Iron complexes of C- and N-methylated 2-aza-21-carbaporphyrin: NMR studies

Insertion of iron(II) into methylated derivatives of N-confused porphyrins 2-aza-2-methyl-5,10,15,20-tetraphenyl-21-carbaporphyrin (MeCTPPH)H, 2-aza-5,10,15,20-tetraphenyl-21-methyl-21-carbaporphyrin (CTPPMe)H2, and 2-aza-2-methyl-5,10,15,20-tetraphenyl-21-methyl-21-carbaporphyrin (MeCTPPMe)H yielded N- or C-methylated high-spin iron(II) complexes (MeCTPPH)Fe(II)Br, (HCTPPMe)Fe(II)Br, and (MeCTPPMe)Fe(II)Br. One electron oxidation of (Me-CTPPH)Fe(II)Br using Br2, accompanied by deprotonation of a C(21)-H(21) fragment and formation of an Fe-C(21) bond, produces an intermediate-spin, five-coordinate iron(III) complex (MeCTPP)Fe(III)Br. Simultaneously, a high-spin complex [(MeCTPPH)Fe(III)Br]+ was formed which preserved the side-on interaction between the metal ion and the inverted pyrrole ring. &[(MeCTPPH)Fe(III)Br]+ was also obtained by titration of (MeCTPP)FeIIIBr with TFA due to the C(21) protonation. A titration of (HCTPPMe)Fe(II)Br and (MeCTPPMe)Fe(II)Br with Br2 yielded solely corresponding high-spin iron(III) species [(HCTPPMe)Fe(III)Br+ and [(MeCTPPMe)Fe(III)Br+. Dioxygen reacts cleanly with (MeCTPPH)Fe(II)Br carbaporphyrin to form solely (MeCTPP)Fe(III)Br. The 1H NMR spectra of paramagnetic iron(II) and iron(III) complexes were examined. The characteristic patterns of pyrrole, C-methyl, and N-methyl resonances were found diagnostic of the ground electronic state of iron and the coordinating nature of the N-confused pyrrole. The characteristic C-Me resonances occur in a unique window (520-420 ppm) for iron(III) C-methylated N-confused porphyrins which remains in contrast with relatively small values found for iron(II) C-methylated derivatives (50-80 ppm).     

4-甲基-4-氮杂-21E-苯亚甲基-5-孕烯-3,20-二酮类化合物的合成

报道了一种以KF/Al_2O_3催化合成4-甲基-4-氮杂-21E-苯亚甲基-5-孕烯-3,20-二酮类化合物的方法。以黄体酮为原料,经NaIO_4/KMnO_4氧化裂解、胺解关环得到重要中间体4-甲基-4-氮杂-5-孕烯-3,20-二酮,后者在KF/Al_2O_3催化下经克莱森缩合得到目标产物。考察了不同的催化剂、反应温度、催化剂用量对目标产物的影响。条件优化的结果为:n(3)∶n(KF/Al_2O_3)=1∶1,回流状态下反应4 h,产率为56%~68%。此方法适用性好,为4-氮杂甾体苯亚甲基衍生物的合成提供了一种方便而有效的方法。     

Pyrrole-inverted isomer of 5,10,15,20-tetraaryl-21-selenaporphyrin

A novel 5,10,15,20-tetraaryl-21-selenaporphyrin isomer with an inverted pyrrole ring, i.e., 5,10,15, 20-tetraaryl-2-aza-21-carba-22-selenaporphyrin (SeC-TArPH) has been produced by a [3 + 1] condensation of 2, 5-bis(phenylhydroxymethyl)selenophene and 5,10-ditolyltripyrrin. The reaction yielded 5,20-diphenyl-10,15-bis(p-tolyl)-21-selenaporphyrin Se-DPDTPH (19%) and its isomer with an inverted pyrrole ring, i.e., 5,10-diphenyl-15,20-bis(p-tolyl)-2-aza-21-carba-22-selenaporphyrin, SeC-DPDTPH (1%). Mechanistically the synthesis of SeC-DPDTPH requires one beta-condensation at the pyrrole moiety of 5, 10-ditolyltripyrrin instead of the stereotypical alpha-condensation. The identity of inverted selenaporphyrin has been confirmed by high-resolution mass spectrometry and (1)H NMR spectroscopy. A saddle distortion mode for the inverted selenaporphyrin macrocycle SeC-DPDTPH has been determined by X-ray crystallography. NMR spectra are consistent with the existence of tautomeric equilibria that involve three tautomeric species of the neutral form of SeC-DPDTPH. The preference for the tautomer with the labile proton located at the peripheral N(2) nitrogen atom has been detected in pyridine-d(5) solution. The density functional theory (DFT) has been applied to determine the molecular and electronic structure of three tautomers of 2-aza-21-carba-22-selenaporphyrin: 2-N, 23-N, 24-NH, 2-N, 23-NH, 24-N, and 2-NH, 23-N, 24-N formally created from SeC-DPDTPH by a replacement of phenyl and tolyl groups with hydrogen. The total energies calculated using the B3LYP/6-311G//B3LYP/6-311G approach, demonstrate that relative stability of postulated tautomers decreases in the order 2-N, 23-NH, 24-N > 2-N, 23-N, 24-NH > 2-NH, 23-N, 24-N. The small energy differences between tautomeric species suggests their simultaneous presence in equilibrium.     

Oxidation and oxygenation of iron complexes of 2-aza-21-carbaporphyrin

Oxidation and oxygenation of (HCTPPH)Fe(II)Br an iron(II) complex of 2-aza-5,10,15,20-tetraphenyl-21-carbaporphyrin (CTPPH)H2 have been followed by 1H and 2H NMR spectroscopy. Addition of I2 or Br2 to the solution of (HCTPPH)Fe(II)Br in the absence of dioxygen results in one-electron oxidation yielding [(HCTPPH)Fe(III)Br]+. One electron oxidation with dioxygen, accompanied by deprotonation of a C(21)H fragment and formation of an Fe-C(21) bond, produces an intermediate-spin, five-coordinate iron(III) complex (HCTPP)Fe(III)Br. In the subsequent step an insertion of the oxygen atom into the preformed Fe(III)-C(21) bond has been detected to produce [(CTPPO)Fe(III)Br]-. Protonation at the N2 atom affords (HCTPPO)Fe(III)Br. The considered mechanism of (HCTPPH)Fe(II)Br oxygenation involves the insertion of dioxygen into the Fe-C bond. The 1H NMR and 2H NMR spectra of paramagnetic iron(III) complexes were examined. Functional group assignments have been made with use of selective deuteration. The characteristic patterns of pyrrole and 2-NH resonances have been found diagnostic of the ground electronic state of iron and the donor nature localized at C(21) center as exemplified by the 1H NMR spectrum of intermediate-spin (HCTPP)Fe(III)Br: beta-H 7.2, -10.6, -19.2, -20.6, -23.2, -24.9, -43.2; 2-NH -76.6 (ppm, 298 K). The structures of two compounds (HCTPP)Fe(III)Br and (HCTPPO)Fe(III)Br, were determined by X-ray diffraction studies. In the first case, the iron(III) is five-coordinate with bonds to three pyrrole nitrogen atoms (Fe-N distances: 1.985(8), 2.045(7), 2.023(8) A), and the pyrrolic trigonal carbon (Fe-C: 1.981(8) A). The iron(III) of (HCTPPO)Fe(III)Br forms bonds to three pyrrole nitrogen atoms (Fe-N distances 2.104(5), 2.046(5), 2.102(5) A). The Fe-O 2.041(5) A and Fe-C(21) 2.192(5) A distances suggests a direct interaction between the iron center and the pi electron density on the carbonyl group in a eta2 fashion.     

Stereospecific intramolecular C-H amination of 1-aza-2-azoniaallene salts

We report that 1-aza-2-azoniaallene salts, generated from α-chloroazo compounds by treatment with halophilic Lewis acids, participate in intramolecular C-H amination reactions to provide pyrazoline products in good to excellent yield. This intramolecular amination occurs readily at both benzylic and tertiary aliphatic positions and proceeds at an enantioenriched chiral center without loss of enantiomeric excess. A competition reaction shows that insertion occurs more readily at an electron-rich benzylic position than an electron-deficient one. These observations are consistent with the 1-aza-2-azoniaallene intermediate reacting as a nitrenium-like ion by a concerted insertion mechanism.     

Conjugate addition to 1-phosphono-2-aza-1,3-butadienes: synthesis of phosphonylated gamma-lactams

Several 1-phosphono-2-aza-1,3-butadienes, 1 and 13-20, were evaluated in the reaction with different enolate-type nucleophiles to induce addition at the 1- or the 4-position of the azadiene. 1-Phosphono-2-azadienes 1 react with sodium malonate at the 1-position, leading to the formation of bisenamines 12 after elimination of the phosphonate moiety. On the contrary, sodium malonate adds at the 4-position of 1-aryl-1-phosphono-2-azadienes 14-19 when the azadienes bear a halogenated phenyl substituent, and the resulting addition products 21-26 are easily transformed into the corresponding phosphonylated gamma-lactams 35-40. The regioselectivity of the addition is explained by reversal of polarization of the azadiene due to the electron-withdrawing character of the halogenated phenyl substituents.     

Remarkable paramagnetically shifted (1)H and (2)H NMR spectra of iron(II) complexes of 2-aza-21-carbaporphyrin: an evidence for agostic interaction

Iron(II) 2-aza-21-carbaporphyrins have been characterized by paramagnetically shifted (1)H and (2)H NMR spectra. The high-spin iron(II) complex (HCTPPH)Fe(II)Br displays the beta-H resonances which reflect the combination sigma and pi routes of spin density delocalization. The uniquely large isotropic shift of the inner H(21) hydrogen (812 ppm, 298 K) indicates an Fe(II)-[C(21)-H] agostic interaction.     

Wagner-Meerwein skeletal rearrangement of 3-spiroannulated 6,8a-epoxy- and 6,8a;7,8-diepoxyisoquinolines (3-aza-11-oxatricyclo[6.2.1.0(1,6)]undec-9-enes). Isolation and identification of 5-aza-2-oxatricyclo[6.2.1.0(3,9)]undec-3-enes

The reactions of 3-acetyl-3-aza-11-oxatricyclo[6.2.1.0(1,6)]undec-9-ene and its 9,10-epoxy derivative with bromine and Ac(2)O/BF(3).OEt(2) under different conditions were studied. Unusual products of Wagner-Meerwein rearrangement bearing the olefin fragment (5-aza-2-oxatricyclo[6.2.1.0(3,9)]undecen-3-enes) were isolated and characterized by X-ray analysis.     

Pyrazolo[3,4-d]pyrimidine ribonucleosides related to 2-aminoadenosine and isoguanosine: synthesis, deamination and tautomerism

The syntheses and properties of 8-aza-7-deazapurine (pyrazolo[3,4-d]pyrimidine) ribonucleosides related to 2-aminoadenosine and isoguanosine are described. Glycosylation of 8-aza-7-deazapurine-2,6-diamine 5 with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (12) in the presence of BF(3) x Et(2)O as a catalyst gave the N(8) isomer 14 (73%) with a trace amount of the N(9) isomer 13a (4.8%). Under the same reaction conditions, the 7-halogenated 8-aza-7-deazapurine-2,6-diamines 6-8 afforded the thermodynamically more stable N(9) nucleosides 13b-d as the only products (53-70%). Thus, a halogen in position 7 shifts the glycosylation from N(8) to N(9). The 8-aza-7-deazapurine-4,6-diamine ribonucleosides 1a-d were converted to the isoguanosine derivatives 3a-d by diazotization of the 2-amino group. Although compounds 1a,b do not contain a nitrogen at position 7 (the enzyme binding site), they were deaminated by adenosine deaminase; however, their deamination occurred with a much slower velocity than that of the related purines. The pK(a) values indicate that the 7-non-functionalized nucleosides 1a (pK(a) 5.8) and 15 (pK(a) 6.4) are possibly protonated in neutral conditions when incorporated into RNA. The nucleosides 3a-d exist predominantly in the keto (lactam) form with K(TAUT) (keto/enol) values of 400-1200 compared to 10(3)-10(4) for pyrrolo[2,3-d]pyrimidine isoguanosine derivatives 4a-c and 10 for isoguanosine itself, which will reduce RNA mispairing with U.     

Novel photoreactions of 2-aza-1,4-dienes in the triplet excited state and via radical-cation intermediates. 2-aza-di-pi-methane rearrangements yielding cyclopropylimines and N-vinylaziridines

Triplet-sensitized irradiation of 2-aza-1,4-dienes affords N-cyclopropylimines via 2-aza-di-pi-methane (2-ADPM) rearrangement pathways. In the case of the pentaphenyl-substituted azadiene 1, irradiation leads to formation of cyclopropylimine 2 as well as N-vinylaziridine 3. The transformations represent the first examples of di-pi-methane rearrangement reactions that yield three-membered heterocyclic products. SET-sensitized irradiation of 2-aza-1,4-dienes, by using 9,10-dicyanoanthracene (DCA) as an electron-acceptor sensitizer and biphenyl as cosensitizer, brings about regioselective formation of N-vinylaziridines. Under these conditions, azadiene 1 also affords cyclopropylimine 37, resulting from an aryl-di-pi-methane rearrangement. This result demonstrates that di-pi-methane reactions can also take place via radical-cation intermediates. In some instances, imine and olefin centered cation-radical intermediates, generated by SET-sensitized irradiation, undergo alternative reactions to produce isoquinoline and benzoazepine products.     

Free-radical addition of phenyl- and diphenylphosphines to 2-vinyl-1,3-dioxa-6-aza-2-silacyclooctanes

Conclusions Phenyl- and diphenylphosphines add to 2,6-dimethyl-2-vinyl-1,3-dioxa-6-aza-2-silacyclooctane upon the action of UV irradiation to form 2,6-dimethyl-2-[(2-phenylphosphino)ethyl)]-1,3-dioxa-6-aza-2-silacyclooctane and 2,6-dimethyl-2-[(2-diphenylphosphino)ethyl]-1,3-dioxa-6-aza-2-silacyclooctane, respectively.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2615–2616, November, 1985.     

Modification of regioselectivity in cycloadditions to C70 under microwave irradiation

The regioselectivity of the cycloaddition of N-methylazomethine ylide to C70 can be modified by using microwave irradiation as the source of energy. Under microwave irradiation and by choosing the appropriate solvent and irradiation power, the 5-6 isomer is the major product, a situation that is in contrast to conventional heating where the 1-2 isomer predominates. Moreover, isomer 7-21, which represents 13% of monoadducts under classical heating, is not formed under microwave irradiation and with ODCB as solvent. Theoretical calculations predict an asynchronous mechanism and suggest that the modification of the regiochemical outcome is related to the relative energies and hardnesses of the transition structures involved.     

Synthesis of N-vinyl 2,2-bisphosphonoaziridines from 1,1-bisphosphono-2-aza-1,3-dienes

N-Vinyl 2,2-bisphosphonoaziridines are formed by treatment of 1,1-bisphosphono-2-aza-1,3-dienes with diazomethane. Depending on the substituents at the 4-position of the 1,1-bisphosphono-2-aza-1,3-dienes, exclusively 1-(ethenylamino)-2-phosphonoethenylphosphonates or mixtures of 1-(ethenylamino)-2-phosphonoethenylphosphonates and 2-imino-2-phosphonoethylphosphonates are obtained as side products.     

6-Azauracil or 8-aza-7-deazaadenine nucleosides and oligonucleotides: the effect of 2'-fluoro substituents and nucleobase nitrogens on conformation and base pairing

The stereoselective syntheses of 6-azauracil- and 8-aza-7-deazaadenine 2'-deoxy-2'-fluoro-beta-d-arabinofuranosides and employing nucleobase anion glycosylation with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-d-arabinofuranosyl bromide as the sugar component are described; the 6-azauracil 2'-deoxy-2'-fluoro-beta-d-ribofuranoside was prepared from 6-azauridine via the 2,2'-anhydro intermediate and transformation of the sugar with DAST. Compounds show a preferred N-conformer population (100% N for , and 78% N for ) being rather different from nucleosides not containing the combination of a fluorine atom at the 2'-position and a nitrogen next to the glycosylation site. Oligonucleotides incorporating and were synthesized using the phosphoramidites and . Although the N-conformation is favoured in the series of 6-azauracil- and 8-aza-7-deazaadenine 2'-deoxy-2'-fluoroarabinonucleosides only the pyrimidine compound shows an unfavourable effect on duplex stability, while oligonucleotide duplexes containing the 8-aza-7-deazaadenine-2'-deoxy-2'-fluoroarabinonucleoside were as stable as those incorporating dA or 8-aza-7-deaza-2'-deoxyadenosine .     

First example of a covalently bound dimeric inverted porphyrin

Reaction of 5,10,15,20-tetraphenyl-2-aza-21-carbaporphyrinatonickel(II) with dihalomethanes in the presence of a proton scavenger gives a 2,21'-CH2-linked dimer of Ni(II) inverted porphyrins with the yield reaching 90% and its 2,2'-linked isomer as a minor product.     

Synthetic and structural study of 4-phosphacyclohexanones and 3-aza-7-phosphabicyclo[3.3.1]nonan-9-ones

The synthesis of bicyclic phosphorus–nitrogen (PN) compounds containing the rigid bicyclo[3.3.1]nonan-9-one framework was attempted using the Mannich condensation reaction of four different phosphorinanone classes with amines and aldehydes. Three different isomers of 4-tert-butyl-2,6-di(methoxycarbonyl)-3,5-bis(p-dimethylaminophenyl)-4-phosphacyclohexanone were obtained from the Michael addition reaction of tert-butylphosphine with 2,4-di(methoxycarbonyl)-1,5-bis(p-dimethylaminophenyl)penta-1,4-dien-3-one. The reaction of the all-equatorial isomer with methylamine and formaldehyde produced the bicyclic PN compound 7-tert-butyl-1,5-di(methoxycarbonyl)-6,8-bis(p-dimethylaminophenyl)-3-methyl-3-aza-7-phosphabicyclo[3.3.1]nonan-9-one. The identical Mannich reaction of the enol tautomer also yielded the same product, as well as the PN compound 4-tert-butyl-6-methoxycarbonyl-5-(p-dimethylaminophenyl)-2-methyl-2-aza-4-phosphacyclohexanone and the E/Z isomers of 3-(p-dimethylaminophenyl)methyl-2-propenoate. The newly synthesised 3-aza-7-phosphabicyclo[3.3.1]nonan-9-one PN compound adopts a chair–chair conformation both in solution and the solid state.     

2-aza-2'-deoxyadenosine: synthesis, base-pairing selectivity, and stacking properties of oligonucleotides

2-Aza-2'-deoxyadenosine (2, z2Ad) is synthesized via its 1,N6-etheno derivative 7 and enzymatically deaminated to 2-aza-2'-deoxyinosine (3). Compound 2 is converted into the phosphoramidite building block 10b. This is employed in solid-phase oligonucleotide synthesis. The 2-azapurine base forms a strong base pair with guanine, but a much weaker one with adenine, thymine, and cytosine. Oligonucleotide duplexes with dangling nucleotide residues, such as 2-aza-2'-deoxyadenosine and 7-deaza-2'-deoxyadenosine (4, c7Ad), either on one or both termini, are synthesized, and the thermal stability of the duplexes is correlated with the hydrophobic properties of the dangling nucleotide residues.     

Synthesis and thermolysis of heterocyclic 3-aza-3-ene-1,5-diynes(1)

[reaction: see text] Simple, acyclic 3-aza-3-ene-1,5-diynes undergo an aza-Bergman rearrangement to a fleeting 2,5-didehydropyridine (2,5-ddp) intermediate that rapidly ring-opens to beta-alkynylacrylonitrile products. In an effort to access longer-lived 2,5-ddp intermediates, we have prepared heterocyclic 3-aza-3-ene-1,5-diynes. The thermolysis of one such heterocyclic aza-enediyne does not afford products derived from trapping a 2,5-ddp intermediate but rather cyclopropanes that appear to arise from a carbene intermediate and a product that appears to be a trapping product from a 2,3-ddp intermediate.     

6,7-diaza-dithiafulvalenes and 5-aza-8a-azonia-dithiafulvalenes

3-Dimethylamino- and 3,5-Bis-dimethylamino-pyrazoles react with 1,2- and 1,3-dithiolium salts to form 6,7-diaza-dithiafulvalenes and 5-aza-8a-azonia-dithiafulvalenes, a new type of heterofulvalenes.     

Derivatives of 4-aza-9-fluorenone

Derivatives of 1,3-indandione containing in position 2 a carbon chain with a δ-carbonyl group cyclize on heating with ammonium acetate in glacial acetic acid to form derivatives of 1,4-dihydro-4-aza-9-fluorenone. The latter are readily oxidized to the corresponding 4-aza-9-fluorenones. The IR and UV spectra of the compounds obtained are discussed.