Carbonyl Azide Research Articles

A facile method for vancomycin C-terminus functionalization and derivatization through hydrazide

Over 60-year clinical use of vancomycin led to the emergence of vancomycin-resistant bacteria and threatened our health. To combat vancomycin-resistant strains, numerous vancomycin analogues were developed, such as Telavancin, Oritavancin and Dalbavancin. Extra structures embedded on C-terminus has been proved to be an effective strategy to promote antibacterial activity of vancomycin against vancomycin-resistant strains. Here, we reported a facile strategy, inspired by native chemical ligation, for vancomycin C-terminus functionalization and derivatization. The introduction of C-terminal hydrazide on vancomycin not only provided us an accessible method for C-terminus functionalization through carbonyl azide and thioester, also acted as an efficient site for vancomycin structure modifications. Based on hydrazide-vancomycin, we effectively conjugated cysteine and cysteine containing peptides onto vancomycin C-terminus, and two fluorescent FITC-vancomycin were prepared through Cys-Maleimide conjugation. Meanwhile, we introduced lipophilic structures onto vancomycin C-terminus via the hydrazide moiety. The obtained vancomycin derivatives were evaluated against both Gram-positive and negative bacteria strains.

Metalloradical activation of carbonyl azides for enantioselective radical aziridination

Organic azides have been increasingly employed as nitrogen sources for catalytic olefine aziridination due to their ease of preparation and generation of benign N2 as the only byproduct. Among common organic azides, carbonyl azides have not been previously demonstrated as effective nitrogen sources for intermolecular olefin aziridination despite the synthetic utilities of N-carbonyl aziridines. As a new application of metalloradical catalysis, we have developed a catalytic system that can effectively employ the carbonyl azide TrocN3 for highly asymmetric aziridination of alkenes at room temperature. The resulting enantioenriched N-Trocaziridines have been shown as valuable chiral synthons for stereoselective synthesis of other chiral aziridines and various chiral amines. The Co(II)-based metalloradical system, which proceeds with distinctive stepwise radical mechanism, may provide a general method for asymmetric synthesis of chiral aziridines from alkenes with organic azides.

Nitrocarbamoyl Azide O2NN(H)C(O)N3: A Stable but Highly Energetic Member of the Carbonyl Azide Family.

The diazotization of nitrosemicarbazide (1) resulted in the formation and isolation of nitrocarbamoyl azide (2), which was thoroughly characterized by spectroscopic and structural methods. This compound shows surprising stability but also high reactivity and sensitivity, with a melting point of 72 °C and a detonative decomposition point at 83 °C. In addition, five selected salts were synthesized by careful deprotonation. The decomposition mechanism of 2 in solution was investigated and could be clarified by performing experiments using methanol and hydrazine as trapping reagents. The energetic and physicochemical properties of all these compounds were investigated and classified.

Why does 4-biphenyl carbonyl azide have ultra-short lived excited states? An ultrafast UV-vis spectroscopic and computational study.

Upon excitation at 308 nm, 4-biphenyl carbonyl azide (4-BpCON3) shows unusually fast decay of transient absorption associated with the first excited singlet state, with time constants of several ps in MeOH, acetonitrile, and CHCl3. In cyclohexane and cyclohexene, the lifetimes are ca. 0.3 ps, which is in stark contrast to the lifetimes of hundreds of ps in the case of 2-naphthoyl azide. Furthermore, photolysis at 266 and 308 nm brought about the same yields of nitrene and isocyanate products. To understand these findings, we also applied ultrafast transient absorption spectroscopy to the structurally related molecule, fluorene-2-carbonyl azide (F2CON3), in which the two phenyl rings are fixed in a plane by a methylene group. Both carbonyl azides (biphenyl and fluorenyl) have very short lived excited states in different solvents, indicating that the twisting of phenyl rings is not the reason for the fast decay. Theoretical studies using time dependent density functional theory (TDDFT), especially with PBE0 and CAM-B3LYP functionals, suggest that excited-state potential energy surface crossings lead to the efficient and fast decomposition of carbonyl azides upon photoexcitation. Especially, the decay of the Franck-Condon state to the S1 state with π(CON3)-π*(N3') transition character, where -N3 is in a bent conformation (∠NNN = ca. 125°), is the key step. Finally, a model is presented to explain solvent dependence, different decaying rates, and other experimental findings.

Photoinduced Curtius rearrangements of fluorocarbonyl azide, FC(O)N3: a QM/MM nonadiabatic dynamics simulation.

Upon either photolysis or pyrolysis, carbonyl azide can eliminate molecular nitrogen along with the formation of isocyanate. Though two different pathways (namely stepwise versus concerted) have been proposed, the detailed decomposition mechanism is still elusive to date. Herein, we have employed combined electronic structure calculations and nonadiabatic dynamics simulations to study the radiationless deactivation and rearrangement mechanisms of FC(O)N3 in the S3, S2, S1, and S0 states in an argon matrix. On the basis of QM(CASPT2)/MM calculations, we found that, upon 193 nm irradiation, the excited-state decay of FC(O)N3 from the S3 state via S2 and S1 to the S0 state is an ultrafast process and could be completed within 100 fs, and a subsequent Curtius rearrangement occurs in the period of ∼300 fs; the elimination of N2 and the formation of fluorocarbonyl nitrene FC(O)N could take place in both S1 and S0 states rather than in higher excited states; the isomerization from FC(O)N to FNCO involves a stepwise mechanism and could only be found in the S0 state. This mechanistic scenario has been verified by both electronic structure calculations and full-dimensional trajectory-based "on the fly" QM(CASPT2)/MM nonadiabatic dynamics simulations. Finally, the currently calculated results provide important mechanistic insights for similar carbonyl azides.

Aspartic Acid Side-Chain Benzyl Ester as a Multifunctionalization Precursor for Synthesis of Branched and Cyclic Arginylglycylaspartic Acid Peptides

Here, we report a peptide aspartic acid side-chain benzyl ester as a useful precursor that can be efficiently converted into various functional groups, including acid, amide, carbonyl hydrazide, carbonyl azide, or thio ester groups, without other protection for the peptide. With this strategy, we synthesized a series of novel branched and cyclic arginylglycylaspartic acid peptides through successive peptide C-terminal ligation and side-chain ligation based on a side-chain carbonyl azide or thio ester.

ChemInform Abstract: Cu(0) Nanoparticle Catalyzed Efficient Reductive Cleavage of Isoxazoline, Carbonyl Azide and Domino Cyclization in Water Medium.

AbstractSmall Cu(0) nanoparticles fabricated in situ exhibit high catalytic reduction properties towards the heteroatomic cleavage of N—O bonds, homoatomic N—N bonds and domino cyclizations to afford 2‐hydroxy‐ketones (II), primary amides (V) and pyrroline‐5‐ones (III).

Chlorodifluoroacetyl Azide, ClF2CC(O)N3: Preparation, Properties, and Decomposition

Chlorodifluoroacetyl azide, ClF(2)CC(O)N(3), was prepared and characterized by IR (gas, Ar matrix), Raman (liquid), UV-vis (gas), and (19)F, (13)C NMR spectroscopy. The vibrational spectra were analyzed in terms of a single conformer, gauche-syn, where the Cl-C and the N(α)═N(β) bonds are gauche and syn to the C═O bond, respectively. The photo and thermal decomposition reactions of the azide were studied with the aid of matrix isolation. In both cases, a new isocyanate species ClF(2)CNCO was produced and characterized by matrix IR spectroscopy. The conformational properties and the Curtius rearrangement pathways of this new carbonyl azide were theoretically explored, which suggest the preference of a concerted over stepwise decomposition for the global minimum gauche-syn conformer.

Cu(0) nanoparticle catalyzed efficient reductive cleavage of isoxazoline, carbonyl azide and domino cyclization in water medium

Small Cu(0)-nanoparticles (NPs) are fabricated utilizing CuSO4·5H2O, surfactant (SDS) and ascorbic acid in aqueous medium. Its outstanding catalytic activity under low catalyst loading is developed toward reductive cleavage of isoxazoline, carbonyl azide and domino cyclization to furnish valuable 2-hydroxy-4-keto esters, primary amides and a new class of heterocycle, 4-hydroxy-2-pyrroline-5-one.

Why Lewis acids accelerate the thermal Curtius rearrangement of benzoyl azide into phenyl isocyanate

The thermal Curtius rearrangement of benzoyl azide in the presence of Lewis acids has been studied by DFT (PBE/TZ2P) method. The complexation of Lewis acids (BF 3, AlCl 3, SbCl 5) with benzoyl azide leads to the formation of 1:1 and 1:2 stable complexes with interaction of catalysts with O and N atoms of carbonyl azide group. The potential energy surfaces of the catalytic rearrangement have been calculated for each complex and the relation between the complexes and the transition states on potential energy surface have been established by IRC calculation. The energy barriers for catalytic reactions are significantly lower in the most cases in comparison with an uncatalyzed reaction. The activation energy is decreasing in the range of Lewis acids AlCl 3 > SbCl 5 > BF 3 and it correlates with the decreasing of Lewis acids strength. The Mulliken bond population analysis has been done for three compounds RCON 3 (R = H, Me, Ph) and for their complexes, and for all corresponding transition states using the B3LYP/6-311G∗ approximation. The interaction of Lewis acids with carbonyl azide group causes the decreasing of N1 N2 bond strength and it helps the thermal Curtius rearrangement to proceed.

Hydroxyl‐ and amine‐terminated hyperbranched polyurethanes using AB2‐type azide monomers: Synthesis, characterization, fluorescence, and charge‐transfer complexation studies

AbstractNovel AB2‐type azide monomers such as 3,5‐bis(4‐methylolphenoxy)carbonyl azide (monomer 1), 3,5‐bis(methylol)phenyl carbonyl azide (monomer 2), 4‐(methylol phenoxy) isopthaloyl azide (monomer 3), and 5‐(methylol) isopthaloyl azide (monomer 4) were synthesized. Melt and solution polymerization of these monomers yielded hydroxyl‐ and amine‐terminated hyperbranched polyurethanes with and without flexible ether groups. The structures of theses polymers were established using FT‐IR and NMR spectroscopy. The molecular weights (Mw) of the polymers were found to vary from 3.2 × 103 to 5.5 × 104 g/mol depending on the experimental conditions used. The thermal properties of the polymers were evaluated using TGA and DSC: the polymer obtained from monomer (1) exhibited lowest Tg and highest thermal stability and the polymer obtained from monomer (2) registered the highest Tg and lowest thermal stability. All the polymers displayed fluorescence maxima in the 425–525 nm range with relatively narrow peak widths indicating that they had pure and intense fluorescence. Also, the polymers formed charge transfer (CT) complexes with electron acceptor molecules such as 7,7,8,8‐tetracyano‐quino‐dimethane (TCNQ) and 1,1,2,2‐tetracyanoethane (TCNE) as evidenced by UV‐visible spectra. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3337–3351, 2009

Hyperbranched poly(ether–urea)s using AB2‐type blocked isocyanate monomer and azide monomer: Synthesis, characterization, reactive end functionalization, and copolymerization with AB monomer

Abstract3,5‐bis(4‐aminophenoxy)phenyl phenylcarbamate—a novel AB2‐type blocked isocyanate monomer and 3,5‐bis{ethyleneoxy(4‐aminophenoxy)}phenyl carbonyl azide—a novel AB2‐type azide monomer were synthesized in high yield. Step‐growth polymerization of these monomers were found to give a first example of hyperbranched poly (aryl‐ether‐urea) and poly(aryl‐alkyl‐ether‐urea). Molecular weights (Mw) of the polymer were found to vary from 1,858 to 52,432 depending upon the monomer and experimental conditions used. The polydispersity indexes were relatively narrow due to the controlled regeneration of isocyanate functional groups for the polymerization reaction. The degree of branching (DB) was determined using 1H‐NMR spectroscopy and the values ranged from 87 to 54%. All the polymers underwent two‐stage decomposition and were stable up to 300 °C. Functionalized end‐capping of poly(aryl‐ether‐urea) using phenylchloroformate and di‐t‐butyl dicarbonate (Boc)2O changed the thermal properties and solubility of the polymers. Copolymerization of AB2‐type blocked isocyante monomer with functionally similar AB monomer were also carried out. The molecular weights of copolymers were found to be in the order of 6 × 105 with narrow dispersity. It was found that the Tg's of poly(aryl‐alkyl‐ether‐urea)s were significantly less (46–49 °C) compared to poly(aryl‐ether‐urea)s. Moreover the former showed melting transition at 154 °C, which was not observed in the latter case. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2959–2977, 2007

Pyridazine Derivative and Related Compound, Part 18:1 Pyridazino [3′,4′:3,4]pyrazolo [5,1-c]-1,2,4-triazine-3-carboxylic Acid: Synthesis, Reactions, and Antimicrobial Activity

A series of 3-substituted pyridazino[3′,4′:3,4]pyrazolo[5,1-c]-1,2,4-triazens have been synthesized starting from the 3-carboxylic acid derivative 2. The reaction of the acid chloride 3 with amines gave the corresponding anilides 4. The reaction of 2 with ethyl chloroformate and sodium azide in the presence of triethyl amine gave the carbonyl azide 5, which underwent a Curtius rearrangement in boiling ethanol to afford the carbamate 6, which converted to the 3-amino derivative 7 upon alkaline hydrolysis, and the reaction with acid chloride resulted in N-substituted products 9. On other hand, the reaction of the carboxylic acid 2 with POCl3 and thiosemicarbazide afforded 2-amino-1,3,4-thiadiazole derivative 13. The condensation of 13 with aldehydes furnished 14 in a good yield. The products were screened for their antimicrobial activity against six microorganisms.

A Facile Route for the One‐Step Synthesis of New Fully Aromatic Poly(urea‐imide)s

The direct preparation of various aromatic poly(urea‐imide)s (5a1 –5b4 ) from N‐[3,5‐bis(trimellitimido)phenyl]phthalimide (1) using diphenylphosphoryl azide (DPPA) was investigated. The polymers were obtained by the conversion of imide ring‐containing diacid 1 to corresponding di(carbonyl azide) 2 with DPPA and then to diisocyanate 3 through the Curtius rearrangement of compound 2. This was followed by polyaddition of 3 with two aromatic diamines (4a and 4b). In order to compensate the diisocyanate shortage against the diamines, some excess amounts of the initial triimide‐dicarboxylic acid 1 were used. The molecular weights of the resulting poly(urea‐imide)s were evaluated viscometrically. The poly(urea‐imide)s exhibited an excellent solubility in a variety of polar solvents. The crystallinity nature of the polymers was estimated by means of WXRD. The glass transition temperatures and the 10% wt loss temperatures of the polymers 5a3 and 5b3 were determined by DSC and TGA/DTG methods in nitrogen atmosphere, respectively. The transparent films of the resulting polymers were also prepared by casting the solution.

Direct synthesis of new soluble and thermally stable poly(urethane‐imide)s from an imide ring‐containing dicarboxylic acid using diphenylphosphoryl azide

AbstractThe direct preparation of various aromatic poly(urethane‐imide)s from 4‐p‐biphenyl‐2,6‐bis(4‐trimellitimidophenyl)pyridine (1) using diphenylphosphoryl azide (DPPA) was investigated. The polymers were mainly obtained by the conversion of imide ring‐containing diacid 1 to corresponding di(carbonyl azide) 2 with DPPA and then to diisocyanate 3 through the Curtius rearrangement of compound 2 followed by polyaddition of 3 in different amounts with aromatic dihydroxy compounds. The molecular weights of the resulting poly(urethane‐imide)s were evaluated viscometrically. All of the resulted polymers were thoroughly characterized by spectroscopic methods and elemental analyses. The poly(urethane‐imide)s exhibited an excellent solubility in a variety of polar solvents. Crystallinity nature of the polymers was estimated by means of WXRD. The glass‐transition temperatures of the polymers determined by DSC method were in the range of 191–202°C. The 10% weight loss temperatures of the poly(urethane‐imide)s from their thermal gravimetric analysis curves were found to be in the range of 392–416°C in nitrogen. The films of the resulting polymers were also prepared by casting the solution. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 869–877, 2006

Synthesis and characterization of N‐substituted hyperbranched polyureas

AbstractN,N′‐disubstituted hyperbranched polyureas with methyl, benzyl, and allyl substitutents were synthesized starting from AB2 monomers based on 3,5‐diamino benzoic acid. Carbonyl azide approach, which generates isocyanate group in situ on thermal decomposition, was used for the protection of isocyanate functional groups. The N‐substituted hyperbranched polymers can be considered as the new class of internally functionalized hyperbranched polyureas wherein the substituent can function either as receptor or as a chemical entity for selective transformations as a tool to tailor the properties. The chain‐ends were also modified by attaching long chain aliphatic groups to fully realize the interior functionalization. This approach opens up a possible synthetic route wherein different functional substituents can be used to generate a library of internally functionalized hyperbranched polymers. All the hyperbranched polyureas were characterized by FTIR, 1H‐NMR, DSC, TGA, and size exclusion chromatography. Degree of branching in these N,N′‐disubstituted hyperbranched polyureas, as calculated by 1H‐NMR spectroscopy using model compounds, was found to be lower than the unsubstituted hyperbranched polyurea and is attributed to the lower reactivity of N‐substituted amines compared to that of unsubstituted amines. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5134–5145, 2004

Enzymatic and hyperglycemia stability of chemically modified insulins with hydrophobic acyl groups

The acylated insulins were synthesized by the reaction of insulin protected by p-methoxybenzoxy carbonyl azide at Gly-A1 site with N-hydroxysuccinimide ester of caproic acid or benzoic acid (Cap-insulin and Bz-insulin). The noteworthy aspects are as follows: (a) the acylated insulins were more stable to the decomposition by various digestive enzymes as compared with native insulin in vitro. (b) Animal experiments using normal rats in vivo revealed that the Bz-insulin had an effective hypoglycemia activity almost similar to that of native insulin.

Synthesis of 4,5-difluoroimidazole

5-Fluoroimidazole-4-carboxylic acid ethyl ester was converted to the corresponding hydrazide. Oxidation of the hydrazide to the carbonyl azide and Curtius rearrangement in t-butyl alcohol produced 4- t-butyloxycarbonylamino-5-fluoroimidazole. Dissolution of the t-butyl carbamate in 50% HBF 4, in situ diazotation of the resulting amine, and irradiation produced the target compound.

Hyperbranched polyurethanes with varying spacer segments between the branching points

Hyperbranched polyurethanes, with varying oligoethyleneoxy spacer segments between the branching points, have been synthesized by a one-pot approach starting from the appropriately designed carbonyl azide that incorporates the different spacer segments. The structures of monomers and polymers were confirmed by IR and 1H-NMR spectroscopy. The solution viscosity of the polymers suggested that they were of reasonably high molecular weight. Reversal of terminal functional groups was achieved by preparing the appropriate monohydroxy dicarbonyl azide monomer. The large number of terminal isocyanate groups at the chain ends of such hyperbranched macromolecules caused them to crosslink prior to its isolation. However, carrying out the polymerization in the presence of 1 equiv of a capping agent, such as an alcohol, resulted in soluble polymers with carbamate chain ends. Using a biphenyl-containing alcohol as a capping agent, we have also prepared novel hyperbranched polyurethanes with pendant mesogenic segments. These mesogen-containing polyurethanes, however, did not exhibit liquid crystallinity probably due to the wholly aromatic rigid polymer backbone. © 1996 John Wiley & Sons, Inc.

Functionalization of carbon fibres

AbstractThis work reports on a study conducted to achieve carbon fibre functionalization by means of a diazide derivative(p‐(azidosulfonyl)benzoyl azide) in two stages. The first stage comprises surface oxidation of the fibres, which causes an increase of the number of superficial COOH groups. During the second stage the oxidated fibres are brought to react with the diazide derivative via the isocyanate group, obtained by means of the Curtius transposition of the carbonyl azide groups. Fibre oxidation depends on reaction time, following a similar patterns as the one described for carbon black particles. Oxidized fibres functionalization is evidenced both in the progressive decreases in SO2N3 groups in the reagent solution and through differential scanning calorimetry analysis (DSC), which shows an exothermal peak around 190°C due to the decomposition of the azide grafted onto the carbon fibre.The degree of attainable functionalization is a function of COOH groups concentration, generated during fibre oxidation, and the ratio of the functionalizing agent with regard to the carboxy groups formed.