New synthesis routes to 2-halopyridines. II. 2-bromopyridine

The use of bromine chloride (equilibrium mixture) in substitution reactions has been extended to heterocyclic substrates. The vapor phase bromination of pyridine (I) with bromine chloride at temperatures as low as 375° (carbon tetrachloride diluent) gave the following product distribution: 2-bromopyridine (IV) (75%) > 2-chloropyridine (VI) (21%) > 3-bromopyridine (II) (2.0%) ? 2,6-dibromopyridine (VI) (1.5%). In contrast, when bromine was employed in place of bromine chloride (450°; carbon tetrachloride diluent), product orientation was significantly altered to give nearly equal quantities of 3-bromopyridine (II) (17%) and 2-bromopyridine (IV) (22.7%).     

New synthesis routes to 2-halopyridines. I. 2-chloropyridine

In contrast to the wide variety of products previously reported from the non-photolytic liquid or vapor phase chlorination of pyridine (I), it has been demonstrated that the corresponding photochemical chlorination of I in carbon tetrachloride under reflux conditions gave 2-chloropyridine (IV) in 62–78 percent yield.     

New synthesis of 3-fluoropyridine derivatives

The reaction of 2,2-bis(dimethylamino)-3,3-difluoro-1-methylcyclobutane-carbonitrile with alkyl lithiums leads to the formation of 6-alkyl-2-(dimethylamino)-3-fluoro-5-methylpyridines in moderate to good yields.     

Microwave rotational spectra and structures of 2-fluoropyridine and 3-fluoropyridine

The ground state rotational spectra of 2-fluoropyridine and 3-fluoropyridine have been investigated using both Fourier transform microwave (FTMW) and chirped pulse Fourier transform microwave (cp-FTMW) spectroscopies. In addition to the parent species, the spectra of the (13)C and (15)N singly substituted isotopologues were recorded in the 8-23 GHz region in natural abundance. The rotational constants determined for the seven isotopologues of each were used to calculate relevant geometric parameters including the bond distances and angles of the pyridine ring backbone. The derived structures show a more pronounced deviation from the pyridine ring geometry when the fluorine substituent is ortho to nitrogen which is consistent with ab initio predictions at various levels of theory. Analysis of the (14)N hyperfine structure provided an additional source of information about the electronic structure surrounding the nitrogen atom as a function of fluorine substitution. Together, the experimental results are consistent with a bonding model that involves hyperconjugation whereby fluorine donates electron density from its lone pair into the π-system of pyridine.     

Directed lithiation of 4-halopyridines: Chemoselectivity,regioselectivity and application to synthesis

4-Chloro and 4-fluoropyridines were ortho-lithiated by n-butyllithium-TMEDA chelate or lithium diiso-propylamide at low temperature. The resulting 3-lithio 4-halopyridines were reacted with electrophiles which led to various 3,4-disubstituted pyridines. The versatility of this functionalization is enhanced by the 4-halogen reactivity towards nucleophiles such as water, methylate and amines. Some of the 3,4-disubstituted synthons were annelated to naphthyridine, xanthone and coumarin or condensed to Hantsch-ester or to “chlotrimazol” analogues. Lithiation of 4-fluoropyridine led in one step to 3,4-pyridyne, which was trapped by cycloaddition with furans.     

Nucleophilic substitution in 2-nitro-3-halopyridines

Nucleophilic substitution occurs in the 2 or 3 position in 2-nitro-3-halopyridines depending on the nature of the halogen and the substituting agent. A series of new 2,3-substituted pyridines were obtained as a result of the reactions.     

2-氨基-4-氟吡啶合成工艺研究

2-氨基-4-氟吡啶是制备酪氨酸激酶抑制剂、PI3K抑制剂和醛固酮合酶抑制剂等酶抑制剂的重要中间体.已报道的制备方法均存在一些缺陷,难以满足工业化生产.本文以4-氯吡啶-2-甲酰胺为原料,经酰胺脱水、卤素交换、氰基水解、霍夫曼降解等反应得到目标化合物.产物结构经1 H NMR和GC-MS确证.本文采用的合成方法简单、反...     

He I and He II spectra of 2-halopyridines

The He I and He II ultraviolet photoelectron spectra of 2-fluoro-, 2-chloro-, 2-bromo-, and 2-iodopyridine have been recorded and interpreted in terms of a composite-molecule model. The sequence of the four lowest ionization energies for 2-fluoro- and 2-chloropyridine is: π₃ (1a₂) > n_N (11a₁) > π₂ (2b₁) > π_pyr (7b₂), whereas for 2-bromo- and 2-iodopyridine the assignment is: π₃ (1a₂) - π_X > n_N (11a₁) > π_X > π₂ (2b₁), where X represents a bromine and iodine lone-pair. Comparison of the He I and He II band intensities confirmed this assignment. However, ab initio calculations at the STO-3G*/STO-3G* and 6–31G**/STO-3G* levels did not agree with the sequence predicted by either the composite-molecule model, simple correlations and the He I/He II cross-section ratios. For the 2-fluoropyridine, a comparison using the HAM/3 model was found to be in agreement with this assignment.     

New routes in the synthesis of metal oxides,I

Single crystals of numerous new metal oxides “rich in cations” are prepared by using methods such as dis- or conproportionation, thermal decomposition of higher valence oxides, or oxidation of metals and intermetallic compounds (“reactions with the wall”). Exchange reactions allow growth of single crystals even outside of thermodynamic equilibrium. The role of vacancies in structural chemistry as well as in “tailor-made” syntheses is emphasized and illustrated. Molecular aspects of solid state chemistry are demonstrated by cutting chains or rings and by dimerization of small entities. Many examples are provided.     

New routes for the synthesis of 2,5-disubstituted 4-formylthiazoles

New 2,5-disubstituted 4-formylthiazoles have been obtained by the reaction of acetal-containing -chloroxiranes or their rearrangement products, chloroketones, with thioamides and N-allylurea.Kazan' State Technological University, Kazan' 420015, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 124–129, January, 1998.     

The synthesis of triphenylene-based discotic mesogens New and improved routes

The synthesis of discotic liquid crystal materials based on the triphenylene core normally involves the preparation of hexahydroxytriphenylene. This has traditionally been accomplished by a chloranil promoted trimerization of 1,2-dimethoxy-benzene followed by demethylation of the hexamethoxytriphenylene produced. Hexahydroxytriphenylene is subsequently alkylated to give the required derivative. The overall yield of this three step procedure is low and it is difficult to perform on a large scale. It is herein shown that a modified procedure using iron III chloride instead of chloranil yields hexa-alkoxytriphenylenes in a single step. The reaction is high yielding and can be performed on a large scale. This also provides a better route than those currently available for making the unsymmetrically substituted tri-phenylenes required in the synthesis of polymeric discotic liquid crystals. Some related elaborations of the triphenylene nucleus are also discussed.