Gary W. Breton

Acetylation of unsymmetrical diols in the presence of Al2O3

Abstract The effect of the presence of chromatographic grade Al2O3 on the acetylation of a series of unsymmetrical 1,5-diols was investigated. For diols containing both a primary and a secondary hydroxyl group, it was observed that higher yields of the more hindered secondary acetates were formed in the presence of Al2O3 than the corresponding reactions in solution.

Use of Cyclic Allylic Bromides in the Zinc-Mediated Aqueous Barbier-Grignard Reaction

The zinc–mediated aqueous Barbier–Grignard reaction of cyclic allylic bromide substrates with various aldehydes and ketones to afford homoallylic alcohols was investigated. Aromatic aldehydes and ketones afforded adducts in good yields (66–90%) and with good diastereoselectivities. Non–aromatic aldehydes also reacted well under these conditions, but only poor yields were obtained with non–aromatic ketones. Regioselectivity was high when some substituted cyclic allylic bromides were investigated.

Application of Radical Cation Spin Density Maps toward the Prediction of Photochemical Reactivity between N-Methyl-1,2,4-triazoline-3,5-dione and Substituted Benzenes

Visible light irradiation of N-methyl-1,2,4-triazoline-3,5-dione in the presence of substituted benzenes is capable of inducing substitution reactions where no reaction takes place thermally. In addition to the formation of 1-arylurazole products resulting from ring substitution, side-chain substitution occurs in some cases where benzylic hydrogens are accessible to form benzylic urazole products. Formation of both types of products is most consistent with the involvement of a common intermediate, a radical ion pair, generated from photoexcitation of an initially formed charge-transfer complex. The charge-transfer complexes have been observed spectroscopically. Additionally, application of a modified Rehm-Weller model suggests that the electron-transfer processes are feasible for all of the substrates examined. In most cases, the spin density maps of the aromatic radical cation intermediates calculated at the DFT UB3LYP/6-31G* level are excellent predictors of the observed product distributions.

One-Pot Synthesis of Novel 2,3-Dihydro-1H-indazoles

A copper(I)-mediated one-pot synthesis of 2,3-dihydro-1H-indazole heterocycles has been developed. This synthetic route provides the desired indazoles in moderate to good yields (55%–72%) which are substantially better than those achievable with an alternative two-step reaction sequence. The reaction is tolerant of functionality on the aromatic ring.

Intermediacy of a Persistent Urazole Radical and an Electrophilic Diazenium Species in the Acid-Catalyzed Reaction of MeTAD with Anisole

The reaction of N-methyl-1,2,4-triazoline-3,5-dione (MeTAD) with anisole in the presence of trifluoroacetic acid affords unexpected disubstituted urazole products instead of the expected monosubstituted urazole as typically observed in the reactions of MeTAD with other substituted benzenes. Our investigation into the mechanism of formation of these disubstituted products suggests that MeTAD is capable of further reaction with the initially formed monosubstituted urazole to afford a persistent urazole radical. The identity of this radical has been established by UV-vis spectroscopy, the nature of its self-dimerization reaction, and via independent generation. Electrochemical oxidation of this radical was carried out, and the resulting diazenium ion was demonstrated to be reactive with added substituted benzenes, including anisole. When oxidation was carried out chemically using thianthrenium perchlorate in the presence of anisole it was shown to produce the same disubstituted products (and in the same ratio) as observed in the acid-catalyzed reaction. A common diazenium species is proposed to be active in both cases. We also report the synthesis and characterization of three interesting tetrazane dimers resulting from unstable urazole radicals.

Computational, 1H NMR, and X-ray structural studies on 1-aryl­urazole tetra­zane dimers

Nitrogen-centered urazole radicals exist in equilibrium with tetrazane dimers in solution. The equilibrium established typically favors the free-radical form. However, 1-arylurazole radicals bearing substituents at the ortho position favor the dimeric form. We were able to determine the structure of one of the dimers (substituted at both ortho positions with methyl groups), namely 1,2-(2,4-dimethylphenyl)-2-[2-(2,4-dimethylphenyl)-4-methyl-3,5-dioxo-1,2,4-triazolidin-1-yl]-4-methyl-1,2,4-triazolidine-3,5-dione, C24H28N6O4, via X-ray crystallography. The experimentally determined structure agreed well with the computationally obtained geometry at the B3LYP/6-311G(d,p) level of theory. The preferred syn conformation of these 1-arylurazole dimers results in the two aromatic rings being proximate and nearly parallel, which leads to some interesting shielding effects of certain signals in the 1H NMR spectrum. Armed with this information, we were able to decipher the more complicated 1H NMR spectrum obtained from a dimer that was monosubstituted at the ortho position with a methyl group.

Convenient Synthesis of Monobenzylated Hydrazides via Aqueous Zinc-Mediated Addition Reactions

Abstract Addition of substituted benzyl bromides to dialkyl azodicarboxylates under aqueous zinc-mediated addition conditions occurs readily to afford monobenzylated hydrazides in good to excellent yields. The reaction is tolerant of a variety of substituents on the benzyl bromide ring. Several dialkyl azodicarboxylates were successfully tested under the reaction conditions. The limitations of the reaction are also addressed. [Supplementary materials are available for this article. Go to the publishers online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.] GRAPHICAL ABSTRACT

Unexpected σ bond rupture during the reaction of N-methyl-1,2,4-triazoline-3,5-dione with acenaphthylene and indene.

The reaction of N-methyl-1,2,4-triazoline-3,5-dione (MeTAD) with acenaphthylene and indene leads not only to the formation of the expected [2 + 2] diazetidine cycloadducts but also to unexpected 2:1 adducts of MeTAD with substrate. The structures of the products derived from acenaphthylene were confirmed by X-ray crystallography. A similar distribution of products was afforded from indene. The 2:1 adducts appear to derive from a diradical intermediate, the radical centers of which are strongly stabilized by the bridging urazoyl ring and benzylic delocalization. The triplet states of these diradical intermediates may be trapped via exposure to molecular oxygen to afford oxygen-containing adducts. Computational studies at the (U)B3LYP/6-31G* level provide additional support for the conclusions of our experimental work.

Unanti­cipated formation of a novel octa­aza­cyclo­decane ring upon oxidation of a 1,1-bis-urazole

Tetrahydrotetrazoles are a little-explored class of five-membered heterocycles with four contiguous singly-bonded N atoms. Recent work in our labs has demonstrated that urazole radicals are amenable to N-N bond formation via radical combination to form such a chain of four N atoms. Previously described 1,1-bis-urazole compounds appeared to be convenient precursors to the target tetrazoles via their oxidation to intermediate urazole diradicals, which upon N-N bond formation would complete the tetrazole framework. While oxidation proceeded smoothly, the novel 10-membered octaaza heterocycle 7,7,18,18-tetraacetyl-4,10,15,21-tetraphenyl-1,2,4,6,8,10,12,13,15,17,19,21-dodecaazapentacyclo[17.3.0.02,6.08,12.013,17]docosan-3,5,9,11,14,16,20,22-octone, C42H32N12O12, was obtained (36% yield) instead of the expected tetrazole product, as confirmed by X-ray crystallography. Calculations at the (U)B3LYP/6-311G(d,p) level of theory suggest that the desired tetrazoles have weak N-N bonds connecting the two urazole units.