Unprecedented Synthesis of 1,3‐Dimethylcyclobutadiene in the Solid State and Aqueous Solution

Abstract

Cyclobutadiene (CBD), the smallest cyclic hydrocarbon bearing conjugated double bonds, has long intrigued chemists because of its chemical characteristics. The question of whether the molecule could be prepared at all has been answered, but the parent compound and its unperturbed derivatives have eluded crystallographic characterization or synthesis "in water". Different approaches have been used to generate and to trap cyclobutadiene in a variety of confined environments: a) an Ar matrix at cryogenic temperatures, b) a hemicarcerand cage enabling the characterization by NMR spectroscopy in solution, and c) a crystalline guanidinium-sulfonate-calixarene G(4)C matrix that is stable enough to allow photoreactions in the solid state. In the latter case, the 4,6-dimethyl-α-pyrone precursor, Me(2)1, has been immobilized in a guanidinium-sulfonate-calixarene G(4)C crystalline network through a combination of non-covalent interactions. UV irradiation of the crystals transforms the entrapped Me(2)1 into a 4,6-dimethyl-Dewar-β-lactone intermediate, Me(2)2, and rectangular-bent 1,3-dimethylcyclobutadiene, Me(2)CBD(R), which are sufficiently stable under the confined conditions at 175 K to allow a conventional structure determination by X-ray diffraction. Further irradiation drives the reaction towards Me(2)3&Me(2)CBD(S)/CO(2) (63.7 %) and Me(2)CBD(R) (37.3 %) superposed crystalline architectures and the amplification of Me(2)CBD(R). The crystallographic models are supported by additional FTIR and Raman experiments in the solid state and by (1)H NMR spectroscopy and ESI mass spectrometry experiments in aqueous solution. Amazingly, the 4,6-dimethyl-Dewar-β-lactone, Me(2)2, the cyclobutadiene-carboxyl zwitterion, Me(2)3, and 1,3-dimethylcyclobutadiene, Me(2)CBD, were obtained by ultraviolet irradiation of an aqueous solution of G(4)C{Me(2)1}. 1,3-Dimethylcyclobutadiene is stable in water at room temperature for several weeks and even up to 50 °C as demonstrated by (1)H NMR spectroscopy.

A Computational Evaluation of the Evidence for the Synthesis of 1,3‐Dimethylcyclobutadiene in the Solid State and Aqueous Solution

“…Computational support for this hypothesis was claimed by the citation in reference 3 of Figure 2 in a 1978 report8 of a CNDO/2 calculation on the parent cyclobutadiene, which shows an energy minimum corresponding to distances of approximately 1.6 A for an end‐on CBD/CO 2 complex. In contrast, an ab initio HF/STO‐3G calculation also reported in the same article8 as Figure 3, but not discussed by Barboiu et al,3 implied such an approach would be repulsive at all distances, and that the closest approach was more likely to be approximately 3.2 Å, widely accepted as more typical of a van der Waals complex 9. Since the quantitative accuracy of computational procedures has improved enormously since 1978, it seemed desirable to re‐investigate these various aspects using a more modern method.…”

“…Crystallographic characterisation of the trapped species was claimed to reveal two geometric forms, rectangular Me 2 CBD R in close proximity to the eliminated CO 2 and square‐planar Me 2 CBD in the form of a CO 2 complex 2. Recently, the same group has further proposed that Me 2 CBD under the protection of G 4 C can also persist in aqueous solution “even at 50 °C”, the evidence for this phase being predominantly based on solution 1 H NMR measurements 3…”

“… The notation is that previously used;3 additional species considered here are denoted by 1 – 6 , of which 2 is the Lewis structure corresponding to Me 2 3 . …”

“…The issue might be summarised by asking what the anticipated structures of Me 2 CBD S,R /CO 2 might be in the ground thermal (S 0 ) state, the certain resting state for both the solid‐state X‐ray and solution NMR characterisations. The conclusions from the original crystallographic analysis,2 re‐iterated in a later split‐model refinement,3 were that Me 2 CBD S,R + CO 2 are best described as a “van‐der‐Waals” like complex brought about by cage and hydrogen bonding effects, in which the CC and CO distances of the bonds connecting the two components are in the range 1.5–1.6 Å, and where a distinctly non‐linear angle of approximately 120° is subtended at the OCO. Computational support for this hypothesis was claimed by the citation in reference 3 of Figure 2 in a 1978 report8 of a CNDO/2 calculation on the parent cyclobutadiene, which shows an energy minimum corresponding to distances of approximately 1.6 A for an end‐on CBD/CO 2 complex.…”

“…The conclusions from the original crystallographic analysis,2 re‐iterated in a later split‐model refinement,3 were that Me 2 CBD S,R + CO 2 are best described as a “van‐der‐Waals” like complex brought about by cage and hydrogen bonding effects, in which the CC and CO distances of the bonds connecting the two components are in the range 1.5–1.6 Å, and where a distinctly non‐linear angle of approximately 120° is subtended at the OCO. Computational support for this hypothesis was claimed by the citation in reference 3 of Figure 2 in a 1978 report8 of a CNDO/2 calculation on the parent cyclobutadiene, which shows an energy minimum corresponding to distances of approximately 1.6 A for an end‐on CBD/CO 2 complex. In contrast, an ab initio HF/STO‐3G calculation also reported in the same article8 as Figure 3, but not discussed by Barboiu et al,3 implied such an approach would be repulsive at all distances, and that the closest approach was more likely to be approximately 3.2 Å, widely accepted as more typical of a van der Waals complex 9.…”