Posts Tagged ‘diazo’

Are diazomethanes hypervalent molecules? An attempt into more insight by more “tuning” with substituents.

Tuesday, December 26th, 2017

Recollect the suggestion that diazomethane has hypervalent character[1]. When I looked into this, I came to the conclusion that it probably was mildly hypervalent, but on carbon and not nitrogen. Here I try some variations with substituents to see what light if any this casts.

I have expanded the resonance forms of diazomethane by one structure from those shown in the previous two posts (a form by the way not considered in the original article[1]) to include a nitrene. This takes us back to an earlier suggestion on this blog that HC≡S≡CH is not a stable species but a higher order saddle point which distorts down to a bis-carbene, together with the suggestion that hypervalent triple bonds have the option of converting four of the six electrons into two carbene lone pairs, replacing the triple bond with a single bond. This in turn harks back to G. N. Lewis’ 101 year old idea for acetylene itself!

To explore this mode, I start by replacing the terminal ≡N in diazomethane with a ≡C-Me group, which cannot absorb electrons into lone-pairs in the manner that nitrogen can. A ωB97XD/Def2-TZVPP calculation‡ reveals that the linear form is a transition state for interconversion into a carbene. The IRC for the process (below) shows this carbene is ~10 kcal/mol lower than the linear “hypervalent” form. 

NBO analysis of this transition state reveals a similar orbital pattern to diazomethane itself, including a non-bonding orbital on the H2C carbon. The Wiberg carbon bond indices are 3.6764 and N 3.6454 and the bond orders C=N 1.1390 and N=CMe 1.6192.

ELF analysis of this transition state reveals the presence of two non-bonding pairs on the carbon atoms either side of the nitrogen but unshared with it, with populations of 1.19e and 1.37e (DFT). That nitrogen really does not like excess electrons! The four atoms C,N,C,C have ELF valence basins totalling 8.00, 6.94, 7.69 and 7.92e (DFT) or 8.07, 7.07 and 7.61e (CASSCF), suggesting that unlike diazomethane itself, the octet-excess induced hypervalence on carbon is slightly decreased.

Pumping even more electrons in by replacing the ≡C-Me group with ≡C-NH2 does not increase any hypervalence, but does induce more electrons to reside in “lone pairs”. Of the four atoms along the chain, three have “lone pairs” associated with them, a total of 4.83e that do not contribute to bonds (valence).

An electron withdrawing ≡C-CN group replacing the ≡C-NH2 reverses the effect of the latter, but this linear species is still a transition state for carbon isomerisation:

Finally, combining all we have learnt by adding in nitro groups on the first carbon. This is no longer a transition state but now a stable species; the sum of the ELF basin integrations around the carbon on the left reaches 8.95e, slightly higher than the dinitro-diazomethane discussed in the previous post. The numerical Wiberg atom bond indices are C 3.8713, N 3.6898, C 3.8503, C 3.9958 and N 3.0288 for the atoms along the chain, with the first nitrogen the “least-valent”.

So we see that “hypervalence”, or at least “octet-excess”, which is not exactly the same as hypervalence since it includes contributions from non-bonding electrons, is balanced on a knife-edge. Trying to increase the octet-excess by pumping electrons in turns the system into a transition state for carbene formation. Octet-excess is seen as a metastable property, to be relieved by geometric distortions where possible or localization of electrons into non-bonding lone pairs. And I remind yet again that no evidence has manifested in calculations of the molecules above that the central nitrogen of these diazomethane-like systems has any propensity for octet or valence-excess as implied by the formula C=N≡X.[1]

‡FAIR data for all calculations is available at DOI: 10.14469/hpc/3476

References

  1. M.C. Durrant, "A quantitative definition of hypervalency", Chemical Science, vol. 6, pp. 6614-6623, 2015. https://doi.org/10.1039/c5sc02076j

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Are diazomethanes hypervalent molecules? An attempt into more insight by more "tuning" with substituents.

Tuesday, December 26th, 2017

Recollect the suggestion that diazomethane has hypervalent character[1]. When I looked into this, I came to the conclusion that it probably was mildly hypervalent, but on carbon and not nitrogen. Here I try some variations with substituents to see what light if any this casts.

I have expanded the resonance forms of diazomethane by one structure from those shown in the previous two posts (a form by the way not considered in the original article[1]) to include a nitrene. This takes us back to an earlier suggestion on this blog that HC≡S≡CH is not a stable species but a higher order saddle point which distorts down to a bis-carbene, together with the suggestion that hypervalent triple bonds have the option of converting four of the six electrons into two carbene lone pairs, replacing the triple bond with a single bond. This in turn harks back to G. N. Lewis’ 101 year old idea for acetylene itself!

To explore this mode, I start by replacing the terminal ≡N in diazomethane with a ≡C-Me group, which cannot absorb electrons into lone-pairs in the manner that nitrogen can. A ωB97XD/Def2-TZVPP calculation‡ reveals that the linear form is a transition state for interconversion into a carbene. The IRC for the process (below) shows this carbene is ~10 kcal/mol lower than the linear “hypervalent” form. 

NBO analysis of this transition state reveals a similar orbital pattern to diazomethane itself, including a non-bonding orbital on the H2C carbon. The Wiberg carbon bond indices are 3.6764 and N 3.6454 and the bond orders C=N 1.1390 and N=CMe 1.6192.

ELF analysis of this transition state reveals the presence of two non-bonding pairs on the carbon atoms either side of the nitrogen but unshared with it, with populations of 1.19e and 1.37e (DFT). That nitrogen really does not like excess electrons! The four atoms C,N,C,C have ELF valence basins totalling 8.00, 6.94, 7.69 and 7.92e (DFT) or 8.07, 7.07 and 7.61e (CASSCF), suggesting that unlike diazomethane itself, the octet-excess induced hypervalence on carbon is slightly decreased.

Pumping even more electrons in by replacing the ≡C-Me group with ≡C-NH2 does not increase any hypervalence, but does induce more electrons to reside in “lone pairs”. Of the four atoms along the chain, three have “lone pairs” associated with them, a total of 4.83e that do not contribute to bonds (valence).

An electron withdrawing ≡C-CN group replacing the ≡C-NH2 reverses the effect of the latter, but this linear species is still a transition state for carbon isomerisation:

Finally, combining all we have learnt by adding in nitro groups on the first carbon. This is no longer a transition state but now a stable species; the sum of the ELF basin integrations around the carbon on the left reaches 8.95e, slightly higher than the dinitro-diazomethane discussed in the previous post. The numerical Wiberg atom bond indices are C 3.8713, N 3.6898, C 3.8503, C 3.9958 and N 3.0288 for the atoms along the chain, with the first nitrogen the “least-valent”.

So we see that “hypervalence”, or at least “octet-excess”, which is not exactly the same as hypervalence since it includes contributions from non-bonding electrons, is balanced on a knife-edge. Trying to increase the octet-excess by pumping electrons in turns the system into a transition state for carbene formation. Octet-excess is seen as a metastable property, to be relieved by geometric distortions where possible or localization of electrons into non-bonding lone pairs. And I remind yet again that no evidence has manifested in calculations of the molecules above that the central nitrogen of these diazomethane-like systems has any propensity for octet or valence-excess as implied by the formula C=N≡X.[1]

‡FAIR data for all calculations is available at DOI: 10.14469/hpc/3476

References

  1. M.C. Durrant, "A quantitative definition of hypervalency", Chemical Science, vol. 6, pp. 6614-6623, 2015. https://doi.org/10.1039/c5sc02076j

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I’ve started so I’ll finish. The ionisation mechanism and kinetic isotope effects for 1,3-dimethylindolin-2 one

Thursday, January 7th, 2016

This is the third and final study deriving from my Ph.D.[1]. The first two topics dealt with the mechanism of heteroaromatic electrophilic attack using either a diazonium cation or a proton as electrophile, followed by either proton abstraction or carbon dioxide loss from the resulting Wheland intermediate. This final study inverts this sequence by starting with the proton abstraction from an indolinone by a base to create/aromatize to a indole-2-enolate intermediate, which only then is followed by electrophilic attack (by iodine).  Here I explore what light quantum chemical modelling might cast on the mechanism.

Indole diazocoupling

The concentration of I3– is used to follow the reaction, given by the expression:  [I3–] = k1[B][indolinone]t – k-1/k2*ln[I3–] + const, where  k2* = k2/715[I–] + k2' , the latter being the rate coefficient for the reaction between the enolate intermediate and I3–. With appropriate least squares analysis of this rate equation,‡ a value for k1 using either 1H or 2H (≡ D) isotopes can be extracted and this gives an isotope effect k1H/k1D of 6.3 ± 0.6. Note that this value does NOT depend on [B]. Here, I am going to try to see if I can construct a quantum mechanical model which reproduces this value.

Indole diazocoupling

  1. Model 1 uses just three water molecules as a proton relay (B3LYP+D3/Def2-TZVP/SCRF=water).
  2. Model 2 uses 2H2O.NaOH solvated by two extra passive water molecules. Since under these conditions, the NaOH is largely ionic, [B] ≡ [OH–]
Model ΔG‡298 (ΔH‡298) kH/kD (298K) DataDOIs
1 28.0 (22.9) 10.3 [2],[3],[4]
2 2.5 (2.8) 4.4 [5],[6],[7]

The plot of rate vs [B] shows[1] that the uncatalysed (water) rate is very slow (intercept passes more or less through zero) and the calculated free energy barrier (28.0 kcal/mol) confirms a slow rate at ambient temperatures. Note in the final (aromatized) product, there is a noticeable hydrogen bond between the 3-carbon and a water molecule (2.14Å). The calculated kinetic isotope effect[8] is substantially larger than observed experimentally for the base catalysed contribution.

Indolineone ionization using 3 water molecules

In the presence of NaOH (standard state = 1 atm = 0.044M), the enthalpy barrier drops very substantially to 2.8 kcal/mol and the free energy to 2.5 kcal/mol. Similar behaviour was noted previously on this blog for the hydrolysis of thalidomide. Although the magnitude of the reduction in barrier in fact implies an extremely fast reaction, recollect that [B]=[OH–] appears in the rate equation  and since its value is very much less than 0.044M, the observed rate is relatively slow.

Indolineone ionization using 3 water molecules + NaOH

The calculated KIE for the hydroxide catalysed mechanism is much smaller that for the water route, but also smaller than is observed. This is a value uncorrected for tunnelling, which given the small barrier might be significant. 

These calculations show how a model for ionization of indolinone can be constructed, and used to e.g. probe the sensitivity of KIE to perturbations induced by ring substituents, which may form the basis of a future post.

‡This is a non-linear equation with kinetics that straddle zero and first order behaviour. In 1972, it was not easily possible to graph such functions in a manner where the slope of a linear plot would yield the rate constant. It was only computers and languages such as Fortran which allowed such non-linear least squares analysis of the rate. In the event, it turned out that the presence of 50% methanol in the mixed aqueous solutions was the cause; in other solvents the kinetics approximated zero order behavour very well.

References

  1. B.C. Challis, and H.S. Rzepa, "Heteroaromatic hydrogen exchange reactions. Part VIII. The ionisation of 1,3-dimethylindolin-2-one", Journal of the Chemical Society, Perkin Transactions 2, pp. 1822, 1975. https://doi.org/10.1039/p29750001822
  2. H.S. Rzepa, "C 10 H 17 N 1 O 4", 2016. https://doi.org/10.14469/ch/191786
  3. H.S. Rzepa, "C 10 H 17 N 1 O 4", 2016. https://doi.org/10.14469/ch/191765
  4. H.S. Rzepa, "C10H17NO4", 2016. https://doi.org/10.14469/ch/191784
  5. H.S. Rzepa, "C 10 H 20 N 1 Na 1 O 6", 2016. https://doi.org/10.14469/ch/191787
  6. H.S. Rzepa, "C 10 H 20 N 1 Na 1 O 6", 2016. https://doi.org/10.14469/ch/191782
  7. H.S. Rzepa, "C10H20NNaO6", 2016. https://doi.org/10.14469/ch/191785
  8. H. Rzepa, "Mechanisms and kinetic isotope effects for the base catalysed ionisation of 1,3-dimethyl indolinone.", 2016. https://doi.org/10.14469/hpc/202

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Janus mechanisms (the past and the future): Reactions of the diazonium cation.

Saturday, December 11th, 2010

Janus was the mythological Roman god depicted as having two heads facing opposite directions, looking simultaneously into the past and the future. Some of the most ancient (i.e. 19th century) known reactions can be considered part of a chemical mythology; perhaps it is time for a Janus-like look into their future.

Reaction of the diazonium cation with cyanide.

The phenyl diazonium ion is often introduced early in most chemistry teaching; it is used to produce spectacularly coloured solutions from colourless starting materials and makes an immediate impression.1 The reaction of this species with cyanide salts often appears in introductory courses of aromatic chemistry as a means of producing aryl cyanides. It entered the text books around a century ago as the Sandmeyer reaction (using copper(I)cyanide, but it is also reported as occurring using more ionic cyanide salts as well).2 The mechanism of the ionic reaction however has been given little attention recently. One common representation is as a unimolecular reaction to lose nitrogen gas forming an arene cation, which is mechanistically then followed by fast quenching with cyanide anion to replace the diazo group with the cyano group.

Computational modelling of such ion-pair reactions has now become possible,3 and is going to be used here to peek into the future. A B3LYP/6-311G(d,p)/SCRF calculation shows a transition state involving C-N cleavage, with an adjacent cyanide ion doing rather more than merely spectating. The dipole moment of the transition state is 11D (in acetonitrile as solvent). The structure shows the ion-pair endeavouring to minimise the charge separation, with the cyanide approaching at a rather different angle from the departing diazo group. This sort of SN2 displacement at an sp2 (as opposed to sp3) carbon centre is mechanistically quite unusual.4 The free energy of activation for this mechanism is calculated as 24.9 kcal/mol, which is slightly worryingly high for what is considered a room-temperature reaction (the same method gave quite reasonable barriers for another ion-pair mechanism3).

Phenyldiazonium cation + cyanide anion; substitution mechanism. Click for 3D

So time to see if all is what it might seem. There are many other mechanisms that might be explored; below is what seems quite a reasonable one, the elimination of the diazo-group with accompanying proton abstraction to form a benzyne. This transition state has an activation free energy of 17.8 kcal/mol, a much more reasonable value for a room temperature reaction. The dipole moment is 17.1D (the reactant ion-pair is 19.7D).

Benzyne mechanism, in acetonitrile solvent. Click for 3D

So could it be that this veritable reaction actually proceeds via a different mechanism from that in the text books? Benzyne would be formed as a very reactive intermediate, and presumably in the presence of cyanide anions, it would react by nucleophilic addition to form benzonitrile, the same product as before. How could this be verified? Well, if the carbon atom carrying the diazonium group were to be labelled as say 14C, the original mechanism would carry all that label at one carbon in the benzonitrile product. But the benzyne mechanism would scramble the label between two carbons. Janus therefore sees the future in the shape of a useful experiment which could be done to distinguish the two alternative mechanisms.

It is also noteworthy that the two alternative transition states have different dipole moments, and so are affected differently by solvent polarity. Thus in water, the activation free energies are respectively (substitution/elimination) 25.1 and 17.9, whilst in benzene as solvent they are much higher: 48.7 and 39.0 kcal/mol. The effect of the solvent upon the structure of the transition state is also considerable. Below is shown the benzyne elimination mechanism as calculated in the non polar benzene as solvent. Note how the proton transfer is much more advanced, and the C…N cleavage is less advanced than in acetonitrile as solvent.

Benzyne transition state, in benzene solvent. Click for 3D

We are seeing something of a revolution here. Gradually, the mechanisms of the reaction library built up over the last 100 years or so are increasingly being explored using quantitative calculations. It seems entirely likely that more surprises will crop up.

  1. At the age of ~12 I was introduced to chemistry via this reaction, an exposure at least in part why almost 50 years later I am still doing chemistry and why I write this blog.
  2. Kazitsyna, L. A.; Gruzdneva, V. N. Vestnik Moskovskogo Universiteta, Seriya 2: Khimiya, 1975, 16, 331-7.
  3. The ion-pair mechanism of the racemisation of iso-bornyl chloride, another ancient and almost mythological reaction, has recently been studied in this manner; J. Kong, P. v. R. Schleyer and H. S. Rzepa, “Successful Computational Modeling of Iso-bornyl Chloride Ion-Pair Mechanisms”, J. Org. Chem., 2010, DOI: 10.1021/jo100920e
  4. Z. Wu and R. Glaser, “Ab Initio Study of the SN1Ar and SN2Ar Reactions of Benzenediazonium Ion with Water. On the Conception of “Unimolecular Dediazoniation” in Solvolysis Reactions”,  J. Am. Chem. Soc., 2004, DOI: 10.1021/ja047620a



Archived as Henry Rzepa, Janus mechanisms (the past and the future): Reactions of the diazonium cation, URL:http://www.ch.ic.ac.uk/rzepa/blog/?p=3003. Accessed: 2010-12-12. (Archived by WebCite® at http://www.webcitation.org/5uv90cJnU)

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