Synthesis of some derivatives of imidazo[1,2-a]pyridine,pyrazolo[1,5-b]imidazole,and 4-(3H)quinazolinone from α-ketohydrazidoyl bromides

α-Aroyl-N-arylhydrazidoyl bromides 1 react with 2-aminopyridine in ethanol and give 2-aryl-3-arylazo-imidazo[1,2-α]pyridines 2 in 60-75% yield. The reaction of 1 with 3-phenyl-5-aminopyrazole in ethanol leads to 2,6-diaryl-3-arylazo-1H-pyrazolo[1,5-b]imidazoles 3 in almost quantitative yield. Also, 1 react with anthran-ilic acid in the presence of triethylamine giving 3-arylamino-2-aroyl-4-(3H)quinazolinones 4 in 80-85% yield. The structures of the products were assigned and confirmed on the basis of their elemental analysis and electronic absorption, infrared and nmr spectra.     

Die Aminoalkylierung von Phtalazinen und Phtalazonen mit Hilfe der GRIGNARD-Reaktion. 4. Mitteilung über GRIGNARD-Reaktionen mit Halogenalkylaminen [1]

Phtalazines and 4(3H)-phthalazones are aminoalkylated in high yield by 3-dimethylaminopropyl-magnesiumchloride. Phthalazines add only one molecule of the GRIGNARD reagent at the C?N-double bond, giving mono-aminoalkylated 1,2-dihydrophthalazines which undergo no further reaction without previous oxydation. Phthalazones react with the carbonyl and the C?N-group yielding in one step di-aminoalkylated dihydrophthalazines. The dihydrophthalazines are easily oxydized with K₃Fe(CN)₆ to the corresponding phthalazines.     

Synthesis of 3-N-acetyl-N-arylaminoacetyl-4-ethoxycarbonyl-5-methylpyrazoles

The acetylation of 2-N-arylaminomethylene-4-ethoxycarbonyl(or acetyl)-5-melhyl-3(2H)furan-ones produces N-acetylated compounds which react with hydrazine to yield substituted pyrazoles.     

Synthesis of crosslinked poly(α-amino acids) with various functional groups

The esterification of the carboxyl group in copoly(γ-benzyl-L -glutamyl-L -glutamic acid) was carried out using N-hydroxysuccinimide and dicyclohexylcarbodimide to yield the activated site for the coupling reaction with amino compounds. The α-helix stability of the reactive copolymer thus obtained is remarkably affected in the presence of succinimide ring. This copolymer was proved to react nearly completely with amino alcohols such as 2-aminoethanol, 3-aminopropanol, and diethanolamine. The copoly(N⁵-hydroxyalkyl-L -glutamine) thus prepared is insoluble in water, since the benzyl ester remains in this copolymer. The copoly(α-amino acids) having another functional group were also prepared using aminoalkylsilane. Crosslinked poly(α-amino acids) were prepared by the reaction of the reactive copolymer with a low-molecular-weight polymer of PBLG having one amino group on each end of its main chain which was obtained from the corresponding NCA using p-diaminobenzene as an initiator. Another crosslinked polymer was prepared using an alkyl diamine such as 1,6-diaminohexane or 1,12-diaminododecane as a crosslinking reagent. The crosslinked copoly(α-amino acids) bearing the activated site are able to further react with various compounds having amino groups.     

Synthesis of heterocycles. Part VI. Synthesis and antimicrobial activity of some 4-amino-5-aryl-1,2,4-triazole-3-thiones and their derivatives

4-Amino-5-aryi-1,2,4-triazole-3-thiones I react with acid chlorides to yield 4-acylamino-5-aryl-1,2,4-triazole-3-thiones II. Compounds I also react with methylene iodide, chloroacetonitrile and methyl bromoacetate to give bis-(4-amino-5-aryl-1,2,4-triazol-3-ylthio)methanes III, 4-amino-5-aryl-3-cyanomethylthio-1,2,4-triazoles IV and 4-amino-5-aryl-3-carbomethoxymethylthio-1,2,4-triazoles V, respectively. Compounds V react with hydrazine hydrate to give the corresponding acid hydrazides VI which in turn condenses with acid chlorides and aldehydes to afford respectively 1-[(4-amino-5-aryl-1,2,4-triazol-3-ylthio)acetyl]-2-aroylhydrazines VII and aryl methylene (4-amino-5-aryl-1,2,4-triazol-3-ylthio)acethydrazones VIII. The antimicrobial activities of the above compounds were screened against different strains of bacteria and fungi.     

Reactions with Carbo(heterylhydrazonoyl) Halides. I. Chemistry of Carbo(3-phenylpyrazol-5-yl-hydrazonoyl) Chlorides

The Carbo(3-phenylpyrazol-5-yl-hydrazonoyl) halides 1a , b react with active methylene compounds to yield the 1-(3-phenylpyrazol-5-yl)-pyrazole derivatives 2a – k (Scheme 1). The acyclic intermediates 3a , b could be isolated from reaction of 1a , b with acetylacetone, thus establishing the substitution mechanism for these reactions. Compounds 1a , b reacted with carbon disulfide, phenyl isothiocyanate, methyl cyanide, and with p-chlorobenzaldehyde to yield the corresponding heterocyclic derivatives 5 – 8 , respectively (Scheme 2). The behaviour of compounds 2 with hydrazine hydrate is reported.     

Reactions of alkyl 2-benzylidene-2-polyfluoroacylacetates with N,N-dinucleophiles

Alkyl 2-benzylidene-2-polyfluoroacylacetates react with urea and thiourea to yield 5-ethoxycarbonyl-4-fluoroalkyl-4-hydroxy-6-phenylhexahydropyrimidin-2-ones and -2-thiones and with guanidine sulfate to form 2-amino-5-ethoxycarbonyl-4-fluoroalkyl-6-phenyl-1,6-dihydropyrimidines and 3,6-diethoxycarbonyl-2,7-difluoroalkyl-4,5-diphenyl-4,5-dihydro-1H-pyrido[1,2-a]pyrimidines, and they react with phenylhydrazine to afford 4-alkoxycarbonyl-3-fluoroalkyl-3-hydroxy-1,5-diphenylpyrazolidines. Hydrazine hydrate catalyzes the formation of 3,5-diethoxycarbonyl-2,6-difluoroalkyl-2,6-dihydroxy-4-phenyltetrahydropyrans. When treated with anhydrous hydrazine and o-phenylenediamine, these esters cleave to form the products of condensation of fluoroacyl ester and benzaldehyde with diamines.     

Reactions of 4,6-bis(acetyl)resorcinol with alkoxycarbonylalkylidene(triphenyl)phosphoranes. Preparation of coumarin derivatives

Reaction of compound 1 with ylide 2a affords compounds 3a, 3b and coumarins 4a, 5a, 5b, 6a in 77% total yield. Reaction of 1 with ylide 2b affords coumarin 4b . The acetylderivatives obtained, react further with ylides 2a-c to give pyrano[3,2-g]chromene-2,8-diones 6b-d .     

Die Aminoalkylierung von Chinoxalinen und Chinoxalonen 6. Mitteilung über grignard-reaktionen mit halogenalkylaminen [1]

Quinoxaline and 2(1H)-quinoxalones react with organomagnesium salts differently from the corresponding phthalazines and quinazolines. 3-Dimethylaminopropyl-magnesiumchloride alkylates quinoxaline easily by addition to the 2 and 3 position forming a tetrahydroquinoxaline 2 , which can be dehydrogenated to the corresponding dialkylated quinoxaline 3 . The monosubstituted dihydroquinoxaline 5 is obtained only with difficulty. It can equally be dehydrogenated, yielding 6 . Quinoxalones react with CH₃MgI, C₆H₅MgBr, (CH₃)₂N? (CH₂)₃? MgCl by addition to the 3,4-C?N bond (not at the CO-group), yielding 11–13 . These dihydroquinoxalones are dehydrogenated to the 3-substituted 2(1H)-quinoxalones 14–16 . Only 3-phenyl-quinoxalone adds a Grignard reagent at the CO group, forming a 2-substituted 3-phenylquinoxaline ( 26 ). 3-Methyl-quinoxalone exhibits an abnormal behaviour: It is deprotonated by the mentioned reagents at the CH3 group, and the 3-methylenequinoxalone-anion so formed attacks another molecule of methylquinoxalone, finally yielding 32 and 33 .     

Synthesis of 1,3,4-thiadiazolo[3′,2′∶1,2]pyrimidino[5,6-d]-1,3-thiazine derivatives

2-R-5-Imino-6H-1,3,4-thiadiazolo[3,2-a]pyrimidin-7-ones react with aromatic and heterocyclic aldehydes in the presence of Et₃N to give condensation products on the methylene group, which react with carbon disulfide to yield the corresponding 2,6-disubstituted 8-thioxo-9,9a-dihydro-1,3,4-thiadiazolo[3′,2′∶1,2]pyrimidino[5,6-d]1,3-thiazin-5-ones. Deceased. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 366–368, February, 1999.     

On the formation and reactivity of N(2),N(2′)-tetrasubstituted 2,4-diamino-5-(2-amino-4-thiazolyl)thiazoles

By the reaction of weak bases with N(2)-disubstituted 2-amino-4-thiazoliniminium chlorides 3, easily available by the reaction of thioureas 1 with α-chloroacetonitrile 2, N(2),N(2′)-persubstituted 2,4-diamino-5-(2-amino-4-thiazolyl)thiazoles 8 are formed. These new bis-thiazoles react, as exemplified with the dimorpholino derivative 8a, with different electrophilic reagent, such as phenyl isothiocyanate 9, 4-nitro-phenyldiazonium salt 11, or 4-dialkylaminobenzaldehydes 13 at their 5H-substituted thiazole moieties to give the corresponding thioanilides 10, azo compounds 12, and methine dyes 14, respectively. With sodium nitrite and the Vilsmeier reagent the thiazole 8a is transformed, via unstable intermediates, into the tricyclic 2,7-dimorpholinothiazolo[4,5-c]thiazolo[4,5-e]pyridazine 16 and 2,7-dimorpholinothiazolo[4,5-b]thiazolo[4,5-d]pyridine 19, respectively.     

An improved synthesis of 2‐amino‐5‐[(4‐chlorophenyl)thio]‐4‐morpholinopyrimidine (BW 394U) — A potential antisenility agent

This paper describes the synthesis of 2‐amino‐5‐[(4‐chlorophenyl)thio]‐4‐morpholinopyrimidine (BW 394U, compound 4 ), a potential antisenility agent. The key intermediates 3a/3b were obtained from an in situ‐generated Vilsmeier‐Haack reagent that simultaneously protected the 2‐amino group prior to further manipulations. Displacement of the chloro group in 3a gave 4 in 40% yield and 4‐dimethylamino analogue 5. However, displacement of 3b with morpholine followed by treatment with aqueous base gave 4 in 74% yield.     

3-Oxo-4,4,4-trifluorobutyronitriles as building blocks of trifluoromethyl substituted heterocycles 2. Heterocyclization to 3-aryl-4-trifluoromethyl-2H-1-benzopyran-2-ones under hoesch reaction conditions

Resorcinol and 5-methylresorcinol, respectively, react with 3-oxo-2-aryl-4,4,4-trifluorobutyronitrile using zinc chloride as a catalyst in dibutyl ether under the Hoesch reaction conditions to give a low yield of 3-aryl-7-hydoxy-4-trifluoromethyl- or 3-aryl-5-hydroxy-7-methyl-4-trifluoromethyl-2H-l-benzopyran-2-ones. However, the related reaction with m-methoxyphenol was found to produce poor yields of 3-aryl-7-methoxy-4-trifluoromethyl-2H-1-benzopyran-2-one and its 3,4-dihydro-4-hydroxy derivative.     

3-羟基十四酸的合成

以环氧氯丙烷为起始原料,经5步反应合成了3-羟基十四酸,总收率52.48%。以氯癸烷替代溴癸烷做格氏反应,有效地降低了偶联副产物的生成;从中间产物1-氯-2-羟基十三烷直接上氰基,避免了环化后上氰基时生成氢氰酸的危险。     

Cyclopropanization of Methyl Carboxylates with Tebbe-Type Reagents

The methylenation reaction of methyl azulene-2-carboxylates (cf. Schemes 1 and 2) with Tebbe's or Takai's reagent is described. When the prescribed amount of Takai's reagent is applied in a four-fold excess, the corresponding cyclopropyl methyl ethers are formed instead of the enol ethers (cf. Schemes 2 and 3). Similarly, methyl benzoate and methyl 2-naphthoate yield, after treatment with Takai's reagent and hydrolysis, the corresponding cyclopropanols 18 and 19 , respectively (Scheme 3). The cyclopropyl methyl ether 4 or cyclopropanol 5 rearrange, on acid catalysis, into the l-(azulen-2-yl)propan-l-one 20 (Scheme 4). whose reduction with Et₃SiH in CF₃COOH yields the 2-propylazulene 21 .     

Reaction of N-(4-pyridylmethyl)benzamide N-oxides with ethyl cyanoacetate in the presence of acetic anhydride

Reaction of N-(4-pyridylmethyl)benzamide N-oxides 2a-f with ethyl cyanoacetate in the presence of acetic anhydride yield dimerization compounds 3a-f and (E)-ethyl 2-cyano-3-(4-pyridyl)-3(benzoylamino)acrylates 4a-f , which react with hydrazine to give 4-cyano-3-(4-pyridyl)-3-pyrazolin-5-one 9 and the corresponding benzamides 10a-f .     

Nickel-katalysierte Synthese von α-Nornicotin-Derivaten. Vorläufige Mitteilung

Nickel-catalysed Synthesis of α-Nornicotines Schiff's bases 1 and butadiene generally co-oligomerize on nickel catalysts to yield octatrienyl-substituted amines 2 and octadienyl-substituted imines 3 . Schiff's bases 4 and 5 , on the other hand, react with 1, 3-dienes to give new [3+2]-cycloadducts 6 . In addition to the appropriately functionalized α-nornicotine derivatives some higher oligomers are formed.     

Synthesis of aromatic aldehydes via 2-aryl-n,n'-diacyl-4-imidazolines

Diacylimidazolium ions yield adducts with aromatic compounds. Thus the N,N'-diacetylimidazolium ion and indole gives 1,3-diacetyl-2-(3-indolyl)-4-imidazoline. Less reactive substrates such as thiophene, anisole and 1,3-dimethylbenzene fail to react with this reagent but do form adducts (e.g. 1,3-bis-(trifluoroacetyl)-2-(2-thienyl)-4-imidazoline) with an imidazole/trifluoroacetic anhydride reagent. All of the adducts could be converted to the corresponding aldehyde under mild conditions. The synthetic scope of the new synthesis is similar to that of the Vilsmeier-Haack reaction.     

(Perhalogenmethylthio)heterocyclen. XXI. Reaktionen halogenierter perhalogenmethylthiopyrrole: Salz- und radikalbildung,dimerisierung

2-Chloro-3,4,5-tris(trifluoromethylthio)pyrrole ( 2a ), 3-Chloro-2,4,5-tris(trifluoromethylthio)pyarrole ( 2b ) and 3,4-dichloro-2,5-bis(trifluromoethylthio)pyrrole ( 2c ) react with silver nitrate/silver acetate in good yield to give the corresponding N-silver salts 3a-c . Compound 2b forms with an aqueous potassium hydroxide solution the N-potassium salt 4 . Compounds 3a and 3b react with iodine to give the dimeers 2,2′-dichloro-3,3,′ 4,4′5,5′-hexakis(trifluoromethylthio)-2,2′-bi-2H-pyrrolyl ( 5a ) and 3,3′-dichloro-2,2′,4,4′,5,5′-hexakis(trifluoromethylthio)-2,2′-bi-2H-pyrrolyl ( 5b ). The dimers dissociate in solution to the corresponding pyrrolayl radicals. The esr and endor spectra of 3-chloro-2,4,5-tris(trifluoromethylthio)pyrrolyl were measured; coupling constants are given. For the newly prepared substances melting-points, ¹⁹F-nmr and ir spectroscopical data are provided.     

Pentafluoroethylbenziodoxole (BIX‐C2F5): A Shelf‐Stable Reagent for Pentafluoroethylation of β‐Ketoesters and Arylboronic Acids

An improved method for the preparation of pentafluoroethylating reagent pentafluoroethyl‐substituted benziodoxole (BIX‐C₂F₅) was described. Under mild conditions, BIX‐C₂F₅ was able to react with β‐ketoesters or aryl/heteroaryl boronic acids to generate pentafluoroethylated compounds in good yields.