2/4-Bromopyridine derivatives

The Sonogashira coupling of halopyridines was also achieved by other means. Resin bound bromopyridine derivatives, for example, underwent smooth coupling with acetylenes as well as with arylboronic acids and aryltin reagents.44 The advantageous effect of microwave irradiation on the coupling of halopyridines and trimethylsilylacetylene was also reported.45... 

The palladium catalyzed cross-coupling of organosilicon compounds and aryl halides found only limited application with azines compared to the Suzuki or Negishi coupling. In a recent paper DeShong reported the efficient coupling of bromopyridine derivatives with aryl siloxanes (7.44.) 62 The transmetalating ability of the siloxane was enhanced by the addition of tetrabutylammonium fluoride. 

Direct formation of aza-anthraquinones 181 has been achieved using in situ generated lithio cyanophthalide 177 (a 1,4-dipole equivalent) and 3,4-pyridyne 178 (Scheme 52) [88H(27)2643]. Thus, addition of 3-bromopyridine derivative to a solution of LDA and 177 at -40°C leads, when warmed to room temperature, to aza-anthraquinones 181 in good yields via intermediates 179 and 180. This type of reaction has also been applied to 4-bromoquinoline to give benzo[rf]-2-azaanthraquinone in 60% yield [88H(27)2643]. 

This method was applied to 2- or 4-bromopyridine derivatives and used to produce the corresponding bipyridines, useful as intermediates for herbicide manufacture. Because arylsilvers are more stable, heating was required in this case (Scheme 10.15).29... 

Vincadifformine and tabersonine derivatives are selectively brominated at (C-ll) by Br2/HF/SbF51047. Significant amounts of 2-bromopyridine derivatives are obtained by bromination of lutidines in 20% oleum at 155-175 °C1048. 

The reaction of the bromopyridine derivative (245) with thioesters (R2(EtO)C=S) gives the pyrido[2,3- ]thiopyrans (246) (59-73% yield) <89S456> and this transformation corresponds to a synthesis of the general type (161)- (151). 

C6H40Pr ) [12] and the 3-bromopyridine derivative (H2lMes)(3-BrPy)(Cl)2Ru=CHPh [12] (Figure 6.7) are capable of reactions such as CM between acrylonitrile and allyl-benzene. This improvement in activity is presumably because the corresponding cy-ano-carbene species are less likely to remain trapped by the more weakly bound ether and pyridine ligands. 

Recently, Nadin and Harrison [70] made a similar observation with pyridones, employing a rare example of a pyridine radical. Reaction of the 3-bromopyridine derivative 278 with BusSnH and AIBN furnished the 1-exo trig cyclized product 279 along with 10% of uncyclized reduction product. It is worth noting that the same reaction failed under the Heck conditions. 

The bipyridyl derivative 10 was prepared by treating bromopyridine derivative 11 (made from diacetone-D-glucose) with nickel(II) chloride-zinc-triphenyl-phosphine in DMF. The products were regarded as potential chiral ligands. ... 

The above-mentioned conditions were recently employed to perform a C5 arylation between 4-methyl-2-(Al-acetyl)aminothiazole and a 4-bromopyridine derivative (eq 28). The arylated thiazole thus obtained was used in the preparation of a selective phosphatidylinositol-3 kinase alpha-inhibitor. 

Ethoxy-3,4-pyridyne (46) is involved in the amination of 3- and 4-bromo-2-ethoxypyridine, and mixtures of aminoethoxypyridines of the same composition are formed in both reactions. Thus, from 4-bromo-2-ethoxypyridine only the 3-hydrogen atom, situated between the bromine and ethoxyl groups (and not the 5-hydrogen atom) is abstracted. Pyridyne 47 is an intermediate in the amination of 4- and 5-bromo-3-ethoxypyridine. In the last-mentioned substance, just as in 5- (or 3-)bromopyridine, only the 4-hydrogen atom, and not the 2-hydrogen atom, is abstracted. The amination of 3-bromo-6-ethoxypyridine proceeds via 6-ethoxy-3,4-pyridyne (48). again the 2,3-pyridyne derivative is not formed. 

Amination of derivatives of 2-bromopyridine gave, just as did the same reaction of 2-bromopyridine itself, no decisive answer concerning the mechanism of these processes, except that 2-bromo-3-ethoxy-... 

Attempts to get more information on this interesting meta-rearrangement by choosing derivatives of 2-bromopyridine containing various substituents in the 6-position for the starting material led to a remarkable result. Whereas 2-bromo-6-picoline gave a mixture of 2-and 4-amino-6-picoline (in a ratio of 60 1) in 25% total yield together with a resinous mass, 2,6-dibromopyridine (79) was converted into a pyrimidine, i.e. 4-amino-2-methylpyrimidine (80), in 20% yield. The same pyrimidine was obtained from 2,6-dichloropyridine and, in small amount, also from 2,4-dibromopyridine (81). The course of the... 

In an extensive investigation of the behavior of halogeno-pyridines and -quinolines towards potassium amide in liquid ammonia, tendencies to react according to the hetaryne type and other mechanisms were compared. The following results may be mentioned. 3-Fluoropyridine does not react via 3,4-pyridyne, but yields fluoro derivatives of 4,4 - and 2,4 -bipyridine. 3,6-Dibromopyridine is converted first into 6-bromo-3,4-pyridyne and not into 6-amino-3-bromopyridine. 2-Bromoquinoline yields 2-methylquinazoline together with 2-aminoquinohne. ... 

Amino group of 7-aminomethyl-2-substituted perhydropyrido[l,2-u]pyr-azines were reacted with 2-bromopyridine and 2-chloropyrimidines to give 7-(hetarylamino)methyl derivatives in the presence of Na2C03 in DMF at 100-120°C for 18h in 13-51% yields (00MIP15). An aminomethyl group of... 

Poly(methyl 3-(l-oxypyridinyl)siloxane) was synthesized and shown to have catalytic activity in transacylation reactions of carboxylic and phosphoric acid derivatives. 3-(Methyldichlorosilyl)pyridine (1) was made by metallation of 3-bromopyridine with n-BuLi followed by reaction with excess MeSiCl3. 1 was hydrolyzed in aqueous ammonia to give hydroxyl terminated poly(methyl 3-pyridinylsiloxane) (2) which was end-blocked to polymer 3 with (Me3Si)2NH and Me3SiCl. Polymer 3 was N-oxidized with m-ClC6H4C03H to give 4. Species 1-4 were characterized by IR and H NMR spectra. MS of 1 and thermal analysis (DSC and TGA) of 2-4 are discussed. 3-(Trimethylsilyl)-pyridine 1-oxide (6), l,3-dimethyl-l,3-bis-3-(l-oxypyridinyl) disiloxane (7) and 4 were effective catalysts for conversion of benzoyl chloride to benzoic anhydride in CH2Cl2/aqueous NaHCC>3 suspensions and for hydrolysis of diphenyl phosphorochloridate in aqueous NaHCC>3. The latter had a ti/2 of less than 10 min at 23°C. 

Transition metal complexes have been used in a number of reactions leading to the direct synthesis of pyridine derivatives from acyclic compounds and from other heterocycles. It is pertinent also to describe two methods that have been employed to prepare difficultly accessible 3-alkyl-, 3-formyl-, and 3-acylpyridines. By elaborating on reported194,195 procedures used in aromatic reactions, it is possible to convert 3-bromopyridines to products containing a 3-oxoalkyl function196 (Scheme 129). A minor problem in this simple catalytic process is caused by the formation in some cases of 2-substituted pyridines but this is minimized by using dimethyl-formamide as the solvent.196... 

Upon microwave ( rw) irradiation, benzotriazole and its derivatives react readily with 2-chloropyridine to afford products 113-115 in 87%, 72%, and 70% yield, respectively (Scheme 9). 2-Chloroquinoline reacts similarly. 2-Bromopyridine and 2-bromoquinoline give generally lower yields in these reactions <20060L415>. 

Carbon-linked sugar-heterocycles were also obtained by reaction of the lithiated derivatives obtained from 2-bromopyridine, a-picoline, and ben-zothiazole with 4-0-benzyl-2,3 6,7-di-0-cydohexylidene-D-g(ycero-D-gulo-htplono-1,5-lactone (55). The corresponding o-glycero-D-gulo-hepto-pyranose-substituted compounds 56a-c were isolated in 35-43.5% yields. With other heterocycles (for example furan), 1-disubstituted guloheptitols were obtained (59). 

Low temperatures are necessary with orr/io-halolithiopyridines in order to prevent pyridyne formation, and an added complication with some bromopyridines is that rearrangement of the initial lithio derivative can occur via an intermolecular transmetalation process (Scheme 108)(79T1625 85T3433). This result has been used synthetically to give 2-bromo-3-substituted derivatives from 2,6-dibromopyridine [90JOM-... 

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