Transannular reactions in the dibenzo[a,d]cycloheptene series. III. Preparation of 11-substituted-10,11-dihydro-10,5-(iminomethano)-5H-dibenzo[a,d]cycloheptenes

1968 ◽  
Vol 46 (21) ◽  
pp. 3391-3397
Author(s):  
T. A. Dobson ◽  
M. A. Davis ◽  
A. M. Hartung
Keyword(s):  
Sodium Hydride ◽  
Ammonium Hydroxide ◽  
Grignard Reagents ◽  
Lithium Aluminium Hydride ◽  
Tertiary Alcohols ◽  
Lithium Aluminium

Treatment of the syn-epoxyamide 3 with either ammonium hydroxide or sodium hydride gives 10,11-dihydro-anti-11-hydroxy-10,5-(iminomethano)-5H-dibenzo[a,d]cyclohepten-13-one (1a). This compound is readily converted to the syn-epimer 1c by oxidation to 1b and subsequent hydrogenation. The ketone 1b reacts with Grignard reagents to give the tertiary alcohols 1k,l which undergo hydrogenolysis to give the 11-substituted lactams 1q,r. Reduction of the lactams with lithium aluminium hydride gives the corresponding amines.

Synthesis of piperidine derivatives as potential analgetic agents

1990 ◽  
Vol 55 (7) ◽  
pp. 1828-1853 ◽  
Author(s):  
Jiří Jílek ◽  
Miroslav Rajšner ◽  
Vladimír Valenta ◽  
Miloš Borovička ◽  
Jiří Holubek ◽  
...  
Keyword(s):  
Model Compound ◽  
Lithium Aluminium Hydride ◽  
Sodium Cyanoborohydride ◽  
Sulfurous Acid ◽  
Phosphorus Pentasulfide ◽  
Tertiary Alcohols ◽  
Lithium Aluminium ◽  
Propionyl Chloride ◽  
Fentanyl Analogues ◽  
Neurotropic Agents

Reaction of N-(1-(2-phenylethyl)-4-piperidinyl)propionanilide (I) with phosphorus pentasulfide gave the thioamide VI. Acylation of N-(1-(2-phenylethyl)-4-piperidinyl)aniline with 2-(methoxy)acetic and 2-(methylthio)acetic anhydrides afforded the amides II and III. Treatment of 4-anilino-1-benzylpiperidine-4-methanol with thionyl chloride gave the spirocyclic sulfurous acid ester amide XIV. Reduction of the hydrochloride of ethyl 3-(1-ethoxycarbonyl-4-phenylimino-3-piperidinyl)propionate (XXII) with sodium cyanoborohydride gave the perhydro-1,6-naphthyridine derivative XIX, a model compound in the synthesis of the cyclic analogue of fentanyl (I). Ethyl 4-anilino-1-(2-phenylethyl)-1,2,3,6-tetrahydropyridine-3-carboxylate (XXIX) hydrochloride, obtained by reaction of ethyl 4-oxo-1-(2-phenylethyl)piperidine-3-carboxylate hydrochloride with aniline, was reduced with lithium aluminium hydride to 4-anilino-1-(2-phenylethyl)piperidine-3-methanol (XXXI). 1-Methyl- and 1-benzyl-4-piperidone were reacted with 4-cyclopropylphenylmagnesium bromide and the tertiary alcohols XXXVII and XXXVIII obtained were acylated with propionyl chloride to give the esters XXXIX and XL. The piperidine derivatives XLI, XLVI and XLVIII were prepared as potential neurotropic agents. Alkylation of 8-hydroxy-6,11-dimethyl-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocine (XLIX) with 2-(2-chloroethyl)-1,3-dioxane and -1,3-dioxolane resulted in the 6,7-benzomorphan derivatives L and LI. Out of the compounds prepared, only the closest fentanyl analogues II, III, and VI showed very strong analgetic activity.

Preparation of Phosphonomethyl Ethers Derived from 2-Phenylethanol and Its Amino Derivatives

1995 ◽  
Vol 60 (4) ◽  
pp. 659-669
Author(s):  
Marcela Krečmerová ◽  
Antonín Holý
Keyword(s):  
Antiviral Activity ◽  
Cell Cultures ◽  
Sodium Hydride ◽  
Amino Group ◽  
Lithium Aluminium Hydride ◽  
Adenine Ring ◽  
Lithium Aluminium ◽  
Amino Derivatives ◽  
Acyclic Nucleoside

A series of compounds derived from the acyclic nucleoside antiviral 9-(2-phosphonomethoxyethyl)adenine (PMEA), in which the adenine ring is replaced by phenyl, 4-aminophenyl, 3-aminophenyl or 3,5-diaminophenyl group, has been prepared starting from the corresponding phenethyl alcohols. 2-(3-Aminophenyl)ethanol was prepared from 3-nitrobenzoyl chloride using the Arndt-Eistert reaction. The primarily formed diazoketone Ia was converted into ethyl 3-nitrophenylacetate (IIa) which on catalytic hydrogenation afforded ethyl 3-aminophenylacetate (IIIa). Compound IIIa was reduced with lithium aluminium hydride to give 2-(3-aminophenyl)ethanol (IVa). 2-(3,5-Diaminophenyl)ethanol (IVb) was prepared analogously from 3,5-dinitrobenzoyl chloride. After protection of the amino group with dimethylaminomethylene group, the alcohol IVa was converted to diisopropyl 2-(3-aminophenyl)ethoxymethylphosphonate (XII) by reaction with sodium hydride and diisopropyl p-toluenesulfonyloxymethanephosphonate, followed by deprotection of the amino group by treatment with ammonia. Reaction of diisopropyl ester XII with bromotrimethylsilane gave free 2-(3-aminophenyl)ethoxymethylphosphonic acid (XVII). The same procedure, applied to the corresponding aminophenethyl alcohols, afforded: 2-(4-aminophenyl)ethoxymethylphosphonic acid (XVI) and 2-(3,5-diamino phenyl)ethoxymethylphosphonic acid (XVIII). The synthesized compounds were tested in vitro on cell cultures for the cytostatic and antiviral activity (HSV-1, HSV-2, VSV, VZV, CMV). No antiviral activity has been found for any of the compounds.

Phosphonium salts. II. The reaction of bis-phosphonium salts with metal hydrides

1969 ◽  
Vol 22 (7) ◽  
pp. 1399 ◽  
Author(s):  
JJ Brophy ◽  
MJ Gallagher
Keyword(s):  
Alkaline Hydrolysis ◽  
Metal Hydrides ◽  
Sodium Hydride ◽  
Lithium Aluminium Hydride ◽  
Phosphonium Salts ◽  
Lithium Aluminium

Ethane-1,2-bis-phosphonium salts are cleaved by sodium hydride to phos- phines in 55-80% yields with loss of the two-carbon bridge. The reaction is independent of the substituents at the phosphorus atoms. The same reaction is observed with an ethene-1,2-bis-salt and with but- 2-ene-1,4-bis(triphenylphosphonium) dibromide. It is suggested that a phosphorane is formed which subsequently fragments in a manner analogous to alkaline hydrolysis. ��� Lithium aluminium .hydride behaves similarly but loss of the bridge is competitive with loss of benzyl groups, and yields are generally better (> 70%).

Convenient Synthesis of (Z)-7- and (E)-9-dodecene-1-yl Acetate, Components of Some Lepidoptera Insect Sex Pheromone

2017 ◽  
Vol 68 (1) ◽  
pp. 180-185
Author(s):  
Adriana Maria Andreica ◽  
Lucia Gansca ◽  
Irina Ciotlaus ◽  
Ioan Oprean
Keyword(s):  
Sex Pheromone ◽  
Coupling Reaction ◽  
Coupling Scheme ◽  
Lithium Aluminium Hydride ◽  
Terminal Alkyne ◽  
Mercury Derivative ◽  
Lithium Aluminium ◽  
Convenient Synthesis ◽  
Practical Synthesis ◽  
Insect Sex

Were developed new and practical synthesis of (Z)-7-dodecene-1-yl acetate and (E)-9-dodecene-1-yl acetate. The routes involve, as the key step, the use of the mercury derivative of the terminal-alkyne w-functionalised as intermediate. The synthesis of (Z)-7-dodecene-1-yl acetate was based on a C6+C2=C8 and C8+C4=C12 coupling scheme, starting from 1,6-hexane-diol. The first coupling reaction took place between 1-tert-butoxy-6-bromo-hexane and lithium acetylide-ethylendiamine complex obtaining 1-tert-butoxy-oct-7-yne, which is transformed in di[tert-butoxy-oct-7-yne]mercury. The mercury derivative was directly lithiated and then alkylated with 1-bromobutane obtaining 1-tert-butoxy-dodec-7-yne. After acetylation and reduction with lithium aluminium hydride of 7-dodecyne-1-yl acetate gave (Z)-7-dodecene-1-yl acetate with 96 % purity. The synthesis of (E)-9-dodecene-1-yl acetate was based on a C8+C2=C10 and C10+C2=C12 coupling scheme, starting from 1,8-octane-diol. The first coupling reaction took place between 1-tert-butoxy-8-bromo-octane and lithium acetylide-ethylendiamine complex obtaining 1-tert-butoxy-dec-9-yne, which is transformed in di[tert-butoxy-dec-9-yne]mercury. The mercury derivative was directly lithiated and then alkylated with 1-bromoethane obtaining 1-tert-butoxy-dodec-9-yne. After reduction with lithium aluminium hydride of 1-tert-butoxy-(E)-9-dodecene and acetylation was obtained (E)-9-dodecene-1-yl acetate with 97 % purity.

3-(s-Hydrindacen-4-yl)propylamines and 4-(s-hydrindacen-4-yl)butylamines; Synthesis and pharmacological screening

1981 ◽  
Vol 46 (8) ◽  
pp. 1800-1807 ◽  
Author(s):  
Zdeněk Vejdělek ◽  
Marie Bartošová ◽  
Miroslav Protiva
Keyword(s):  
Malonic Acid ◽  
Local Anaesthetics ◽  
Lithium Aluminium Hydride ◽  
Spasmolytic Activity ◽  
Lithium Aluminium ◽  
Malonic Acid Derivatives ◽  
Pharmacological Screening ◽  
Hydroxyethyl Piperazine

4-Chloromethyl-s-hydrindacene (VIIa) was transformed via the malonic acid derivatives VIIIa and IXa to the acid Xb which afforded in four steps the homological acid Xc. Reactions of chlorides of both acids (XIbc ) with dimethylamine, 1-methylpiperazine and 1-(2-hydroxyethyl)piperazine led to the amides XIIbc-XIVbc which were reduced with lithium aluminium hydride to the title compounds IVcd-VIcd. The amines obtained show central neuroleptic effects only in subtoxic doses; they are also potent local anaesthetics and have significant spasmolytic activity of the neurotropic as well as musculotropic type.

Substituted N,N-Dimethyl-3-(phenylthio)- and -4-(phenylthio)benzylamines

1992 ◽  
Vol 57 (1) ◽  
pp. 194-203 ◽  
Author(s):  
Karel Šindelář ◽  
Vojtěch Kmoníček ◽  
Marta Hrubantová ◽  
Zdeněk Polívka
Keyword(s):  
Serotonin Receptors ◽  
Hydrobromic Acid ◽  
Antidepressant Activity ◽  
Benzoic Acids ◽  
Lithium Aluminium Hydride ◽  
Acid Chlorides ◽  
Activity Inhibition ◽  
Lithium Aluminium ◽  
The Brain

(Arylthio)benzoic acids IIa - IIe and VIb - VId were transformed via the acid chlorides to the N,N-dimethylamides which were reduced either with diborane "in situ" or with lithium aluminium hydride to N,N-dimethyl-(arylthio)benzylamines Ia - Ie and Vb - Vd. Leuckart reaction of the aldehydes IX and X with dimethylformamide and formic acid afforded directly the amines Va and Ve. Demethylation of the methoxy compounds Ia and Ve with hydrobromic acid resulted in the phenolic amines If and Vf. The most interesting N,N-dimethyl-4-(phenylthio)benzylamine (Va) hydrochloride showed affinity to cholinergic and 5-HT2 serotonin receptors in the rat brain and some properties considered indicative of antidepressant activity (inhibition of serotonin re-uptake in the brain and potentiation of yohimbine toxicity in mice).

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