Pyridine—continued phenylation

A mixture of 16.8 g of 2-aminobenzophenone, 11.9 g of glycine ethyl ester hydrochloride and 200 cc of pyridine was heated to reflux. After one hour, 20 cc of pyridine was distilled off. The solution was refluxed for 15 hours, then 11.9 g of glycine ethyl ester hydrochloride was added and the refluxing was continued for an additional 4 hours. The reaction mixture was continued for an additional 4 hours. The reaction mixture was concentrated in vacuo, then diluted with ether and water. The reaction product, 5-phenyl-3H-1,4-benzodiazepin-2(1 H)-one, crystallized out, was filtered off, and then recrystallized from acetone in the form of colorless rhombic prisms, MP 182°Cto 183°C. 

Attempts to synthesize transition metal alkyl compounds have been continuous since 1952 when Herman and Nelson (1) reported the preparation of the compound C H6>Ti(OPri)3 in which the phenyl group was sigma bonded to the metal. This led to the synthesis by Piper and Wilkinson (2) of (jr-Cpd)2 Ti (CH3)2 in 1956 and a large number of compounds of titanium with a wide variety of ligands such as ir-Cpd, CO, pyridine, halogen, etc., all of which were inactive for polymerization. An important development was the synthesis of methyl titanium halides by Beerman and Bestian (3) and Ti(CH3)4 by Berthold and Groh (4). These compounds show weak activity for ethylene polymerization but are unstable at temperatures above — 70°C. At these temperatures polymerizations are difficult and irreproduceable and consequently the polymerization behavior of these compounds has been studied very little. In 1963 Wilke (5) described a new class of transition metal alkyl compounds—x-allyl complexes,... 

In the course of the continuing study [9a,b] on the enantioselective addition of dialkylzincs to aldehydes by using chiral amino alcohols such as diphenyl(l-methyl-2-pyrrolidinyl)methanol (45) (DPMPM) [48] A. A -dibutylnorephedrine 46 (DBNE) [49], and 2-pyrrolidinyl-l-phenyl-1-propanol (47) [50] as chiral catalysts, Soai et al. reacted pyridine-3-carbaldehyde (48) with dialkylzincs using (lS,2/ )-DBNE 46, which gave the corresponding chiral pyridyl alkanols 49 with 74-86% ee (Scheme 9.24) [51]. The reaction with aldehyde 48 proceeded more rapidly (1 h) than that with benzaldehyde (16 h), which indicates that the product (zinc alkoxide of pyridyl alkanol) also catalyzes the reaction to produce itself. This observation led them to search for an asymmetric autocatalysis by using chiral pyridyl alkanol. 

Phenyl terminated polybutadiene (M 1300 daltons, 45% vinyl) was reacted with trichlorosilane and chloroplatinic acid and then mixed with a slurry of 105 p particle size silica gel having a 250 A average pore diameter in dry toluene for 24 hours. The quantity of trichlorosilane used was 2 mol per mole of polybutadiene. Pyridine was added to remove HCl, and the slurry was gently shaken for 18 hours at ambient temperature. The surface of the silica was blocked by addition of 1,2-bis(trichlor-osilyl)ethane, and the mixture was treated with pyridine. After three hours of shaking the reaction was worked up by vacuum filtration in a sintered glass funnel and washed with toluene and methanol. The modified silica gel was dried in the filter funnel by continued application of vacuum to the filter funnel. 

The Yukawa-Tsuno equation continues to find considerable application. 1-Arylethyl bromides react with pyridine in acetonitrile by unimolecular and bimolecular processes.These processes are distinct there is no intermediate mechanism. The SnI rate constants, k, for meta or j ara-substituted 1-arylethyl bromides conform well to the Yukawa-Tsuno equation, with p = — 5.0 and r = 1.15, but the correlation analysis of the 5 n2 rate constants k2 is more complicated. This is attributed to a change in the balance between bond formation and cleavage in the 5 n2 transition state as the substituent is varied. The rate constants of solvolysis in 1 1 (v/v) aqueous ethanol of a-t-butyl-a-neopentylbenzyl and a-t-butyl-a-isopropylbenzyl p-nitrobenzoates at 75 °C follow the Yukawa-Tsuno equation well, with p = —3.37, r = 0.78 and p = —3.09, r — 0.68, respectively. The considerable reduction in r from the value of 1.00 in the defining system for the scale is ascribed to steric inhibition of coplanarity in the transition state. Rates of solvolysis (80% aqueous ethanol, 25 °C) have been measured for 1-(substituted phenyl)-l-phenyl-2,2,2-trifluoroethyl and l,l-bis(substi-tuted phenyl)-2,2,2-trifluoroethyl tosylates. The former substrate shows a bilinear Yukawa-Tsuno plot the latter shows excellent conformity to the Yukawa-Tsuno equation over the whole range of substituents, with p =—8.3/2 and r— 1.19. Substituent effects on solvolysis of 2-aryl-2-(trifluoromethyl)ethyl m-nitrobenzene-sulfonates in acetic acid or in 80% aqueous TFE have been analyzed by the Yukawa-Tsuno equation to give p =—3.12, r = 0.77 (130 °C) and p = —4.22, r — 0.63 (100 °C), respectively. The r values are considered to indicate an enhanced resonance effect, compared with the standard aryl-assisted solvolysis, and this is attributed to the destabilization of the transition state by the electron-withdrawing CF3 group. 

Car bobutoxyphenyl ehloroformate added drop wise with stirring at 25-35° to phenylethylamine in dry pyridine, and stirring continued at room temp for several hrs. -> p-carbobutoxyphenyl N-phenyl-N-ethyl-carbamate. Y 88%.—Pyridine proved a good solvent for condensation with ar. amines. However, more basic amines had to be condensed in an inert solvent, using 2 moles of the amine. (F. e. s. M. T. Leffler and E. J. Matson, Am. Soc. 70, 3439 (1948).)... 

Treatment of 6-ethoxy-2-phenyl-3-carboxy-5,6-dihydro-4/7-pyran with hydroxylamine transforms the heterocycle to 2-phenylnicotinate <97JHC93>. However, an isoxazole is obtained if the pyran is substituted with an acyl group rather than the ester functionality. Nitriles continue to be key components in pyridine synthesis. The bicyclic ketal 8 is converted cleanly to the pyridine 9 in the presence of an alkyl nitrile using 5 equiv of TMSOMs and 1 equiv of BFrEt20. This combination, generating the active ingredient boron difluoromethanesulfonate, avoids the byproduct cyclohexanones <97JHC325>. 

Equivalent amounts of p-t rt-butylbenzoyl chloride and N-methylaniline refluxed 0.5 hr. in dry pyridine under anhydrous conditions, cooled, P4S13 added, and refluxing continued 2 hrs. 2-methyl-N-phenyl-p-t rt-butylbenzothioamide. Y i... 

Sym. acyl peroxides. Ethereal HgOg-soln. added at -15° to a soln. of phenyl-propiolic chloride in abs. ether, then pyridine added dropwise with stirring, which is continued 2 hrs. diphenylpropiolyl peroxide (Caution, explosive). Y 74.5%. C. Bischoff and K.-H. Platz, J. pr. 312, 2 (1970) also mixed acyl peroxides s. Do Linh Khuong, G. S. Bylina, and Y. A. OPdekop, Akad. Navuk Belarus. SSR, Ser. Khim. Navuk 1970 (3), 74 (Russ) C. A. 73, 87570. 

Pyrolysis of pyridine derivatives is a method for allylic and benzylic deamination the preparation of nitriles from aldehydes, and the preparation of isocyanates from acid chlorides or hydrazides Flash vacuum pyrolysis continues to yield interesting reactions and products. Recently, it has been reported that quite sensitive acetylene derivatives can be obtained by this method from 4-alkylideneisoxazol-5(4H)-ones by ring degradation. On the other hand, 2 carbamyl azide molecules cyclize under these conditions to form l,2,4-triazolidine-3,5-dione 1,2-ylids . 2H-Cyclohepta[b]furan-2-ones have been obtained by ring expansion of phenyl propiolates... 

A soln. of tri-n-butyltin hydride in benzene added to a stirred soln. of N-[2-(l-phenyl-ethenyl)-5-hexenyl]-4-(phenylthio)oxazolidin-2-one and AIBN in the same solvent at reflux, and heating continued for 4 h 5,5a,6,7,8,8a,9,9a-octahydro-8-methyl-8a-phenyl-l//,3//-oxazolo[3,4- z]cyclopenta[i/]pyridin-3-one. Y 57%. F.e.s. S. Kano et al., Chem. Pharm. Bull. 36, 2934 9 (1988). 

Benzoyl chloride added dropwise with stirring to chloromethanesulfonamide in pyridine at such a rate that the temp, rises to 70-75°, heating at 80° continued for 30 min. 5-phenyl-1,3,4-oxathiazoline 3,3-dioxide. Y 83%. F. e. s. K. Dickor, ... 

Phenyl isothiocyanate added dropwise to a heated and stirred mixture of 5-amino-l-y -D-ribofuranosylimidazole-4-carboxamide and pyridine, heating continued 3.5 hrs. in a stream of Ng 2-mercaptoinosine. Y 85% as the K-salt. F. e. s. K. Imai et al., Chem. Pharm. Bull. 19, 576 (1971). 

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