A New Route for the Synthesis of 1,4-Dicarbonyl Compounds: Synthesis of Jasmone,Dlhydrojasmone and a Prostaglandin Intermediate

1,4-Dicarbonyl compounds are versatile intermediates for the synthesis of a variety of natural products such as jasmonoids, prostanoids, steroids and terpenoids having a cyclopentenone or furan ring system. Although many synthetic routes for the preparation of these compounds are known and continue to appear¹, most of the existing methods involve lengthy procedures and are limited to the synthesis of 1,4-diketones. Herein, we report a convenient three step approach for the synthesis of 1,4-dicarbonyl compounds starting from tosyl methyl isocyanide² (TosMIC). This method is general for the preparation of 1,4-ketoaldehydes as well as 1,4-diketones.     

Synthesis and Metal-Binding Properties of Polybipyridine Ligands Derived from Acyclic and Macrocyclic Polyamines

Synthetic procedures have been developed for the preparation of ligands bearing two to six pendent, unsubstituted or substituted 2, 2′-bipyridine groups attached to acyclic (tripode, tetrapode) and macrocyclic (triazanonade-cane, cyclam, hexacyclen, bis(bipyrido)hexaazamacrocycle) polyamines. Ligands 1-5 have been obtained in high yield by condensation of 6-(bromomethyl)-2, 2′-bipyridine ( 9b ) with the corresponding amines in the presence of NaOH, H₂O, and MeOH. Ligands 6-8 have been prepared in good yield by condensation of 9b or the di- or tetrasubstituted mono (bromomethyl) bipyridine 10b or 11b , respectively, with the corresponding amines in the presence of Na₂CO₃ and MeCN. Ligand 1 forms hemi-cage complexes with Ru^II, Fe^I, Cr^II, and Cr^III cations and trinuclear complexes with [RuCl²(bpy)²] and [ReCl(CO)⁵]. Tetrapode 2 and hexapode 4 gave tetranuclear and dinuclear complexes, respectively, by reaction with Fe11 salts. These complexes possess a variety of interesting physical and chemical properties.     

Synthesis of an Isostegane from Matairesinol

In a recent communication,¹ we reported that the inclusion of boron trifluoride etherate in a thallium(III) trifluoroacetate (TTFA)-induced oxidative aryl-benzyl coupling reaction dramatically altered its outcome in that demethylation of a-phenyl methyl ether no longer accompanied the cyclization. A preliminary investigation also revealed that use of the combined reagents improved the yield of the dibenzocyclooctadiene obtained from a non-phenolic aryl-aryl coupling of a 1,4-diaryl substituted butane.²     

Improved Aldehyde Synthesis: Preparation of 3α, 7α, 12α-Triacetoxy-5β-Cholan-23-al with Ruthenium Tetroxide in Neutral Medium

In relation to our studies on the metabolism of neutral sterols² we have prepared several substituted 24-norcholanic acids. Ruthenium tetroxide was selected as the oxidizing agent^3,4 in the formation of 24-norcholic acid^5,6 from the olefin, 3α, 7α, 12α-triacetoxy-24, 24-diphenyl-5β-chol-23-ene (II), (Fig. 1) since CrO₃ provided multiple products⁵.     

Double nucleophilic attack on η6-arene(pentamethylcyclopentadienyl)iridium dications. Routes from substituted benzenes to substituted cyclohexenes by addition of two hydrides and two protons

The complexes [(C₅Me₅)Ir(η⁶-arene)][BF₄]₂ (arene = toluene, toluene-d₈, t-butylbenzene, methoxybenzene, chlorobenzene, o-xylene, p-xylene, tetralin and phenol) were prepared from the arene and reduced with NaBH₄ to the η⁵-cyclohexadienyl complexes. Attack was exo at the arene and, with one exception, never at the substituent. Toluene showed no site preference but t-butylbenzene was attacked preferentially para, and chlorobenzene, ortho. Methoxybenzene was attacked ipso as well as ortho, meta (predominant), and para, and phenol gave only the meta-isomer. p-Xylene gave one isomer and o-xylene and tetralin gave two. Further reduction occurred on reaction with stronger hydride reducers (e.g., sodium bis(methoxyethoxy)dihydroaluminate) to give mixtures of 1- and 2-substituted cyclohexa-1,3-diene complexes (t-Bu, 2- ( > 95%); Me, 1- (25%), 2- (75%); Cl, 1- ( > 95%); and OMe, 1- (33%), 2- (67%)). The p-xylene complex gave a mixture of the η⁴-1,4-dimethylcyclohexa-1,3- and 1,4-diene complexes. Reaction of the cyclohexadiene complexes with HCl gas gave the free substituted cyclohexenes and [(C₅Me₅Ir)₂Cl₄]. The product from t-butylbenzene was predominantly (92%) the 3-substituted cyclohexene; that isomer (65%) and the 1-isomer (34%) were formed from toluene and the 1- (34%) and the 4-isomer (58%) were formed from chlorobenzene. Phenol gave only cyclohexanone. Overall these reactions yield the cyclohexene from the substituted benzene by addition of two hydrides and two protons and the iridium can be recycled.     

Oxidation of Flavanones with Thallium(III) Nitrate(ttn). A Convenient Route to Flavones

During the course of our work^1–2 on thallium(III) nitrate(TTN) oxidation of chalcones we synthesised some naphthalene analogues³ of isoflavone. While preparing a phenanthrene analogue the reaction of 2-(9-phenanthrenyl)-chroman-4-one(1) with thallium(III) nitrate was examined; this gave the corresponding chromone (2) in 72% yield. Further exploration of this oxidation has revealed that the formation of (2) is representative of a general step suitable for the preparation of a variety of flavones from flavanones.     

Novel fluoro-substituted benzo- and benzothieno fused pyrano[2,3-c]pyrazol-4(1H)-ones

A straightforward, two-step synthesis of fluoro substituted chromeno[2,3-c]pyrazol- and [1]benzothieno[2′,3′:5,6]pyrano[2,3-c]pyrazol-4(1H)-ones, respectively, is presented. Hence, treatment of 1-substituted or 1,3-disubstituted 2-pyrazolin-5-ones with fluoro substituted 2-fluorobenzoyl chlorides or 3-chloro-6-fluoro-1-benzothiophene-2-carbonyl chloride using calcium hydroxide in refluxing 1,4-dioxane gave the corresponding 4-aroylpyrazol-5-ols, which were cyclized into the fused ring systems. 5-Fluorochromeno[2,3-c]pyrazol-4(1H)-one was obtained upon treatment of the 1-(4-methoxybenzyl) protected congener with trifluoroacetic acid. Treatment of 5-fluorochromeno[2,3-c]pyrazol-4(1H)-ones with methylhydrazine afforded novel tetracyclic ring systems such as 2-methyl-7-phenyl-2,7-dihydropyrazolo[4′,3′:5,6]pyrano[4,3,2-cd]indazole. Detailed NMR spectroscopic investigations (¹H, ¹³C, ¹⁵N, ¹⁹F) with the obtained compounds were undertaken.     

A Convenient Procedure for the Hydrolysis of Hindered Esters

Although several procedures for the hydrolysis of hindered esters have been developed, most of them suffer from one or more disadvantages, either in lack of convenience or in stringent conditions which affect other functional groups. Among the presently available methods for effecting this conversion are lithium in ammonia, a strong reducing agent¹; boron trichloride, a Lewis acid²; and a variety of reagents which bring about alkyl-oxygen cleavage. Among the latter are lithium iodide in a variety of solvents, usually at elevated temperatures, or in the presence of an organic base³; 1,5-diazabicyclo [4, 3, 0] nonene-5, in boiling xylene⁴, a reaction which failed in this laboratory⁵; various mercaptides^6,7, which in addition to being experimentally offensive, also cleave aryl alkyl ethers.     

Ethyl 1,4‐Dihydro‐4‐oxo‐1,8‐naphthyridine‐3‐carboxylates by a Tandem SNAr‐Addition‐Elimination Reaction

A series of N‐substituted 1,4‐dihydro‐4‐oxo‐1,8‐naphthyridine‐3‐carboxylate esters has been prepared in two steps from ethyl 2‐(2‐chloronicotinoyl)acetate. Treatment of the β‐ketoester with N,N‐dimethylformamide dimethyl acetal in N,N‐dimethylformamide (DMF) gave a 95% yield of the 2‐dimethylaminomethylene derivative. Subsequent reaction of this β‐enaminone with primary amines in DMF at 120^oC for 24 h then afforded the target compounds in 47–82% yields by a tandem S_NAr‐addition‐elimination reaction. Synthetic and procedural details as well as a mechanistic rationale are presented.     

A Prussian blue-based reactive electrode (reactrode) for the determination of thallium ions

A reactive electrode (reactrode) made of Prussian blue (PB), graphite and paraffin can be used for a selective determination of thallium ions down to a concentration of 2 · 10^–8 mol 1^–1. The working principle of the reactrode is that thallium ions can be pumped into Prussian blue during alternating oxidation-reduction cycles. After a preconcentration of thallium ions in PB, the voltammetric determination follows as usually in anodic stripping voltammetry, i.e. the thallium ions are reduced to thallium metal which is subsequently oxidized to give the anodic stripping signal. The peculiarity of the Prussian blue-thallium system is that the thallium ions are situated in the holes of the PB matrix. When reduced to metallic thallium, they are substituted by potassium ions. Cd²⁺, Fe³⁺, Zn²⁺, Cu²⁺ and Ni²⁺ do not interfere up to a hundredfold excess, NH₄⁺ does not interfere up to a thousandfold – and Bi³⁺ up to tenfold excess. The interference by Pb²⁺ can be suppressed with EDTA.     

Synthesis of Novel 4‐((Substituted bis‐indolyl)methyl)‐benzo‐15‐crown‐5 for the Colorimetric Detection of Hg2+ Ions in an Aqueous Medium

A practical, two‐step synthesis of novel 4‐(substituted bis‐indolyl)methyl)benzo‐15‐crown‐5 has been reported. The strategy employed for the synthesis of the desired molecules involved Duff formylation of benzo‐15‐crown‐5 to get 4‐formyl benzo‐15‐crown‐5 followed by subsequent reactions with substituted indoles in trifluoroacetic acid to yield novel 4‐(substituted bis‐indolyl)methyl)benzo‐15‐crown‐5 in moderate to good yield. One of the reported novel molecule tested for the complexation behavior with various metal cations, such as Li⁺, Na⁺, K⁺, Mg²⁺ Ca²⁺, Al³⁺, Fe²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, Sn²⁺, Ba²⁺, Hg²⁺, and Pb²⁺, showed a visual colorimetric probe for the detection of mercury cations (Hg²⁺) in an aqueous medium.     

Reactions of Sterically Protected 1-Halo- and 1-Pseudohalo-2-Phosphaethenyl-Lithiums

Abstract

Phosphorus analogs of alkylidenecarbenoid, Ar-P=C(X)Li, where X equals halogen or pseudohalogen atom, such as C1, Br, or SPh, have been generated by use of the 2,4,6-tri-t-butylphenyl group (abbreviated to Ar in the Scheme) as a protecting group for low coordinated organophosphorus compounds. The reaction with methyl iodide and with some aldehydes or ketones, at low temperature, gave the corresponding alkylation products^[l]. The reaction with copper salts gave 1,4-diphosphabutadiene (1) or 1,4-diphosphabutatriene (2), depending upon the substituent X^[2,3], as well as reaction conditions, such as reaction tenlperature and time, solvent, presence or absence of oxygen. Upon warming the phosphaethenyllithiun1s, thus generated, the chloro derivative of E-configuration gave a phosphaalkyne (3) via [1,2]-aromatic migration^[4], whereas the bromo derivative of Z-configuration gave a l-phospha-3,4-dihydronaphthalene derivative (4), that is a formal C-H insertion product of a phosphinidenecarbene intermediate^[5].     

Investigation of routes to indeno[2,1-f] -2H-1,2,4-triazepinediones

The synthesis of a number of 3-(substituted thiosemiearbazido)-2-(a]koxycarbonyl)indones (1) from 2-alkoxycarbonyl-1, 3-indandiones and substituted thiosemicarbazides is described. Cyeliza-tion of compounds 1 in the presence of a variety of catalysts gave substituted Δ²-1,2,4-triazoline-5-thiones (³) and (⁴), instead of the expected substituted 3(4H)-thioxoindeno[2,1-f]-2H-1,2,4-triazepine-5(5aH),6-diones (2). The preparation of 4-(2-methyl-1,3-dioxo-2-indanylmethyl)semi-carbazide ( 9 ) is reported. Cyelization of 9 gave 5,5a-dihydro-5a-methylindeno[2,1-f]-2H-1,2,4-triazepine-3(4H),6-dione ( 10 ). Structure assignments of these compounds are discussed.     

Synthesis and properties of axially-phenoxycyclotriphosphazenyl substituted silicon phthalocyanine

An hydroxyl substituted hexa(phenoxy)cyclotriphosphazene (3) is reacted with silicon phthalocyanine (4), SiPc(Cl)₂, to give an axially-disubstituted phenoxycyclotriphosphazenyl silicon phthalocyanine (5). In this study, an axially phosphazene substituted phthalocyanine complex synthesized at the first time. Newly synthesized silicon phthalocyanine complex has been fully characterized by elemental analysis, ESI mass spectrometry, FT-IR, ¹H, ¹³C and ³¹P NMR spectroscopy. Photophysical (fluorescence quantum yield and lifetime) and photochemical (singlet oxygen generation and photodegradation quantum yield) properties of complex 5 are reported in DMSO. The fluorescence quenching behaviour of this complex by 1,4-benzoquinone (BQ) is also reported in DMSO.     

Thallium in organic synthesis preparation of steroidal 1,4-dien-3-ones

Steroidal 1,4-dien-3-ones are obtained as major products of the reaction between thallium (III) acetate and Δ¹ or Δ⁴-3-keto steroids in acetic acid. 5α-cholestan-3-one, similarly treated, followed by esterification, gives mainly 2α-carbomethoxy-A-nor-5α-cholestane.     

A New Method of Synthesizing Phenalen-1-one: Reduction of 3-Hydroxyphenalen-1-one Using NaBH4 and Lanthanoid Chlorides

Phenalen-1-one was obtained in considerable yield by reducing 3-hydroxyphenalen-1-one. Most of known preparation methods are not very practical, either because their yields are very poor or because their processes have many steps. This regioselective 1,2-reduction proceeded by the action of NaBH₄ and various cations of rare-earth elements and metals. The yields of phenalen-1-one were examined as a function of typical lanthanoids, molar ratios of lanthanoid ions to 3-acetoxy-phenalen-1-one, and differing methods of protecting the hydroxyl group. Lanthanum chloride (LaCl₃) gave the greatest yield (45.3%) of phenalen-1-one at molar ratios higher than a third, probably because La³⁺ ion is a hard acid and coordinates easily to a hard solvent such as methanol. Further, it has the largest ionic radius among all lanthanoid ions.     

Solvent-free one-pot synthesis of thallium complexes of Tp [BH(Pz)3] (Pz = pyrazolate) and its derivatives

Heating a 0.5:1:3 mixture of Tl₂SO₄, KBH₄, and HPz or 3-, 4-, and/or 5-substituted derivatives without the use of any solvent afforded the corresponding thallium complexes of hydrotris(1-pyrazolyl)borate (Tp), and its various substituted forms in high yields. This simple and efficient method should enhance the utility of TlTp-related complexes, which are widely used as mild Tp ligand transfer reagents in the preparation of a variety of transition metal Tp complexes.     

New synthesis of substituted 3-aryl-1-naphthaldehydes

A general, unequivocal procedure for the preparation of specifically substituted 3-aryl-1-naphthaldehydes was developed. Benzylmagnesium bromides with 5-aryl-2, 2-dimethyl-4-pentene-3-ones (12) gave exclusively 1,4-addition products, 5,6-diaryl-2,2-dimethyl-3-hexanones (13). The hexanones on oxidation with peracetic acid gave 3,4-diarylbutanoic acids (14), which were cyclized to tetralones (15). The tetralones on treatment with MeMgI followed by dehydration and dehydrogenation gave 3-aryl-1-methylnaphthalenes (10), which were converted into corresponding aldehydes (11). When benzylmagnesium bromides were added to 4-aryl-3-butene-2-ones (1), mixtures of 1,2 and 1,4-addition products were formed. Further treatment of these mixtures also yielded the desired methylnaphthalenes along with various identified side products.     

Tautomeric composition and tautomeric transformation sequence of 1,4-bis(alkylamino)anthraquinones

Compounds widely known as 1,4-bis(alkylamino)-9,10-anthraquinones are in fact neither individual substances nor substituted 9,10-anthraquinones but equilibrium mixtures of tautomers. Their aminoimine tautomeric transformations follow the sequence 4,9-bis(alkylamino)-1,10-anthraquinones ? 9-alkylamino-4-(alkylimino)-10-hydroxy-1,4-dihydroanthracen-1-ones ? N ¹,N ¹⁰-dialkyl-4,9-dihydroxy-1,10-dihydroanthracene-1,10-diimines.