Reissert compound studies. XXX. Synthesis and alkylation of some new reissert compounds

The synthesis of several new isoquinoline Reissert compounds is described. Alkylation reactions of the anions of these new Reissert compounds and a rearrangement reaction are reported.     

Bromohydrins of reissert compounds

Reissert compounds that are derivatives of quinoline and isoquinoline are converted in high yields to the corresponding bromohydrins under the influence of N-bromosuccinimide in aqueous dimethyl sulfoxide. The reactions proceed regio-and stereospecifically.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 544–547, April, 1985.     

1 - 烃基异喹啉Reissert Compounds 的合成及其氢化研究

1-苄基异喹啉Reissertcompound经RaneyNi(w-2)催化氢化,分离得到二个未见报道的氢化产物,经化学和波谱分析推定其结构为:1-亚氨基-1-苄基-2-苯甲酰基-1,2-二氢异喹啉(4)和3-苯基-10b-苄基-1,10b-二氢咪唑骈[5,1-a]异喹啉(5)。据此提出了一条1-苄基异喹啉Reissertcompound高压催化氢化的途径,并对异喹啉eissertcompound高压催化氢化反应中酰基转位进行了讨论。试图以环已基溴作为烷化剂,在氢化钠条件下,与异喹啉Reissertcompound作用来制备1-环已基异喹啉Reissertcompound,结果只得到了1-氰基异喹啉,产率达75%,为制备1-氰基异喹啉提供了一个新方法。     

Synthesis of substituted isoquinolines via Pd-catalyzed cross-coupling approaches

Palladium complexes incorporating ligands based on a 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phosphaadamantanyl scaffold were used to catalyze the arylation of ethyl cyanoacetate, malononitrile, and various ketones. The products from these reactions can be elaborated to substituted β-arylethylamines and used in microwave-assisted Pictet-Spengler reactions. The protocol developed is suitable for the synthesis of libraries of substituted isoquinolines.     

Synthesis of new bicyclic compounds containing fused sulfolane and pyrazolidine rings

3-Aryl-6а-methyl-6-nitro-1-carbamoylhexahydrothieno[2,3-d]pyrazole-4,4-dioxides, novel original bicyclic species consisting of fused pyrazolidine and sulfolane rings, and 1,4-adducts were obtained by reacting 2-benzylidene-3-methyl-4-nitro-3-thiolene-1,1-dioxide and its derivatives with semicarbazide.     

Organic sonochemistry. Synthesis and use of reissert compounds under PTC-ultrasound

Use of phase transfer catalysis and ultrasound stirring improved the synthesis, alkylation and hydrolysis of several Reissert derivatives.     

The mass spectra of reissert compounds

A series of Reissert compounds containing the quinoline, isoquinoline and phthalazine nuclei show the common feature in their mass spectra of the initial loss of the N-substituent and either of the substituents attached to the adjacent carbon atom.     

Heterocyclic monomers via reissert chemistry

An AA bisphenolic monomer ( 13 ), an AB activated fluoro‐phenolic monomer ( 14 ), and an AB₂ alcohol‐diester monomer precursor ( 17 ), all based on the isoquinoline nucleus, were prepared using Reissert compound chemistry. Additionally, model reactions established the efficiency of condensation of isoquinoline Reissert compounds with dihaloalkanes, providing evidence of the potential of this reaction to produce high molecular weight polymers, which was subsequently realized. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis of fused N-heterocycles via tandem C-H activation

The synthesis of fused N-heterocycles has been developed using an intramolecular cyclisation of purines or benzimidazoles. A range of medium and large rings were prepared.     

Synthesis of some new fused coumarin derivatives

2-Hydrazino-4-hydroxy-5H- [1] -benzopyrano- [ 4,3-d ] -pyrim-idin-5-one (3) was prepared via condensation of 2 with hy-drazine hydrate. Treatment of 3 with methylene chloride, ethyl chloroformate, ethyl chloroacetate and benzaldehyde yielded the corresponding 2 - ( substituted ) hydrazino - 4 -hydro-xy-5H-[1]-benzopyrano-[4, 3-d]-pyrimidin-5-one (4, 5, 6, and 10), followed by cyclization of 4, 5 and 6 with dimethyl fonnamide and fused sodium acetate under reflux, while compound 10 was cyclized with bromine and sodium acetate in acetic acid. Compound 3 reacted with β-(toloyl) acrylic acid, ethyl α-cyano-p-methoxytinnamate, diethyl mal-onate and acetyl chloride affording the corresponding 2-(substituted) hydrazino-4-hydroxy-5H-[1]-benzopyrano-[4, 3-d]-pyrimidin-5-one (12, 13, 14, 15 and 16).     

A convenient procedure for the synthesis of fused fluoro isoquinolines

A base-promoted conversion of ortho-trifluoromethyl benzyl derivatives of NH-heterocycles into a respective fluorinated isoquinolines (38-57% isolated yields) is reported. The reaction is general for the benzylated derivatives of the electron-rich NH-heterocycles and the respective derivatives of pyrazole. The outcome of the reaction could be explained by an intermediate formation of a highly reactive quinone methide species.     

Synthesis of fused polycyclic nitrogen-containing heterocycles via cascade cyclization

A novel strategy for the synthesis of fused polycyclic-nitrogen containing heterocycles via cascade cyclization is described. The methodology involves condensation of 1-(2-aminophenyl)-9H-β-carboline-3-carboxylic acid amide with isothiocyanates followed by in situ treatment of the resulting thioureas with HgCl₂ for 1 h at rt. The one-pot cascade cyclization leads to interesting changes in molecular structure and an increase in molecular complexity. A mechanistic rationale for the cascade cyclization is discussed.     

Synthesis of fused tetrazole- and imidazole derivatives via iodocyclization

The possibility to prepare fused tetrazole- and imidazole derivatives by iodocyclization in moderate to excellent yields is demonstrated. In some examples the cyclizations were not following Baldwin's rules entirely, i.e. exo-selectivity. Nucleophilic substitution of the formed iodides gave different results depending on the hardness of the nucleophile. Thus, elimination of the iodide could be a problem but a substitution reaction with ethyl potassium xanthate and a radical reaction using acrylonitrile were tolerated. In addition, we showed that it is possible to selectively use three iodo substituents individually in one of the fused imidazole derivatives.     

Base- and acid-catalyzed condensation reactions of reissert compounds with vinylpyridines

The hydrochloric acid-catalyzed condensation of 2-p-anisoyl-1,2-dihydroisoquinaldonitrile ( 3 ) with 2-vinylpyridine gave 2-(1-isoquinolyl)-3-(2-pyridyl)-5-p-anisylpyrrole ( 4 ), and the corresponding reaction of 3 with 4-vinylpyridine afforded 2-(1-isoquinolyl)-3-(4-pyridyl)-5-p-anisylpyrrole (5). The condensation of the lithium salt of 3 with 4-vinylpyridine gave α-(4-pyridyl)-β-(1-iso-quinolyl)-p-methoxypropiophenone ( 10 ), which was cyclized to 2-(4-pyridyl)-3-p-anisylpyrrolo-[2,1-a]isoquinoline (7) by the action of concentrated hydrochloric acid. 2-(4-Pyridyl)-3-phenyl-pyrrolo[2,1-a]isoquinoline ( 6 ) and 2-(2-pyridyl)-3-p-anisylpyrrolo[2,1-a]isoquinoline ( 8 ) were prepared by analogous sequences of reactions.     

Synthesis of new acetal aza-cage compounds via ozonolysis of bis-endo-diol- and diacylnorbornene derivatives

We synthesized acetal aza-cage compounds directly via ozonolysis of 2,3-bis-endo-diol- and diacylnorbornenes in dichloromethane at ?78 °C. Ozonolysis of the diols followed by addition of amines gave the aza-cage compounds in high yields. The reaction mechanism for the formation of this type of aza-cage compounds is proposed to proceed via the hydroperoxide intermediate. Ozonolysis of the diacetyl norbornene followed by addition of (1) primary amines gave monoaza-cages and diaza-cage, (2) tert-butylamine gave hydroxyl lactone and diaza-cages, and (3) amino acid ester gave optically active aza-cages, in which one compound was converted into chiral aminoalcohol and structure of another was proven by X-ray analysis. A mechanism via the final ozonide and the imine intermediates is proposed for the formation of this type of aza-cages.     

Synthesis of fused polycycles from propargylic compounds with terminal alkynes via a palladium-catalyzed tandem C-H activation/biscyclization process

Various benzo[b]fluorene and fluorene derivatives have been prepared from propargylic compounds with terminal alkynes through a novel palladium-catalyzed tandem biscyclization reaction. This reaction involved a sequence of carboannulation, coupling, C-H activation and C-C bond formation process. A plausible mechanism has been proposed that was consistent with the deuterium-labeling experiment.     

Synthesis of bridged azabicycles from isoquinolines via a tandem of allylboration and intramolecular metathesis

A method for the synthesis of bridged azabicyclic compounds from isoquinolines was developed. The method is based on a combination of allylboration and ruthenium-catalyzed intramolecular metathesis. Reductive 1,3-diallylation of bromoisoquinolines with triallylborane gave trans-1,3-diallyl-1,2,3,4-tetrahydroisoquinolines. When heated with triallylborane, these compounds yielded mixtures of cis-and trans-isomers in the ratio ∼1: 1. The structure of cis-1,3-diallyl-5-bromo-1,2,3,4-tetrahydroisoquinoline was confirmed by X-ray diffraction analysis. In a similar way, trans-3-allyl-1-vinyl-1,2,3,4-tetrahydroisoquinoline synthesized by sequential vinylation (with vinyllithium) and allylboration of isoquinoline, yielded a mixture of cis-and trans-isomers in the ratio 1.6: 1. Intramolecular metathesis reactions of N-Boc derivatives of cis-isomers in the presence of the Grubbs catalyst (2.0–2.5 mol.%) afforded 7,8-benzo-10-azabicyclo[4.3.1]dec-2-enes or 7,8-benzo-9-azabicyclo[3.3.1]non-2-ene in nearly quantitative yields. Dedicated to Academician V. A. Tartakovsky on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1510–1515, August, 2007.