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A commercially available L-glutamic acid γ-methyl ester was converted into the corresponding urea-containing α-amino acid via the hydrazide, the azide, and then the isocyanate. The condensation of the urea-containing α-amino acid with β-diketones under acidic conditions afforded 2(1H)-pyrimidinone-containing α-amino acid derivatives in reasonable yields. The 1H-NMR analysis of the dipeptide indicated that no detectable racemization had occurred during the chemical modification of L-glutamic acid.

The reaction of N-(benzyloxy)urea with 1,1,3,3-tetraethoxypropane, 4,4-dimethoxy-2-butanone, and 2,4-pentanedione under acidic conditions gave the corresponding 1-benzyloxy-2(1H)-pyrimidinones (3 and 3′) in moderate yields. In contrast, the reaction of N-(benzyloxy)urea or N-methoxyurea with 1-phenyl-1,3-butanedione exclusively gave 3-alkoxyimino derivatives (4). 1-Benzyloxy-2(1H)-pyrazinones (9a and 9b) were synthesized via three steps starting from N-(t-butoxycarbonyl)glycine. The hydrogenation or treatment with 30% HBr in acetic acid of compounds 3c, 9a, and 9b afforded 1-hydroxy-4,6-dimethyl-2(1H)-pyrimidinone (HOPY), and 1-hydroxy- (HOPR-H), and 1-hydroxy-5,6-dimethyl-2(1H)-pyrazinone (HOPR-Me), respectively. They form 3 : 1 complexes of iron(III) with the N-hydroxyamide groups in the acidic region, but the stability constants of their iron(III) complexes are far below that of natural ferrioxamine B.

Synthesis of pyrido[1′,2′:1,2]imidazo[4,5-b]quinoxalines by the facile cyclizations of 2,3-dichloroquinoxalines with 2-aminopyridines and of 2-amino-3-chloroquinoxalines with various substituted pyridines is described.

3-Bromo-1,1,1-trifluoropropan-2-one (2) reacted with thiourea and N-monosubstituted thioureas to give the corresponding 4-trifluoromethylthiazoles, respectively. In the reactions with N,N'-diphenylthiourea and thioamides, the considerably stable intermediates, 4-hydroxy-4-trifluoromethylthiazoline derivatives 7 and 8, were isolated. The reaction of ethyl 2-bromo-4,4,4-trifluoro-3-oxobutanoate (4) with thiourea was carried out under the gentle conditions to give both thiazole-5-carboxylate 10 and 4-hydroxythiazoline 11. The thiazole 10 was applied to the azo dye synthesis and the absorption maxima of thus obtained azo dyes were discussed.

2-(Pyrid-2'-yl)amino-3-chloro-5,6-dicyanopyrazines (IIa, IId, and IIe) and 2-(pyrid-2'-yl)amino-3-chloro-6-nitroquinoxalines (Va-c) were isolated for the first time in the course of the reaction of 2,3-dichloro-5,6-dicyanopyrazine (I) and 2,3-dichloro-6-nitroquinoxaline (IVa), respectively, with 2-aminopyridines. Furthermore, the yield of pyrido[1',2': 1,2]imidazo[4,5-b]quinoxalines was remarkably improved due to the modification of the reaction conditions

N-Hydroxyamide-containing heterocycles, 1-hydroxy-4,6-dimethyl-2(1H)-pyrimidinone and -5,6-dimethyl-2(1H)-pyrazinone, are prepared. Judging from the result of model dipeptide (Z-Ala-Phe-OMe) formation, these compounds are found to be new effective additives for peptide synthesis by the dicyclohexylcarbodiimide (DCC) method at the points of high yield and no detectable racemization.

The reactions of N-benzoyl- and N-acetyl-1-chloro-2,2,2-trifluoroethylamines with various carbon-nucleophiles gave the corresponding 1-substituted N-acyl-2,2,2-trifluoroethylamines in good yields and the efficient reactivity was applied on the synthesis of 2-acylamino-2-trifluoromethylethanol derivative.

Trifluoromethylated azomethine ylide 1, generated in situ by the conrotatory ring opening of cis-2-benzoyl-1-methyl-3-trifluoromethylaziridine, cycloadded with both electron-deficient and -rich monosubstituted olefins to give exclusively the corresponding 3-substituted pyrrolidines. This high regioselectivity is discussed in connection with the interaction between 1-LUMO and olefin-HOMO.

Additions of various carbanion nucleophiles to 3,3,3-trifluoro-1-nitropropene (1) proceeded regiospecifically at the C-2 position of 1 to give the corresponding adducts. The nitro group of the adducts, derived from the reactions with acetylacetone and ethyl acetoacetate, was reduced to the corresponding amines, which were cyclized in situ to the 3-(trifluoromethyl)pyrrole derivatives.

N-Hydroxyamide-containing heterocycles, 1-hydroxy-4,6-dimethyl-2(1H)-pyrimidinone and -5,6-dimethyl-2(1H)-pyrazinone, are prepared. Judging from the result of model dipeptide (Z-Ala-Phe-OMe) formation, these compounds are found to be new effective additives for peptide synthesis by the dicyclohexylcarbodiimide (DCC) method at the points of high yield and no detectable racemization.

Synthesis of pyrido[1′,2′:1,2]imidazo[4,5-b]quinoxalines by the facile cyclizations of 2,3-dichloroquinoxalines with 2-aminopyridines and of 2-amino-3-chloroquinoxalines with various substituted pyridines is described.

Trifluoroacetaldehyde hydrazones are condensed with glyoxals to give 4-hydroxy-3-trifluoromethylpyrazoles, the reaction offering a novel route to 4-hydroxypyrazoles carrying trifluoromethyl group. The 4-hydroxyl group was easily converted to its derivatives by the reaction with various electrophiles.

3-Bromo-1,1,1-trifluoropropan-2-one (2) reacted with thiourea and N-monosubstituted thioureas to give the corresponding 4-trifluoromethylthiazoles, respectively. In the reactions with N,N'-diphenylthiourea and thioamides, the considerably stable intermediates, 4-hydroxy-4-trifluoromethylthiazoline derivatives 7 and 8, were isolated. The reaction of ethyl 2-bromo-4,4,4-trifluoro-3-oxobutanoate (4) with thiourea was carried out under the gentle conditions to give both thiazole-5-carboxylate 10 and 4-hydroxythiazoline 11. The thiazole 10 was applied to the azo dye synthesis and the absorption maxima of thus obtained azo dyes were discussed.

Trifluoromethylated azomethine ylide 1, generated in situ by the conrotatory ring opening of cis-2-benzoyl-1-methyl-3-trifluoromethylaziridine, cycloadded with both electron-deficient and -rich monosubstituted olefins to give exclusively the corresponding 3-substituted pyrrolidines. This high regioselectivity is discussed in connection with the interaction between 1-LUMO and olefin-HOMO.

The reactions of N-benzoyl- and N-acetyl-1-chloro-2,2,2-trifluoroethylamines with various carbon-nucleophiles gave the corresponding 1-substituted N-acyl-2,2,2-trifluoroethylamines in good yields and the efficient reactivity was applied on the synthesis of 2-acylamino-2-trifluoromethylethanol derivative.

3-(Aryl)substituted 2,4(1 H,3H)-pteridinediones are synthesized in high yields by addition and simultaneous cyclization of methyl 3-amino-2-pyrazinecarboxylate with isocyanates. The remarkable difference in the reactivity is observed among heterocumulenes. The absorption and fluorescence spectroscopic characteristics of the titled compounds are also discussed

2-(Pyrid-2'-yl)amino-3-chloro-5,6-dicyanopyrazines (IIa, IId, and IIe) and 2-(pyrid-2'-yl)amino-3-chloro-6-nitroquinoxalines (Va-c) were isolated for the first time in the course of the reaction of 2,3-dichloro-5,6-dicyanopyrazine (I) and 2,3-dichloro-6-nitroquinoxaline (IVa), respectively, with 2-aminopyridines. Furthermore, the yield of pyrido[1',2': 1,2]imidazo[4,5-b]quinoxalines was remarkably improved due to the modification of the reaction conditions

N-Methyl-C-(trifluoromethyl)nitrone (1) cycloadds with various olefins to give 2-methyl-3-trifluoromethyl-isoxazolidines. Predominant formation of 5-substituted isoxazolidines in the cycloadditions with monosubstituted olefins is observed and this high regioselectivity is attributed to the dipole-LUMO controlled interaction, being rationalized on the basis of molecular orbital calculation of 1. ‘Anti’-favorable approach of 1 to olefin in the transition state is considered from the configuration of the cycloadducts, pointing out the very weak secondary orbital interaction between trifluoromethyl group and olefin-substituents including phenyl or ester group.

The photoinitiated reaction of 1,1′-bis(methoxycarbonyl)divinylamine with various maleates and fumarates afforded novel 7-azabicyclo[2.2.1]heptane-1,2,3,4-tetracarboxylates. The spectral investigation of the products showed that the reaction proceeded stereoselectively, retaining the original configuration of the reagents.

N-Phenyltrifluoroacetohydrazonoyl bromide (1) reacted with potassium isothiocyanate and isocyanate to give 5-imino-4-phenyl-2-trifluoromethyl-δ2-1,3,4-thiadiazoline and 1-phenyl-3-trifluoromethyl-δ2-1,2,4-triazolin-5-one, respectively. On treatment with several types of cumulative double bonds such as alkyl isothiocyanate, isocyanate, and carbodiimide, 1 afforded regioselectively the corresponding trifluoromethylthiadiazoline, -oxadiazoline, and -triazoline, respectively. These cycloadducts were assumed to form through the stepwise path involving the addition of 1 toward the cumulative double bond followed by the intramolecular cyclization. Concerning cyanamides, the corresponding triazoles were obtained and the reactions with pyridines afforded the triazolopyridinium bromides. The reactivity of the latter was found to depend on the substituents on the pyridine nucleus.

Several bismaleimides were treated with 1, 1′-bis(methoxycarbonyl)divinylamine(BDA)under photoirradiation. Whereas the equimolar reaction gave a mixture of 1: 1- and 2: 1cycloadducts, the use of twice molar amount of BDA to bismaleimides afforded only 2: 1adducts, novel bis-type 7-azanorbornane derivatives, in fairly high yields. Spectral analyses of the products showed that the cycloaddition proceeded stereoselectively, giving the exoadducts.Difference of the reactivity of bismaleimides from that of conjugated unsaturated compounds, reported previously, is discussed.

Three isomeric aminopyridines were reacted with an excess of benzoyl chloride in the presence of an excess of triethylamine, giving the corresponding dibenzoylaminopyridines in high yields. As an application of the dibenzoylation, the aminopyridines were also reacted with phthaloyl dichloride, resulting in appreciable yields of the respective N-pyridylphthalimides. The rate of the conversion under various conditions was studied with high pressure liquid chromatography in order to investigate the difference in reactivity among the three isomers.

The reactions of 4,5-dicyanoimidazoles with methyl isocyanate gave 7-cyano-1-imino-2-methyl-2,3-dihydro-1H-imidazo[3,4-c]imidazol-3-ones (2), while the similar reactions with phenyl isocyanate resulted in the formation of the tricyclic imidazoles, 1 1-imino-6,10-diphenyl-2,4,6,8,10-pentaazatricyclo[5.4.1.04,12]dodeca-1(12),2,7-triene-5,9-diones (3) and the same type of the tricyclic imidazoles 4 were obtained by carbamoylation of 2 with phenyl isocyanate. The reactions of 2, 3, and 4 with amines were further investigated.

シアナミドの共存下,第一級アミンとカルボン酸をジエチルケトンなどの溶媒中で還流加熱下反応させ,対応するアミドを容易に得ることができた。つぎに,シアナミドの役割を検討するため,シアナミドとアニリンと安息香酸を,反応溶媒,モル比など種々異なる条件下で反応させ, GLC を用いて経時的に追跡した。その結果,アニリン量よりもカルボン酸とシアナミドの共存量が多いほど,また,溶媒の性質には依存せず,反芯温度が高いほど本縮合反応が促進されることなどを明らかにした。また,本反応を置換アニリンおよび置換安息香酸を対象に行ない,生成置換ベンズアニリドの収率から,アミン成分の置換基は電子供与性の強いほど,またカルボン酸成分の置換基は電子求引性の強いほど反応が進行しやすいことがわかった。これらのことから反応機構について考察した。

The title compound was reacted with four types of electrophiles and the respective reaction sites were investigated. The reaction with aryl isocyanates in the conventional way yielded the corresponding ureas. In the presence of triethylamine, the 3-amino group was diacylated with acyl chlorides. On the other hand, in the cases with arylsulfonyl chlorides and p-nitrobenzaldehyde under similar conditions, the methyl group at 5-position was preferentially attacked to give arylsulfonylmethyl and p-nitrostyryl derivatives, respectively.

The regio- and stereoselectivity of the cydoadditions of trifluoroacetonitrile oxide (1) with olefins and acetylenes were described. The oxide 1, generated in situ from trifluoroacetohydroximoyl bromide etherate in the presence of triethylamine, reacted with various monosubstituted olefins and acetylenes to give exclusively 5-substituted 3-trifluoromethyl-2-isoxazolines and -isoxazoles, respectively, whereas 1 cyclized with 1,2-disubstituted olefins and acetylenes to result in the formation of a mixture of two regioisomeric products. On the other hand, the cycloaddition of 1 with (Z)-β-methylstyrene afforded a mixture consisting of two regioisomeric isoxazolines retaining Z-configuration and one diastereoisomeric isoxazoline.

Trifluoroacetonitrile oxide reacted with conjugated olefins such as styrenes, indenes, and acyclic conjugated dienes to give not only the cycloadduct but also its linear isomeric oxime. Methyl or phenyl group attached to the unsaturated carbon of the dipolarophiles was found to favor the formation of oxime. Such a concomitant reaction was interpreted in terms of a competition between a concerted cycloaddition and a two-step substitution through an electrophilic attack of nitrile oxide. Similar competitions were also investigated with cyclic conjugated dienes, where the competitive ratio of the products was found to depend on the ring size.

The reaction sites of 3-substituted pyrazolin-5-ones and their O- and N-blocked analogues toward various isocyanates were investigated. 3-Methyl and 3-ethoxycarbonylpyrazolin-5-ones gave the corresponding 1-carbamoylpyrazolinones, whereas the O-alkylpyrazoles afforded 2-carbamoylpyrazoles. On the other hand, the N-alkylpyrazolinones were carbamoylated at 4-position under drastic conditions.

The reaction rates of the conversion of various substituted picolinic and quinaldinic acids to the corresponding trichloromethylpyridines and quinolines by treatment with phosphorus pentachloride in refluxing thionyl chloride have been measured, and the apparent second-order kinetic constants determined. The logarithmic rate constants (log k) were found to be linear with the basicities (pKa) of the unsaturated ring nitrogens in the substrates. The reaction constant, p, of the conversion was estimated.

A novel and convenient synthesis of 1H -pyrrole-2,3,4,5-tetracarboxylates is described. Photocyclization of 1,1′-bis(methoxycarbonyl)divinylamine with acetylenedicarboxylates gave 7-azabicyclo[2.2.1]hept-2-ene-1,2,3,4-tetracarboxylates 2a-i, which on melting split ethylene off to yield 1H-pyrrole-2,3,4,5-tetracarboxylates 3a-i quantitatively.

Various substituted quinaldinic acids were treated with phosphorus pentachloride in an excess of thionyl chloride. Carboxyl groups of quinaldinic acid, 6-methyl-, 6-chloro-, 4-phenyl- and 4-(p-chlorophenyl)quinaldinic acids and benzo[f]quinoline-3-carboxylic acid were converted to the trichloromethyl group, while those of 8-methyl-, 4-(3,4-dichlorophenyl)-, 4-(p-nitrophenyl)-quinaldinic acids and benzo[h]quinoline-2-carboxylic acid were not. The difference is discussed on the basis of the effects of the basicity of ring nitrogen and steric factors.

5-Amino-3-trifluoromethylisoxazole- and -pyrazole-4-carboxylic acids were prepared by the reactions ot trifluoroacetonitrile oxide or -imines with cyanoacetic acid derivatives, respectively. The behavior of thus obtained aminoazole-4-carboxylic acids toward some electrophiles was examined. In acylation with acyl chlorides, the aminoisoxazole-4-carboxylate 2a was diacylated to give the (diacylamino)isoxazole-4-carboxylate 7, whereas the analogous aminopyrazole 5a produced the cyclized pyrazolooxazinone 13. Moreover, carbamoylation of 2a with isocyanates gave the trifluoromethylisoxazolouracils 10.

Thermal ring transformation of 3-benzoylisoxazolidines gives 2-hydroxydihydrofurans together with α-benzoylenamines, the product ratio of both compounds depending on the 4- and 5-substituents of the isoxazolidine ring. The ring transformation is in contrast to the case of analogous 3-phenylisoxazolidines, resulting in 1,3-dipolar cycloreversion.

Trifluoroacetonitrile oxide and N-phenyl-C-(trifluoromethyl)nitrilimine cycloadded with norbornenes, resulting in the exclusive formation of the exo-adducts, while the concomitant formation of the endo-adducts was observed in their cycloadditions with norbornadienes. The nitrile oxide was subjected to the cycloaddition with 2,3-disubstituted norbornadienes to evaluate the effect of the substituents on the exo/endo stereoselectivity. The electron-withdrawing substituents tend to favor the formation of the exo-adducts.

The polycondensation reactions of ferrocene with terephthaloyl and adipoyl chloride were investigated in the presence of AlCl3, ZnCl2, or FeCl3 as the catalyst and in dichloromethane, n-hexane, carbon tetrachloride, or dioxane as the solvent. With terephthaloyl chloride, the highest polymer yield was obtained when AlCl3 in n-hexane was used, and the product was mainly of a polyketone structure. The polycondensation with adipoyl chloride afforded the most satisfactory result when ferrocene was treated in liquid adipoyl chloride with neither catalyst nor solvent, and a product with the expected structure was obtained. The average molecular weights of the products are in the range of 3000–7000. Polymers obtained by polycondensation with terephthaloyl and succinyl chloride are paramagnetic and show the temperature dependence characteristic of semi-conductivity.

数種の脂肪酸ビニルエステルと塩化ビニルとの共重合体を調製し, その融点および平行板型プラストメーターによる軟化度試験から, ビニルエステルの内部可塑効果を検討した。これらの結果, 高級脂肪酸のビニルエステルほど軟化効果は大きく,また可塑化成分の同一含有wt%に対しては,フタル酸ジオクチルで外部可塑化したポリ塩化ビニルより共重合系の方が可塑効果が大きいこと,特に軟化度の温度依存性が著しく大きいことを明らかにした。これらの相違は,共重合系の場合は各ポリマー鎖がすべてビニルエステルを含み,これが長い側鎖を張り出してポリマー鎖間の結合を弛めるのに対し,外部可塑系では可塑剤がただ単にポリマー鎖の集団の間隙に入り込むだけで個々のポリマー鎖を可塑化するものではないためと考えられる。