guard (anti-wormer), Maxicaine (local anesthetic), Malathion (organophosphate), Mebendazole (antihelmenthic), Demerol (narcotic analgesic) and Equinil (sedative) are also esters.
The starting reactants for this experiment are salicylic acid and acetic anhydride (structures are shown above).

Salicylic acid reacts better with acetic anhydride than acetic acid, so acetic acid will provide the acetyl group which will react with the alcoholic -OH group on the salicylic acid. (The reaction is on the top of the post.)

Chemicals needed for the reaction: Salicylic acid, Acetic anhydride, and Concentrated sulfuric acid.

Equipment: 250 mL Erlenmeyer flask, Hot water bath, Ice bath, Buchner funnel and filter paper, Glass stirring rod, and Electronic pan balance and weighing boat.

For the full text, click on http://tooldoc.wncc.nevada.edu/aspirin.htm

EduFrag blog

As I mentioned previously, you may submit your blog assignment as an Unreal Tournament map. A blog for information about this has been created. Subscribe to the feed if you want to keep on top of this project, either as a map developer or a player.

Sunday, July 03, 2005

Catalytic hydrogenation of an ether to an alcohol



This is one of the synthesis steps to produce tolterodine tartrate. The focus of the study was to find a cost-effective and impurity-free process to produce tolterodine tartrate. This compound is a muscle relaxant used to treat bladder disorders. Although ethers are inert to most reagents, a benzyl ether, like the one above, can be hydrogenated under mild conditions (H2/Raney/Ni/MeOH/25-30 C) to an alcohol. The phenyl group stays and the methylbenzene group leaves. Article link.

Saturday, July 02, 2005

Eco-Friendly Halogenation of Alkynes



This reaction is a summary of an ecologically friendly process for halogenating alkynes. The reaction works with both hydrobromic and hydrochloric acid, and produces water as its only waste product. It also gives a good yield of the halogenated product.
Instead of undergoing anti-Markovnakov addition of HBr, the alkynes are halogenated. This is due to the way the reactants are mixed. Mixing a hydrohalogenic acid with a solution of t-butylhydroperoxide (TBHP) and hydrogen peroxide will oxidize the halogens, causing them to become positively charged. The charged halogens will then attack the alkynes, and a halogenation reaction will occur.

For the full text of the article describing this process, see this report.

Friday, July 01, 2005

Reaction of an alcohol with thionyl chloride (Ch. 11)

This is an example of a reaction involving thionyl chloride. The alcohol is halogenated with excess thionyl chloride to yield chloro lactone. The paper is a study on the biomimetic (mimicking a biological process) synthesis of bisesquiterpene lactones, specifically biatractylolide and biepiasterolide which have been extracted from Atractylodes macrocephala (Chinese medicinal plant). Article link.

Reduction of an ester to an alcohol

This is one of the steps in the synthesis of Taxol. Taxol is an anticancer drug found in the bark of the Pacific yew tree. In the step outlined, an ester is reduced by LiAlH4 and THF to an alcohol. Here is a reference with the synthesis.