Chemo- and regio-divergent access to fluorinated 1-alkyl and 1-acyl triazenes from alkynyl triazenes

The 1,1,2,2-tetrafluoroethylene unit is prevalent in bioactive molecules and functional materials. Despite being in principle a straightforward strategy to access this motif, the direct tetrafluorination of alkynes involves very hazardous or inconvenient reagents. Therefore, safer and convenient alternatives are sought after. We developed a mild and operationally simple perfluorination method converting 1-alkynyl triazenes into 1,1,2,2-tetrafluoro alkyl triazenes, employing cheap and readily accessible reagents. Moreover, a judicious tuning of the reaction conditions enables access to α-difluoro triazenyl ketones. Complementary, electrophilic fluorination of alkynyl triazenes gives rise to the regioisomeric α-difluoro acyl triazenes. These three chemo- and regio-divergent protocols enable access to elusive fluorinated 1-alkyl and 1-acyl triazenes, thus expanding the chemical space for these unusual entities. Furthermore, several reaction intermediates and side products revealed insights on the reaction pathways that may be useful for further fluorination chemistry of alkynes.

Three mild and operationally simple fluorination protocols convert 1-alkynyl triazenes either into attractive 1,1,2,2-tetrafluoro alkyl triazenes, α-difluoro α-triazenyl ketones or α-difluoro acyl triazenes.     

Meerwein arylation with 3-fluorobutenone

3-Fluorobutenone (7) reacts with aryl triazenes in the presence of zinc iodide to give 4-aryl-3-fluoro-3-iodo-2-butanones (9a-9f) in moderate yields. The products arise from a free radical process that terminated by iodination of an alkyl radical. The process yields unusual geminal iodo-fluoro compounds.     

Divergent Asymmetric Synthesis of Polycyclic Compounds via Vinyl Triazenes

Vinyl triazenes were obtained by enantioselective [2+2] cycloaddition reactions of bicyclic alkenes with 1‐alkynyl triazenes in the presence of a Ru^II catalyst with a chiral cyclopentadienyl ligand. These triazenes serve as unique vinyl cation surrogates. Under acidic conditions, the triazene functionality can be replaced with a variety of groups, including halides, alkoxides, sulfoxides, amides, arenes, and heteroarenes, thus providing efficient access to a pool of chiral polycyclic compounds.     

Synthesis and reactivity of furazanyl- and furoxanyldiazonium salts

Diazotization of aminofurazans (1) and 4-aminofuroxans (2) with nitrosylsulfuric acid in a mixture of conc. H₂SO₄ and H₃PO₄ has been studied and offered as a general method for preparing furazanyl- (3) and furoxanyldiazonium (4) salts. It has been shown that reactions with the retention of the N-N-group (azo coupling, formation of triazenes and azides) are typical of salts3 and4, while elimination of the N₂ molecule (Sandmeyer reaction, hydrolysis, reduction) is not typical.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1949–1953, November, 1993.     

Iodination of lactate dehydrogenase isoenzymes using radioactive and inactive iodine

The iodination of lactate dehydrogenase isoenzymes which has not been attempted so far has been performed using radioactive and inactive iodine. A new method for the determination of trace amounts of protein-bound iodine in the range of 10–100 μg has been developed. Out of two methods employed for iodination, chloramine-T method was found to be superior to the lactoperoxidase method for iodination with both radioactive and inactive iodine. It was found that the amount of iodinated LDH formed during iodination depends on the amount of LDH and of the reagents used for iodination. Completely purified LHD-1 and LDH-2 isoenzymes were iodinated using both inactive and radioactive iodine. The iodinated isoenzymes were separated from the unreacted iodide by gel permeation chromatography using Sephadex G-75-120 column. The ratio of radioiodinated LDH to unreacted¹²⁵I was largest (3.72) when the amount of LDH used was 4.54 μg. The specific activity obtained when iodination was carried out under optimum conditions was 238 μCi/μg. No radiation damage for the radioiodinated LDH was observed when it is kept for as long as two weeks after iodination.     

Nouveaux types de sucres triazotés: triazènes et phénylimino-2-oxadiazoles-1,3,4. Communication préliminaire

Novel types of sugars bearing three nitrogen atoms: triazenes and 2-phenylimino-1, 3, 4-oxadiazoles . A series of aminodeoxysugars treated with p-nitrobenzenediazonium tetrafluoroborate led to the corresponding triazenes, each of which in chloroform solution existing as an equilibrium between its two tautomeric forms. The free energy of activation of the exchange of the proton between the two nitrogen atoms has been estimated by variable temperature ¹H-NMR. measurements. Each triazenylsugar gave on acetylation an unique positional isomer bearing its acyl group on the nitrogen atom directly attached to the glycosyl group. Phenylsemicarbazones of two keto-sugars were oxidized with El Khadem's reagent (I₂, HgO, MgO) to give the corresponding spiro-2-phenylimino-1, 3, 4-oxadiazoles.     

Deciphering the peptide iodination code: Influence on subsequent gas-phase radical generation with photodissociation ESI-MS

Iodination of tyrosine was recently discovered as a useful method for generating radical peptides via photodissociation of carbon-iodine bonds by an ultraviolet photon in the gas phase. The subsequent fragmentation behavior of the resulting odd-electron peptides is largely controlled by the radical. Although previous experiments have focused on mono-iodination of tyrosine, peptides and proteins can also be multiply iodinated. Tyrosine and, to a lesser extent, histidine can both be iodinated or doubly iodinated. The behavior of doubly iodinated residues is explored under conditions where the sites of iodination are carefully controlled. It is found that radical peptides generated by the loss of a single iodine from doubly iodinated tyrosine behave effectively identically to singly iodinated peptides. This suggests that the remaining iodine does not interfere with radical directed dissociation pathways. In contrast, the concerted loss of two iodines from doubly iodinated peptides yields substantially different results that suggest that radical recombination can occur. However, sequential activation can be used to generate multiple usable radicals in different steps of an MS ⁿ experiment. Furthermore, it is demonstrated that in actual peptides, the rate of iodination for tyrosine versus mono-iodotyrosine cannot be predicted easily a priori. In other words, previous assumptions that mono-iodination of tyrosine is the rate-limiting step to the formation of doubly iodinated tyrosine are incorrect.     

Convenient and Efficient Method for the Iodination of Benzylic and Aliphatic Alcohols by Using Al(HSO4)3/KI in Nonaqueous Solution

A simple and efficient method for the iodination of benzylic and aliphatic alcohols by using Al(HSO₄)₃/KI in n‐hexane as solvent is reported. Mild reaction conditions and good to excellent yields of the products are the noteworthy advantages of the method.     

An iodine-123 generator/iodination kit: A preliminary report

Preliminary results are described of a¹²³Xe filled device to serve as a combination¹²³I generator/iodination kit.¹²³X was produced in the Brookhaven Linac Isotope Producer (BLIP) by the reaction¹²⁷I(p, 5n)¹²³Xe. The device consists of a small glass ampoule containing an internal glass breakseal and a flanged neck on which was crimped a multi-injection type septum. The ampoule contained a hydrogen sulfide atmosphere to assure that the iodine generated from the decay of the xenon was in the form of iodide. Following an adequate period for¹²³Xe to decay (this period can be used for shipment), a needle is forced through the septum breaking the seal and residual gases are pumped off. The¹²³I in the form of iodide can then be rinsed from the ampoule with any desired solvent or reagent added directly to the device to carry out an iodination in an enclosed environment. Preliminary results of both iodine recovery and iodinations have been promising. This research was supported by the US Department of Energy under Contract No. DE-ACO2-76CH0016.     

Rapid aerobic iodination of arenes mediated by hypervalent iodine in fluorinated solvents

Arenes are rapidly converted to the corresponding iodides by aerobic oxidative iodination at room temperature by treatment with iodine and catalytic quantities of nitrous acid in a fluorinated solvent. Dichloroiodic acid is proposed as the actual iodination reagent.     

The photochemical behaviour of bis aryl-1,3 triazenes

The photolysis of bis aryl-1,3 triazenes carried out in non-aromatic solvents gives products whose structures are consistent with a cage recombination process of homolytically formed radicals and the subsequent abstraction of hydrogen from the solvent molecules by these arylamino radicals.In aromatic solvents, a free-radical chain process leads to the formation of products resulting from the homolytic substitution on the solvent.     

A convenient iodination of indoles and derivatives

We report a direct iodination of indole and derivative compounds with iodine monochloride (ICl) in the presence of Celite^®. This procedure has now been extended to the iodination of substituted indoles, azaindoles and pyrroles. The scope of this procedure is exemplified by the iodination of melatonin in 98% yield.     

Pentafluoroethylation of Arenediazonium Tetrafluoroborates Using On‐Site Generated Tetrafluoroethylene

Copper‐mediated pentafluoroethylation of arenediazonium tetrafluoroborates with tetrafluoroethylene (TFE) on‐site generated from TMSCF₃ has been developed as a new method to prepare pentafluoroethyl arenes. The active pentafluoroethylation reagent “CuC₂F₅” is pre‐generated from CuSCN, TFE and CsF, and its generation and further reaction are strongly solvent‐dependent. This pentafluoroethylation reaction represents the first example of Sandmeyer‐type pentafluoroethylation, which exhibits good functional group tolerance and potential applications for the synthesis of complicated bioactive compounds.     

Synthèse de N-Alkyl-arylamines par Thermolyse ou Photolyse d'Alkyl-3-diaryl-1,3-triazènes

Synthesis of N-Alkyl-arylamines by Thermolysis or Photolysis of 3-Alkyl-1,3-bis(p-chlorophenyl)triazenes The thermolysis of 3-alkyl-1,3-bis(p-chlorophenyl)triazenes in benzene or methanol leads to the formation of N-alkyl-p-chloroanilines ( 2 ) in 19–50% yield, N-alkyl-bis(p-chlorophenyl)amines ( 3 ) in 7.5–15.5% yield and 4,4′-dichlorobiphenyle ( 4 ) in 1–7% yield; besides with benzene as the substrate, 4-chlorobiphenyle ( 5 ) (12–20% yield) was also formed. The photolysis in methanol gives only the N-alkyl-p-chloroanilines ( 2 ) in 32–40% yield. In these two cases the results are consistent with a radical pair formation in a solvent cage, recombination (thermolysis) and/or diffusion (thermolysis and photolysis) with intermolecular abstraction of hydrogen. A free radical chain mechanism is involved in the photolytic process and the quantum yield is high.     

Zur thermolyse von silyltriazenen

Whilst mono(silyl)triazenes R′N=N---NR′(SiR₃) and organyl triazenes R′N=N---NR′₂ are of comparable thermal stability and decay by a radical reaction, bis(silyl)triazenes R′N=N---N(SiR₃)₂ (R′=aryl, R=Me, Et, OMe) decompose at room temperature in a non-radical reaction to yield amines R′N(SiR₃)₂ and nitrogen. Kinetic investigations of the mechanism of the non-radical thermolysis of triazenes show that the rate of the thermolysis of R′N=N---N(SiR₃)₂ is determined both from an isomerisation equilibrium forming (R₃Si)R′N---N=N(SiR₃) and from the rate of decomposition of this compound to the thermolysis products. Tris(silyl)triazenes, (R₃Si)₂N---N=N(SiR₃), hitherto not synthesized, are expected to be even more unstable than the bis(silyl)triazenes which have been examined by us.     

Direct iodination of alkanes

[reaction: see text] A cheap and efficient iodination of hydrocarbons can be achieved by generating tert-butyl hypoiodite from iodine and sodium tert-butoxide. The alkane is reactant and solvent, and this metal-free process provides a clean solution for their direct iodination.     

1,3-Bis(2-alkyltetrazol-5-yl)triazenes and their Fe(II), Co(II) and Ni(II) complexes: Synthesis,spectroscopy, and thermal properties. Crystal structure of Fe(II) and Co(II) 1,3-bis(2-methyltetrazol-5-yl)triazenide complexes

Complexes ML¹₂ and ML²₂, with M = Fe^II, Co^II, Ni^II, and 1,3-bis(2-R-tetrazol-5-yl)triazenide ligands L¹ (R = Me) and L² (R = ^tBu), have been synthesized by the reaction of corresponding 1,3-bis(2-R-tetrazol-5-yl)triazenes with metal(II) salts in basic media and characterized by IR, UV–Vis spectroscopy, thermal and X-ray diffraction analyses. Both 1,3-bis(2-R-tetrazol-5-yl)triazenes were found to deprotonate on coordination and act as tridentate chelating ligands forming distorted MN₆ octahedra around metal(II) cations.     

A Novel and Regiospecific Synthesis of 1‐Aryl‐1H‐benzotriazoles via Copper(I)‐Catalyzed Intramolecular Cyclization Reaction

1‐Aryl‐1H‐benzotriazole derivatives were synthesized via intramolecular cyclization of easily obtained triazenes, using CuI as the catalyst, DMSO as the solvent, t‐BuONa as the base, and 1,10‐phenanthroline as the ligand, in up to 97% yield. The synthesis is regiospecific and functional group‐tolerant.