New heterocyclic syntheses from hydrazidoyl halides. Convenient syntheses of fused pyrimidines,pyridazines, and quinazolines

Aminocyanopyrazole derivatives and pyrazolo[2,3-a]quinazolones were obtained in good yields from hydrazidoyl halides and malononitrile. Pyrazolo[3,4-d]pyridazine and pyridazo[4′,5′: 1,2]pyrazolo[1,5-a]quinazoline derivatives were synthesized in quantitative yields by reaction of hydrazine hydrate with 2 and 16 , respectively. A novel ring system, a 3-substituted tetrahydro derivative of 7-oxo-6H,8H-pyridazo[3′,4′,5′-c'd']-pyrazolo[3,4-d]pyrimidine was prepared by reaction of 6 with dimethyl carbonate. Pyrazolo[3,4-d]pyrimidine-4,6-dithiones were obtained in good yields by reaction of 2 with carbon disulfide. The structures of the products were assigned and confirmed on the basis of their elemental analyses, spectral data, and alternate synthesis wherever possible. The structures of the parent fused heterocyclic systems discussed in this work are summarized in Scheme 1 .     

Studies on the syntheses of heterocyclic compounds—DLXIX : One-step synthesis of dihydropyridocarbazole derivatives

Heating indole and 4,5-dibromomethyl-3-hydroxy-2-methylpyridine hydrobromide (10), followed by acetylation, gave the desired dihydropyrido[4.3-b]carbazole (12) and its structural isomer, dihydropyrido[3.4-b]carbazole (13). The structures of (12 and 13) were determined by UV spectral investigations of the corresponding dehydrogenated products, 4-acetoxy-3-methyl-6H-pyrido[4.3-b]carbazole (11) and 4-acetoxy-3-methyl-10H-pyrido[3.4-b]carbazole (14).On the other hand, the same reaction in the presence of sodium iodide afforded 12 together with four other coupling products which were not cyclized, such as (16, 17, 18), and a dimer.     

Studies on the syntheses of heterocyclic compounds. part CCLXXIX . Synthesis of O-isobutylcularidine

Although various methods of oxepine formation from phenoxybenzene dicarboxylic acids was attempted, only 11-hydroxy-4-isobutoxy-7,8-dimethoxydibenz[b,f]oxepin-l-ylaeetic acid lactone (XXX) was synthesized successfully. Compound XXX gave O-isobutylcularidine (XXXVlIb) in a few steps. Our synthetic O-isobutylcularidine was identical with that prepared from natural cularidine proving the structure for cularidine proposed by Manske. However, dealkylation of synthetic O-isobutylcularidine was unsuccessful.     

Studies on the syntheses of heterocyclic compounds—CCCLXXI Synthetic approach to camptothecin

Picolinic acid 1-oxide (III) was esterified with thionyl chloride and ethanol to the ester IV, whose treatment with phosphoryl chloride gave ethyl 6-chloropicolinate (V). Hydrolysis of V with hydrochloric acid gave 6-oxo-1,6-dihydropicolinic acid (VI). Simultaneous condensation and cyclisation of the methyl ester of VI with methyl acrylate in the presence of sodium carbonate in dimethylformamide yielded the bicyclic ketoester (VIII). Hydrolysis and decarboxylation of VIII with hydrochloric acid gave 3-keto-pyrrolidino[2.1-f]-2-pyridone (IX). Friedänder condensation of IX with 2-aminobenzaldehyde gave the camptothecin analogue II.     

Studies on the syntheses of heterocyclic compounds—DLIX : A synthesis of benzocarbazole derivatives by thermolysis

A thermal reaction of indolylmagnesium bromide (5) with 1-cyano-4,5-dimethoxybenzocyclobutene (6) gave a mixture of 6-cyano-5a, 6,11,11a-tetrahydro-8,9-dimethoxy-5H-benzo [b] carbazole (8a) and 6-cyano-5a, 6, 11, 11a-tetrahydro-9-hydroxy-8-methoxy-5H-benzo [b] carbazole (10). Compound 8a was easily converted to 6-cyano-8, 9-dimethoxy-5H-benzo [b] carbazole (12) by dehydrogenation on 30% Pd-C.     

Studies on the syntheses of heterocyclic compounds—DCXCIII: A total synthesis of atheroline by photolysis

Atheroline (3) an oxoaporphine alkaloid, has been synthesised by photolysis of 8 bromo 1-(3-hydroxy-4-methoxybenzoyl)-6,7-dimethoxyisoquinoline (13) in the presence of sodium hydroxide.     

Studies on the syntheses of heterocyclic compounds—DXLVII : Synthesis of a yohimbane derivative by thermolysis

Thermolysis of 3,4-dihydro-1-(5-methoxybenzocyclobutenyl)-β-carboline hydrochloride (16) in bromobenzene gave the decadehydroyohimbane (19), which on reduction with sodium borohydride afforded the hexadehydroyohimbane (20) which had already been converted into (±)-yohimbone (21) and (±)-alloyohimbone (22).     

含氟芳杂环化合物的研究 7:含氟氮、硫杂二苯并王冠化合物的合成

本文研究了苯环上含强吸电子基的间硝基对氯三氟甲苯1与一些含氮、氧、硫的亲核试剂作用,经桥接、还原、关环,分别合成了含氟氮杂、硫杂王冠化合10牧11;还得到含氟三氮杂庚环化合物9,并对其生成机理进行了探讨,各步产率都较高.     

Studies on the syntheses of heterocyclic compounds—DXXII : Photolytic synthesis of 1,12-dihydroxy-2,10,11- trimethoxyhomoaporphine

Photolysis of 1-(2-bromo-3-hydroxy-4,5-(dimethoxyphenethyl)-1,2,3,4-tetrahydro-7-hydroxy-6-methoxy-2-methylisoquinoline (8) gave 4,5,6,6a-tetrahydro-1,12-dihydroxy-2,10,11-trimethoxy-6-methylhomoaporphine (7), which is identical with the alkaloid CC-24 isolated from Cholchicum cornigerum.     

Studies on the syntheses of heterocyclic compounds—DXXIII : Enzymic oxidation of homoorientaline with homogenised potato peelings

Homoorientaline 4 was oxidised with homogenised potato peelings along, followed by acetylation, to give 1-hydroxyhomoorientaline triacetate 9, the structure of which was determined by spectroscopic data and an alternative synthesis.     

Studies on the syntheses of heterocyclic compounds—DXLV : An alternative synthesis of the protoberberine ring system

The reaction of 3,4-dihydro-6,7-dimethoxyisoquinoline (11) with 1-bromobenzocyclobutene (10) gave, in one step, 2,3-dimethoxyprotoberberinium bromide (15), which was easily converted into the tetrahydroprotoberberine (16).     

Enaminones as building blocks in heterocyclic synthesis: New syntheses of nicotinic acid and thienopyridine derivatives

Reacting 1,3‐diphenyl‐propan‐2‐one with equimolecular amount of dimethylformamide dimethylacetal afforded the enaminone 4. This when reacted with another equimolecular amount of dimethylformamide dimethylacetal afforded the dienaminone 5. Compound 4 condenses with cyanothioacetamide and with cyanoacetamide to yield 2‐thioxo‐ and 2‐oxo‐pyridine‐3‐carbonitrile derivatives 6a,b respectively. Compound 6a reacted with α‐chloroacetone 8 to yield the thieno[2,3‐b]pyridine derivative 10 that cyclized further into 4,7,8‐trisubstituted pyrido[2′,3′:2,3] thieno[4,5‐d]pyrimidine 12. Compound 4 also afforded 2,5,6‐trisubstituted nicotinic acid ethyl ester 13 by reaction with ethyl acetoacetate in acetic acid in the presence of ammonium acetate. The dienaminone 5 reacted with acetic acid, ammonium acetate/acetic acid, phenylhydrazine and 5‐amino‐3‐methylpyrazole yielding 3,5‐diphenyl‐pyran‐4‐one 15a , 3,5‐diphenyl‐1H‐pyridin‐4‐one 15b and 1,3,5‐trisubstituted pyridin‐4‐ones 16a‐b.     

Enzymic phenol oxidation of N-methylcoclaurine. Studies on the syntheses of heterocyclic compounds. Part cccxxxii

The enzymic phenol oxidation of N-methylcoclaurine (111) with homogenized potato peels in the presence of hydrogen peroxide was examined and found to give a mixture of the dimer (VI) and trimer (VII) with C-O-C head to tail coupling. Furthermore, the same oxidation of III with homogenized rhizome of Nelumbo nucifera Gartner and hydrogen peroxide was also investigated.