Guilford Techno Consultants, Inc

Sunday, September 10, 2023 by Guilford Techno Consultants, Inc. | Alkene Reactions

For whatever reason, alkene reactions and their mechanisms are my favorite topics from the first semester. Although these reactions involve a large number of reagents and can be mechanistically complex, I find them much more straightforward than substitution and elimination reactions. From a mechanistic point of view, substitution and elimination reactions aren’t very complicated but there are so many moving parts to these reactions that I always feel like I’m guessing at what the products should be. Although there are quite a number of alkene reactions, I find product prediction to be fairly manageable. I also find alkene reaction mechanisms to be fairly intuitive with a few exceptions, ozonolysis being one of them.

The sigma and pi bonds of alkene double bonds can be oxidatively cleaved to yield two carbonyl groups as aldehydes or ketones depending on the structure of the alkene. One way of achieving this is through reaction of an alkene with ozone, O₃, followed by a mild reducing step to yield product. Dimethyl sulfide (DMS) and zinc in water are commonly used as reductants. Initially, ozone adds to the alkene double bond to form a five-membered ring called a molozonide. The molozonide is unstable and rearranges through a two step process to yield an ozonide, which is then treated with a reductant to produce the final products. The mechanism for the formation of the ozonide and its reduction by DMS can be found in the following presentation. Practice problems are also included.

Click Here for Ozonolysis of Alkenes

Sunday, August 20, 2023 by Guilford Techno Consultants, Inc. | Name Reactions

Several mechanisms of the second semester of Organic Chemistry involve the migration (shift) of an alkyl group to give a rearranged product. The Hofmann rearrangement, which I wrote about in my last post, is one such mechanism. Another reaction that proceeds through an alkyl shift is the Baeyer-Villiger oxidation of a ketone by a peroxyacid to yield an ester. The reaction was discovered by Adolf von Baeyer and Victor Villiger in 1899 and involves the insertion of an oxygen atom of the peroxyacid in between the carbonyl of the ketone and one of it’s alkyl groups:

 If the ketone is cyclic, a lactone (cyclic ester) is formed:

The mechanism involves the formation of an uncharged tetrahedral intermediate after attack of the protonated carbonyl by the peroxyacid. The carbonyl is reformed through migration of an alkyl group and subsequent deprotonation. The peroxyacid is converted to a carboxylic acid during the process. If the ketone is asymmetric, the reaction is regiospecific with respect to which group will migrate:

H > 3°C > 2°C, phenyl > 1°C > CH₃

In other words, hydrogen will migrate faster than any other group, while methyl will migrate slower than any other group. The mechanism can be found below, along with practice problems.

Click Here for the Baeyer-Villiger Reaction

Thursday, August 3, 2023 by Guilford Techno Consultants, Inc. | Name Reactions

The topic of amines is covered in the second semester of Organic Chemistry. In addition to learning about the physical properties, spectroscopy, and reactivity of amines, students also learn about the ways to prepare them. Of course, threaded throughout the material are the various mechanisms associated with the reactions. To me, amine mechanism is in a category by itself. I don’t find mechanisms involving amines to be very intuitive and consequently, I find them to be the some of the most challenging of the two semesters. 

The Hofmann rearrangement, discovered by August Wilhelm von Hofmann, is a mechanism that many students find particularly challenging. The reaction involves the conversion of a primary amide to a primary amine with the production of carbon dioxide as a side product:

There are two mechanistic pieces to the reaction. The first involves a rearrangement of an N-haloamidate to an isocyante, while the second involves decarboxylation of a carbamate to produce the primary amine. Hydroxide begins the reaction by deprotonating the amide nitrogen to produce an amidate ion. The nitrogen of the amidate ion is subsequently halogenated by X₂. Following this step, hydroxide removes a proton from the nitrogen, yielding an N-haloamidate. A shift of the alkyl group next the carbonyl results in rearrangement to an isocyanate with loss of a halide ion. Under the basic conditions of the reaction, the isocyanate spontaneously hydrates to form a carbamate ion. Loss of CO₂, followed by protonation of the nitrogen, yields the primary amine. Reaction of hydroxide with CO₂ produces bicarbonate, driving the reaction to completion by preventing the amine from reacting with CO₂. A complete mechanism and practice problems can be found in the following presentation.

Click Here for the Hofmann Rearrangement