Pyridines, 4-substituted, amination

The above three reactions employed ortAo-directing groups for assisted C—H activation in the presence of palladium(II) catalysts. The electrophilic fluorination reaction involved cyclopalladation and two electrophilic fluorination processes. Subtly, differential nitrogen atoms (pyridine, substituted amines, and amides) in the molecules were proposed to act as the electron donor, which is required for intramolecular Pd participation in the process. In this case, formation of a flve-membered palladium (II) complex (Schemes 9.12 and 9.13) has been proposed. ... 

A monolayer of the pyridine-substituted alkyl merocyanine (12) was prepared in the 1970s (67), and a noncentro symmetric multilayer stmcture of merocyanine amphiphiles was later prepared (68) using derivatives, but introducing long-chain amines as the counter layer in an ABABAB system (69,70). 

There is evidence from a detailed study of the photolyses of 2-alkyl-substituted aryl azides 40 in diethylamine that A3,7V-diethyl-1 //-azepin-2-amines are formed as oxygen-sensitive, meta-stablc intermediates that can give rise to a variety of byproducts, including 5-acyl- A%V-diethyl-pyridin-2-amines and 6-alkyl-7-(diethylamino)-2//-azepin-2-ones 11 however, formation of these oxidation products can be avoided by refluxing the photolysate mixture with methanol prior to exposure to oxygen, in which case practicable yields of the /V,/V-diethyl-3W-azepin-2-amines 41 result. 

Palladium, (diammine)bis(thiocyanato)-isomerism, 1, 185 Palladium, dichlorobis(amine)-substitution reactions stereochemistry, 1, 318 Palladium, dichlorobis(pyridine)-substitution reactions, 1, 314 Palladium, dinitritobis(triisopropylphosphine)-substitution reactions, I, 314 Palladium, ethylene-synthesis... 

Salts of dithiocarbamic acid can be prepared by the addition of primary or secondary amines to carbon disulfide. This reaction is similar to 16-9. Hydrogen sulfide can be eliminated from the product, directly or indirectly, to give isothiocyanates (RNCS). Isothiocyanates can be obtained directly by the reaction of primary amines and CS2 in pyridine in the presence of DCC. ° In the presence of diphenyl phosphite and pyridine, primary amines add to CO2 and to CS2 to give, respectively, symmetrically substituted ureas and thioureas ... 

The use of an extended arene (tetrahydroanthracene) in [OsCl(en)(ri6-tha)]+ (29) gave rise to a similar potency (112). This is in contrast with the data for ruthenium-arenes, where the same substitution gave rise to a 10-fold increase in activity. Further work therefore needs to determine if the extended Os-arenes can intercalate into DNA in a manner similar to Ru-arenes. Replacement of the iV /V-chelating ligand en for other AyV-bidentates with pyridine, aliphatic amine, or azopyridine donor atoms leads to loss of activity, probably because of slower hydrolysis and higher acidity of the coordinated water (112). 

The stoichiometric enantioselective reaction of alkenes and osmium tetroxide was reported in 1980 by Hentges and Sharpless [17], As pyridine was known to accelerate the reaction, initial efforts concentrated on the use of pyridine substituted with chiral groups, such as /-2-(2-menthyl)pyridine but e.e. s were below 18%. Besides, it was found that complexation was weak between pyridine and osmium. Griffith and coworkers reported that tertiary bridgehead amines, such as quinuclidine, formed much more stable complexes and this led Sharpless and coworkers to test this ligand type for the reaction of 0s04 and prochiral alkenes. 

Nucleophilic substitution occurs at C-2, and to a lesser extent C-4, as might be predicted from similar reactions with pyridine. Chichibabin amination occurs rather more readily than with pyridine, giving 2-aminoquinoline. A typical hydride abstraction process occurs when qninoline is heated with sodinm... 

Reactions involving the [4 + 1 + 1] principle, an example of which is shown in equation (136), are rather uncommon and of strictly limited utility [3 + 2 + 1] and [2 + 2 + 2] processes, on th,e other hand, are well known. Representative [3 + 2+1] three-bond formation processes are given in equations (137)—(141), from which it can be seen that the common situation is where ammonia, a substituted amine or formamide constitutes the one-atom fragment. Many [2 + 2 + 2] atom fragment syntheses are known and some are familiar reactions. Thus, the cobalt(I)-catalyzed condensation of nitriles and isocyanates with alkynes gives pyridines and 2-pyridones, often in excellent yield (e.g. equation 142), while the cyclotrimerizations of nitriles, imidates, isocyanates, etc., are well established procedures for the synthesis of 1,3,5-triazine derivatives (e.g. equation 143). Further representative examples are given in equations (144)-(147), and the reader is referred to the monograph chapters for full discussion of these and other [2 + 2 + 2] processes. Examination of the... 

The synthetic and industrial importance of this reaction lies in its generality, and the ease with which the amino substituent in the products can be subsequently transformed into other functionalities. Pyridine itself is more difficult to aminate than quinoline or isoquinoline, and it does not react with potassium amide in liquid ammonia even on prolonged treatment. However, pyridine is aminated in good yield by sodamide in toluene, and di- and tri-amination can be achieved with excess sodamide at higher temperatures. The 4-position is substituted last in triamination y-amination is very difficult indeed and only takes place when all a -positions are occupied. 

Fluoropyridinium salts with either tetrafluoroborate, hexafluoroantimonate, or hexafluoro-phosphate as a counteranion can be treated with excess base (triethylamine, pyridine, diethyl-amine) at room temperature to give 2-fluoropyridine (bp 125 126°C, d4° 1.131, np° 1.468) in good yield.43 This method has been successfully applied to the preparation of 2-fluoropyridine derivatives 4 possessing electron-donating or -withdrawing substituents using substituted 1-fluoropyridinium tetrafluoroborates.43... 

Publications on other types of rearrangements involving tetrazoles are cited at length in a review <2004SOS(13)861> in particular, the Smiles rearrangement of 2-[(l-alkyl/aryl-17/-tetrazol-5-yl)sulfanyl]pyridine-3-amines 208 to 3-[(l-alkyl/aryl-l/7-tetrazol-5-yl)amino]pyridine-2(l/f)-thiones 209 under acidic conditions and Smiles rearrangement of 5-sulfanyl/sulfone-substituted tetrazoles 210 to tetrazol-5-amines 211 under basic conditions (Scheme 19) <2004SOS(13)861>. 

Thus, using Ni(0) and IMes, amines possessing a wide range of functionalities were obtained in yields ranging from 65 to 99%. No hydrogenation was observed with cyano- and pyridine-substituted imines and is likely due to ligand displacement and subsequent catalyst deactivation. 

The formation of activated iminium intermediates derived from nitrogen heterocycles has been reported by Comins and co-workers.163,163a The activation of pyridine derivative with phenyl chloroformate provides pyridinium salt, which smoothly reacts with the zinc homoenolate (Equation (94)).163 163a 164 The reaction of unsaturated amide with Ph jC 1 BI 4 produces iV-acyliminium ions, which react with PhaZn in CH2CI2 producing the desired a--substituted amine (Equation (95)).165... 

Most nonmetal borates reported in the literature are ammonium and substituted ammonium salts, hi general, boric acid forms salts with alkyl- or aryl-amines that are roughly as or more basic than pyridine. Depending on the reaction conditions, a number of different crystalline borates might be isolated from a given amine. However, the chemistry of substituted amine borates is dominated by the occurrence of pentaborates, and relatively few compounds in this class have been reported containing more basic borates anions. 

Heterocyclic aryl amines, such as pyridine and the pyrimidines, are important in the production of colorants and pharmaceutical products and, apart from mention in the relevant sections of this chapter, have received extensive reviews. Here the emphasis is on the industrial applications of aminotriazines, for which industrial interest followed the bulk commercial availability after 1945, particularly from American Cyanamid, of the chlorotriazine cyanuric chloride (182)96. Reactions of cyanuric chloride with amines and substituted amines afford substituted melamines and various aminotriazines that have found application in pharmaceuticals and herbicides. 

Per-A--(2-pyridylmethyl) substitution of cyclic amines is effected by reaction with 2-(2-chloro-methyl)pyridine. The coordination behavior of 2-pyridylmethyl-substituted amines is similar to that of the 2-ethylamine analogues, but compounds are formed with a wider range of cations. 

Hydrogenolytic ring opening of the 5-substituted 1,2,4-oxadiazole ring of 3-(l,2,4-oxadia-zol-3-yl)pyridin-2-amines 5 in the 3-position creates a C-N -C side chain in the form of an acylated amidine 6. In refluxing xylene this cyclizes with the amino group in the 2-position to yield pyrido[2,3-c/]pyrimidin-4-amines 7.9... 

Several 4-substituted l,4-dihydropyrido[4,3-r/]pyrimidines 5 have been synthesized by connecting the two amino groups in 3-(l-aminoalkyl)pyridin-4-amines by triethyl orthoformate.495... 

Skoog and Jencks initially investigated the rates of transfer of the phosphoryl group from phosphorylated 3-methoxypyridine to a variety of substituted pyri-dines and amines that differ in pK and concluded that free metaphosphate anion is not involved as an intermediate (50). The basis for this experiment is the expectation that if metaphosphate anion is a true intermediate, a change in the rate-determining step should occur as the basicity of the acceptor pyridine or amine is varied. When the acceptor is less basic (nucleophilic) than 3-... 

Amino-l,2-dihydroacronycine (40 ) could be easily converted into variously substituted amines and amides. Treatment of 40 with formaldehyde and sodium borohydride afforded 2-dimethylamino-l,2-dihydroacronycine (42). Both aliphatic and aromatic amides were obtained from 4 upon treatment with acid anhydrides in pyridine. This latter reaction is exemplified by the preparation of 2-acetylamino-l,2-dihydroacronycine (43J and 2-benzoylamino-l,2-dihydroacronycine (44) using acetic anhydride and benzoic anhydride, respectively (53). 

Pyridine-substituted nicotines, nornicotines, and anabasines are available from a-cyano-amines by a new synthesis. The syntheses of ( )-[l - N]nornicotine and ( )-[l - N]nicotine have been described, from cyclopropyl 3-pyridyl ketone and [ N]formamide. 4-Methylnicotine has been prepared it shows no nicotine-like pharmacological activity. " An investigation into the stereochemical factors involved in the behaviour of nicotine and related compounds in the Menschutkin reaction has been conducted.A bridged nicotine , 1,2,3,5,6,10b-hexahydropyrido[2,3-g]indolizine (44), has been synthesized by carboxylation of the dilithium derivative of 2-methylnornicotine followed by cyclisation and reduction with borane in tetrahydrofuran. Several 5-halogeno-nicotines have been prepared and their pK values and biological activities measured. ... 

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