The reactions of some pyranylideneiminium salts with amines. Part 1

The iminium salt, N,N-dimethyl-N-[2-(2,6-diphenyl-4H-pyran-4-ylidene)ethylidene]iminium perolilorate ( 1 ), reacts with secondary amines, such as piperidine, by exchanging the dimethyl-amino function for a piperidine. Primary amines react with 1 to give 1-alkyl-2-phenyl-4-phenacylidene-1,4-dihydropyridines. The bisiminium salt, N,N,N',N' -tetramethyI-N,N'-[2-(2,6-diphenyl-4H-pyran-4-ylidene)-1,3-propanediylidene]bis(iminium perchlorate) ( 2 ), reacts with ammonia to give 3,6-diphenylcopyrine and with primary amines to give the corresponding N,N' -dialkyl quaternary copyrines. The salt 2 reacts with secondary amines with exchange of the dimethylamino groups of 2 by the secondary arnine and addition of the amine at the 2-position of the pyran ring.     

The reactions of some pyraiiylideneiminium salts with amines. II

The iminium salt, N,N-dimethyl-N-[2-(2-phenyl-4H-l-benzopyran-4-ylidene)ethylidene] imin-ium perchlorate ( 3 ), reacts with secondary amines by exchanging the dimethylimino group for the added amine. Primary amines also reacted with 3 in the same manner. The bis iminium salts, N,N,N',N'-tetramethyl-N,N'-[2-(2-phenyl-4H-l-benzopyran-4-ylidene)-1,3-propanediylidene]-bis(immium perclilorate) ( 4 ) and the corresponding thiapyran derivative ( 5 ), react with ammonia to give 5-dimethylamino-2-phenyl-5H-1-benzopyrano[3,4-c]pyridine ( 10 ) and the thia analog 11 . The reactions of 4 and 5 with primary amines give 3-alkyl-5-dimethylamino-2-phenyl-5H-l-beiizopyrano[3,4-c]pyridinium perclilorate salts or the corresponding thiapyrano compounds. Compounds 4 and 5 react with secondary amines by exchanging the dimethylimino groups with the secondary amine and addition of the amine at the 2-position of the pyran or thiapyran ring.     

Synthesis of 1,2-di-(4-pyridyl)ethylenediamine and related compounds

Hydrolysis of N,N'-diacyl-1,2-di(4-pyridyl)ethylenediamines 1 in aqueous sulfuric acid gave the corresponding imidazolines 3. 1,2-Di-(4-pyridyl)ethylenediamine 2 was prepared in 61 % yield by treating N,N'-di-t-butyl-oxycarbonyl-1,2-di(4-pyridyl)ethylenediamine 4 with trifluoroacetic acid or in 94% yield by the hydrolysis under basic conditions of N,N'-diphthaloylglycyl-1,2-di(4-pyridy)ethylenediamine 13.     

Diheterocyclic compounds from dithiocarbamates and derivatives thereof. I. 2,2′-(arylenediamino)bisbenzoazoles, 2,2′-(arylenediamino)bis(imidazopyridines) and 8,8′-(arylenediamino)bispurines

A general method for the synthesis of the title compounds 5, 6, 10, 14, 15 and 16 is reported. All of them were prepared in one step from readily available dimethyl N,N'-(arylene)bisdithiocarbamates 1 and red mercury(II) oxide. The superiority of these reagents over the corresponding diisothiocyanates 7 and the synthetic utility of tetramethyl N,N'-(arylene)bisdithiocarbonimidates 2 are also discussed.     

Synthesis and Characterization of Binuclear (μ-Oxalato) Copper(II) Complexes with N,N′-Diethylethylenediamine or N,N,N′-Trimethylethylenediamine

Three new binuclear w -oxalato copper(II) complexes of composition [(Cu(N,N' -dieten) H₂O)₂ox](ClO₄)₂ ·H₂O (1) (N,N'-dieten = N,N'-diethylethylenediamine, H₂ox = oxalic acid), [(Cu(trimeen)H₂O)₂ox](ClO₄)₂·2H₂O (2) (trimeen = N,N,N'-trimethylethylenediamine) and [(Cu(trimeen)H₂O)₂ox](NO₃)₂ ·2H₂O (3) have been isolated from the reactions of Cu(ClO₄)₂ ·6H₂O (or Cu(NO₃)₂ ·3H₂O), the appropriate amine and Na₂ox in water and have been characterized by IR and electronic spectroscopy and magnetic measurements. The crystal structure of [(Cu(N,N' -dieten)H₂O)₂ ox](ClO₄)₂.H₂O (1) has been determined by single-crystal X-ray analysis. The structure of ( 1 ) consists of binuclear cations [(N,N'-dieten)H₂O)Cu(ox)Cu(N,N'-dieten)H₂O)]²⁺, perchlorate anions and water molecules of crystallization. The copper atom is coordinated by two oxygen atoms of the oxalato ligand, two nitrogen atoms belonging to N,N'-dieten and one oxygen atom of water in a distorted square-pyramidal arrangement. The temperature dependence of magnetic susceptibilities (78-293 K) was measured for 1-3 . Magnetochemical measurements show that copper(II) ions in these compounds are antiferromagnetically coupled with J = -172 cm^-1, -172 cm^-1 and -168 cm^-1 (H = -2JS ₁ S ₂, S ₁= S ₂ = 1/2) for 1, 2 and 3, respectively.     

Investigation of the preparation of pyrimidine isocyanates

Uracil-5-yl isocyanate and 1,3-dimethyluracil-5-yl isocyanate were prepared from the corresponding new carboazides. 1,3-Dimethyluracil-5-ylmethyl isocyanate obtained from the chloro compound and silver cyanate, was polymerized with an anionic initiator to the cyclic trimer. Attempts to isolate uracil-6-yl isocyanate, 1,3-dimethyluracil-6-yl isocyanate, pyrimidinyl-4-isocyanate, and 2,6-dichloropyrimidinyl-4-isocyanate were unsuccessful. Ethyl carbamate derivatives were made from all new azides and isocyanates. Other new pyrimidine derivatives included N,N'-bis(pyrimidine-4-carbonyl)hydrazine, N,N'-bis(1,3-dimethyluracil-5-yl)urea, N,N'-bis(1,3-dimethyluracil-6-yl)urea and N,N'-bis(2,5,6-trichloro-4-pyrimidinyl)oxamide.     

Proton-ionizable crown compounds. 20. The synthesis of polyazatriazolo-, polyazabistriazolo- and bispyridono-crown ligands containing lipophilic hydrocarbon substituents

Four new macrocyclic polyaza-crown compounds containing a triazole subcyclic group and two to five lipophilic hydrocarbon substituents have been prepared from the appropriate polyamine and N-THP-protected 2,5-triazoledimethyl dichloride. N,N,N',N'-Tetrabenzyltetraazabistriazolo-18-crown-6 was prepared from N,N'-dibenzylethylenediamine and N-THP-protected 2,5-triazoledimethyl dichloride. Biscyclohexano-bispyridono-18-crown-6 was prepared from trans- 1,2-cyclohexanediol and THP-protected 4-hydroxy-2,6-pyridinedimethyl ditosylate.     

Preparation of N,N′-di pivot lariat 1,4-diaza-15-crown-5 and 18-crown-6 macrocycles

Twelve diaza-15-crown-5 and 18-crown-6 macrocycles containing different side arms on the nitrogen atoms have been prepared. These diaza-N,N'-di pivot lariat crown ethers were prepared either from N,N'-bishydroxyethyl-1,4-diaza-15-crown-5 or 18-crown-6 ligands or from the corresponding unsubstituted diaza-crowns.     

A facile synthesis of benzo[b]thiophene derivatives

Lithiation of S-(2-methylphenyl) N,N,N',N'-tetramethylphosphorodiamidothioate with sec-BuLi at -105° gave the corresponding benzylic anion which was acylated with various aromatic esters to give various deoxybenzoin derivatives in moderate to high yields. Acidic treatment of these products in refluxing formic acid gave 2-arylbenzo[b]thiophene derivatives. 2-Methylbenzo[b]thiophene and benzo[b]thiophen-2(3H)-one were also prepared using the similar procedure.     

Preparation of Polymeric Analogs of Tetramethylurea and Their Use as Liquid-Liquid Phase-Transfer Catalysts

Polymeric analogs of tetramethylurea were prepared by free-radical polymerization of N,N,N'-trimethyl-N'-p-vinylbenzylurea and copolym-erization of this monomer with styrene. These polymers are soluble in toluene and have the ability to extract alkali metal ions such as lithium, sodium, and potassium. Moreover, these polymers act as phase-transfer catalysts for typical S _N 2 reactions, although the monomeric analogs tetramethylurea and N,N,N'-trimethyl-N'-benzylurea do not. A plausible mechanism for these catalytic reactions is proposed.     

Synthesis of phenylated phthalimides. The diels-alder reaction of tetraphenylcyclopentadienone with maleimides

A series of phenylated dihydrophthalimides has been synthesized by the Diels-Alder reaction of tetraphenylcyclopentadienone with maleimide, N-phenylmaleimide, and N,N'-o-, -m-, and -p-phenylenedimaleimide. Subsequent dehydrogenation of these compounds yielded the corresponding phenylated phthalimides. These phthalimides were also obtained in one step when the initial reactions were carried out in refluxing nitrobenzene.     

A convenient preparation of 4,8-dimethoxy-3-substituted-2(1H)-quinolones by an electrophilic reaction through base-induced deprotonation and its synthetic application for the synthesis of new alkaloids, 3,4,8-trimethoxy-2(1H)-quinolone and 3-formyl-4,7,8-trimethoxy-2(1H)-quinolone(glycocitridine)

Some 4,8-dimethoxy-3-substituted-2(1H)-quinolones were prepared by electrophilic reaction of 4,8-dimethoxy-2(1H)-quinolone with electrophiles in the presence of n-butyllithium-N,N,N',N'-tetramethylethyl-enediamine in fairly good yields. This present method was successfully applied for the synthesis of two new alkaloids bearing the 4,8-dimethoxy-2(1H)-quinolone skeleton.     

Alkylation of N-boc-1,2,3,4-tetrahydroisoquinolines in the 1-position and its application to the synthesis of isoquinoline alkaloids

Boc-protected 1,2,3,4-tetrahydroisoquinolines 2 can be lithiated with t-butyllithium in the presence of N,N,N',N',-tetramethylethylenediamine. Reaction of the anion with alkyl halides provides 1-alkyl N-Boc-1,2,3,4-tetrahydroisoquinolines in 67–71% yield. The protecting group is easily removed in high yield with trifluoroacetic acid. The alkaloids salsolidine ( 8 ) and laudanosine ( 11 ) were synthesized in racemic form using this method.     

Reaction of benzofurazan N-Oxide with 1-aza-1,3-butadienes. Synthesis of a novel class of quinoxaline N,N′-dioxide imines

1-Aza-1,3-butadienes react with benzofurazan N-oxide (BFO) to give a new class of N,N'-dioxide imines.     

Synthesis and polymerization of novel formamidinium salts: A new pathway to polyamides derived from aromatic diamines

A new polycondensation pathway has been developed for the preparation of polyamides at high temperatures. p-Phenylenediamine was converted to N,N-p-phenylene bis(N′,N′-dimethylformamidine) (I), which formed 1–1 and 2–1 salts with terephthalic and adipic acids, respectively: Dicarboxylate salts were polymerizable by heating in bulk or suspension. Low-molecular-weight poly(p-phenyleneterephthalamide) was obtained from N,N-p-phenylene bis(N',N'-dimethylformamidinium) terephthalate above 225°C. The low degree of polymerization was due to terephthalic acid sublimation as well as to the well-known intractability of poly(p-phenyleneterephthalamide). High-viscosity poly(p-phenyleneadipamide) was obtained from N,N-p-phenylene bis(N′,N′-dimethylformamidinum hydrogen adipate) above 200°C. Both salts liberated dimethylformamide (DMF) during polymerization. The adipate salt also released 1 mole of adipic acid during the high-temperature vacuum stage of polymerization. A polycondensation mechanism was proposed for each salt, based on thermal gravimetric analysis (TGA-MS) and infrared (IR) analyses. The hydrolysis of N,N-p-phenylene bis(N',N'-dimethylformamidine), N,N-p-phenylene bis(N',N'-dimethylformamidinium chloride), and the two dicarboxylate salts of (I) was monitored by nuclear magnetic resonance (NMR) at room temperature. The dihydrochloride salt was most resistant to hydrolysis (k_H 6.9 × 10^?9 sec^?1; relative rate 1.0) followed by (I) 7.1, terephthalate salt, 14.9, and adipate salt, 27.2. Both dicarboxylate salts possessed sufficient hydrolytic stability for use as polycondensation monomers     

Reduction of substituted 1H-4,5-dihydroimidazolium salts

Reactions of several substituted 1H-4,5-dihydroimidazolium salts 1 with nucleophilic and electrophilic reducing agents acting via hydride transfer were explored. Reaction of compounds 1 with lithium aluminum hydride in THF afforded the corresponding imidazolidines 2 . When alkaline borohydrides (sodium borohydride, potassium borohydride, sodium cyanoborohydride) in ethanol at room temperature were used, partial or total over-reduction of compounds 2 leading to N,N,N'-trisubstituted ethylenediamines took place on occasion. Results may be explained taking into account that reductive cleavage of 2 proceeds via a stabilized iminium ion present in protic solvents. Treatment of compounds 1 with an excess of borane in THF afforded the corresponding imidazolidines 2 or their borane complexes, according to the substituent type.     

Heterocycles from substituted amides II. Novel behavior of a reactive thiophene in some cyelo- and acyclo-addition reactions

N,N'-Diisopropyl-N,N'-diphenyl-2,4-thiophenediamine ( 1 ) has demonstrated its remarkable electron-donating abilities and atypical behavior as a thiophene, by its facile reaction with a number of electron deficient dienophiles. Thus, β-nitrostyrene, ethoxymethylene malononitrile, diethyl azodicarboxylate and dimethyl acetylenedicarboxylate undergo Michael-type addition at the 5-position of 1 to form adducts 2, 3, 4 , and 5 . Alternatively, the dienophiles, acrylonitrile, N-phenylrnaleimide and phenyl-1,2,4-triazoline-3,5-dione gave novel cyclic materials 6, 9 , and 11 , not necessarily arising from simple Diels Alder addition. Structure proofs for the products as well as alternative mechanisms for their formation are discussed.     

Synthesis of bis‐intercalators with an aminochloropyrimidine ring as potential anticancer agents

The synthesis of a series of polymethylene chain‐bridged aminochloropyrimidines as potential DNA intercalators is described. N,N'‐Bis(2‐amino‐6‐chloro‐4‐pyrimidyl)‐1,3‐diaminopropane ( 3 ), N,N'‐bis(2‐amino‐6‐chloro‐4‐pyrimidyl)‐1,4‐diaminobutane ( 4 ), N,N'‐bis(2‐amino‐6‐chloro‐4‐pyrimidyl)‐1,6‐diaminohexane ( 5 ), N,N'‐bis(2‐amino‐6‐chloro‐4‐pyrimidyl)‐1,8‐diaminooctane ( 6 ), N,N'‐bis(2‐amino‐6‐chloro‐4‐pyrimidyl)‐1,10‐diaminodecane ( 7 ), and N,N'‐bis(2‐amino‐6‐chloro‐4‐pyrimidyl)‐1,12‐diaminododecane ( 8 ) were synthesized from 2‐amino‐4,6‐dichloropyrimidine ( 1 ) and 1,3‐diaminopropane, 1,4‐diaminobutane, 1,6‐diaminohexane, 1,8‐diaminooctane, 1,10‐diaminodecane, and 1,12‐diaminododecane, respectively. The spectral data and other physical properties of the new compounds are discussed.     

The transformations of 4-heteroarylaminomethylene-5(4H)-oxazolones into dehydropeptide derivatives

2-Phenyl-4-heteroarylaminomethylene-5(4H)-oxazolones 3 , which were prepared from the corresponding N,N-dimethyl-N'-heteroarylformamidines 1 and hippuric acid 2 in acetic anhydride, react with amino acids giving dehydropeptide derivatives 4, 5 , and 6 as products. Dehydration of N-protected peptides 7–10 , containing glycine at the C-terminal, followed by the reaction with formamidines 1 gave 2-substituted-4-heteroarylaminomethylene-5(4H)-oxazolones 11–14 .     

The Synthesis of Some New (S)‐1‐Aryl‐N‐(1‐hydroxy‐3‐phenylpropan‐2‐yl)‐5‐methyl‐1H‐1,2,3‐triazole‐4‐carboxamide

Some new (S)‐1‐aryl‐N‐(1‐hydroxy‐3‐phenylpropan‐2‐yl)‐5‐methyl‐1 H‐1,2,3‐triazole‐4‐carboxamides 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j have been synthesized and established by ¹H and ¹³C NMR, IR, MS spectra, CHN analyses, and x‐ray diffraction crystallography. The molecular conformation and packing is stabilized by interactions of intermolecular H‐bond O2’‐H2'···O1, O2‐H2···O1’ and intramolecular H‐bond N4’‐H4'N···N3’, N4’‐H4'N···O2’, N4‐H4N···N3, N4‐H4N···O2. The two rings of five numbers were formed by H‐bond in a molecular.