Question

Laboratory synthesis of isopentenyl diphosphate - the 'building block' molecule used by nature for the construction of isoprenoid molecules (section \(1.3 \mathrm{~A}\) ) - was accomplished by first converting isopentenyl alcohol into an alkyl tosylate then displacing the tosylate group with an inorganic pyrophosphate nucleophile. Based on this verbal description, draw a mechanism for the second (nucleophilic substitution) step, showing starting and ending compounds for the step and curved arrows for electron movement.

Short answer

Question: Draw a detailed mechanism for the nucleophilic substitution reaction of isopentenyl alkyl tosylate with an inorganic pyrophosphate, including starting and ending compounds, and curved arrows representing electron movement. Answer: The detailed mechanism for the nucleophilic substitution reaction involves the starting compound isopentenyl tosylate (CH₂=C(CH₃)CH₂CH₂-OTs) and the nucleophile inorganic pyrophosphate (P₂O₇⁴⁻). First, the oxygen of one of the phosphate groups attacks the carbon bonded to the tosylate group in isopentenyl tosylate, represented by a curved arrow. Then, the tosylate group departs, indicated by another curved arrow starting from the C-OTs bond towards the oxygen atom of the tosylate group. The final product formed is isopentenyl diphosphate (CH₂=C(CH₃)CH₂CH₂-OPP), where the pyrophosphate group is bonded to the carbon that was previously bonded to the tosylate group.

Step-by-step solution

Determine the starting compound

To draw the mechanism, first determine the starting compound - isopentenyl tosylate. Its structure consists of an isopentenyl group with a tosylate group (OTs) attached to the alcohol. The general structure of isopentenyl tosylate is CH₂=C(CH₃)CH₂CH₂-OTs.

Identify the nucleophile

The nucleophile in this reaction is an inorganic pyrophosphate group. This group has the general formula PPi, or P₂O₇⁴⁻, which consists of two phosphate groups linked together.

Draw the arrow representing the nucleophilic attack

The next step is to draw the curved arrow representing the nucleophilic attack of the pyrophosphate group on the isopentenyl tosylate. The arrow should start from the oxygen of one of the phosphate groups and point towards the carbon atom bonded to the tosylate group in isopentenyl tosylate.

Draw the arrow representing the leaving group departure

The tosylate group acts as a leaving group in this reaction. Draw another curved arrow starting from the bond between the carbon and the tosylate group, and pointing towards the oxygen atom of the tosylate group. This represents the breaking of the C-OTs bond and the departure of the tosylate group.

Draw the products of the reaction

After the nucleophilic attack by the pyrophosphate group and the departure of the tosylate group, the final product is formed - isopentenyl diphosphate (IPP). The structure of IPP is CH₂=C(CH₃)CH₂CH₂-OPP, where the pyrophosphate group is now bonded to the carbon atom that was previously bonded to the tosylate group. In summary, the nucleophilic substitution reaction mechanism for the conversion of isopentenyl tosylate to isopentenyl diphosphate with an inorganic pyrophosphate nucleophile can be represented by showing the starting and ending compounds with arrows that depict electron movement. The reaction consists of a nucleophilic attack by the pyrophosphate group on the isopentenyl tosylate, followed by the departure of the tosylate group as a leaving group, resulting in the formation of isopentenyl diphosphate.

Key concepts

Isopentenyl Diphosphate

Isopentenyl diphosphate (IPP) is a fundamental building block in the biosynthesis of isoprenoids, the largest class of natural products. It is also known industrially for its role in the synthetic creation of these compounds. IPP contains five carbon atoms, making it the smallest of the isoprenoid precursors, yet it is the cornerstone for constructing more complex molecules by the process of head-to-tail coupling. The molecule has two phosphate groups (hence the term 'diphosphate') linked to an isopentenyl chain, a structure that is pivotal because the phosphates provide the reactive sites for subsequent bond formations.

Isoprenoid Molecule Synthesis

Isoprenoid molecules, or terpenoids, are diverse organic compounds that include hormones, pigments, and fragrances found in nature. Synthesis of these complex molecules begins with the aforementioned isopentenyl diphosphate (IPP) and its isomer, dimethylallyl diphosphate (DMAPP). IPP serves as both a substrate and a product in the isoprenoid synthesis pathways, particularly through the reaction known as isoprenoid chain elongation. This process involves the sequential addition of IPP units to a growing prenyl chain. Didactically, understanding the role of IPP in this biosynthetic pathway clarifies the numerous ways through which nature constructs a vast array of essential and bioactive compounds.

Alkyl Tosylate

Alkyl tosylates are sulfonate esters where the sulfonyl group is derived from toluenesulfonic acid and serves as a leaving group in nucleophilic substitution reactions. In synthetic chemistry, converting an alcohol to an alkyl tosylate is a standard method for activating the alcohol, thereby making it susceptible to nucleophilic attack. The tosylate group (OTs) is excellent for this purpose because it can readily leave, thanks to the stabilization of the negative charge it acquires upon departure by the electron-withdrawing sulfonate group. This feature is exploited in the laboratory synthesis of isopentenyl diphosphate, where isopentenyl tosylate's tosyl group is displaced in a nucleophilic substitution reaction.

Pyrophosphate Nucleophile

In a nucleophilic substitution reaction, a pyrophosphate nucleophile (PPi) is often involved in the transfer of a phosphate group to an organic molecule. Pyrophosphate essentially consists of two phosphate units connected by an anhydride bond, which holds high-energy bonds pivotal for cellular biochemistry. As a nucleophile, the pyrophosphate ion provides a pair of electrons to form a new bond with a suitable electrophile, such as the carbon atom in an alkyl tosylate. The reaction typically results in the good leaving group, such as the tosylate, being displaced, thereby forming a bond between the carbon and the oxygen of the incoming pyrophosphate. This mechanism is crucial in the synthesis of isopentenyl diphosphate, underscoring the importance of pyrophosphate as a reactive entity in biochemistry and organic synthesis.