Heterocyclic variants of the 1,5-benzodiazepine system. V. Derivatives of 2-(ortho-R1-anilino)-4-(p-R2-phenyl)-3H-1,5-benzodiazepines

Mono-N-methylation of 2-(ortho-R₁-anilino)-4-(p-R₂-phenyl)-3H-1,5-benzodiazepines IV is achieved in moderate yield with sodium hydride in methyl iodide. Reaction of the N-methyl derivatives I with methoxyacetyl chloride gave the compounds II and III . The structure of all products was confirmed by ir, ¹H-nmr and mass spectrometry.     

A Reductive homo-coupling polymerization of aromatic diisocyanates promoted by samarium iodide

The selective reductive homo-coupling polymerization of aromatic diisocyanates via one-electron transfer promoted by samarium iodide in the presence of hexamethylphosphoramide (HMPA) produced the corresponding poly(oxamide)s ( 1 ) nearly quantitatively. The ob-tained polymers were insoluble in common organic solvents. The alkylation of 1 with methyl iodide or allyl bromide in the presence of potassium tert-butoxide provided the highly soluble alkylated polymer in good yields. In either case, the alkylation was almost complete, and both N-and O-alkylation proceeded. The ratio of N-and O-methylation was found to be 64 : 36 by ¹H-NMR spectrum, and that of N- and O-allylation was 3 : 1 from ¹³C-NMR analysis. The present polymerization system could be applied to a variety of diisocyanates, including diphenylmethanediisocyanate (MDI), tolylene 2,6-diisocyanate (TDI), 2,6-naphthyl diisocyanate (NDI) and o-tolidine diisocyanate (TODI). The molecular weights of the polymers were estimated by GPC and found to be 2000–9000. The TGA measurement of the corresponding polymers showed T_d10 at 248–320°C. © 1995 John Wiley & Sons, Inc.     

Simple Conversion of Colchicine into Demecolcine

N-Deacetylcolchiceine ( 7 ), readily available from colchicine ( 1 ), was converted into N-trifluoroacetyl-deacetylcolchiceine ( 8 ). Methylation of 8 with methyl iodide in the presence of potassium carbonate afforded a mixture of N-trifluoroacetyl-demecolcine ( 10 ) and its isomer 11 . The mixture of 10 and 11 was detrifluoroacetylated and separated by chromatography to afford demecolcine ( 2 ) and isodemecolcine ( 12 ). A more practical route to 2 started with 8 , and gave N-trifluoroacetyl-deacetylcolchicine ( 13 ) and its isomer 14 after O-methylation with diazomethane. N-Methylation of 13 and 14 with methyl iodide and potassium carbonate afforded 10 and 11 . The overall yield in the conversion of colchicine ( 1 ) into demecolcine ( 2 ) via 7, 8 and 13 was 55%.     

13C n.m.r. investigation on the nitrogen methylation of some azabenzenes

The ¹H and ¹³C n.m.r. spectra of N-methylated pyridine, pyridazine, pyrimidine and pyrazine and N,N-dimethylated pyrimidine and pyrazine have been recorded and analysed. The change in the ¹³C chemical shifts under the influence of N-methylation (Δδ) in the diazabenzenes could be predicted by the Δδ values of pyridine. A comparison of the Δδ values of N-methylation with those of N-protonation showed that both reactions have a similar effect.     

Carbon-13 n.m.r. investigation on the nitrogen methylation of the mono- and diazanaphthalenes

The ¹³C n.m.r. spectra of the N-methylated mono- and diazanaphthalenes have been recorded and analysed. It has been shown that N-methylation as well as N-protonation in cinnoline occur predominantly at the β-nitrogen atom. N-methylation and N-protonation show a similar effect on the ¹³C chemical shifts.     

Constrained Dipeptide Surrogates: 5- and 7-Hydroxy Indolizidin-2-one Amino Acid Synthesis from Iodolactonization of Dehydro-2,8-diamino Azelates

The constrained dipeptide surrogates 5- and 7-hydroxy indolizidin-2-one N-(Boc)amino acids have been synthesized from L-serine as a chiral educt. A linear precursor ∆⁴-unsaturated (2S,8S)-2,8-bis[N-(Boc)amino]azelic acid was prepared in five steps from L-serine. Although epoxidation and dihydroxylation pathways gave mixtures of hydroxy indolizidin-2-one diastereomers, iodolactonization of the ∆⁴-azelate stereoselectively delivered a lactone iodide from which separable (5S)- and (7S)-hydroxy indolizidin-2-one N-(Boc)amino esters were synthesized by sequences featuring intramolecular iodide displacement and lactam formation. X-ray analysis of the (7S)-hydroxy indolizidin-2-one N-(Boc)amino ester indicated that the backbone dihedral angles embedded in the bicyclic ring system resembled those of the central residues of an ideal type II’ β-turn indicating the potential for peptide mimicry.     

High-Resolution Experimental Study on Photodissocaition of N2O

We study the photodissociation dynamics of nitrous oxide using the time-sliced ion velocity imaging technique at three photolysis wavelengths of 134.20, 135.30, and 136.43 nm. The O(¹S_J=0)+N₂(X¹∑_g⁺) product channels were investigated by measuring images of the O(¹S_J=0) products. Vibrational states of N₂(X¹∑_g⁺) products were fully resolved in the images. Product total kinetic energy releases (TKER) and the branching ratios of vibrational states of N₂ products were determined. It is found that the most populated vibrational states of N₂ products are v=2 and v=3. The angular anisotropy parameters (β values) were also derived. The β values are very close to 2 at low vibrational states of the correlated N₂(X¹∑_g⁺) products at all three photolysis wavelengths, and gradually decrease to about 1.4 at v=7. This indicates the dissociation is mainly through a parallel transition state to form products at lower vibrational states, and the highly vibrational exited products are from a more bent configuration. This is consistent with the observed shift of the most intense rotational structure in the TKER as the vibrational quantum number increases.     

Proton and carbon-13 nuclear magnetic resonance studies of substituted pyridines and pyrimidines: VII—The structure of hydroxy- and mercapto- pyridines and pyrimides from J(HH) and J(CH) values

Accurate values of ⁱJ(HH) and ⁱJ(CH) were obtained for a series of hydroxy-and mercaptopyridines and-pyrimidines. It is shown that the ³J(CH) values provide a valuable criterion for differentiating aromatic from quinoidal structures, and is an easy method for determining N-methylation or N-addition sites.     

Preferential protonation and methylation at the nitrogen atoms of N,N-dimethylamino derivatives of pyridine

The relative reactivity toward protonation and methylation of the two nitrogen atoms in N,N-dimethylaminopyridines has been examined by ¹H NMR. The ring position of the dimethylamino group has no influence on protonation, which occurs in all the derivatives at the heterocyclic nitrogen. The N-methylation reaction does not follow a homogeneous behaviour, occurring at the exocyclic nitrogen in the 2-substituted dimethylamino derivative. The electronic characteristics of the molecules, determined by MO calculations at a semi-empirical level, indicate that both protonation and methylation should occur at the heterocyclic nitrogen; the calculated relative stabilites, however, of the N-protonated and N-methylated forms are in full agreement with the experimental results, and it appears that the anomalous behaviour of 2-dimethylaminopyridine in the N-methylation reaction is caused by steric factors.     

Functional monomers and polymers. CXXI. Methylation and interaction studies on adenine containing polymethacrylate derivatives

Studies of the methylation of polymethacrylate derivatives with adenine bases were made in comparison to those with uracil bases. The polymethacrylate derivatives with adenine bases were methylated by using methyl iodide in dimethyl sulfoxide solution to produce polymers that contained N¹-methyladenine and N¹, N⁶-dimethyladenine units. The products were identified by spectroscopic data and by preparing their model compounds. The methylated polymers obtained were further applied in a study of polymer complex formation with uracil-base polymers.     

Determination of Iodide and Thiocyanate in Seawater by Liquid Chromatography with Poly(ethylene glycol) Stationary Phase

Novel, simple, rapid, highly sensitive, and direct determination of iodide and thiocyanate ions in seawater has been performed by liquid chromatography (LC) with UV detection at 220 nm. The separation was achieved on a C₃₀ column of conventional size (150 mm × 4.6 mm i.d.) modified with poly(ethylene glycol); an aqueous solution of 300 mM sodium sulfate and 50 mM sodium chloride was used as mobile phase. Detection limits (S/N=3) obtained by injecting a 20-L sample were 0.5 and 6 ng mL^–1 for iodide and thiocyanate, respectively. The method was successfully used for rapid and direct determination of iodide and thiocyanate in seawater samples, collected from the coasts of Japan, without any extra pretreatment.Dedicated to Professor K. Jinno on the occasion of his 60^th birthday     

Ureas as a New Nucleophilic Reagents for SNAr Amination and Carbamoyl Amination Reactions in 1,3,7‐Triazapyrene Series

The ability of urea anions to react as nucleophiles with alkoxy derivatives of 1,3,7‐triazapyrenes has been investigated. It was found that against all expectations, the products of the substitution of an alkoxy groups (S_N^ipso ) by amino group were isolated in good yields. The reactions proceed in anhydrous dimethyl sulfoxide solution at room temperature. But when anions of the mono‐substituted ureas containing bulky substituents were used, the first products of the earlier unknown S_NAr reactions of alkyl carbamoyl amination were obtained.     

Synthesis and biological activities of tetrahydroquinazoline analogs of aminopterin and methotrexate

(6R,6S)-5,8-Dideaza-5,6,7,8-tetrahydroaminopterin ( 1 ) and (6R,6S)-5,8-dideaza-5,6,7,8-tetrahydromethotrexate ( 2 ) were synthesized as potential inhibitors of dihydrofolate reductase (DHFR) and as antitumor agents. Cyclohexanone-4-carboxaldehyde dimethyl acetal, a key intermediate [10] was synthesized from cyclohexane-1,4-dione monoethylene ketal, which was converted via a Wittig reaction to its exocyclic 4-methylene derivative which in turn, was converted to the 4-aldehyde via a hydroboration-oxidation sequence. Selective protection of the 4-aldehyde as the dimethylacetal and cyclization with dicyandiamide afforded the 6-dimethylacetal of 2,4-diamino-5,6,7,8-tetrahydroquinazoline. Protection of the 2,4-diamino moieties and selective deprotection of the 6-aldehyde followed by reductive amination with p-aminobenzoyl-L-glutamate afforded 2,4-bisacetamido-5,8-dideaza-5,6,7,8-tetrahydroaminopterin ( 11 ). Deprotection of 11 afforded 1 . Compound 2 was obtained from 11 via N¹⁰-methylation and deprotection. The N¹⁰-methyl analogue 2 was 2–10 fold more potent than 1 as an inhibitor of various DHFRs. In the in vitro preclinical screening program of the National Cancer Institute, compound 2 inhibited the growth of eighteen of the twenty nine tumor cell lines in culture at a GI₅₀ > 1.0 × 10^?8 M.     

Conformational Features of 7,8,13β,14α-Tetrahydro-N7-methylcorysaminium,a biosynthetic intermediate to the protopine-type alkaloid corycavine

The crystal structure of (±)-7,8,13β,14α-tetrahydro-N⁷-(¹³C)methylcorysaminium iodide (¹³C- 3a ·I) was investigated by X-ray analysis and thus the relative configuration (7S*,13S*,14S*) established (Fig. 1). The conformation of 3a was shown to have a cis-junction of the B/C rings and the rings A and D in an antiperiplanar position relative to the C(13)? C(14) bond (‘anti-cis’), a twisted half-chair for ring B, and a half-chair for ring C (Figs. 2 and 3). Conformation analysis by ¹H-NMR data indicated that the crystal conformation of 3a is also the preferred one in MeOH solution.     

Reactions of 6-thiotheophylline with alkylating agents and epichlorohydrin: Isolation of S-alkylated 6-thiotheophylline and 7-(2,3-thioepoxypropyl)theophylline

Alkylation of 6-thiotheophylline ( 1 ) under the aprotic basic condition affords S-alkylated 6-thiotheophylline ( 3 ) together with an N⁷ -alkylated product 4 . There is a tendency that the more reactive the alkylating agents are, the higher the yields of S-alkylated products are. On the other hand, treatment of 6-thiotheophylline ( 1 ) with epichlorohydrin afforded an unexpected product, 7-(2,3-thioepoxypropyl)theophylline ( 6 ), neither an S-alkylated compound 3g nor an N⁷ -alkylated compound 4g . The chemical structure was determined by nmr spectroscopic analysis.     

The α‐effect exhibited in gas‐phase SN2@N and SN2@C reactions

In order to explore the existence of α‐effect in gas‐phase S_N2@N reactions, and to compare its similarity and difference with its counterpart in S_N2@C reactions, we have carried out a theoretical study on the reactivity of six α‐oxy‐Nus (FO^?, ClO^?, BrO^?, HOO^?, HSO^?, H₂NO^?) in the S_N2 reactions toward NR₂Cl (R = H, Me) and RCl (R = Me, i‐Pr) using the G2(+)_M theory. An enhanced reactivity induced by the α‐atom is found in all examined systems. The magnitude of the α‐effect in the reactions of NR₂Cl (R = H, Me) is generally smaller than that in the corresponding S_N2 reaction, but their variation trend with the identity of α‐atom is very similar. The origin of the α‐effect of the S_N2@N reactions is discussed in terms of activation strain analysis and thermodynamic analysis, indicating that the α‐effect in the S_N2@N reactions largely arises from transition state stabilization, and the “hyper‐reactivity” of these α‐Nus is also accompanied by an enhanced thermodynamic stability of products from the n_(N) → σ*_(O?Y) negative hyperconjugation. Meanwhile, it is found that the reactivity of oxy‐Nus in the S_N2 reactions toward NMe₂Cl is lower than toward i‐PrCl, which is different from previous experiments, that is, the S_N2 reactions of NH₂Cl is more facile than MeCl. © 2013 Wiley Periodicals, Inc.     

N-Heterocyclic carbene complexes of palladium(II) and rhodium(I) with pendant ferrocenylmethyl groups: synthesis and electrochemistry

1-Ferrocenylmethyl-3-benzylimidazolidinium iodide and 1-ferrocenylmethyl-3-(2,4,6-trimethylbenzyl)imi-dazolidinium iodide were prepared in good yields by boiling, under reflux, a solution of (ferrocenylmethyl)- trimethylammonium iodide and the appropriate N-alkyl-2-imidazoline in MeCN. From the 1-ferrocenylmethyl-3-ben- zylimidazolidinium iodide salt, N-heterocylic carbene complexes of Pd^II and Rh^I were synthesized by in situ deprotonation and subsequent trapping. The new compounds were characterized by C, H, N analyses, ¹H-n.m.r., ¹³C-n.m.r. and by cyclic voltammetry. The n.m.r. properties of the complexes are compared with those of non-ferrocenylated carbene derivatives. The c.v.'s of these compounds show a number of resolved redox processes, indicating that CH₂Fc substituents are electronically isolated from the remaining molecular framework.     

Reaktionen von Tetraphosphortrichalkogeniden mit Alkyliodiden

Reactions of Tetraphosphorus Trichalcogenides with Alkyl Iodides Reactions of alkyl iodides RI (R = CHI₂, CH₂I or tert-Butyl) with P₄E₃ (E = S or Se) under the influence of light resulted in cleavage of the basal P₃ ring. β-P₄E₃(I)R was formed initially, then it rearranged to the more stable α-P₄E₃(I)R structure. ³¹P NMR data of these products were measured and discussed, along with ⁷⁷Se data for α- and β-P₄⁷⁷SeSe₂(I)CHI₂. On reaction of P₄S₃ with tert-butyl iodide in CS₂ or with sec-butyl iodide or iso-propyl iodide in dioxane, the new type of compounds P₅S₂R was observed. In this a sulfur bridge of P₄S₃ is replaced by a P? R group. ³¹P-NMR data for these compounds are reported.     

New functional triethoxysilanes as iodide sources for dye-sensitized solar cells

Three new triethoxysilanes bearing quaternary ammonium alkyl iodides are reported, N,N,N-triethyl-3-(triethoxysilyl)propan-1-aminium iodide 1, N,N,N-triheptyl-3-(triethoxysilyl)propan-1-aminium iodide 2 and N,N,N-tridodecyl-3-(triethoxysilyl)propan-1-aminium iodide 3. ¹H and ¹³C NMR spectroscopy and electrospray mass spectrometry were used to confirm the synthesis of pure products. Electrolytes based on these ionic liquids were developed and their performance in dye-sensitized solar cells (DSSCs) evaluated. The electrolytes incorporated 1 and 2 (in 30–60 wt%) as iodide sources together with I₂ (0.08 M), 0.1 M guanidinium thiocyanate and 0.5 M tert-butylpyridine in acetonitrile (AN); and I₂ (0.15 M) and N-methylbenzimidazole (0.5 M) for 2-methoxyproprionitrile (MPN) as co-solvent. Testing of DSSCs to analyze the influence of chain length (ethyl and heptyl) on cell efficiency revealed that, for silanes concentration of 1 M, electrolyte B (based on 2 in AN) and electrolyte C (based on 1 in MPN) gave the best cell efficiency at simulated full sunlight (AM 1.5, 1000 W m⁻²) illumination (5.0–5.3%). At 0.1 Sunlight (AM 1.5, 100 W m⁻²), electrolyte B gave the best performance of 8.0%. High open circuit voltages (V_OC) of 750–850 mV were achieved for a number of quite efficient cells (5–6%). For silane 2, variation of the I⁻/I₂ ratio and total silane content (1–2 M 2) on DSSC efficiency gave a consistent efficiency of 8.0% at 0.1 Sunlight. At full sunlight, the cell efficiency decreased as the silane concentration increased from 1 M (5.0%) to 2 M (3.7%), largely due to a drop in short circuit current.