Lecture 5 Flashcards
Describe the mechanism of the photo activated reaction between enones and alkenes
- stepwise
- diradical intermediates
- The mechanism begins with enone excitation to the singlet state, which quickly decays to the triplet state via ISC before forming an exiplex with the alkene. The expilex is a triplet diradical that decays to the singlet state and forms a cyclobutane ring
- Alternatively after the ISC the radical anion and radical cation are formed and recombine to form the product
- can form head to head or head to tail products depending on sterics and electronic factors
Why are photochemical reactions hard in bulk?
- In order to proceed the reaction must absorb light, which is hard in the bulk due to the penetration of light into solution
- As the distance the light has to penetrate increases the absorbtion decreases rapidly according to the Beer-Lambert Law
- Absorbance is proportional to the extinction coefficient, concentration and path length of the sample
- If light penetration to the surrounding solution is limited by the high absorption of the substrate it falls off rapidly with distance from the lamp
How can Flow benefit photochemistry
- under flow only a small amount of the solution ‘sees’ the UV light at once, leading to very efficient absorbtion
- The UV exposure time can be controlled by flow rate and reactor volume, solving both under and over radiated reaction problems seen in batch
- As a continuous flow device is scale independent, a single reactor can in principle be used to process a few milligrams of substrate up to nearly a kilogram per day (see macroreactors).
- at much shorter path lengths, higher concentrations can be irradiated
- Large volumes of very low concentration solutions can be irradiated. This is particularly useful for reactions with competing intermolecular side reactions, e.g., dimerisation and polymerisation.
- The photolysate can be concentrated by continuous evaporation and the solvent recycled with the starting material. This can cut down the solvent footprint, particularly in dilute reactions where large volumes of solvent would be required to process quantities of substrate.
- Safety. By allowing the bulk solution to be kept remote from the lamp, only a minimal amount of flammable solvent is near a potential ignition source at any one time.
What is the design of a micro flow system?
- fabricated micro-channels and range from bespoke “lab- on-a-chip” designs engineered in glass and metal systems.
- Channels less than 1 mm in thickness and typical throughput flow rates range from a few microliters up to 1 mL per minute.
What is the design of a macro flow system for photochemical reactions
• Macroflow systems. These devices generally involve UV-transparent tubing (>0.5 mm, i.d.) wrapped around a high-power UV source and have flow rates usually greater than 1 mL/min (Figure 4).
Advantages of macro flow systems
• The main advantage at present of the flow photochemical reactors is the control over reaction conditions they can offer. The precisely engineered channels can be made shallow enough to ensure uniform irradiation of concentrated or strongly absorbing solutions.
- Temperature control is also more effective than in larger systems offering the possibility of studying photochemistry outside the normal range.
- The most efficient method of capturing the maximum number of photons, and hence to maximise productivity, is to construct the reactor around the lamp.
- These reactors can easily be constructed using cheap, readily available materials.
Why is the synthesis of artimisin hard?
- Transformation of artemisinic acid to artemisinin involves a series of challenging steps. - - The reaction sequence starts with the reduction of artemisinic acid to the corresponding dihydroartemisinic acid. Reaction between 2 and singlet oxygen gives rise to the formation of tertiary allylic hydroperoxide 3. Then 3 is treated with trifluoroacetic acid to promote the Hock cleavage of the hydroperoxide, followed by migration of the allyl functional group and opening of the ring to enol 4.
- The highly reactive enol 4 reacts with triplet oxygen to generate hydroperoxide 5.
- Finally, a series of condensation reactions generate the three missing rings of artemisinin.
- The crucial step in the transformation requires singlet oxygen, a photochemically generated, highly reactive molecule that must be prepared in situ.
Why is the synthesis of artemisinin unsuitable for batch reactions?
• Problems with the bulk reaction include safety implications (fires and explosions), inefficient irradiation of bulk solution and short singlet oxygen lifetimes meaning long irradiation times
How can flow improve this reaction?
- The reaction was completed so that gas-liquid segments of the biphasic mixtures allows a large surface area of reactant to be exposed to oxygen
- Oxygen concentration was also increased by increasing pressure to 6.9 Pa using a back flow regulator
- Enables a safe, controlled reaction of oxygen and efficient irradiation
- Allows a yield of this stemp of 75%
What causes microwave irradiated chemical transformations
bulk thermal phenomena associated with rapid heating to elevated temperatures
Why is the synthesis of tetrazole hard>
- The formation of the tetrazole nucleus involves the direct addition of hydrazoic acid (HN3) to organic nitriles – this is the most direct way to form tetrazoles
- Unfortunately, HN3 is extremely toxic (comparable to HCN) and owing to the explosive nature and low boiling point (37 oC)
- procedures involving free HN3 have not found any practical application in tetrazole synthesis so far.
How does flow chemistry improve the synthesis of tetrazoles?
- Continuous flow synthesis of 5-substituted 1H-tetrazole derivatives via addition of HN3 to organic nitriles.
- Key to this process is the in situ generation of HN3 from NaN3 and acetic acid in a microreactor coupled to an intensified high-temperature/high-pressure flow addition step to the nitrile.
- residence times of a few minutes
- excellent purities and yields of isolated product.
