Gary W. Breton

Gary W. Breton
Berry College · Department of Chemistry

Doctor of Philosophy

About

60
Publications
3,386
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957
Citations
Citations since 2016
15 Research Items
317 Citations
20162017201820192020202120220102030405060
20162017201820192020202120220102030405060
20162017201820192020202120220102030405060
20162017201820192020202120220102030405060

Publications

Publications (60)
Article
The cover image is based on the Research Article Competition between the stabilizing effects of saturated alkyl substituents and pi bonds on complexes of silver ion (Ag+) with alkenes by Gary W. Breton, https://doi.org/10.1002/poc.4301.
Article
The coordination of Ag+ ions to alkenes is of both theoretical and practical interest. While much attention has been paid to how the nature of the C=C π bond affects the coordinative process, little attention has been directed toward the effect of saturated side chains on complex stabilization despite experimental evidence suggesting its importance...
Article
The Cover Feature shows a representation of the subtle structural differences between the trans‐amide and 1,2,3‐triazole bioisosteres. As amide looks into the mirror and sees triazole, the question arises: do they look alike? Below the cartoon is an X‐ray structure of an amide‐containing cystic fibrosis drug. The atoms in yellow highlight the drug'...
Article
Dynamic covalent chemistry (DCvC) describes systems in which readily reversible bond formation allows for control of product distributions by straightforward manipulation of reaction conditions (e.g., changes in temperature, solvent, concentration, etc.). Nitrogen-centered 1-aryl urazole radicals reversibly form tetrazane dimers in solution via N–N...
Article
While the 1,2,3‐triazole is a commonly utilized amide bioisostere in medicinal chemistry, the structural implications of this replacement have not been fully studied. Employing X‐ray crystallography and computational studies, we report the spatial and electronic consequences of replacing the amide with the triazole in analogs of cystic fibrosis dru...
Article
Tetrahydrotetrazoles are five-membered-ring heterocycles containing four contiguous saturated nitrogen atoms. Very few examples of such compounds have been reported in the literature. Our previous attempt at the synthesis of a member of this class of compound suggested that the N—N bonds may be more labile than expected. This finding raised the que...
Article
There has recently been greater appreciation for the impact that n→π* interactions have on the conformational preferences of molecules in the gas phase, solution, and in crystalline form. Earlier studies, both experimental and computational, have demonstrated that suitably placed substituents can affect the extent of these interactions. A thorough...
Article
The 1,2,3‐triazole has been successfully utilized as an amide bioisostere in multiple therapeutic contexts. Based on this precedent, triazole analogs derived from VX‐809 and VX‐770, prominent amide‐containing modulators of the cystic fibrosis transmembrane conductance regulator (CFTR), were synthesized and evaluated for CFTR modulation. Triazole 11...
Article
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 conve...
Article
The phenyl cation has been the subject of many experimental and theoretical studies because of its importance in synthetic organic chemistry. Based on interesting experimental observations from the literature, we have computationally studied the electronic and structural effects of introducing a nitrogen atom into the aromatic ring (i.e., pyridyl r...
Article
Phenyl urazole radicals are persistent air-stable nitrogen-centered radicals that engage in an equilibrium with the corresponding N―N tetrazane dimers in solution. While the equilibrium typically weakly favors the dimer form, for some 1-phenyl urazole radicals bearing substituents at the ortho position of the benzene ring, the equilibrium instead s...
Article
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 posi...
Article
The n→π* interaction is a weak but important non-covalent interaction present in biomolecules and other compounds. Complexes between 7-azaindole and 2,6-difluorinated pyridines were demonstrated earlier to interact not only via an expected strong hydrogen bond, but also by a weaker and unexpected n→π* interaction between the nucleophilic nitrogen a...
Article
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...
Article
The Bürgi-Dunitz trajectory traces points along the pathway of bond formation between a nucleophile and electrophile. Previous X-ray crystallographic studies of some molecules containing a nucleophilic nitrogen atom and electrophilic carbonyl group provided some initial evidence for various degrees of bond formation via initial n-->pi* interactions...
Article
N-Methyl-1,2,4-triazoline-3,5-dione (MeTAD) is a powerful electrophile and a versatile synthetic reagent. In this Letter we describe two methods for the synthesis of N-methylurazole, the direct precursor to MeTAD, on gram scales and in good yields. Both methods provide pure urazole while avoiding the necessity of large scale purification via column...
Article
The reaction of N-Methyl-1,2,4-triazoline-3,5-dione (MeTAD) with acenaphthylene and indene leads not only to the formation of expected [2+2] diazetidine cycloadducts, but also to unexpected 2:1 adducts of MeTAD to substrate. The structures of the products derived from acenaphthylene were confirmed by X-ray crystallography. A similar distribution of...
Article
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 re...
Chapter
[7782-79-8] HN3 (MW 43.04)
Article
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 formation of 1-arylurazole products resulting from ring substitution, side-chain substitution occurs in some cases where benzylic hydrogens are...
Article
Full-text available
The acid-catalyzed reactions of N-methyl-1,2,4-triazoline-3,5-dione with naphthalene, anthracene, and phenanthrene have been studied using trifluoroacetic acid as catalyst. Quite different results between these reactions were ultimately observed. Reaction with naphthalene appears to be the result of a straightforward acid-catalyzed DA reaction. Rea...
Article
Full-text available
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 rin...
Article
The reaction of 4-methyl-1,2,4-triazoline-3,5-dione (MeTAD) with substituted benzenes under the influence of trifluoroacetic acid catalysis was investigated. Generally, good-to-high yields of 1-arylurazoles resulting from aromatic substitution were obtained. Successful reaction required moderately electron-rich aromatics with proper substitution pa...
Article
Two stereochemically defined diazetine N,N'-dioxides were synthesized. Thermal decomposition at 200 degrees C resulted in 95% retention of stereochemistry in the alkene product relative to the starting stereochemistry. These results suggest that decomposition occurs via cleavage of the two C-N bonds either simultaneously or in rapid succession.
Article
Diazetine dioxide 1a has been synthesized in a single step via oxidation of meso-2,3-diphenyl-1,2-ethanediamine with dimethyldioxirane, albeit in low yield (7%). Thermal decomposition of 1a afforded predominantly either trans-stilbene or diphenyl glyoxime depending on solvent, temperature, and the presence of an amine catalyst. Reaction in chlorofo...
Article
A homologous series of tricyclic diazetines (6a-c), differing by the number of methylene groups in the saturated bridges of the fused carbon bicycles, was synthesized. The DeltaH++ of decomposition for each of the diazetines to afford N2 and the corresponding alkene was determined experimentally: 6a, 31.7; 6b, 39.3; 6c, 38.8 kcal/mol. The ground-st...
Article
A thorough experimental and computational investigation of the aromaticity of the 1,2-dihydrodiazete ring system was carried out. The X-ray crystal structure of 1,2-dihydrodiazete 6 is reported, and the alkene-like reactivity of compound 6 is described. The compound's structure and reactivity suggest that 6 is not aromatic. This conclusion is corro...
Article
Full-text available
This study describes the chemical ecology of a tritrophic interaction among species endemic to the island of Hawaii, USA: a tree (Sophora chrysophylla: mamane), an endangered bird (Loxioides bailleui; palila), and moth larvae (Cydia spp.). Palila and Cydia both specialize on the seed embryos of mamane but avoid eating the seed coats. Palila activel...
Article
The use of writing as a tool to achieve active learning in the undergraduate research experience is described. Every student participating in undergraduate research is required to submit a journal-quality paper to our in-house publication, The Berry College Journal of Chemistry. Keywords (Audience): Second-Year Undergraduate
Article
[reaction: see text] A novel method for the synthesis of Delta(1)-1,2-diazetines is presented. Diels-Alder cycloaddition of dienophile 4 with five dienes afforded cycloadducts in good to excellent yields. Four of the obtained cycloadducts were converted to the corresponding diazetines.
Article
Full-text available
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, bu...
Chapter
[7782-79-8] HN3 (MW 43.04) InChI = 1S/HN3/c1-3-2/h1HInChIKey = JUINSXZKUKVTMD-UHFFFAOYSA-N(adds electrophilically to alkenes, alkynes, and related conjugated systems;1c converts carboxylic acids to amines (Schmidt reaction)1 and alcohols to azides;11a cleaves epoxides;17 aminates arenes;19 affords sulfoximines from sulfoxides;21c reacts with a vari...
Article
MeTAD thermally reacted with naphthalene (2) and methylated naphthalenes to give equilibrium mixtures of starting materials and [4 + 2] cycloadducts. Methyl substitution on the naphthalene ring generally increased both the amount of cycloadduct formed and the rate of cycloaddition relative to 2. The isolated cycloadducts were all thermally labile a...
Article
Silica gel and alumina have been found to mediate the oxidation of sulfides and sulfoxides with (CH3)(3)COOH and OXONE. With all combinations except (CH3)(3)COOH/alumina, sulfides were oxidized with reasonably good selectivity to sulfoxides. These studies afforded insights into the mechanisms of surface-mediated processes. Adsorption studies, combi...
Article
The use of an inexpensive analog-to-digital converter for interfacing gas chromatographs to computers in a teaching laboratory environment is described. Raw data may be read, processed, and printed from software supplied with the converter to afford chromatograms of acceptable quality. Alternatively, data may be imported into readily available comm...
Article
Many tables of values exist for the rapid calculation of approximate chemical shifts of protons in organic molecules. These tables are usually simply handed to students to use without discussion of the source of such data. Herein we describe a laboratory experiment in which students themselves determine values for the calculation of chemical shifts...
Article
This undergraduate laboratory experiment challenges students to use their combined knowledge of organic reaction mechanisms and spectroscopic analysis to determine the product of a reaction that has several possible outcomes. The result is that students gain the “real-life” experience, commonly encountered by most research chemists, of characterizi...
Article
A photochemical experiment is described which requires only common laboratory equipment. The experiment involves the photochemical dimerization of anthracene, characterization of the product by UV, IR and NMR spectroscopy, and thermolysis of the dimer. Keywords (Audience): Second-Year Undergraduate
Article
The addition of a Grignard reagent to a carbonyl-containing compound to form an alcohol is an important reaction to demonstrate in organic chemistry laboratory courses. However, the reaction presents several practical problems for the lab instructor including the need for anhydrous solvents (e.g., ether), dry glassware, and the occasional problem o...
Article
The study of charged aromatic species greatly enhances discussions of the theory of aromaticity. The conveniently low acidity of cyclopentadiene (pK a = 15) affords the opportunity to generate the aromatic cyclopentadienyl anion in an organic laboratory class. This experiment describes the preparation of a solution of deuterated dimethylsulfinyl an...
Article
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...
Article
An experiment has been devised that illustrates three important concepts in organic chemistry: the synthesis of an alkene via the Wittig reaction, characterization of a reactive intermediate by 1H NMR, and site - specific deuterium labelling. Deprotonation of ethyltriphenylphosphonium iodide (1) by methylsulfinyl carbanion (generated in situ by the...
Article
Adsorption of a variety of acids to chromatographic silica gel results in substantial enhancement of their catalytic activity-affording easily prepared, environmentally benign heterogeneous acids that are highly effective in mediating a number of processes. This was shown for the isomerization of allene 1 and dimerization of the corresponding 1,3-d...
Article
Silica gel mediates the reactivity of (CH3)3COOH, affording a convenient, environmentally benign method for oxidizing sulfides, sulfoxides, and alkenes. Electrophilic oxidation of sulfides and alkenes (Scheme 1A) and nucleophilic oxidation of sulfoxides (Scheme 1B) are apparently involved. Basic alumina mediates the oxidation of sulfoxides.
Article
Appropriately prepared silica gel and alumina have been found to mediate the addition of HCl, HBr, and HI to alkenes. The technique has been rendered even more convenient by the use of various organic and inorganic halides that undergo hydrolysis in the presence of silica gel or alumina to generate hydrogen halides in situ. Under these conditions a...

Questions

Questions (2)
Question
Perhaps not surprisingly, if one tries to optimize the structure of the anion of ethyl bromide [CH2–CH2Br]-1 using, for example the wB97XD/aug-cc-pvdz computational method, the optimization process results in spontaneous formation of ethylene via elimination of Br-. In a sense, the computational optimization predicts the success of the E2 elimination process (or, probably more accurately, the E1cB mechanism).
I am interested in finding additional examples of where novel forms of reactivity or novel reaction routes has been discovered as a result of a process observed computationally during an optimization. If someone could lead me to some examples, I would be very grateful!
Question
I have a compound with a dimethyl amino group. The exchange is quick at room temperature so a singlet is observed. I expect that if i cool the system sufficiently the two methyls will be individually frozen out since the two chemical environments will be sufficiently different. I can cool it to -80c and see significant broadening of the signal of interest but I cannot cool further to find the coalescence point. Is there a way to determine an estimate for the rate constant at different temperatures with this limited information?

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