The substitution electrophilic unimolecular mechanisms are termed SE1 reactions. These mechanisms follow first order reaction kinetics with respect to the substrate. The SE1 mechanism is analogous to the unimolecular mechanisms for nucleophilic substitution (SN1).

SE1 mechanism

The SE1 mechanism involves two steps: the first step is a slow rate determining ionization step leading to formation of the carbanion. The second step involves fast combination of electrophile resulting in to the products.

Stereochemistry of SE1 mechanism

The stereochemical outcome of SE1 reactions are difficult to predict owing to the complicated configuration of carbanions formed during the first step of ionization. The typical carbanion in theory may have a pyramidal (sp3) or planar (sp2) configuration or may be depending upon the substituent a configuration in between the two forms. On minimum energy grounds, pyramidal configurations are favored as the lone pair resides in sp3 orbital.

If the carbanion is pyramidal and it can hold its structure, then the product should be with retention of configuration. Even a pyramidal carbanion has been reported to give racemized products owning to pyramidal inversion (fig: 1) as is observed with amines (amines; R3N: and carbanions R3C- are isoelectronic).

If the carbanion has a planar structure than also the attack of electrophile might lead to racemization of products. Therefore, racemization is almost always observed for the products of SE1 mechanism (fig 2), although whether this is caused by planar carbanions or by oscillating pyramidal carbanions in equilibrium is not settled.

Common reactions involving SE1 mechanism

1. Decarboxylation of aliphatic acids

Aliphatic acids with certain functional groups, such as double or triple bonds at or β position undergo facile decarboxylation. The reaction proceeds via involvement of a carbanion intermediate that subsequently acquires a proton from the solvent or other source. For such reactions loss of CO2 is the rate limiting step. Thus the rate law for the following reaction is, Rate = k[Z-CH2COO-]

Where, Z= COOH, COR, Ar, NO2, CN, CH3

2. Halogenation of ketones

The acid/base catalyzed halogenations of aldehydes/ketones is a classical example of SE1 mechanism.

In unsymmetrical ketones, the preferred site of proton abstraction and halogenation is usually the more substituted carbon atom. The preferred order for halogenations being CHR2>CH2R>CH3. Under alkaline conditions one position of a ketone is completely halogenated before the other position is attacked and generally the reaction cannot be stopped until all the hydrogens of the first carbon have been replaced with the halogen atom. This is because the electron withdrawing inductive effect exerted by the halogen makes the -H atoms of the CH2X group more acidic than those of CH3. Therefore the second halogenation is faster than the first and the third halogenations are faster still.

Haloform reaction is a special case of halogenations of ketones where one of the substituent on ketone/secondary alcohol is CH3 group. In Haloform reaction in the presence of excess base and excess of halogen, a methyl ketone is first converted into a trihalo-substituted ketone.

3. Nitrosation

Compounds with acidic protons such as active methylene group in F3CCOCH2COCF3 can be nitrosated with nitrous acid or alkyl nitrites. The attacking species is either NO+ or a carrier of it. The initial product formed is the C-nitroso compound,that is stable only when there is no hydrogen that can undergo tautomerism. When the substrate is F3CCOCH2COCF3, the mechanism goes through the enol form as follows:

This reaction is often used to prepare amino acids since oximes and nitroso compounds can be reduced to primary amines.

When benzene diazonium chloride reacts with phenol in which the phenol molecule at its para position coupled with the diazonium salt to form p- hydroxyazobenzene. This is known as the coupling reaction.A coupling reaction in organic chemistry is a general term for a variety of reactions where two hydrocarbon fragments are coupled with the aid of a metal catalyst. Ans : In this type of reaction, two different molecules react to form one new molecule. It is also known as hetero coupling reactions.

The coupling reaction is used in various applications, including the synthesis of new and complex conjugated polymers and natural products. It is also used in the manufacture of new pharmaceutical drugs. Many conjugated polymers are made with the aid of a metal catalyst in coupling reactions.

Many reaction occur in single step which is also the rate determining step and the other reactions occur through a series of steps but one of these steps is the slowest step which is the rate determining step of the reaction,It determine the rate of the reaction and the other are called intermediate steps.Concentration of the reactants in rate determining step is equal to the order of the reaction.Reaction intermediates are formed in one step and then consumed in a later step of the reaction mechanism.

Synthetic is a term used to describe the starting point of a product. Fully synthetic molecules may have naturally originated versions found in the natural world. Synthetic means that a skilled chemist manipulated chemical constituents to form the same molecule as the naturally occurring one found in nature.

The advantage of fully synthetic molecules is that it is much easier to synthesize isolate and purify, as well as develop dose specific medicine by removing the need for extraction of the API and it's time consuming and depletion of the resource reasonable for producing the active desired alkaloid. Many if not all plants, or bacterial samples used in the initial extractions contain many different undesirable alkaloids that need to be identified and removed.

The difference in the reaction technics used while constructing a molecule differ from other reactions employed in a laboratory. Addition reactions, substitution reactions and the rearranging of atoms are mainly focused on the adding of a atom or functional group to a specific location in the molecule. All the the work of a skilled chemist.

Also the mass-produced pharmaceuticals available today are all the products formed from synthetic formation routes. The ability of companies to offer quantifiable doses of the smallest active measure are only possible by synthetic means.

I am not really sure what you mean by “which way” do you mean uphill or downhill ? Or do you mean predicting the mechanism of a reaction ?

if you mean the former , we use thermodynamics to determine the delta G of the reaction and then we can predict whether it is exergonic or endergonic.

The latter is much more complicated ,

you have about 4 main reaction types in chemistry

addition

elimination

substitution

rearrangement

There are archetypes of each type , you can predict what happened by looking at your products whether any of the following occured. Next you have archetypes of each of the four , which you determine by knowing conditions such as temperature , pH media , nature of the reactants (good nucleophile , weak nucleophile) steric factors , electronic factors , resonance forms , regiochemistry , solvent And many more ! You learn about each factor individually and then connect everything and then you can predict the way reactions proceed just by studying your reactants very well and the conditions. It is like having a mind map and making decisions according to the conditions given.

The steps for a chemical reaction can be called the “mechanism”, or the “reaction pathway.” I’m sure that there are other terms that some people use.

There are myriad ways that chemical reactions may take place that involve reactions between different molecules or the same molecules, or with molecules of intermediate compounds, or with catalysts.

A hypothetical reaction of A and B in the presence of Q, a catalyst,

2A + B → C

A + Q → X
B + X → Y
A + Y → C + Q
———————
2A + B → C

Q is a catalyst. It is a reactant in an early step and a product in a subsequent step. X and Y are intermediates.

But of course that is only one mechanism. There may be others.
A + A → X
X + Q → Y
B + Y → C + Q
———————
2A + B → C