Rauk Orbital Interaction Theory of Organic Chemistry

EXERCISES 299

…a†

…b†

Figure B15.1. (a) Intermediate diradical. (b) State correlation diagram for the Norrish Type II reaction.

(a)Provide an analysis of the photoreduction of benzophenone to benzpinacol in isopropyl alcohol (the reaction you carried out in the laboratory). What was the photoreactive state for the reaction? What was the e¨ect of added naphthalene and why did it have this e¨ect?

(b)A characteristic of the photochemistry of cyclohexadienones is cleavage of the CÐC bond next to the carbonyl, as shown below for 2,2-dimethyl-2,4-cyclo- hexadienone. Develop a Dauben±Salem±Turro state correlation diagram for the photochemical step shown and, on the basis of your diagram, discuss the e½ciency of the reaction on the singlet and triplet manifold [see also question 1(d)].

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4.This question involves the analysis of carbonyl photochemistry using Dauben± Salem±Turro state correlation diagrams.

(a)2,4-Di-t-butylbenzophenone yields the benzocyclopentanol 2 upon photolysis. An intermediate diradical is involved. Show the structure of the intermediate diradical. Develop a Dauben±Salem±Turro state correlation diagram for the photochemical step and, on the basis of your diagram, discuss the e½ciency of the reaction on the singlet and triplet manifold.

5.Photolysis of a-chloro-o-methylacetophenones yields 1-indanones. The mechanism has been studied by laser ¯ash photolysis (Netto-Ferreira, J. C.; Scaiano, J. C., J. Am. Chem. Soc., 1991, 113, 5800). Develop a Dauben±Salem±Turro state correlation diagram for the photochemical step and, on the basis of your diagram, discuss the e½ciency of the reaction on the singlet and triplet manifold. Do the experimental results agree with your analysis?

6.The photochemistry of 1,5-hexadien-3-ones has been examined by Dauben and coworkers. A relatively rare dependence of the intramolecular enone±ole®n photoaddition of several derivatives has been observed. Discuss the mechanistic possibilities in terms of Dauben±Salem±Turro state correlation diagrams. (See Dauben, W. G.; Cogen, J. M.; Ganzer, G. A.; Behar, V., J. Am. Chem. Soc., 1991, 113, 5817.)

7.The mechanism of photoenolization in 1-methylanthraquinone has been studied in detail (Gritsan, N. P.; Khmelinski, I. V.; Usov, O. M., J. Am. Chem. Soc., 1991, 113, 9615). The reaction was found to occur in both the singlet and triplet …np † states. Develop a Dauben±Salem±Turro state correlation diagram for the photochemical step and, on the basis of your diagram, discuss the e½ciency of the reaction

EXERCISES 301

on the singlet and triplet manifold. Do the experimental results agree with your analysis?

8.The mechanism of photocyclization of a-(o-tolyl)acetophenones has been explored [(a) Wagner, P. J.; Meador, M. A.; Zhou, B.; Park, B.-S., J. Am. Chem. Soc., 1991, 113, 9630. (b) Wagner, P. J.; Zhou, B.; Hasegawa, T.; Ward, D. L., J. Am. Chem. Soc., 1991, 113, 9640]. Develop a Dauben±Salem±Turro state correlation diagram for the photochemical step and, on the basis of your diagram, discuss the e½ciency of the reaction on the singlet and triplet manifold. Do the experimental results agree with your analysis?

Miscellaneous

1.Using orbital interaction theory wherever appropriate, discuss the chemistry of the diazenium dication of 2,7-diazatetracyclo[6.2.2.23;602;7]tetradecane 12B (see Nelsen, S. F.; Wang, Y., J. Am. Chem. Soc., 1991, 113, 5905).

2.Discuss the mechanism of action of brewer's yeast pyruvate decarboxylase using orbital interaction theory wherever appropriate. For the mechanism, see Zeng, X.; Chung, A.; Haran, M.; Jordan, F., J. Am. Chem. Soc., 1991, 113, 5842.

Answer. The mechanism of pyruvate decarboxylase involves use of the cofactor thiamine pyrophosphate TPP (called thiamine diphosphate; TDP in the reference) which contains the thiazolium ring. It is shown in Figure B.1. Each of the ®ve steps involves some aspect that can be addressed by orbital interaction theory. In step 1, a zwitterionic carbanion is generated. This may alternatively be regarded as a carbene (not zwitterionic at all!) stabilized by two X:-type substituents. Such carbenes are nucleophilic, as we have seen in Chapter 7. In step 2, nucleophilic attack occurs at the keto carbonyl group. The principles governing carbonyl reactivity were discussed in Chapter 8. Alternatively, an SHMO calculation reveals that pyruvate has a very low LUMO …a ‡ 0:266jbj† and the largest coe½cient of the LUMO is at this carbon atom (0.60 vs. 0.39 at C1). Loss of CO2 in step 3 is facile if the CÐC bond can adopt a position perpendicular to the plane of the ring, since then overlap with the highly polarized and low LUMO of the aminium group is maximized and electron transfer can occur. The resulting species, shown as a zwitterionic carbanion, may also be viewed as a neutral enolamine, which by SHMO is seen to have a very high HOMO …a ÿ 0:471jbj† and the largest coe½cient on the carbon shown as being protonated by the enzyme in step 4. E2 elimination of acetaldehyde in step 5 is possible if the CÐC bond and OH bonds can adopt a coplanar arrangement.

3.Allylic acetals rearrange under acid catalysis to produce tetrahydrofurans.

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Figure B.1. Mechanism for the conversion of pyruvic acid to acetaldehyde and CO2 by pyruvate decarboxylase.

The mechanism has been shown to involve a cyclization step followed by a pinacol rearrangement (Hopkins, M. H.; Overman, L. E.; Rishton, G. M., J. Am. Chem. Soc., 1991, 113, 5354; see also Bach et al., p. 5365, and Woods et al., p. 5378, mentioned in questions 4 and 5, respectively). Provide a detailed mechanism for the reaction and discuss features of the steps and intermediates from the point of view of orbital interactions.

4.The mechanism of oxidation of amines by hydrogen peroxide has been investigated theoretically (Bach, R. D.; Owensby, A. L.; Gonzalez, C.; Schlegel, H. B.; McDouall, J. J. W., J. Am. Chem. Soc., 1991, 113, 6001) and has been shown to be analogous to an SN2 attack by nitrogen on the OÐO bond with simultaneous transfer of hydrogen. Compare the ab initio results of Bach et al. to expectations based on orbital interaction theory.

5.The mechanism of epoxidation of ole®ns by peroxyacids has been probed by an ``endocyclic restriction test'' (Woods, K. W.; Beak, P., J. Am. Chem. Soc., 1991, 113, 6281):

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Figure B.2. (a) Orbital interactions for a nucleophilic attack by pCC on sOO. (b) 1,3 Dipolar addition to alkene.

It was established that the oxygen transfer takes place via an SN2-like transition state (a), rather than a pathway which resembles a 1,3-dipolar addition (b). Comment on the relative merits of the two transition states using principles of orbital interaction theory. A spiro structure similar to (a) for the transition state has been located by ab initio calculations (Bach, R. D.; Owensby, A. L.; Gonzalez, C.; Schlegel, H. B.; McDouall, J. J. W., J. Am. Chem. Soc., 1991, 113, 2338).

Answer. The orbital interaction diagram for path (a) is shown in Figure B.2a. The LUMO of the peracid is the sOO orbital. It is placed near a since the two oxygen atoms are very electronegative. The primary interaction, i, is with the HOMO of the alkene. The perpendicular orientation of the alkene (leading to a spiro transition state) is dictated not by sOO but by the nonbonded orbital on the oxygen of the OH group. In this orientation, a favorable secondary interaction, j, is maximized. Path (a) would be further enhanced by X:- or ``C''-type substituents on the alkene. Path (b) is possible if the proton is transferred to the carbonyl oxygen. The SHMO orbitals of the zwitterionic form are shown in Figure B.2b. It is clear that a 1,3 dipolar cycloaddition mode is also favored since both HOMO±LUMO interactions, k and l, are favored by one large coe½cient. One must conclude that path (b) is not seen due to the low abundance of the tautomeric form of the peracid.

6.The photochemical elimination of H2 from 1,4-cyclohexadiene has been shown experimentally to proceed through a transition state with C2v or C2 symmetry (Cromwell, E. F.; Liu, D.-J.; Vrakking, M. J. J.; Kung, A. H.; Lee, Y. T., J. Chem. Phys.,

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1991, 95, 297). Decide on the basis of orbital and state correlation diagrams whether or not the reaction is photolytically allowed.

7.Predict the structure of the van der Waals complex between ozone and acetylene. Indicate which frontier orbital interactions should be most important. How does your prediction compare with the experimental structure (Gillies, J. Z.; Gillies, C. W.; Lovas, F. J.; Matsumura, K.; Suenram, R. D.; Kraka, E.; Cremer, D., J. Am. Chem. Soc., 1991, 113, 6408)?

8.The laboratory preparation of azulene [(a) Lemal, D. M.; Goldman, G. D., J. Chem. Ed., 1988, 65, 923. (b) Brieger, G., J. Chem. Ed., 1992, 69, A262] involves as a key reagent, dimethylaminofulvene, 2 (R ˆ NMe2), which is used in a reaction with thiophene-1,1-dioxide to assemble the ®nal azulene skeleton. Unsubstituted fulvene, 2 (R ˆ H), is a very reactive compound. It forms a dimer via a cycloaddition reaction in manner entirely analogous to the reaction between dimethylaminofulvene and thiophene-1,1-dioxide.

(a)Show the most likely product of a reaction of fulvene with itself (i.e., the dimerization). Hint: Postulate a transition state for the reaction based on the most favorable interaction of the frontier orbitals, and from it deduce the structure of the most likely product.

(b)Develop a two-orbital interaction diagram for the amino-substituted fulvene, 2 (R ˆ NMe2) (for the purposes of the diagram you may treat the methyl groups as if they were H atoms). Show clearly the relative positions of the initial and ®nal orbitals (recall that for a tricoordinated nitrogen atom, aN ˆ a ÿ 1:37jbj), and sketch the initial and ®nal orbitals in the correct orientation.

(c)Use your orbital interaction diagram to discuss the e¨ect of the dimethylamino group on the reactivity of the fulvene.

9.``Y''-conjugation is often discussed in the literature as a di¨erent kind of ``aroma-

ticity'' because of the prevalence of structures such as NOÿ3 , CO32ÿ, and urea (NH2C(O)NH2). Develop a bonding scheme for the p orbitals of 3, in which A and B can each donate one p orbital to the p system and A is less electronegative than B.

Discuss the optimum number of electrons (two, four, or six). Why is it desirable that A is the less electronegative element or group? Do BF3 and tert-butyl cation ®t the pattern? Hint: The compound has threefold symmetry and some MOs will be degenerate.

10.Predict the structure of the van der Waals complexes between BF3 and CO. Both 1 : 1 and 1 : 2 complexes have been observed (Sluyts, E. J.; van der Veken, B. J., J. Am. Chem. Soc., 1996, 118, 440±445) by IR spectroscopy in liquid argon and

EXERCISES 305

enthalpies of complexation determined (ÿ7:6 and ÿ14:5 kJ/mol, respectively). Why is it reasonable that the second CO binds almost as strongly as the ®rst?

11.Dative bonded complexes between alane (AlH3) and amines have long been known. Complexes with one and two amines are common. For example, bis-(trimethylamine) alane, AlH3(N(CH3)3)2, is a white crystalline solid with a low vapor pressure. Using ammonia as a model for trimethylamine, apply orbital interaction analysis to describe the bonding in the 1 : 1 and 1 : 2 complexes. Theoretical studies on the ammonia complexes of AlH3 have led to the conclusion that there is little dative bonding (as judged by the amount of charge transfer) (Marsh, C. M. B.; Schaefer III, H. F., J. Phys. Chem., 1995, 99, 14309±14315). Comment on the theoretical results.

12.Use orbital interaction diagrams to explain each of the following (show the orbitals clearly):

(a) Describe the NÐN bond in hydrazinium dichloride, H3N‡ÐN‡H3 2Clÿ.

(b) Account for the fact that trans-2,5-dichloro-1,4-dioxane 4 preferentially adopts the diaxial conformation (KoritsaÂnszky, T.; Strumpel, M. K.; Buschmann, J.; Luger, P.; Hansen, N. K.; PichonPesme, V., J. Am. Chem. Soc., 1991, 113, 9148). Hint: This is an example of the anomeric e¨ect in operation.

(c)O¨er an explanation for the observation that the lowest ionization potential for the diacetylene 5 (IP ˆ 8.47 eV) is lower than the corresponding IP of 6 (9.13 eV) (Gleiter, R.; Kratz, D.; SchaÈfer, W.; Schehlmann, V., J. Am. Chem. Soc., 1991, 113, 9258).

(d)Show why CÐH bonds next to a carbocationic center are especially acidic and why proton abstraction yields ole®ns.

R2C‡ÐCHR2 ‡ B: ! R2CÐCHR2 ‡ ‡BÐH (B: a weak base)

13.The mechanism for the oxidative photofragmentation of a; b-amino alcohols is consistent with a preference for anti geometry in the cleavage step (Ci, X.; Kellett, M. A.; Whitten, D. G., J. Am. Chem. Soc., 1991, 113, 3893). Provide a rationalization based on the frontier orbitals of the system.

14.Carboxylic acids may be converted to alkyl bromides with the loss of one carbon atom by the Hunsdiecker reaction:

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The mechanism is a free-radical chain reaction which is believed to involve the following steps:

The reaction is initiated in step 2 and propagated by steps 3 and 4. Analyze each of the steps of the Hunsdiecker reaction in terms of simple orbital interaction theory.

(a)Using a two-orbital interaction diagram, show the interaction which results in the formation of the bromoxy acid, 7, and displacement of bromide ion in step 1.

(b)Use an appropriate orbital interaction diagram to describe the OÐBr bond of 7, which ruptures upon heating in step 2. Why is it feasible that this is the weakest bond in this compound?

(c)Show the electronic structure of the acyloxy free radical, 8, which is produced in step 2. Is it a s or p radical? Hint: You may wish to construct the MOs of 8 from the interaction of two monocoordinated oxygen atoms, bearing in mind the local symmetry of the carboxylate group.

(d)Use your bonding description from part (b) to explain why the alkyl radical should attack at the Br atom of 7 and not at some other site in step 4.

Answer

(a)This is a simple nucleophilic substitution on Br2. The BrÐBr s-type interaction is very weak, and as a consequence, the LUMO …sBrBr† is low in energy. The interaction is of the two-electron, two-orbital type, the other orbital being the HOMO of the carboxylate group, the out-of-phase combination of the in-plane nonbonded orbitals of the oxygen atoms [p2 will be a little lower; see part (c)].

(b)The s bond of the bromoxy acid is very weak because of the poor intrinsic interaction between a 2p orbital and a 4p orbital.

(c)The interaction diagram for the carboxylate group is shown in Figure B.3. Be-

cause the in-plane p orbitals …ps† overlap more strongly than the out-of-plane orbitals …pp†, the HOMO of the carboxylate anion will be a s orbital, and the neutral carboxylate free radical is predicted to be a s radical.

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Figure B.3. The MOs of a carboxylate anion and free radical. The dashed lines indicate the result of interaction with the central carbon 2p orbital.

(d)To understand why the Br atom is abstracted, we must realize that bromine is

less electronegative than oxygen. Therefore the LUMO which is the sBrO orbital is polarized toward Br. Since the alkyl radical SOMO is high in energy (i.e., at a), the SOMO±LUMO interaction will be more important than any interaction with the occupied orbitals.

15.Reductive decyanations of 2-cyanotetrahydropyran derivatives with sodium in ammonia yield predominantly axially protonated products. The observations are consistent with the reductive decyanation proceeding via the pyramidal, axial radical which accepts a second electron to give a con®gurationally stable carbanion, which in turn abstracts a proton from ammonia with retention of con®guration (Rychnovsky, S. D.; Powers, J. P.; LePage, T. J., J. Am. Chem. Soc., 1992, 114, 8375± 8384). Provide an explanation for the axial preference of the intermediate free radical on the basis of orbital interactions. Hint: The title of the paper by Rychnovsky et al. is ``Conformation and Reactivity of Anomeric Radicals.''