Potential non-steroidal estrogens and antiestrogens,IV Organic azides in heterocyclic synthesis,part 13: Synthesis of aza- and diazacoumestrols via azido derivatives

Summary 4-Chloro-3-aryl-coumarins and quinolones2 a–e undergo thermolytic ring closure by reaction with sodium azide in refluxing dimethyl formamide to yield indolo[3,2-c]coumarins and indolo[3,2-c]quinolin-6(5H)-ones6 a–e. In the case of the coumarin2 a the azido coumarin5 can be isolated. The mono- and diazacoumestrol-dimethylethers6 a–c are converted into the coumestrol analogues7 a–c and their diacetyl derivatives8 a–c.

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Potentielle nichtsteroidale Östrogene und Antiöstrogene, 4. Mitt.: Organische Azide in der Heterocyclensynthese, Teil 13: Synthese von Aza- und Diazacumöstrolen über Azidzwischenstufen

Zusammenfassung 4-Chlor-3-arylcumarine und-chinolone2 a–e reagieren thermolytisch mit Natriumazid in siedendem Dimethylfomamid unter Ringschluß zu Indolo[3,2-c]cumarinen und Indolo[3,2-c]chinolin-6(5H)-onen6 a–e. Nur aus dem Cumarinderivat2 a kann das zwischenzeitlich gebildete Azidocumarin5 isoliert werden. Die so erhaltenen Mono- und Diazacumöstroldimethylether6 a–c werden in die entsprechenden Cumöstrole7 a–c und ihre Diacetylderivate8 a–c umgewandelt.

     

Studies of the Reaction Behavior of Nitryl Compounds Towards Azides: Evidence for Tetranitrogen Dioxide,N4O2

The reaction behavior of NaN₃, AgN₃, and Me₃SiN₃ towards FNO₂, CINO₂, NO₂SbF₆, and NO₂BF₄ was investigated. At -30°C or below in a solvent-free system sodium azide did not react with CINO₂, NO₂BF₄, or NO₂SbF₆. Below -30°C silver azide did not react either with neat C1NO₂. Treatment of Me₃SiN₃ with pure C1NO₂ led to the formation of C1N₃, N₂O, and Me₃SiOSiMe₃. A mechanism for this reaction has been proposed. Pure chlorine azide was isolated by fractional condensation and identified by its low-temperature Raman spectrum (liquid state). The reaction of Cp₂Ti(N₃)₂ with C1NO₂ also yielded C1N₃ as the only azide-containing reaction product. Treatment of FNO₂ with NaN₃ at temperatures as low as -78°C always ended in an explosion which was probably due to the formation of FN₃ as one of the reaction products. The reaction of NO₂SbF₆ with NaN₃ in liquid CO₂ (-55°C· T· -35°C) as the solvent afforded a new azide species which was stable at low temperature in solution only and was investigated by means of low-temperature Raman spectroscopy. The obtained vibrational data give strong evidence for the presence of tetranitrogen dioxide, N₄O₂, which can be regarded as nitryl azide (NO₂N₃). The structure and vibrational frequencies of N₄O₂ were computed ab initio at correlated level (MP2/6-31 + G^*). In liquid xenon (-100°C· T· -60°C) NaN₃ did not react with NO₂SbF₆. A previous literature report on the preparation of N₄O₂ could not be established.     

Supramolecular framework adducts constructed of hexamethylenetetramine,aquated alkali metal cationic clusters,and hexacyanoferrates(II/III)

The reaction of alkali metal hexacyanoferrate(II/III) with (CH₂)₆N₄ (hexamethylenetetramine, abbreviated HMT) in an acidic medium yielded crystalline compounds of stoichiometries HK₂[Fe¹¹¹(CN)₆]·2HMT·4H₂O, H₂K₂[Fe¹¹(CN)₆]·2HMT·4H₂O, and HNa₂[Fe¹¹¹(CN)₆]· 2HMT·5H₂O. Their crystal structures are based on a packing of three molecular components: neutral and/orprotonated HMT, hexacyanoferrate, and an alkali metal ion-water cluster. The resulting three-dimensional supramolecular framework is constructed from the coordination of the alkali metal ion by aqua ligands as well as [Fe(CN)₆]{n–} and HMT units, and further stabilization is achieved by hydrogen bonding between water molecules and the noncoordinated nitrogen atoms of HMT and hexacyanoferrate.     

Matrix-dependent instability of selenium(IV) stored in teflon containers

Solutions of selenium(IV) standards with different acid matrices were stored in containers constructed of boosilicate glass, conventional polyethylene, and fluorinated ethylenepropylene (teflon FEP). After 50 days of storage in FEP, there were highly significant losses of Se(IV) from standards in either 5% HCl/5% H₂SO₄, or 5% H₂SO₄. Increasing the hydrochloric acid concentration, e.g., 15% HCl/5% H₂SO₄, greatly reduced this loss. Addition of selenium-75 (selenate-free) indicated that the losses did not result from physical adsorption onto container surfaces. It is shown that the losses were caused by oxidation of Se(IV) to Se(VI).     

A new palladium catalyst system for the cyanation of aryl chlorides with K4[Fe(CN)6]

The development of a novel Pd-catalyzed synthesis of (hetero)aromatic nitriles from the corresponding aryl chlorides and potassium hexacyanoferrate(II) is described. This novel protocol avoids the use of highly toxic alkali cyanides and proceeds in the presence of small amounts of palladium catalysts. High yields and selectivities of the corresponding aryl nitriles were achieved applying di(1-adamantyl)-1-butylphosphine (cataCXium^® A) as the ligand.     

Hydroxamic acid polymers

A polymer bearing hydroxamic acid groups and having a high affinity for iron(III) was prepared through the following procedure. Acryloylalanine (III), prepared by the reaction of acryloyl chloride with alanine, was treated with N-hydroxysuccinimide in the presence of dicyclohexylcarbodiimide to give the N-hydroxysuccinimide ester (IV). The ester IV was polymerized by using AIBN in dioxane to give polymer V. Treatment of polymer V with methylhydroxylamine in DMF gave the hydroxamic acid polymer II. The water-soluble polymer II was purified by dialysis or by gel-permeation chromatography (GPC) on Sephadex G-25. Analytical GPC on Sephadex G-200 and Sepharose 4B indicate that the average molecular weight of the polymer is in the range of 5 × 10⁵ to 1 × 10⁶. The presence of hydroxamic acid groups is confirmed by the intense red-brown color produced by the addition of iron(III) to a 50% aqueous DMF solution of the polymer under acidic conditions. In pure water the polymer-iron complex precipitates as a tan solid. Iron-binding studies of the polymer reveal that the iron(III) trihydroxamic acid complex FeA₃ forms at low concentrations of iron. At higher iron levels a lower order of stability is apparent, which can be accounted for by the conversion of FeA₃ to FeA₂⁺. In contrast, the FeA₃ complex of the trihydroxamic acid deferoxamine-B is stable at all iron levels. These results are consistent with the polymer structure, which for steric reasons would favor a stable complex, FeA₂⁺, between iron and two adjacent hydroxamic acid groups. An FeA₃ complex would be expected to have a lower stability as a result of either bond angle strain and atomic compression, or a lower probability in bringing a third hydroxamic acid into position to form the octahedral complex.     

A simple cobalt catalyst system for the efficient and regioselective cyclotrimerisation of alkynes

The intermolecular cyclotrimerisation of terminal and internal alkynes can be catalysed by simple cobalt complexes such as a CoBr2(diimine) under mild reaction conditions when treated with zinc and zinc iodide with high regioselectivity in excellent yields.     

The Synthesis and Reactions of Yomogi Alcohol. Conversion of the artemisyl skeleton to the santolinyl skeleton by a 1,2-shift of a vinyl group. Synthesis of santolinatriene

The synthesis of yomogi alcohol (2, 5, 5-trimethylhepta-3,6-dien-2-ol, 2 ) is described, and experiments directed towards its allylic rearrangement to artemisia alcohol detervatives have been carried out. Acidic reagents open the ring of yomogi alcohol epoxide ( 16 ) at with participation of the 6,7-double-bond, a shift of the vinyl group results to yield a compound with the santolinyl skeleton. The same reagents are without effect when this double bond reduced. Action of butyllithium of the benzaldehyde acetal ( 41 ) of 2, 5-dimethyl-4-vinyl-2, dihydroxy-hex-5-ene ( 28 ), obtained by acid-catalyzed ring opening of yomogi alcohol epoxide in the presence of benzaldehyde, leads to santolinatriene ( 42 ). This vinyl shift is not observed in the case of O-acetyl yomogi alcohol epoxide ( 46 ), from white a compound believed to be an oxetan 48 (R ? COCH₃) is formed with concomitent shift of the acetate group. Further unusual reactions of the oxetan are described, and some observation about the epoxidation of sterically hindered allyl alcohols and their acetates are made.     

Synthesis of unsymmetrical 2,4-dialkylpyrazolo[1,5-a]-1,3,5-triazines

The reaction of 3-aminopyrazole with imidate esters such as ethyl acetimidate, gave N-(pyrazol-3-yl)acetamidine (1) rather than the isomeric 2-acetamidoyl-3-aminopyrazole. Ring closure of 1 with orthoesters such as ethyl propionimidate, afforded unsymmetrically substituted 2.4-dialkylpyrazolo[1,5-a]-1,3,5-triazines such as 4-ethyl-2-methylpyrazolo[1,5-a]-1,3,5-triazine (3). The structure of 1 was confirmed by several alternate syntheses. The unique feature of this two-step synthetic approach to the synthesis of pyrazolo[1,5-a]-1,3,5-triazines is that it is a convenient method of preparing fused triazines based on available pyrazoles rather than the less accessible dialkyltriazines.     

Stochastic coupling and thermodynamic inequalities

Let ₁ and ₂ be thermodynamic Gibbs measures on ^m and ⁿ , respectively. Diffusions are constructed having ₁, and ₂ as invariant measures. These diffusions are then coupled; inequalities between expectations of certain random variables on the two spaces result.Partially supported by NSF-MCS 74-07313-A03