Reactive Intermediates

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[A--B]≠

Reactive intermediates are molecular entities with lifetimes appreciably longer than a molecular vibration, formed during the conversion of reactants to products for a chemical reaction. Examples of reactive intermediates are reactive oxygen species (including hydroxyl radical, superoxide radical anion, and hydroperoxyl radical), carbenes, and nitrenes. Study of these transient species not only provide detailed understanding of the potential energy surface for the specific reaction, but also find numerous applications in fields such as organic synthesis, photo-lithography, photo-crosslinking and photoaffinity labeling. Potential energy surfaces (PES) for the hypothetical reaction A + B → D, via two different pathways is shown in the figure. The upper surface indicates the formation of a metastable complex [A--B]≠, known as the transition state, which is a saddle point in the PES. The lower surface shows that a transient species C is formed through a transition state TS-1, which yields the product D, via transition state TS-2. Species C is an example of a reactive intermediate.

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1. Moss, R. A.; Platz, M.; Jones, M., Reactive intermediate chemistry. Wiley-Interscience: Hoboken, N.J., 2004

2. Platz, M.; Moss, R. A.; Jones, M., Reviews of reactive intermediate chemistry. Wiley ; Chichester : John Wiley : Hoboken, N.J., 2007.

3. Wentrup, C., Reactive molecules : the neutral reactive intermediates in organic chemistry. Wiley: New York ; Chichester, 1984.

4. Knipe, A. C.; Watts, W. E., Organic reaction mechanisms 1998. Wiley: New York ; Chichester, 2003.

5. Orchin, M., The vocabulary and concepts of organic chemistry. 2nd ed. / Milton Orchin. ed.; Wiley: Hoboken, N.J., 2005.

References

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Key Question

What is the mechanism for these reactions?

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Automerization of Naphthalene (The Cume Question from Hell!)

Provide a Mechanism for this Transformation

Evidence of early (1944) research on methylene. CH2 by D. Duck. (As unearthed by Professors P. P. Caspar and G. S. Hammond of the California Institute of Technology.) 6

A generic name for an uncharged species containing a dicovalent carbon atom. Because this carbon atom is surrounded by a sextet rather than an octet of valence electrons, it is electron-deficient and, hence, is electrophilic.

Example. Singlet dichlorocarbene (Fig. a); triplet dichlorocarbene (Fig. b); and singlet methylenecarbene (Fig. c).

CARBENE, R2C:

Definition

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Organometal carbenes are a class of organometal complexes involving a divalent carbon atom doubly bonded to a transition metal and are called carbenes, Carbenes are involved in many types of reactions, for example, metathesis reactions and the Wolff rearrangement.

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METHYLENE

The one specific carbene that has the molecular formula :CH2. The carbene, methylene, should be distinguished from the dicovalent methylene group - CH2- involving tetravalent carbon, which occurs in an infinite number of real and possible compounds as well as the carbon atom of a C-terminal double bond, CH2.

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SINGLET CARBENE

A carbene that has an electron spin multiplicity of 1 (no unpaired electrons). Example. Singlet methylene (Fig. a) and singlet phenylcarbene (Fig. b). The pair of nonbonding electrons occupies a single sp2 orbital. The empty p orbital is responsible for the singlet carbene’s electrophilic character as illustrated in the reaction with olefins, (Fig. c.)

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TRIPLET CARBENE

A carbene that has an electron spin multiplicity of 3 (two unpaired electrons). Example. Triplet methylene (Fig. a) and triplet methylcarbene (Fig. b)(ground-state triplets). In the ground-state triplets, the unpaired electrons occupy separate sp3 orbitals, The HCH angle is approximately 136°.

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CARBENOID SPECIES

A species that, when undergoing reaction, has the characteristics of a carbene, but in fact is not a free carbene. Example. The carbenoid species, iodomethylzinc iodide , reacts with ethylene to yield the same product, cyclopropane, as the reaction of ethylene with methylene, a free carbene.

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A carbene in which at least one of the groups attached to the dicovalent carbon atom is an acyl group. Example. Acetylcarbene

α-KETOCARBENE, RC(O)-C-R ..

Synonymous with α-ketocarbene.

ACYLCARBENE

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This is an uncharged species containing a monocovalent nitrogen atom; this nitrogen is surrounded by a sextet of valence electrons and hence is electron-deficient and, like carbene, acts as an electrophile. Nitrenes, like carbenes, can exist in two spin states, singlet and triplet, with the latter as the lower-energy ground state. Example. Phenylnitrene Low-temperature (77 K) matrix studies of the ultraviolet spectrum of triplet phenylnitrene show: absorption bands between 300 and 400 nm, and the ESR spectrum suggests delocalization of a single electron into the ring.

NITRENE R-N .. ..

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This is a nitrene in which an acyl group is attached to the monocovalent nitrogen atom; it is analogous to an α-ketocarbene. Nitrenes are intermediates in a variety of reactions, for example, the Curtius reaction, Hofmann degradation, Schmidt degradation, and Lossen reaction. All these reactions lead to the formation of isocyanates and are thought to proceed through reactive intermediate acyl nitrenes. Example. Benzoylnitrene and its rearrangement

ACYL NITRENE RC(O)-N .. ..

α-KETONITRENE

Synonymous with acyl nitrene. 15

1862: The idea that carbenes can be liberated from chloroalkanes was formulated by Geuther (Ann. 1862, 123, 121): 1876: Reimer-Thieman reaction (Ber. 1876, 9, 423): Verification of the mechanism by J. Hine and W. von E. Doering (JACS 1949, 2438; JACS 1954, 6162)

1. History

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1896: Stieglitz invokes nitrenes in the Curtius rearrangement (JACS 1896, 18, 751) 1903, E. Buchner (Ber. 1903, 36, 3509): Simmons-Smith reaction (JACS 1959, 4256)

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• the History of the Singlet-Triplet Gap

Method Author HCH Ground

State S-T Splitting (Kcal/mol)

1932 Intuitive Qual. mullikan 90-109° singlet

1947 Thermochem Walsh 180° triplet Year small

1957 Extended Huckel Gallup 160° triplet 30

1969 ab initio Harrison 138° triplet >33.4

1971 Kinetics Hase –– triplet 8–9

1971 SCF Pople 132° triplet 37

1974 MINDO/3 Dewar 134° triplet 8.7

1976 Expt(photoelec. Detach.) Lineberger 138° triplet 19.5

1976 Ab initio Schaeffer ––– triplet 19.7

1978 Expt(photolysis of ketene) Zare ––– triplet 8.1

1982 Expt(Mol. Beam exp.) Haydon ––– triplet 8.5

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