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.

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.

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.

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.

According to the frontier orbital theory, the chemistry of conjugated π systems is largely determined by the HOMO and LUMO π orbitals in the reactant molecules. The outcome of reactions involving interaction of π orbitals can be rationalized using the concepts of orbital phase and symmetry. The figure on the right illustrates what is meant by the orbital phase using 1,3-butadiene as an example. In this molecule, four atomic p orbitals form four π molecular orbitals. The four molecular orbitals differ by the extent of favorable overlap, and thus in energy. The lowest energy MO forms from the in-phase overlap of all four p atomic orbitals; the next one forms when two pairs or in-phase atomic orbitals overlap; the third when one pair of in-phase atomic orbitals overlaps, and the highest energy molecular orbital forms when there are no in-phase overlaps. The MO’s are filled with electrons starting with the lowest-energy orbital such that two electrons occupy an MO. In case of 1,3-butadiene, there are 4 π electrons, thus the second lowest-energy orbital is the HOMO.

The Diels-Alder Reaction

The Diels-Alder reaction is a cycloaddition reaction between a conjugated diene and dienophile.

Diels-Alder reaction has high synthetic utility for making unsaturated six-membered rings. The reaction with unsubstituted dienophile (as shown above) is very slow but the Diels-Alder reactions occur readily when the alkene has a electron-withdrawing substituent. For example, acrolein is a good dienophile. Cycloalkenes, especially ones where the double bond is conjugated to a carbonyl, can be used as dienophiles. The diene is required to have an s-cis conformation and cyclic dienes work well in this reaction. For example, a reaction between 1,3-cyclohexadiene and chloroethene yields a bicyclic reaction product.

Note that chlorine is a relatively poor π-electron withdrawing group and the reaction above in not very fast. Interestingly, many Diels-Alder reactions occur much faster in water than in organic solvents. Scientists are still working on finding out why aqueous environment accelerates this reaction.

Molecular Orbitals in Diels-Alder Reaction

The Diels-Alder reaction is highly stereoselectivive: cis-substituted dienophiles yield cis-substituted cyclohexenes and trans-substituted dienophiles yield trans-substituted cyclohexenes. Stereoselectivity in Diels-Alder reaction can be rationalized considering the overlap of HOMO of one reactant with LUMO of the other. Table below shows π molecular orbitals for ethylene (dienophile) and 1,3-butadiene; clicking on the image will bring up Virtual Reality Modeling Language models for orbitals.

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Dienophile	LUMO (Lowest-Energy Unoccupied Pi Orbital). This orbital accepts electrons from the diene during the reaction. Electron-widtawing substituents conjugated to the double-bond reducing the Pi-electron density and allow for better “flow” of electrons to this orbital. In practice, alkenes with a conjugated carbonyl group are good dienophiles in the Diels-Alder reaction.
Dienophile	HOMO (Highest-energy Occupied Pi Orbital)

Diene	LUMO+1 High-energy unoccupied Pi molecular orbital in butadiene has three nodes and is asymmetric. This molecular orbial rearranges to become the asymmetric LUMO of the reaction product.
Diene	LUMO Lowest unoccupied Pi molecular orbital in butadiene has two nodes and is symmetric. This orbital allows for a favorable overlap with symmetric HOMO of the dienophile during the reaction.
Diene	HOMput DielsAlder.html O Highest occupied Pi molecular orbital in butadiene has one node and is asymmetric. Electrons from this Pi orbital could “flow” to the antisymmetric LUMO of dienophile during the reaction, allowing for formation of two new carbon-carbon bonds.
Diene	HOMO-1 Lowest-energy occupied Pi molecular orbital has no nodes and is symmetric. This molecular orbial rearranges to become the symmetric HOMO of the reaction product.