Taming the Reactivity of Alkyl Azides by Intramolecular Hydrogen Bonding: Site-Selective Conjugation of Unhindered Diazides

Organic azides are still in the center of click chemistry connecting two molecules. However, taming the conjugation selectivity of azides is difficult without the help of the bulky groups. We...

Photochemical Deracemization of Chiral Sulfoxides Catalyzed by a Hydrogen-Bonding Xanthone Sensitizer

Several chiral sulfoxides with a lactam hydrogen-bonding site were prepared and their photochemical behavior was studied in the presence of xanthone and thioxanthone sensitizers. While acyclic sulfoxides showed only decomposition, chiral benzothiazinone-1-oxides with a stereogenic sulfur atom underwent a stereomutation upon irradiation at λ = 366 nm in the presence of catalytic quantities of a xanthone sensitizer. A chiral xanthone with a 1,5,7-trimethyl-3-azabicyclo-[3.3.1]nonan-2-one backbone was employed in catalytic quantities (5 mol%) to achieve a deracemization reaction of racemic benzothiazinone-1-oxides in acetonitrile solution. Five substrates could be successfully deracemized in good yields and with up to 55% ee.

Hydroquinone-Based Anion Receptors for Redox-Switchable Chloride Binding

A series of chloride receptors has been synthesized containing an amide hydrogen bonding site and a hydroquinone motif. It was anticipated that oxidation of the hydroquinone unit to quinone would greatly the diminish chloride binding affinity of these receptors. A conformational switch is promoted in the quinone form through the formation of an intramolecular hydrogen bond between the amide and the quinone carbonyl, which blocks the amide binding site. The reversibility of this oxidation process highlighted the potential of these systems for use as redox-switchable receptors. 1H-NMR binding studies confirmed stronger binding capabilities of the hydroquinone form compared to the quinone; however, X-ray crystal structures of the free hydroquinone receptors revealed the presence of an analogous inhibiting intramolecular hydrogen bond in this state of the receptor. Binding studies also revealed interesting and contrasting trends in chloride affinity when comparing the two switch states, which is dictated by a secondary interaction in the binding mode between the amide carbonyl and the hydroquinone/quinone couple. Additionally, the electrochemical properties of the systems have been explored using cyclic voltammetry and it was observed that the reduction potential of the system was directly related to the expected strength of the internal hydrogen bond.

Site-selective nitrenoid insertions utilizing postfunctionalized bifunctional rhodium(ii) catalysts

Site-selective nitrenoid insertions are made possible with a postfunctionalized dirhodium(ii)-catalyst equipped with a remote hydrogen bonding site.

Sulfur as hydrogen-bond acceptor in cocrystals of 2-thio-modified thymine

Doubly and triply hydrogen-bonded supramolecular synthons are of particular interest for the rational design of crystal and cocrystal structures in crystal engineering since they show a high robustness due to their high stability and good reliability. The compound 5-methyl-2-thiouracil (2-thiothymine) contains an ADA hydrogen-bonding site (A = acceptor and D = donor) if the S atom is considered as an acceptor. We report herein the results of cocrystallization experiments with the coformers 2,4-diaminopyrimidine, 2,4-diamino-6-phenyl-1,3,5-triazine, 6-amino-3H-isocytosine and melamine, which contain complementary DAD hydrogen-bonding sites and, therefore, should be capable of forming a mixed ADA–DAD N—H...S/N—H...N/N—H...O synthon (denoted synthon 3s N·S;N·N;N·O), consisting of three different hydrogen bonds with 5-methyl-2-thiouracil. The experiments yielded one cocrystal and five solvated cocrystals, namely 5-methyl-2-thiouracil–2,4-diaminopyrimidine (1/2), C5H6N2OS·2C4H6N4, (I), 5-methyl-2-thiouracil–2,4-diaminopyrimidine–N,N-dimethylformamide (2/2/1), 2C5H6N2OS·2C4H6N4·C3H7NO, (II), 5-methyl-2-thiouracil–2,4-diamino-6-phenyl-1,3,5-triazine–N,N-dimethylformamide (2/2/1), 2C5H6N2OS·2C9H9N5·C3H7NO, (III), 5-methyl-2-thiouracil–6-amino-3H-isocytosine–N,N-dimethylformamide (2/2/1), (IV), 2C5H6N2OS·2C4H6N4O·C3H7NO, (IV), 5-methyl-2-thiouracil–6-amino-3H-isocytosine–N,N-dimethylacetamide (2/2/1), 2C5H6N2OS·2C4H6N4O·C4H9NO, (V), and 5-methyl-2-thiouracil–melamine (3/2), 3C5H6N2OS·2C3H6N6, (VI). Synthon 3s N·S;N·N;N·O was formed in three structures in which two-dimensional hydrogen-bonded networks are observed, while doubly hydrogen-bonded interactions were formed instead in the remaining three cocrystals whereby three-dimensional networks are preferred. As desired, the S atoms are involved in hydrogen-bonding interactions in all six structures, thus illustrating the ability of sulfur to act as a hydrogen-bond acceptor and, therefore, its value for application in crystal engineering.

Hydrophobic fluorine mediated switching of the hydrogen bonding site as well as orientation of water molecules in the aqueous mixture of monofluoroethanol: IR, molecular dynamics and quantum chemical studies

Fluorination of ethanol changes orientation of water in its aqueous mixture.

One barbiturate and two solvated thiobarbiturates containing the triply hydrogen-bondedADA/DADsynthon, plus one ansolvate and three solvates of their coformer 2,4-diaminopyrimidine

A path to new synthons for application in crystal engineering is the replacement of a strong hydrogen-bond acceptor, like a C=O group, with a weaker acceptor, like a C=S group, in doubly or triply hydrogen-bonded synthons. For instance, if the C=O group at the 2-position of barbituric acid is changed into a C=S group, 2-thiobarbituric acid is obtained. Each of the compounds comprises twoADAhydrogen-bonding sites (D= donor andA= acceptor). We report the results of cocrystallization experiments of barbituric acid and 2-thiobarbituric acid, respectively, with 2,4-diaminopyrimidine, which contains a complementaryDADhydrogen-bonding site and is therefore capable of forming anADA/DADsynthon with barbituric acid and 2-thiobarbituric acid. In addition, pure 2,4-diaminopyrimidine was crystallized in order to study its preferred hydrogen-bonding motifs. The experiments yielded one ansolvate of 2,4-diaminopyrimidine (pyrimidine-2,4-diamine, DAPY), C4H6N4, (I), three solvates of DAPY, namely 2,4-diaminopyrimidine–1,4-dioxane (2/1), 2C4H6N4·C4H8O2, (II), 2,4-diaminopyrimidine–N,N-dimethylacetamide (1/1), C4H6N4·C4H9NO, (III), and 2,4-diaminopyrimidine–1-methylpyrrolidin-2-one (1/1), C4H6N4·C5H9NO, (IV), one salt of barbituric acid,viz. 2,4-diaminopyrimidinium barbiturate (barbiturate is 2,4,6-trioxopyrimidin-5-ide), C4H7N4+·C4H3N2O3−, (V), and two solvated salts of 2-thiobarbituric acid,viz. 2,4-diaminopyrimidinium 2-thiobarbiturate–N,N-dimethylformamide (1/2) (2-thiobarbiturate is 4,6-dioxo-2-sulfanylidenepyrimidin-5-ide), C4H7N4+·C4H3N2O2S−·2C3H7NO, (VI), and 2,4-diaminopyrimidinium 2-thiobarbiturate–N,N-dimethylacetamide (1/2), C4H7N4+·C4H3N2O2S−·2C4H9NO, (VII). TheADA/DADsynthon was succesfully formed in the salt of barbituric acid,i.e.(V), as well as in the salts of 2-thiobarbituric acid,i.e.(VI) and (VII). In the crystal structures of 2,4-diaminopyrimidine,i.e.(I)–(IV),R22(8) N—H...N hydrogen-bond motifs are preferred and, in two structures, additionalR32(8) patterns were observed.