Photochemistry of Carbonyl Compound, Norrish type I and Type II Reaction

The homolytic cleavage of covalent bonds in carbonyl compound under photochemical conditions known as Norrish Type Reactions

They are divided into two types
Norrish Type I
Norrish Type II reaction

1. 20/01/2021 1 Presented By Nilesh S. More Department of Medicinal Chemistry MC/2019/14 राष्ट्रीय औषधीय शिक्षा एवं अनुसंधान संस्थान (नाईपर), हैदराबाद National Institute of Pharmaceutical Education and Research (NIPER), HYDERABAD Photochemistry of Carbonyl Compound, Norrish type I and Type II Reaction

2. 20/01/2021 2

3. Carbonyl compounds undergo various photochemical reactions in both gas and liquid phases. Carbonyl compound are best suited for Photochemical reactions because ketones are much stable and undergo no. of interesting reactions The initiation of a photochemical reaction depends on the capacity of reactant(s) to absorb the light from an emitting source. The light photon-energy must match with the energy necessary to excite one electron from HOMO to LUMO of a ground state molecule - a quantized process - to its excited state INTRODUCTION 20/01/2021 3 Dantas JA. Photochemistry of Carbonyl Compounds: Application in Metal‐Free Reactions . ChemPhotoChem . 2019 Jul;3(7):506-20.

4. It involves an n →π* excitation of an oxygen lone pair electron (n) to the π* lowest unoccupied molecular orbital of the C ═ O chromophore excitation is from the S0 electronic ground state to the first singlet excited state, S1, which correlates to excited state products Dissociation on both T1 and S0 leads to ground-state radical products Internal conversion (IC) from S1 or two ISC steps, S1 → T1 → S0, can also lead to photolysis on the S0 ground state ISC is spin forbidden, the geometries of S1 and T1 excited-state carbonyls are generally very similar, and the energy separation between the states is small, leading to fast S1 → T1 ISC rates 20/01/2021 4 Rowell KN. Structural Effects on the Norrish Type I α-Bond Cleavage of Tropospherically Important Carbonyls. The Journal of Physical Chemistry A. 2019 Nov 1;123(48):10381-96.

5. The reactive excited states of saturated ketones are the n → π* states, whereas that of conjugated ketones are π → π* states. Both these n → π* and π → π* transitions of carbonyl compounds may occur by singlet or triplet excited states Both singlet and triplet excited states of a carbonyl compound react in different rates to give same type of products in different ratios. Saturated ketones, the activation energies for singlet and triplet excited states are about 80–85 and 75–80 kcal/mol, respectively, and hence require UV light of wavelengths of about 270–280 nm (near-UV region) for conjugated ketones, the activation energy for singlet and triplet excited states is below 80 kcal/mol, in the range 45–78 kcal/mol, and require light in the far-UV region (310–330 nm). 20/01/2021 5 Rowell KN. Structural Effects on the Norrish Type I α-Bond Cleavage of Tropospherically Important Carbonyls. The Journal of Physical Chemistry A. 2019 Nov 1;123(48):10381-96.

6. DIFFERENT TYPES OF PHOTOCHEMICAL REACTIONS OF CARBONYL COMPOUNDS 20/01/2021 6

7. 20/01/2021 7 NORRISH TYPE REACTION Kirkbride and Norrish identifying α-bond cleavage as the dominant photolysis pathway in small carbonyls in 1931 The homolytic cleavage of covalent bonds in carbonyl compound under photochemical conditions known as Norrish Type Reactions They are divided into two types Norrish Type II Norrish type I Rowell KN. Structural Effects on the Norrish Type I α-Bond Cleavage of Tropospherically Important Carbonyls. The Journal of Physical Chemistry A. 2019 Nov 1;123(48):10381-96.

8. 20/01/2021 8 Norrish Type I The Norrish type I reaction is the photochemical cleavage or homolysis of aldehydes and ketones into two  free radical  intermediates The carbonyl group accepts a photon and is  excited  to a photochemical  singlet state Light energy is sufficient to break the alpha bond Through intersystem crossing the triplet state can be obtained On cleavage of the α-carbon carbon bond from either state, two radical fragments are obtained which are alkyl or acyl radicle

9. 20/01/2021 9 Distinctive Features of Norrish type I reaction Reaction intermediates are free radicals – acyl, alkyl Reaction proceeds to form more stable free radicle Reaction is more effective on vapour state The SP 2 and SP nature of alpha carbon never participated in Norrish Type I reaction Compound which are formed stable free radicals undergoes Norrish Type I reaction even in Liquids state

10. 20/01/2021 10 Reaction Mechanism

11. 20/01/2021 11 Norrish Type II reaction Photochemical reaction of aldehydes or ketones bearing γ –hydrogens An aldehyde or ketone bearing a γ -hydrogen atom can upon irradiation undergo an intramolecular hydrogen shift by the so-called Norrish type II reaction The resulting diradical species can undergo a subsequent ring closure reaction to yield a cyclobutanol, or suffer fragmentation to yield an enol and an alkene γ -hydrogens can undergo the intramolecular hydrogen abstraction from the singlet excited (S1)-state as well as the triplet excited (T1)-state β, γ – carbon always converted to olefins

12. 20/01/2021 12 Norrish type II reactions are very limited in carbonyl compound In Norrish type II reaction there are possibilities of formation of cyclobutanol derivative as by product

13. 20/01/2021 13 Reaction Mechanism

14. 20/01/2021 14 Distinctive Features of Norrish type II reaction [ n- π *] 1 & [ n- π *] 3 give rise to γ-hydrogen transfer However, the singlet & triplet reactions are quit distinguishable Photochemical elimination is highly stereospecific when intermediate biradical is [ n- π *] 1 Photochemical elimination is non-stereoselective when biradical intermediate is [ n- π *] 3

15. 20/01/2021 15 Stabilization of 1,4- biradical It may undergo photo-elimination & form Olefins / Enols It may directly cyclize & form cyclobutanol by- product derivative It may convert into starting material which may due to reversible formation of 1,4- biradical

16. 20/01/2021 Liu W, Li CJ. Recent synthetic applications of catalyst-free photochemistry . Synlett . 2017 Dec;28(20):2714-54. 16 N.T.- I reaction in total synthesis of Herbertenolide Disubstituted cyclohexanone converted into substituted cyclopentane using N.T.-I reaction Reaction is successful due to high stability of radical intermediate of N.T.-I reaction APPLICATIONS

17. 20/01/2021 17 N.T.- II reaction in total synthesis of oubagenin N.T.-II reaction selectively activate remote methyl group Increase over-all product yield Liu W, Li CJ. Recent synthetic applications of catalyst-free photochemistry . Synlett . 2017 Dec;28(20):2714-54.

18. 20/01/2021 18 Β -lactam synthesis from α -amino acid via photolysis Carried out by photo-wolf-rearrangement Generated ketene reacts with amine group without altering stereochemistry Liu W, Li CJ. Recent synthetic applications of catalyst-free photochemistry . Synlett . 2017 Dec;28(20):2714-54.

19. 20/01/2021 19 Total synthesis of lineatin Under UV irradiation cycloadducts is formed by reacting furanone with 1,2-dichloroethylene The cycloadduct then converted to (+)- lineatin by functional group manipulation. Liu W, Li CJ. Recent synthetic applications of catalyst-free photochemistry . Synlett . 2017 Dec;28(20):2714-54.

20. CONCLUSION Photochemically mediated reactions have proven to be highly useful for construction of highly strained and complex molecular frameworks that can otherwise be challenging to access via conventional processes. In the future, it can also be used to expand our classical chemical toolbox by offering improved reaction conditions and can facilitate the discovery of new transformations for efficient bond construction.

21. 20/01/2021 21 REFERENCE Dantas JA, Correia JT, Paixão MW, Corrêa AG. Photochemistry of Carbonyl Compounds: Application in Metal‐Free Reactions. ChemPhotoChem . 2019 Jul;3(7):506-20 Rowell KN, Kable SH, Jordan MJ. Structural Effects on the Norrish Type I α-Bond Cleavage of Tropospherically Important Carbonyls. The Journal of Physical Chemistry A. 2019 Nov 1;123(48):10381-96. Liu W, Li CJ. Recent synthetic applications of catalyst-free photochemistry. Synlett . 2017 Dec;28(20):2714-54. Laue T, Plagens A. Named Organic Reactions 2nd Edition. https://www.chemeurope.com/en/encyclopedia/Norrish_reaction.html#_ref-0/

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