The Use of Organolithium Compounds to Effect the Alkylation of 2- and 4-Picoline<sup>1</sup>

A conceptually new class of cationic amphiphiles, Sunfish amphiphiles, designed for the delivery of genes into cells is introduced. Sunfish amphiphiles have two hydrophobic tails, connected at the 4-and the N-position to the cationic pyridinium headgroup. Two extreme morphologies visualised by backfolding and combining of both tails at one site (matching situation) or unfolding of the tails at distinct interaction sites at biological membranes will lead to considerable differences in morphological behaviour. The underlying rationale allows controlled release by using this morphological alteration of

show abstract

“…4‐Nonylpyridine (8d): 34,35 1 H NMR (CDCl 3 ): δ = 0.82 (t, 3 J = 4.4 Hz, 3 H), 1.25 (br. m, 12 H), 1.57 (br.…”

Section: Methodsmentioning

confidence: 99%

Sunfish Amphiphiles: Conceptually New Carriers for DNA Delivery

Hulst¹,

Muizebelt²,

Oosting³

et al. 2004

Eur J Org Chem

View full text Add to dashboard Cite

show abstract

“…The simplest representative of this type of flexible oligopyridines, 2-(2-pyridylmethyl)pyridine (11), is commonly synthesized by nucleophilic aromatic substitution with lithiated 2-methylpyridine as nucleophile and either pyridine or 2-bromopyridine as electrophilic component. [12] Vedernikov et al developed a synthesis for substituted 2,6-bis(2-pyridylmethyl)pyridine with 2,6-dimethylpyridine-dilithium as bis(nucleophile) and pyridine as electrophile. [13] According to our own results, nucleophilic substitutions of this type with pyridine as well as with 2-bromopyridine as reactants lead to rather of 2,6-difluoropyridine, it is necessary to use at least four equivalents (actually up to eight equivalents) of lithiated 8, leading to an excellent yield of the tris(pyridine) product 9.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Methylene‐ and Methine‐Bridged Oligopyridines

Dyker

Muth

2004

Eur J Org Chem

View full text Add to dashboard Cite

show abstract

“…10 In order to introduce larger alkyl groups at the 6 position of the pyridine ring, the 6-methylpyridine derivative was metallated using LDA and quenched with an appropriate alkyl halide. 11 The pyridine species were quaternised by heating in neat alkyl bromide or iodide inside a sealed tube and, after filtration, the pyridinium halides 13 were converted to the tetrafluoroborate salts 14 using silver carbonate and fluoroboric acid. Chloride 6,8,9 and perchlorate 7 salts have previously been used for photosolvolysis reactions, although we opted to use tetrafluoroborate salts; they were easy to make from the halide salt (which tended to undergo photoinduced charge transfer reactions) and were less likely to detonate than perchlorate salts.…”

Section: Methodsmentioning

confidence: 99%

New Methods of Preparing Cyclopentenone Ketals: The Photosolvolysis of 3-Alkoxypyridinium Tetrafluoroborates

Penkett¹

1999

Synlett

View full text Add to dashboard Cite

A new base catalysed method of ketal formation is reported, such that substituted cyclopentenone ketals are prepared from 3-alkoxypyridinium tetrafluoroborate salts.The photochemical properties of aromatic compounds are a source of amazement to many organic chemists. In particular the metaphotocyclo addition 1 has often been described as the reaction that leads to the greatest increase in molecular complexity. This light induced reaction between an aromatic ring and an olefin was concurrently discovered in 1966 by Wilzbach and Kaplan 2 and also by Bryce-Smith, Gilbert and Orger. 3 The metaphotocycloaddition has been very elegantly utilised by Wender for the synthesis of a number of key natural products, such as (±)-a-cedrene 4 and (±)-modhephene (4) 5 (Scheme 1). Scheme 1As yet there have been no reports of heteroaromatic compounds being involved with similar reaction sequences, although Wilzbach, Kaplan and Pavlik 6 reported an unusual photohydration reaction of pyridinium ions in 1972. These workers described how the irradiation of an alkaline solution of N-methylpyridinium chloride 5 led to the formation of a bicyclic aziridinyl alcohol 7. It was proposed that the reaction proceeded via an azabenzvalene 6 cation that was subsequently captured by water from the least hindered face. Scheme 2A renaissance of interest in this reaction has led to some important discoveries by Mariano 7 and Burger. 8,9 Mariano reported the results of photosolvolysis of various pyridinium salts and subsequent solvolytic aziridine ring opening of the products. 7 Burger then reported how this reaction could be used for b-lactam synthesis 8 and, more recently, has shown how polyhydroxylated aminocyclopentanes 9 can be made. We were intrigued to know what effect an electron donating group at the 3 position on the pyridine ring would have on the photosolvolysis of pyridinium salts. We reasoned that the incipient cation would be very stable and should be readily captured by the solvent to form a geminal bisalkoxy species. To test our hypothesis various 3-alkoxypyridinium salts 8 were irradiated in different solvents using a 400 W medium pressure mercury vapour lamp with a pyrex filter. Analysis of the different products showed that a series of cyclopentenone ketal derivatives 9 had been made (Scheme 3). Scheme 3The pyridinium salts were made according to standard literature procedures, starting from either 3-hydroxypyridine or 3-hydroxy-6-methylpyridine 10. The hydroxyl group was initially protected as an ether 11 using an alkyl halide. 10 In order to introduce larger alkyl groups at the 6 position of the pyridine ring, the 6-methylpyridine derivative was metallated using LDA and quenched with an appropriate alkyl halide. 11 The pyridine species were quaternised by heating in neat alkyl bromide or iodide inside a sealed tube and, after filtration, the pyridinium halides 13 were converted to the tetrafluoroborate salts 14 using silver carbonate and fluoroboric acid. Chloride 6,8,9 and perchlorate 7 salts have previously been used for photos...

show abstract

The Use of Organolithium Compounds to Effect the Alkylation of 2- and 4-Picoline¹

Cited by 66 publications

References 0 publications

Sunfish Amphiphiles: Conceptually New Carriers for DNA Delivery

Sunfish Amphiphiles: Conceptually New Carriers for DNA Delivery

Synthesis of Methylene‐ and Methine‐Bridged Oligopyridines

New Methods of Preparing Cyclopentenone Ketals: The Photosolvolysis of 3-Alkoxypyridinium Tetrafluoroborates

Contact Info

Product

Resources

About

The Use of Organolithium Compounds to Effect the Alkylation of 2- and 4-Picoline1

Cited by 66 publications

References 0 publications

Sunfish Amphiphiles: Conceptually New Carriers for DNA Delivery

Sunfish Amphiphiles: Conceptually New Carriers for DNA Delivery

Synthesis of Methylene‐ and Methine‐Bridged Oligopyridines

New Methods of Preparing Cyclopentenone Ketals: The Photosolvolysis of 3-Alkoxypyridinium Tetrafluoroborates

Contact Info

Product

Resources

About

The Use of Organolithium Compounds to Effect the Alkylation of 2- and 4-Picoline¹