Alkylated 2-methyl-5-ethyl-pyridine

The most thoroughly investigated compounds are the alkyl-pyridines. Coleman and Fuoss compared the reactions of pyridine, 4-picoline, and 4-isopropylpyridine with n-butyl bromide and found a steady increase in the rate in the order given the activation energies are 16.0,15.95, and 15.6 kcal per mole, respectively. Brown and Cahn carried out a detailed study of the reactions of 2-, 3-, and 4-alkyl-pyridines with methyl, ethyl, and isopropyl iodides in nitrobenzene the results are given in Table II. These data show the higher activation... 

In a search for new spasmolytics, Heilbron and Hey and their co-workers synthesized a number of pyridylquinolines by coupling diazotized arainoquinolines with pyridine. Pyridine has also been substituted by the 3-pyridyl radical in the Gomberg reaction, the 2-and 3-substituted products being obtained in 55 and 5% yield, respectively, together with a third product obtained in 20% yield w hich w as tentatively formulated as the 4-isomer. The same radical w as coupled with 4-methyl- and 4-ethyl-pyridine and gave in each case mixtures of the twm possible substitution products in which the radical had coupled predominantly with the carbon atom of pyridine adjacent to the alkyl substituent, as showm in Eq. (19). ... 

Alkylated pyridines such as 3-picoline, 3(5)-ethylpyridine and 2-methyl-5-ethyl-pyridine (MEP) are the natural choice as starting materials for the nicotinates. The choice of alkyl pyridine is governed by their availability and the process being used. 

The first reaction was found by Levy and Szwarc to be predominant when methyl radicals attacked isooctane. The second reaction is predominant, however, for aromatic hydrocarbons. The free radicals formed in the above two reactions will react with each other, with other free radicals, or with impurities. The affinity of the methyl radical to attack an aromatic increases in the following order benzene, diphenyl ether, pyridine, diphenyl, benzophenone, naphthalene, quinoline, phenanthrene, pyrene, and anthracene. The ability of free alkyl radicals to interact with isopropylbenzene and cyclohexene decreases in the following order methyl, ethyl, propyl, butyl, isopropyl, sec-butyl, and tertiary butyl. 

Synthesis of Thiophens by Ring-closure Reactions.—The reaction of dipotassium nitroethylenedithiolate and a-chlorocarbonyl derivatives, followed by oxidation with iodine, gave (1). Treatment of pentane-2,4-dione with carbon disulphide in the presence of potassium hydroxide, followed by treatment with ethyl bromoacetate, methyl iodide, and alkali, gave (2). Compounds of type (3) were formed in the reaction of 1-cyanomethylpyridinium chloride with carbon disulphide and alkylating agents such as chloroacetonitrile, ethyl bromoacetate, phenacyl bromide, or chloroacetamide in the presence of alkali, and intramolecularly cyclized to (4). After 5-methylation, the pyridine ring could be cleaved by reaction with phenylsulphonylacetonitrile and alkali in DMSO... 

TSH readily A( aminates stericaUy hindered p)mdines such as 2,6-di-tert-hutylpyridine, which can only he A( alkylated under forcing conditions. Ethyl pyridine-2-carhoxylate, 2-carhamido-pyridines,, methyl 2-(2-pyridyl)henzoate, and furo[3,2-c]-pyridines were likewise A(-aminated in high yields under mild conditions (eq 3). 

The acronyms employed are as follows we refer to each of the discrete structural moieties by using two letters. For example. Me, Et, Pr, Bu, Hx, Oc, Py, and Im refer to methyl, ethyl, 1-propyl, 1-hexyl, 1-octyl, pyridine, and imidazole, respectively. Unless specified otherwise, the alkyl groups are 1-alkyl. Usually, one of the two groups attached to the imidazolium ring is a long-chain one. We use to denote this group,... 

Etherification. The reaction of alkyl haUdes with sugar polyols in the presence of aqueous alkaline reagents generally results in partial etherification. Thus, a tetraaHyl ether is formed on reaction of D-mannitol with aHyl bromide in the presence of 20% sodium hydroxide at 75°C (124). Treatment of this partial ether with metallic sodium to form an alcoholate, followed by reaction with additional aHyl bromide, leads to hexaaHyl D-mannitol (125). Complete methylation of D-mannitol occurs, however, by the action of dimethyl sulfate and sodium hydroxide (126). A mixture of tetra- and pentabutyloxymethyl ethers of D-mannitol results from the action of butyl chloromethyl ether (127). Completely substituted trimethylsilyl derivatives of polyols, distillable in vacuo, are prepared by interaction with trim ethyl chi oro s il an e in the presence of pyridine (128). Hexavinylmannitol is obtained from D-mannitol and acetylene at 25.31 MPa (250 atm) and 160°C (129). 

Abbreviations Aik, alkyl AN, acetonitrile Ar, aryl Bu, butyl cod, 1,5-cyclooctadiene Cp, cy-clopentadienyl Cp , pentamethylcyclopentadienyl Cy, cyclohexyl dppm, diphenylphosphinome-thane dpme, Ph2PC2H4PMe2 Et, ethyl fod, 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octane-dionate HOMO, highest occupied molecular orbital LUMO, lowest unoccupied molecular orbital Me, methyl MO, molecular orbital nbd, norbornadiene Nuc, nucleophile OTf, triflate Ph, phenyl Pr, propyl py, pyridine THE, tetrahydrofuran TMEDA V,V,M,M-tetramethylethylenediamine. 

Abbreviations acac, acetylacetonate Aik, alkyl AN, acetonitrile bpy, 2,2 -bipyridine Bu, butyl cod, 1,5- or 1,4-cyclooctadiene coe, cyclooctene cot, cyclooctatetraene Cp, cyclopentadienyl Cp, pentamethylcyclopenladienyl Cy, cyclohexyl dme, 1,2-dimethoxyethane dpe, bis(diphenyl-phosphino)ethane dppen, cis-l,2-bis(di[Atenylphosphino)ethylene dppm, bis(diphenylphosphino) methane dppp, l,3-bis(diphenylphosphino)propane eda,ethylenediamine Et,ethyl Hal,halide Hpz, pyrazole HPz, variously substituted pyrazoles Hpz, 3,5-dimethylpyrazole Me, methyl Mes, mesityl nbd, notboma-2,5-diene OBor, (lS)-endo-(-)-bomoxy Ph, phenyl phen, LlO-phenanthroline Pr, f opyl py, pyridine pz, pyrazolate Pz, variously substituted pyrazolates pz, 3,5-dimethylpyrazolate solv, solvent tfb, tetrafluorobenzo(5,6]bicyclo(2.2.2]octa-2,5,7-triene (tetrafluorobenzobanelene) THE, tetrahydrofuran tht, tetrahydrothicphene Tol, tolyl. 

Abbreviations aapy, 2-acetamidopyridine Aik, alkyl AN, acetoniuile Ar, aryl Bu, butyl cod, 1,5-cyclooctadiene COE, cyclooctene COT, cyclooctatetraene Cp, cyclopentadienyl Cp , penta-methylcyclopentadienyl Cy, cyclohexyl DME, 1,2-dimethoxyethane DME, dimethylformamide DMSO, dimethyl sulfoxide dmpe, dimethylphosphinoethane dppe, diphenylphosphinoethane dppm, diphenylphosphinomethane dppp, diphenylphosphinopropane Et, ethyl Ec, feirocenyl ind, inda-zolyl Me, methyl Mes, mesitylene nb, norbomene orbicyclo[2.2.1]heptene nbd, 2,5-norbomadiene OTf, uiflate Ph, phenyl PPN, bis(triphenylphosphoranylidene)ammonium Pi , propyl py, pyridine pz, pyrazolate pz, substituted pyi azolate pz , 3,5-dimethylpyrazolate quin, quinolin-8-olate solv, solvent tfb, teti afluorobenzobaiTelene THE, tetrahydrofuran THT, tetrahydrothiophene tmeda, teti amethylethylenediamine Tol, tolyl Tp, HB(C3H3N2)3 Tp , HB(3,5-Me2C3HN2)3 Tp, substituted hydrotiis(pyrazol-l-yl)borate Ts, tosyl tz, 1,2,4-triazolate Vin, vinyl. 

Methyl or ethyl chloroformate (70 mmol) was added dropwise to a stirred solution of a hydrazone derivative (60 mmol) of 2-amino-5-chlorobcnzophenone in a mixture of CIICI, (200 mL) and pyridine (15 mL) at 10 C. The mixture was left overnight and treated with a further amount of the alkyl chloroformate (40 mmol) and stirred at 20 C for 2 h. If /V-aryl-substituted hydrazones were used, the mixture was refluxed for 3-6 h. The mixture was poured into ice-water and the organic layer was washed successively with H2Oand 10% aq NaH0O3, dried (MgSO ) and evaporated in vacuo to yield 7 or 8 or a mixture of the two. 

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