The halogen bond with isocyano carbon reduces isocyanide odor

Predominantly, carbon atoms of various species function as acceptors of noncovalent interactions when they are part of a π-system. Here, we report on the discovery of a halogen bond involving the isocyano carbon lone pair. The co-crystallization or mechanochemical liquid-assisted grinding of model mesityl isocyanide with four iodoperfluorobenezenes leads to a series of halogen-bonded adducts with isocyanides. The obtained adducts were characterized by single-crystal and powder X-ray diffraction, solid-state IR and 13C NMR spectroscopies, and also by thermogravimetric analysis. The formation of the halogen bond with the isocyano group leads to a strong reduction of the isocyanide odor (3- to 46-fold gas phase concentration decrease). This manipulation makes isocyanides more suitable for laboratory storage and usage while preserving their reactivity, which is found to be similar between the adducts and the parent isocyanide in some common transformations, such as ligation to metal centers and the multi-component Ugi reaction.


SUPPLEMENTARY DISCUSSION
(IAd)•IPFB adduct. The CSD search indicates that the shortest contact between the I and C centers is the adduct of IPFB with the stable N-heterocyclic carbene IAd 2 of the push-push type 3  To reveal the nature of the I•••C contact in the (IAd)•IPFB adduct and quantify the energy of this interaction from theoretical viewpoint, we carried out DFT calculations and performed topological analysis of the electron density distribution within the framework of Bader's theory (QTAIM method) 5 for the experimental XRD geometry of the adduct as well as for their optimized equilibrium geometry in the gas phase. The full geometry optimization of (IAd)•IPFB adduct and single point calculations based on the experimental XRD data have been carried out at the DFT level of theory using the M06-2X functional 6 and CEP-121G basis sets 7,8 with the help of the Gaussian-09 program package. 9 Results of QTAIM analysis are summarized in Supplementary Table 1 Supplementary Table 1 Values of the density of all electrons -(r), Laplacian of electron density - 2 (r), energy density -Hb, potential energy density -V(r), and Lagrangian kinetic energy -G(r) (a.u.) at the bond critical point (3, -1), corresponding to XBs in XRD and optimized gas phase equilibrium structures of (IAd)•IPFB adduct, bond lengthsd (Å), Wiberg bond indexes (WI), as well as energies for these contacts Eint (kcal/mol), defined by different approaches  Table 2). We also defined the direction of charge transfer (CT) in this system by NBO analysis. 15 Second order perturbation theory analysis of Fock matrix in NBO basis reveals also two direction of intermolecular CT along the I•••C interaction in the optimized equilibrium structure of (IAd)•IPFB adduct: the CT lp(Ccarbene) → σ*(C−IIPFB) with appropriate total E(2) values 30.00 kcal/mol and transfer lp(IIPFB) → σ*/π*(C=Ncarbene) with appropriate total E(2) values 7.72 kcal/mol. The obtained values for the for the dissociation energies and CT are not dramatically lower than the dissociation energies for the covalent C-I bond with ca. 40-55 kcal/mol. 16 Thus, the observed I•••C interaction in (IAd)•IPFB adduct should not be considered as noncovalent due to the high energy and significant degree of covalency. The structure PEKWIN was not considered in the search because of the misleading in the deposited structurethe original paper reports p-cyanobenzoic acid instead of p-isocyanobenzoic acid. 1

Supplementary Figure 7
Comparison of chemical shift of isocyano C signal in the solid-state 13 C

GC-MS odor measurements
Supplementary  Figure 11 Average GS-MS peak areas representing the isocyanide concentration in gas phase above the crystal phase for CNMes and its adducts. The error bars represent a standard deviation. The data are taken from Supplementary Table 7.

Reactivity tests
To demonstrate the potential laboratory usage of isocyanide XB adducts we compared the reactivity of the (CNMes)•IPFB adduct, taken as a model system, with the parent CNMes in some most common transformations that include ligation to such metal centers as Au I , Pt II , and Pd II and the multi-component Ugi reaction (Supplementary Figure 12). Complexation. The gold(I) 22 , palladium(II) 23 and platinum(II) 24 mesityl isocyanide complexes were synthesized according a modified literature procedure. 21 Solid CNMes (20 mg, 0.14 mmol) or AuCl(CNMes) 22 6H).

Solid-state 13 C NMR data
Supplementary