Azide Isomers Research Articles

Some Diazodinitrophenol Isomers - A DFT Treatment

The present study considers a series of diazodinitrophenol isomers within the constraints of density functional theory at the level of B3LYP/311++G(d,p). One of the isomers in the series is known as DDNP which is a primary explosive material. Presently various dinitro substituted benzoxadiazol (bicyclic) and 2-diazo-1-oxide (azide) isomers analogous to DDNP have been focus of investigation. In all the cases the azide isomers have been found to be more stable electronically than the bicyclic counterparts. Various properties of them including quantum chemical ones are harvested, compared and discussed. Also NICS(0) values are obtained for the ring(s) and the local aromaticity values are discussed.

Convenient synthesis of regioisomerically pure 5- and 6-functionalized xanthene dyes via SNAr reaction and comparison of their reactivity towards click reaction

In this study, we present an efficient and general strategy for the individual preparation of both isomers of 5(6)-functionalized xanthene-based fluorophores. Spectroscopic analysis of the acid-base equilibrium of 5(6)-nitro xanthene dyes has shown that they exist predominantly in the colorless spirolactone form in certain aprotic dipolar solvents. In such solvents, regioisomerically selective ipso-substitution of the nitro group by sodium azide occurs at the 6- position but not at the 5- position due to the electron-withdrawing spirolactone moiety at the para-position, relative to the nitro group. This reaction allows the separation of the isomer with the 6-azide group and the intact 5-nitro isomer. The 5-nitro group of the latter was then reduced to an amino group and subsequently converted to an azide group. This strategy enables the preparation of both the 5- and 6-functionalized isomers individually from a mixture of precursors, which is otherwise unachievable. The azide isomers were then compared in reactivity by strain-promoted azide-alkyne cycloaddition (SPAAC) with bicycle[6.1.0]non-4-yene (BCN).

IR-Laser Ablation of Potassium Cyanide: A Surprisingly Simple Route to Polynitrogen and Polycarbon Species.

Pulsed laser irradiation of solid potassium cyanide (KCN) produces, besides free nitrogen and carbon atoms, the molecular species KN and KC which are potential candidates for interstellar species of potassium. Additionally, N3, N3 −, KN3, C3, C3 −, and KC3 are produced and isolated in solid noble gases as well as in solid N2. Molecular potassium nitrene (KN) reacts with dinitrogen in neon and argon matrices after photochemical excitation (λ=470 nm) forming molecular end‐on (C ∞v) and side‐on (C 2v) potassium azide isomers. The side‐on isomer (C 2v) is thermodynamically favored at the CCSD(T)/ma‐def2‐TZVP level of theory. It can be obtained from the end‐on isomer by UV‐irradiation (λ=273 nm).

Allylic azides: synthesis, reactivity, and the Winstein rearrangement.

Organic azides are useful synthetic intermediates, which demonstrate broad reactivity. Unlike most organic azides, allylic azides can spontaneously rearrange to form a mixture of isomers. This rearrangement has been named the Winstein rearrangement. Using allylic azides can result in low yields and azide racemization in some synthetic contexts due to the Winstein rearrangement. Effort has been made to understand the mechanism of the Winstein rearrangement and to take advantage of this process. Several guiding principles can be used to identify which azides will produce a mixture of isomers and which will resist rearrangement. Selective reaction conditions can be used to differentiate the azide isomers in a dynamic manner. This review covers all aspects of allylic azides including their synthesis, their reactivity, the mechanism of the Winstein rearrangement, and reactions that can selectively elaborate an azide isomer. This review covers the literature from Winstein's initial report to early 2019.

Synthesis and study of the azide-tetrazole tautomerism in 2-azido-4-(trifluoromethyl)-6-R-pyrimidines (R = H, 4-ClC6H4)

Azide-tetrazole equilibrium in azidopyrimidines bearing trifluoromethyl group on the example of 2-azidopyrimidines has been studied. The latter were synthesized via nitrosation of 2-hydrazino-4-trifluoromethylpyrimidine and reaction of NaN3 with 4-trifluoromethyl-2- chloro-6-(4-chlorophenyl)pyrimidine. The tautomeric equilibrium 5-trifluoro methyl tetrazolo[1,5-a]pyrimidine ⇆ 2-azido-4-trifluoromethylpyrimidine was observed in the absence of solvent and in DMSO-d6 solution, whereas in CDCl3 only an azide form exists. For 2-azido- 4-trifluoromethyl-6-(4-chlorophenyl)pyrimidine, only an azide isomer was detected in CDCl3 solution, and in DMSO-d6 solution it is in equilibrium with 5-(trifluoromethyl)-7-(4-chlorophenyl) tetrazolo[1,5-a]pyrimidine (the tautomer ratio is 99 : 1). Thermodynamic and kinetic parameters of 5-trifluoromethyltetrazolo[1,5-a]pyrimidine ⇆ 2-azido-4-trifluoromethylpyri midine tautomeric rearrangement in DMSO-d6 for 5-trifluoromethyltetrazolo[1,5-a]pyrimidine were determined using the exchange spectroscopy (EXSY) technique.

Stereoselective Dynamic Cyclization of Allylic Azides: Synthesis of Tetralins, Chromanes, and Tetrahydroquinolines.

This report describes the stereoselective synthesis of 3-azido-tetralins, -chromanes, and -tetrahydroquinolines via a tandem allylic azide rearrangement/Friedel-Crafts alkylation. Exposure of allylic azides with a pendant trichloroacetimidate to catalytic quantities of AgSbF6 proved optimal for this transformation. This cascade successfully differentiates the equilibrating azide isomers, providing products in excellent yield and selectivity (>25 examples, up to 94% yield and >25:1 dr). In many cases, the reactive isomer is only a trace fraction of the equilibrium mixture, keenly illustrating the dynamic nature of these systems. We demonstrate the utility of this process via a synthesis of hasubanan.

Long-Range 1H–15N J Couplings Providing a Method for Direct Studies of the Structure and Azide–Tetrazole Equilibrium in a Series of Azido-1,2,4-triazines and Azidopyrimidines

The selectively (15)N labeled azido-1,2,4-triazine 2*A and azidopyrimidine 4*A were synthesized by treating hydrazinoazines with (15)N-labeled nitrous acid. The synthesized compounds were studied by (1)H, (13)C, and (15)N NMR spectroscopy in DMSO, TFA, and DMSO/TFA solutions, where the azide-tetrazole equilibrium could lead to the formation of two tetrazoles (T, T') and one azide (A) isomer for each compound. The incorporation of the (15)N label led to the appearance of long-range (1)H-(15)N coupling constants (J(HN)), which can be measured easily by using amplitude-modulated 1D (1)H spin-echo experiments with selective inversion of the (15)N nuclei. The observed J(HN) patterns enable the unambiguous determination of the mode of fusion between the azole and azine rings in the two groups of tetrazole isomers (2*T', 4*T' and 2*T, 4*T), even for minor isoforms with a low concentration in solution. However, the azide isomers (2*A and 4*A) are characterized by the absence of detectable J(HN) coupling. The analysis of the J(HN) couplings in (15)N-labeled compounds provides a simple and efficient method for direct NMR studies of the azide-tetrazole equilibrium in solution.

A theoretical DFT study on the structural parameters and azide–tetrazole equilibrium in substituted azidothiazole systems

Azido–tetrazole equilibrium is sensitive to: substitution, solvent, temperature and phase. In this work, the effects of the type and position of substitution on the thiazole ring of azidothiazoles on its structural parameters and on the azido–tetrazole equilibrium have been theoretically investigated using the density functional procedures at the B3LYP/6-311G∗∗ level of theory. This study includes the investigation of the equilibrium geometry, the transformation of the trans-conformer to the cis one then the ring closure to the tetrazole isomer. The transition states of the two steps were located, confirmed and the structural parameters were calculated. In all the steps of calculations, geometry optimization was considered.The results obtained indicate that substitution by: –NO2 and –CN group shifts the equilibrium to the azide side and in some cases the tetrazole isomer is not obtained. On the other hand, substitution by: –NH2 and –OH groups shifts the equilibrium to the tetrazole side and in some cases the azide isomer is not obtained and if formed changes spontaneously to the tetrazole isomer.The decisive parameters which determine the position of the equilibrium are: charge density on atoms N3 and N8, rearrangement of bond length and bond angles during the process of cyclization and variation of dipole moment as a result of cyclization.Results of this work indicate that substitution on C5 is more efficient than substitution on C4 of the thiazole ring.

ChemInform Abstract: Kinetically-Controlled Displacement by Azide on an Allylic Chloride: Synthesis of a Highly Potent Serotonin-3 Receptor Ligand Prototype.

Abstract The discovery and selective synthesis of a novel and highly potent serotonin-3 receptor ligand, 4-amino-5-chloro-2-methoxy-N-(1-azabicyclo[2.2.2]-oct-2-enyl-2-methyl) benzamide (4) are described. The key step in the preparation of 4 involves an unusual example of a kinetically controlled displacement to provide a thermodynamically disfavored allytic azide isomer. This azide is a precursor to 2-aminomethyl-1-azabicylo[2.2.2]oct-2-ene (5), a convergent intermediate for the synthesis of analogs related to 4.

The Allylic Azide Rearrangement: Achieving Selectivity.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The Allylic Azide Rearrangement: Achieving Selectivity

Allylic azides undergo a rapid [3.3]-sigmatropic rearrangement which results in dynamic equilibrium of several isomers. Thus, reactions of allylic azides usually result in mixtures of products. However, even small differences in reactivity of the isomeric allylic azides can be amplified to result in a single product in good to excellent yields. For example, the Cu(I)-catalyzed cycloaddition with alkynes selectively captures primary and secondary allylic azide isomers, whereas MCPBA epoxidation favors isomers which contain more electron-rich double olefins.

Reaction of 2,4,6-Triazido-1,3,5-triazine with Triphenylphosphane. Syntheses and Characterization of the Novel 2-Triphenylphosphanimino-4-azidotetrazolo[5,1-a]-[1,3,5]triazine and 2,4,6-Tris(triphenylphosphanimino)-1,3,5-triazine

2-Triphenylphosphanimino-4-azidotetrazolo[5,1-a]-[1,3,5]triazine (6) was obtained by reaction of 2,4,6-triazido-1,3,5-triazine (1) with 1 equiv of triphenylphosphane. Raman and X-ray data revealed that only one azide group formed a tetrazole ring system whereas the second azide group did not undergo ring closure. To investigate the equilibrium between the tetrazole isomer and the open-chain azide structure for these and related species, (31)P NMR studies were carried out. The obtained spectra displayed an equilibrium between the tetrazole and the open-chain azide isomers. 2,4,6-Tris(triphenylphosphanimino)-1,3,5-triazine (4) was prepared by treatment of 1 with 3 equiv of triphenylphosphane, and its X-ray structure is discussed. On the basis of PM3 semiempirical and density functional calculations, the reaction of 1 with triphenylphosphane was studied. The thermodynamics of different isomerization reactions and the activation barriers to cyclization were estimated.

Effect of the 5-Substituent on the Tetrazole–Azide Isomerization in Tetrazolo[1,5-a]pyridines by Ab Initio Calculations

The effect of substituents CH 3, OH, Cl, OCH 3, NO 2 and COOH at the 5-position in tetrazolo[1,5-a]pyridines, on the tetrazole–azide equilibrium, was investigated at the 6-31G ∗∗/MP2 level of theory. For both, the parent and 5-CH 3 compounds, the tetrazole forms are largely favored, while the other substituents-OH, Cl, OCH 3, and NO 2-stabilize the azide isomer. With the COOH group, the tetrazole and azide forms are predicted to be in equilibrium in nearly equal amounts. The influence of these groups on the transition state (TS) was also studied. In general it is observed that, groups which stabilize the azide isomer, lower the E act of the isomerization reaction, and conversely, those that favor the tetrazole form, raise the E act of this reaction, relative to the unsubstituted compound. The TS has a close resemblance to the tetrazole structure.

Kinetically-controlled displacement by azide on an allylic chloride: Synthesis of a highly potent serotonin-3 receptor ligand prototype

The discovery and selective synthesis of a novel and highly potent serotonin-3 receptor ligand, 4-amino-5-chloro-2-methoxy-N-(1-azabicyclo[2.2.2]-oct-2-enyl-2-methyl) benzamide ( 4) are described. The key step in the preparation of 4 involves an unusual example of a kinetically controlled displacement to provide a thermodynamically disfavored allytic azide isomer. This azide is a precursor to 2-aminomethyl-1-azabicylo[2.2.2]oct-2-ene ( 5), a convergent intermediate for the synthesis of analogs related to 4.

Structure and some properties of tetrazole 5-methylpyrimido[4,5-e]-[1,2,4]triazine-6,8-dione and its azide in different phase states

The structure of the tetrazole, 5-methylpyrimido[4,5-e][1,2,4]triazine-6,8-dione was established by x-ray structural analysis. The tautomeric equilibrium with its azide isomer in solution was examined. The effect of bases on this equilibrium was discovered. Analytical criteria were proposed which permit identification of the tetrazole and the azide forms in the gas phase.

Inhibition of monoamine oxidase by phenyl azides.

We had previously shown that 4-fluoro-3-nitrophenyl azide (FNPA) is a competitive inhibitor of both types of monoamine oxidase (MAO) in the dark, but it is a preferential photoaffinity label for only the type B MAO (MAO-B). Recently we synthesized a number of arylazido compounds with structures related to FNPA and determined the effects of these compounds on the two types of MAO in rat brain cortex. We found that the fluoro group of FNPA was not required for the inhibition of MAO activities because neither the presence nor the position of the fluoro group affected its inhibition of MAO. On the other hand, both the nitro and the azido groups of FNPA were shown to be important for FNPA inactivation of two types of MAO. The inhibitory potency was significantly lower for compounds without either group. Furthermore, we found that all nitrophenyl azide isomers except 2-nitrophenyl azide were photodependent inhibitors of MAO-B. Under the same experimental conditions none of the compounds photoinactivated MAO-A. On the basis of these findings, mechanisms for FNPA inhibition of the two types of MAO are discussed.