Bridgehead Nitrogen Atoms Research Articles

Asymmetric Synthesis of Unusual Fused Tricyclic β‐Lactam Structures via Aza‐Cycloadditions/Ring Closing Metathesis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric synthesis of unusual fused tricyclic beta-lactam structures via aza-cycloadditions/ring closing metathesis.

Conveniently substituted bis-beta-lactams, pyrrolidinyl-beta-lactams, and piperidinyl-beta-lactams undergo ring-closing methatesis using Grubbs' carbene, Cl(2)(Cy(3)P)(2)Ru=CHPh, to give medium-sized rings fused to bis-2-azetidinone, pyrrolidinyl-2-azetidinone, or piperidinyl-2-azetidinone systems. The diolefinic cyclization precursors can be obtained from optically pure 4-oxoazetidine-2-carbaldehydes bearing an extra alkene tether at position 1 or 3 of the beta-lactam ring via [2 + 2] cycloaddition of imino 2-azetidinones, N-metalated azometine ylide [3 + 2] cycloaddition, and subsequent N-acylation of the pyrrolidinyl nitrogen atom, or through aza-Diels-Alder cycloaddition of 2-azetidinone-tethered imines. Under standard reaction conditions, the combination of cycloaddition reactions of 2-azetidinone-tethered imines with ring-closing methatesis offers an asymmetric entry to a variety of unusual fused tricyclic 2-azetidinones bearing two bridgehead nitrogen atoms.

NMR spectroscopic studies of some fused thiazoloazinium ring system containing bridgehead-nitrogen atom

Several fused thiazoloazinium salts have been prepared and fully characterized by using modern NMR techniques as NOE experiments and two-dimensional heterocorrelation (g-HSQC and g-HMBC) measurements. Basic molecular parameters like atomic charges and bond orders have been determined by ab initio and DFT calculations in order to rationalize the site selectivity of reactions of these salts with nucleophiles. Satisfactory correlation has been found between these parameters and the experimentally measured 13C NMR chemical shifts.

Heterocyclic synthesis containing bridgehead nitrogen atom: Synthesis of 3‐[(2H)‐2‐oxobenzo[b]pyran‐3‐yl]‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazine and thiazole derivatives

AbstractThe reaction of 2H‐2‐oxobenzo[b]pyran‐3‐hydrazide (2) with carbon disulfide in basic DMF afforded potassium thiocarbamate 3, which readily underwent heterocyclization upon its reaction with hydrazine and/or phenacyl bromide to yield 1,2,4‐tiazole (4) and thiazole 7 derivatives, respectively. Condensation of 4 with substituted phenacyl bromide and/or chloranil gave 1,2,4‐triazole[3,4‐b]thiadiazine (5a,b) and 3,10‐bis‐[2H‐2‐oxobenzo[b]pyran‐3‐yl]‐6,13‐dichloro‐bis‐1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazino[5′,6′‐b:5′,6′‐e]cyclohexa‐1,4‐diene (6), respectively. Cyclization of thiosemicarbazide 10 by refluxing it in sodium hydroxide and/or phosphoryl chloride afforded triazole 13 and thiadiazole 15 derivatives, respectively. Also, 10 reacted with phenacyl bromide in the presence of anhydrous sodium acetate to give the oxothiazolidine derivative 17. The structure of the synthesized compounds were confirmed by elemental analyses, IR, 1H NMR, and mass spectra. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:114–120, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10109

Internal hydrogen bonding and amide co-ordination in zinc(ii) complexes of a tripodal N4 ligand: structural, spectroscopic and reactivity studies

The tripodal N4 ligand N,N-bis(2-pyridylmethyl)-N-(6-pivaloylamido-2-pyridylmethyl)amine (bppapa) presents an N–H group for hydrogen bonding to an adjacent metal-bound ligand, and a carbonyl group for metal co-ordination. These binding features are key in metallopeptidase catalysis, which is an area of considerable current interest. The X-ray crystal structure and 1H NMR studies of bppapa show an intramolecular C–H⋯OC interaction involving the pivaloylamido unit that determines the orientation of the amide N–H and CO groups relative to the N4 metal binding site. The reaction of [Zn(NCCH3)4](PF6)2 with bppapa affords [(bppapa)Zn](PF6)21. The X-ray crystal structure of 1·0.5CH3OH shows a zinc(II) ion in a trigonal-bipyrimidal environment in which the bridgehead nitrogen atom of the ligand and the carbonyl oxygen of the pivaloylamido group co-ordinate axially. 1H and 13C NMR and IR spectra show that this structure is retained in acetonitrile solution. The reaction of ZnCl2 with bppapa in acetonitrile affords the salt [(bppapa)Zn(Cl)](Cl) 2, which in methanol undergoes anion metathesis with NaBPh4 (1 equiv.) to form [(bppapa)Zn(Cl)](BPh4) 2′and NaCl. The X-ray crystal structure of 2′·CH3CN shows that the chloride ion occupies one of the axial co-ordination sites of the trigonal-bipyramidal co-ordination geometry of the zinc(II) center. In addition, this structure reveals internal N–H⋯Cl–Zn, C–H⋯Cl–Zn and C–H⋯OC hydrogen bonding. Remarkably, all these interactions are retained in solution and are clearly reflected in the 1H NMR spectra, which we prove can be used as a powerful diagnostic tool for determining the solution structures of these and related metal complexes. IR spectroscopy was used to determine the strength of the N–H⋯Cl hydrogen bond, which was estimated to be at least 10.3 ± 0.6 kJ mol−1 in acetonitrile solution and 14.9 ± 0.6 kJ mol−1 in the solid state. The [(bppapa)Zn(Cl)]+ cation is very stable to substitution of the chloride ion by water, which may be an indication of the stabilising effect exerted by internal hydrogen bonding.

Heterocyclic Fused Rings with Bridgehead Nitrogen Atoms: Single Step Synthesis of Several Polyfunctionally Substituted Fused Pyridines

Heterocyclic Fused Rings with Bridgehead Nitrogen Atoms: Single Step Synthesis of Several Polyfunctionally Substituted Fused Pyridines

Dopamine interaction in the absence and in the presence of Cu2+ ions with macrocyclic and macrobicyclic polyamines containing pyrazole units. Crystal structures of [Cu2(L1)(H2O)2](ClO4)4 and [Cu2(H-1L3)](ClO4)3*2H2O.

The interaction with Cu2+ and dopamine of three polyazacyclophanes containing pyrazole fragments as spacers is described. Formation of mixed complexes Cu2+-macrocycle-dopamine has been studied by potentiometric methods in aqueous solution. The crystal structures of the complexes [Cu2(L1)(H2O)2](ClO4)4*2H2O (4) (L1 = 13,26-dibenzyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo[22.2.1.1(11,14)]octacosa-1(27),11,14(28),24-tetraene) and [Cu2(H-1L3)](HClO4)(ClO4)2*2H2O (6) (L3 = 1,4,7,8,11,14,17,20,21,24,29,32,33,36-tetradecaazapentacyclo[12.12.12.1(6,9).1(19,22).1(31,34)]hentetraconta-6,9(41),19(40),21,31,34(39)-hexaene) are presented. In the first one (4), each Cu2+ coordination site is made up by the three nitrogens of the polyamine bridge, a sp2 pyrazole nitrogen and one water molecule that occupies the axial position of a square pyramid. The distance between the copper ions is 6.788(2) A. In the crystal structure of 6, the coordination geometry around each Cu2+ is square pyramidal with its base being formed by two secondary nitrogens of the bridge and two nitrogen atoms of two different pyrazolate units which act as exobidentate ligands. The axial positions are occupied by the bridgehead nitrogen atoms; the elongation is more pronounced in one of the two sites [Cu(1)-N(1), 2.29(2) A; Cu(2)-N(6), 2.40(1) A]. The Cu-N distances involving the deprotonated pyrazole moieties are significantly shorter than those of the secondary nitrogens. The Cu(1)...Cu(2) distance is 3.960(3) A. The pyrazole in the noncoordinating bridge does not deprotonate and lies to one side of the macrocyclic cavity. One of the aliphatic nitrogens of this bridge is protonated and hydrogen bonded to a water molecule, which is further connected to the sp2 nitrogen of the pyrazole moiety through a hydrogen bond. The solution studies reveal a ready deprotonation of the pyrazole units induced by coordination to Cu2+. In the case of L2 (L2 = 3,6,9,12,13,16,19,22,25,26-decaazatricyclo[22.2.1.1(11,14)]octacosa-1(27),11,14(28),24-tetraene), deprotonation of both pyrazole subunits is already observed at pH ca. 4 for 2:1 Cu2+:L2 molar ratios. All three free receptors interact with dopamine in aqueous solution. L3 is a receptor particularly interesting with respect to the values of the interaction constants over five logarithmic units at neutral pH, which might suggest an encapsulation of dopamine in the macrocyclic cage. All three receptors form mixed complexes Cu2+-L-dopamine. The affinity for the formation of ternary dopamine complexes is particularly high in the case of the binuclear Cu2+ complexes of the 1-benzyl derivative L1.

ChemInform Abstract: Research on Potentially Bioactive Aza and Thiaza Polycyclic Compounds Containing a Bridgehead Nitrogen Atom. Part 3. Synthesis and Antimicrobial Activity of Some 1,4‐Benzothiazines and Pyrrolobenzothiazines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A parallel preparation of a bicyclic N-chiral amine library and its use for chiral catalyst screening

A parallel library of optically active bicyclic tertiary amines bearing N-chiral bridgehead nitrogen atoms was readily prepared by condensation of primary amines, cyclic amino acids and aldehydes. The enantiocontrolling ability of each of the library members was examined for the asymmetric alkylation of benzaldehyde with diethylzinc, and (3 R,6 R,7a S)-(2,3-diphenyl-6-hydroxy)hexahydro-1 H-pyrrolo[1,2- c]imidazol-1-one, which contains a β-amino alcohol unit, showed high enantioselectivity.

Unusual Fused Tricyclic 2-Azetidinones: Stereocontrolled Synthesis of Rigid Dipeptide Surrogates from β-Lactam-Tethered Imines via Sequential Cycloaddition/Ring-Closing Metathesis

The combination of [3+2] and [2+2] cycloaddition reactions of 2-azetidinone-tethered imines with ring-closing methatesis offers an asymmetric entry to a variety of unusual fused tricyclic 2-azetidinones bearing a bridgehead nitrogen atom, related to conformationally restricted peptidomimetics.

ChemInform Abstract: Synthesis and Reactivity of Linearly Fused Isoquinolines and Isoquinolinium Salts with Bridge‐Head Nitrogen Atom

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Research on potentially bioactive aza and thiaza polycyclic compounds containing a bridgehead nitrogen atom. III. Synthesis and antimicrobial activity of some 1,4‐benzothiazines and pyrrolobenzothiazines

AbstractCyclization reactions of N‐(2,2‐dialkoxyethyl)‐1,4‐benzothiazine lactams 2 and 1,4‐benzothiazine‐sulfones 10 lead to the corresponding pyrrolo[1,2,3‐de]‐1,4‐benzothiazines 4 and 12, respectively, by using the dioxane/p‐toluenesulfonic acid or polyphosphoric acid/chloroform systems. In contrast, in the same reaction conditions, 1,4‐benzothiazines 5a‐h do not provide the expected pyrrolobenzothiazines 7, and as for 5c‐h considerable amount of the 2‐amino‐phenyl‐sulfide 8 was obtained. The results of microbiological assays are reported.

ChemInform Abstract: Polyheterocyclic Ring Systems with Bridgehead Nitrogen Atoms: A Facile Route to Some Novel Azolo-1,2,4-triazine Derivatives.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Complexation Properties of Heteroditopic Cryptands towards Cu2+, Zn2+, Cd2+, and Pb2+ in Aqueous Solution: Crystal Structures of [(H5L1)(ClO4)5]·4 H2O and [(NiL2Cl)Cl]·5.5 H2O·CH3OH

The protonation and metal ion (Cu2+, Zn2+, Cd2+, Pb2+) complexation abilities of three heteroditopic cryptands in solution are described and the relevant equilibrium constants are reported. The two distinct binding subunits of the ligands act cooperatively in the coordination of M(H2O)2+ (M = metal ion) species. The cryptand L1 binds five protons in very acidic solution and crystallizes as [(H5L1)(ClO4)5].4 H2O in the monoclinic space group P21ln with a = 14.281(4), b = 14.313(7), c = 24.082(8) A, β = 92.00(2)°, Z = 4, R = 0.079, and wR2 = 0.2010. The molecule shows an endo-endo conformation with a pseudo-threefold symmetry axis passing through the two bridgehead nitrogen atoms. All the cryptands (L1-L3) readily form inclusion complexes with Cu2+, Ni2+, Zn2+, Cd2+, and Pb2+ ions at the tren end of the cavity. The crystal structure of [(NiL2Cl)Cl].5.5 H2O.CH3OH is also reported [C2/c, a = 26.671(6), b = 16.784(4), c = 18.591(8) A, β = 101.006(14)°, Z = 8, R = 0.091, and wR2 = 0.1424]. The NiII ion resides in a trigonal-bipyramidal coordination environment with the equatorial sites occupied by the three secondary nitrogen atoms of the cryptand and the axial sites occupied by a bridgehead nitrogen atom and a Cl- ion.

Polyheterocyclic Ring Systems with Bridgehead Nitrogen Atoms: A Facile Route to Some Novel Azolo-1,2,4-triazine Derivatives

The synthesis of the entitled azolo-1,2,4-triazines via the reaction of some functionalized thiazole derivatives with several heterocyclic diazonium salts is described.

Synthesis of Heterocyclic Quinones Containing Bridgehead Nitrogen Atom from 2-Aminonaphtho[2,3-d]thiazole-4,9-dione.

Article Synthesis of Heterocyclic Quinones Containing Bridgehead Nitrogen Atom from 2-Aminonaphtho[2,3-d]thiazole-4,9-dione. was published on December 1, 2000 in the journal Heterocyclic Communications (volume 6, issue 6).

Template synthesis, crystal structure, and solution behavior of a hexaaza macrocyclic nickel(II) complex containing two N-aminoethyl pendant arms

A new nickel(II) complex of the 14-membered hexaaza macrocyclic ligand 1,8-bis(2-aminoethyl)-1,3,6,8,10,13-hexaazacyclotetradecane (L 1), in which two 2-aminoethyl pendant arms are attached to the bridgehead nitrogen atoms, has been prepared by the one-pot reaction of ethylenediamine and formaldehyde in the presence of the metal ion. The complex [NiL 1] 2+ has a square-planar coordination geometry in the solid state and in nitromethane; the pendant amino groups are not coordinated to the metal ion. The crystal structure of [Ni(H 2L 1)](ClO 4) 4 (H 2L 1=a protonated form of L 1) shows that the four secondary nitrogen atoms are coordinated to the nickel(II) ion with a 5-6-5-6 chelate ring sequence. The nickel(II) ion is located at the inversion center of the N 4 square. The complex [NiL 1] 2+ exists in aqueous solutions as a mixture of the square-planar and octahedral [NiL l(H 2O) 2] 2+ species. The addition of HCl (0.1–3.0 M) to aqueous solutions of the complex increases the concentration of the square-planar species, in contrast to the case for [NiL 2] 2+ (L 2=1,8-bis(2-aminoethyl)-1,3,6,8,10,13-hexaazacyclotetradecane) and other related hexaaza and pentaaza macrocyclic complexes. On the other hand, the addition of NaOH to the solution of [NiL 1] 2+ or [NiL 2] 2+ increases the proportion of the octahedral species. Synthesis, characterization, and solution behavior of the nickel(II) complexes of L 1 are reported.

Cage peroxides having planar bridgehead nitrogen atoms

Three new cage peroxides, 1,6-diaza-3,4,8,9-tetraoxabicyclo[4.4.2]dodecane (3a),1,6-diaza-3,4,8,9-tetraoxa-11-methylbicyclo[4.4.2]dodecane (3b), and 1,6-diaza-3,4,8,9-tetraoxatricyclo[4.4.2.411,12]hexadecane (4), have been prepared by reaction of 1,2-diaminoethane, 1,2-diaminopropane, and trans-1,2-diaminocyclohexane, respectively, with formaldehyde and hydrogen peroxide in aqueous acidic solution. Their structures have been established by X-ray diffraction, and show the bridgehead nitrogen atoms to be predominantly sp2 hybridized. The structures accord with 1H and 13C NMR spectra. Variable temperature NMR studies show that the diperoxide 3a begins to undergo rapid inversion (on the NMR time scale) at about 303 K; up to 370 K the diperoxides 3b and 4 show no conformational change.Key words: cage compounds, formaldehyde, peroxides, amine nitrogen, hybridization.

Cage peroxides having planar bridgehead nitrogen atoms

Three new cage peroxides, 1,6-diaza-3,4,8,9-tetraoxabicyclo[4.4.2]dodecane (3a),1,6-diaza-3,4,8,9-tetraoxa-11methylbicyclo[4.4.2]dodecane (3b), and 1,6-diaza-3,4,8,9-tetraoxatricyclo[4.4.2.411,12]hexadecane (4), have been prepared by reaction of 1,2-diaminoethane, 1,2-diaminopropane, and trans-1,2-diaminocyclohexane, respectively, with formaldehyde and hydrogen peroxide in aqueous acidic solution. Their structures have been established by X-ray diffraction, and show the bridgehead nitrogen atoms to be predominantly sp2 hybridized. The structures accord with 1H and 13C NMR spectra. Variable temperature NMR studies show that the diperoxide 3a begins to undergo rapid inversion (on the NMR time scale) at about 303 K; up to 370 K the diperoxides 3b and 4 show no conformational change.

Synthesis and crystal structure of the bromide salt of the inside protonated form of the cage amine [(2.3)3]adamanzane, 1,4,8,12-tetraazatricyclo[6.6.3.24,12]nonadecane and synthesis of the bowl amine [(2.3)2.21]adamanzane, 1,5,9,12-tetraazabicyclo[7.5.2]hexadecane

The reaction of 1,4,7-triazacyclononane with tris(3-chloropropyl)amine affords the inside monoprotonated form of the tricyclic amine 1,4,8,12-tetraazatricyclo[6.6.3.24,12]nonadecane (3), which was isolated as the bromide salt, [H[(2.3)3]adz]Br (yield 38%). The crystal structure of [H[(2.3)3]adz]Br·4H2O has been solved by X-ray diffraction at T = 120 K. In the i+,i,i,i-H[(2.3)3]adz+ cation (3a) the acidic hydrogen atom and the lone pairs of the nitrogen atoms are oriented towards the inside of the cavity. The acidic hydrogen atom is attached to the apical nitrogen atom and both are positioned on a three-fold axis. The distances between the nitrogen atoms are in the range of 2.73(2)–2.99(1) Å. The inside coordinated proton in H[(2.3)3]adz+ (3a) is unusually inert to reaction with base (kdiss < 4 × 10–9 s–1 at 25 °C in 0.01 M NaOD). From 1H and 13C NMR it is concluded that in slightly acidic (pH > 2) and in basic aqueous solutions the dominant form of the cage has all four lone pairs pointing into the cavity. In concentrated strong acid protonation occurs and is believed to involve inversion at one or several of the bridgehead nitrogen atoms. In concentrated boiling hydrochloric acid the cage undergoes a slow cleavage of one trimethylene bridge to give the bowl amine [(2.3)2.21]adz (7), 1,5,9,12-tetraazabicyclo[7.5.2]hexadecane, which was isolated as the triprotonated bromide dichloride salt, [H3[(2.3)2.21]adz]BrCl2·H2O (yield 40%).