Reduction studies on benzaza[3.3.3]propellanc derivatives

Sodium borohydride reduction of 3-methyl-2,3-dioxo-7,8-benzo-3-aza[3.3.3]propellan-6-one (1b) gave 2,4-dioxo-3-methyl-7,8-benzo-3-aza[3.3.3]propellan-6-ol, while lithium aluminum hydride reduction gave 3-methyl-7,8-benzo-3-aza[3.3.3]propellan-6-ol, which on oxidation, gave the corresponding ketone. This ketone formed the corresponding thioketal upon reaction with 1,2-ethanedithiol. Raney nickel desulfurization of the thioketal provided 3-methyl-6,7-benzo-3-aza[3.3.3]propellane. The same compound was also obtained in poor yield by forming the thioketal of Ib followed by lithium aluminum hydride reduction and Raney nickel desulfurization of the product. Desulfurization of the thioketal of Ib gave 2,4-dioxo-6,7-Benzo-3-aza[3.3.3]propellane.     

[3.3.2]- and [3.3.3]Propellanes in Reactions with Oxidizing Electrophiles

The structure of [3.3.2]- and [3.3.3]propellanes, their framework analogs, and their radical-cations was investigated by computational methods (BLYP and B3LYP) in the 6-31G* basis set. The reactivity of the propellanes toward model oxidizing electrophiles does not contradict the quantum-chemical calculations. In the case of the tetracyclic framework analog of [3.3.3]propellane the reaction takes place as C—H substitution, whereas in the case of [3.3.2]propellanes it takes place as C—C-oxidative addition.     

Facile Preparation of 3,7-Diazabicyclo[3.3.0]octane and 3,7,10-Triheterocyclic [3.3.3]Propellane Ring Systems from 1,5-Diazacyclooctane 3,7-Derivatives(1)

The cyclodimerization of p-toluenesulfonamide and 3-chloro-2-(chloromethyl)-1-propene to prepare N,N'-bis(p-toluenesulfonyl)-3,7-bis(methylene)-1,5-diazacyclooctane (1a) and its ozonation to the corresponding 3,7-dione 2a are reported. Unusual transannular cyclizations initiated by lithium aluminum hydride treatment or bromination of 1a and oxidative coupling of the dioxime derived from 2a are described. These reactions lead, respectively, to the following derivatives of the little-studied 3,7-diazabicyclo[3.3.0]octane ring system: 1,5-dimethyl-3,7-diazabicyclo[3.3.0]octane (5), N,N'-bis(p-toluenesulfonyl)-1,5-bis(bromomethyl)-3,7-diazabicyclo[3.3.0]octane (8), and N,N'-bis(p-toluenesulfonyl)-1,5-dinitro-3,7-diazabicyclo[3.3.0]octane, (12). Acid-catalyzed hydration of 1a, in contrast, gives the expected 5-methyl-3,7-diazabicyclo[3.3.1]nonan-1-ol (10). Reaction of the dibromide 8 with the nucleophiles, sodium sulfide, sodium oxide, and sodium p-toluenesulfonamide conveniently delivers the corresponding novel 3,7,10-triheterocyclic [3.3.3]propellanes.     

Synthesis of novel 2,4,6,8,10-pentaaza[3.3.3]propellane derivatives

Propellanes and azapropellanes are attractive compounds for their unique structure and valuable applications but there are few synthetic studies for highly N-substituted azapropellanes. Several novel derivatives of 2,4,6,8,10-pentaaza[3.3.3]propellane, such as 3, 4, and 5 were successfully synthesized from readily available diethyl tartrate. Most of the synthetic steps were efficient. Their propellane structures were established by spectroscopic data and confirmed with single crystal X-ray analyses.     

Wagner-Meerwein rearrangement of a [3.3.3]- to a [4.3.3]propellane: deuterium tracer and conformational analysis

Formation of (-)-[4.3.3]propellane 4 from (-)-14-hydroxymodhephene (2) proceeds through a Wagner-Meerwein rearrangement via C3--C4 bond-shift to give a stable intermediate, dimethylcyclohexadienyl cation A, which undergoes deprotonation. Herein, this mechanism was investigated by using a deuterium labeled substrate at the C-14 methylene group of (-)-2, which was incorporated into the C-4 position of (-)-[4.3.3]propellane 4. The stereostructure of (-)-4 was investigated by applying a combination of NMR experimental and theoretical approaches.     

Synthesis of 2,4,6,8,9,11-hexaaza[3.3.3]propellanes as a new molecular skeleton for explosives

Azapropellanes are of great interest in many disciplines, including materials science and medicinal chemistry. Various synthetic approaches for azapropellanes have been explored; however, the synthetic study of the polyazapropellane skeleton containing five or more nitrogen atoms is rare. Here, we report a simple yet highly efficient protocol for the synthesis of the hexaaza[3.3.3]propellane skeleton as a building block for high energy materials for the first time. The key reactions include the Boc₂O-assisted cyclization of glycoluril diamine without a column purification step and the first full reduction of all the three carbonyl groups to the methylene groups through a combination of LiAlH₄ and DIBAL-H. All the structures were confirmed by spectroscopic and X-ray analyses.     

Chemoselective Synthesis of Novel Heterocyclic [3.3.3]Propellane Derivatives via a One‐pot Three‐component Reaction

A highly chemoselective method for the synthesis of heterocyclic [3.3.3]propellane derivatives was developed via sequential three‐component reactions of acenaphthenequinone, malononitrile/cyanoacetate and a variety of 1,3‐dicarbonyl compounds under mild conditions in ethanol. A plausible mechanism for this type of reaction was proposed. The value of this method was highlighted by its high selectivity, simple procedures, and good yields.     

An Improved Synthesis of Bicyclo[3.3.3]undecane

A shorter and significantly higher-yield procedure for the preparation of bicyclo[3.3.3]undecane (manxane) is reported.     

A Convenient Mannich-Type One-Pot Synthesis of Pyrimido[6,1-b][1,3,5]thiadiazines

Summary. 3-(Het)aryl-2-cyanoprop-2-enethioamides easily reacted with primary amines and excessive formaldehyde under mild conditions to afford pyrimido[6,1-b][1,3,5]thiadiazine derivatives in moderate yields. Furthermore, 2-cyano-2-cyclohexylideneethanethioamide reacted in the similar Mannich-type manner to give spiro-conjugated pyrimido-1,3,5-thiadiazines. The structure of 3,7-dibenzyl-8-(fur-2-yl)-3,4,7,8-tetrahydro-2H,6H-pyrimido[6,1-b][1,3,5]thiadiazine-9-carbonitrile was determined by X-ray diffraction analysis.     

A Convenient Mannich-Type One-Pot Synthesis of Pyrimido[6,1-b][1,3,5]thiadiazines

3-(Het)aryl-2-cyanoprop-2-enethioamides easily reacted with primary amines and excessive formaldehyde under mild conditions to afford pyrimido[6,1-b][1,3,5]thiadiazine derivatives in moderate yields. Furthermore, 2-cyano-2-cyclohexylideneethanethioamide reacted in the similar Mannich-type manner to give spiro-conjugated pyrimido-1,3,5-thiadiazines. The structure of 3,7-dibenzyl-8-(fur-2-yl)-3,4,7,8-tetrahydro-2H,6H-pyrimido[6,1-b][1,3,5]thiadiazine-9-carbonitrile was determined by X-ray diffraction analysis.     

Nitrogen bridgehead compounds. Part 88. Synthesis of 3H, 7H-[1,4]diazepino[3,4-b]quinazoline-3,7-diones

3H,7H-[1,4]Diazepino[3,4-b]quinazolone-3,7-diones 9, 11 were synthesized starting from 2-(1-bromo-ethyl)quinazolin-4(3H)-ones 3 and 17 via 2-[1-(4-methoxyphenylamino)ethyl]quinazolin-4(3H)-ones 4 and 18. Cyclization of 3-[2-(1-bromoethyl)-4-oxo-3,4-dihydroquinazolin-3-yl)propionic acid 14 by the action of triethylamine provided the first representative of the tricyclic 7H-[1,4]oxazepino[3,4-b]quinazoline-3,7-dione system, compound 15. The new tricyclic derivatives 9, 11 and 15 are characterized by uv, ir and ¹H nmr spectroscopy.     

1-Trimethoxysilylmethyl-and 1-(2,8,9-trioxa-5-aza-1-silabicyclo[3.3.3]undecan-1-ylmethyl)-1,1-dimethyl-2-(3-alkoxy-3-oxopropyl)hydrazinium halides

Previously unknown 1,1-dimethyl-1-trimethoxysilylmethyl-2-(3-alkoxy-3-oxopropyl)hydrazinium and 1,1-dimethyl-1-(2,8,9-trioxa-5-aza-1-silabicyclo[3.3.3]undecan-1-ylmethyl)-2-(3-alkoxy-3-oxopropyl)-hydrazinium halides were synthesized, and physiological activity of 2-(3-ethoxy-3-oxopropyl)-1,1-dimethyl-1-(2,8,9-trioxa-5-aza-1-silabicyclo[3.3.3]undecan-1-ylmethyl)hydrazinium chloride and bromide was studied.     

Synthesis of heterocyclic [3.3.3]propellanes via a sequential four-component reaction

A highly chemoselective heteroannulation protocol for the synthesis of unreported polysubstituted heterocyclic [3.3.3]propellanes has been developed by sequential four-component reaction of ninhydrin, malononitrile, primary amines, and dialkyl acetylenedicarboxylates under mild conditions in water. To the best of our knowledge, there are no previous reports for the synthesis of these classes of heterocyclic [3.3.3]propellanes. The merit of this sequential Knoevenagel condensation/enamine formation/Michael addition/cyclization sequence is highlighted by its high atom-economy, excellent yields, the use of water as reaction media, and the efficiency of production without the use of any activator or metal promoters. This synthesis serves as a nice addition to group-assistant-purification (GAP) chemistry in which purification via chromatography and recrystallization can be avoided, and the pure products were obtained simply by washing the crude products with 95% ethanol.     

Systematic series of azacycl[3.3.3]azines of varying nitrogen content: Nitrogen-15 magnetic resonance spectra

Nitrogen-15 NMR spectra were obtained for a systematic series of azacycl[3.3.3]azines: 1,3,4,6,7,9-hexaaza-,1,3,4,6,7-pentaaza-,1,3,4,6-tetraaza-, 1,3,4,6,8-pentaaza-, and 1,3,6-triazacycl[3.3.3]azine. The magnetic resonance data were compared with other physical and spectroscopic properties available for the series relative to the diminishing number of peripheral nitrogens in alternating positions. The properties of 1,3,4,6,8-pentaazacycl[3.3.3]azine, which has a peripheral 1,4-diazine-type nitrogen, are distinct from those of the rest of the series.     

The crystal structure of bicyclo [3.3.3]undecane-1,5-diol and the conformation of bicyclo[3.3.3]undecane (manxane)

The crystal structure of bicyclo [3.3.3]undecane-1,5-diol has been determined. It is monoclinic, P2₁/c, a = 12.99(2), b = 14.16(2), c = 12.50(1)A,β = 112.42(2)°, with two independent molecules in the asymmetric unit. One of these is disordered, but the other has almost exact C_3h symmetry and its conformation and precise molecular geometry agree well with previous calculations by molecular mechanics. The molecule shows considerable angle strain, having bridge angles in the range 118–121°     

[f]-Fused purine-2,6-diones: Synthesis of new [1,3,5]- and [1,3,6]-thiadiazepino-[3,2-f]-purine ring systems

Summary 6-Phenyl-1,3-dimethyl-2,4-dioxo-1,2,3,4,8,9-hexahydro-[1,3,5]-thiadiazepino-[3,2-f]-purine (5) was obtained by a three-step synthesis from 8-mercapto-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (1) and 2-(benzoylamino)-ethyl chloride (2)via 8-(benzoylaminoethylthio)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (3) and its chloromido derivative4. The analogous 9-phenyl-1,3-dimethyl-2,4-dioxo-1,2,3,4,6,7-hexahydro-[1,3,6]-thiadiazepino-[3,2-f]-purine (7) was synthesized either from compound1 and N-(2-chloroethyl)-benzimido chloridevia N-(chloroethyl)-S-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-7H-purin-8-yl)-benzothioimide (6), or alternatively from 7-(2-benzoylaminoethyl)-8-bromo-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (9), its 8-mercapto derivative10 and the corresponding chloroimido compound11 being the intermediates.Part of this paper was presented as a preliminary report at the Congress of Czech and Slovak Chemical Societies, Olomouc, Czech Republic, September 13–16, 1993     

Synthesis and rearrangement of functionalized dispiro [3.0.3.3]Undecanes - a new entry to [3.3.3]Propellanes1

The functionalized dispiro[3.0.3.3]undecanes 6 and 7 undergo cascade rearrangements to yield the [3.3.3]propellanes 15 and 11, respectively. The formation of 15 proceeds via the bicyclic enone 16.     

Selenium heterocycles. XXXII . Synthesis of [1]benzoxepino[3,4-d]-thiazole, [1]benzothiepino[3,4-d]thiazole, [1]benzoxepino[3,4-d]selenazole,and [1]benzothiepino[3,4-d]selenazole. four novel heterocycles

Starting from the readily available ethyl 2-phenyl-4-methyl-thiazole-5-carboxylate (III), 2-phenyl-4-chloromethyl-thiazole (VIII) and 2-aryl-4-chloromethylselenazole (XIV), 2-phenyl-4,10-dihydro-10-oxo-[1]benzoxepino[3,4-d]thiazole (Ia), 2-phenyl-4,10-dihydro-10-oxo[1]benzothiepino[3,4-d]thiazole (Ib), 2-aryl-4,10-dihydro-10-oxo[1]benzoxepino[3,4-d]selenazoles (IIa-IIe) and 2-aryl-4,10-dihydro-10-oxo[1]benzothiepino[3,4-d]selenazoles (IIf-IIj) were prepared.     

Photochemistry of 3,7-Bis(arylmethylene)bicyclo[3.3.1]nonane Derivatives

UV irradiation of trans-trans-3,7-bis(arylmethylene)bicyclo[3.3.1]nonane-2,6-diones leads to their complete or partial transformation into the corresponding cis-cis isomers. Irradiation of trans-trans-3,7-bis(arylmethylene)bicyclo[3.3.1]nonane-2,6-diol in ether in the presence of CuCl results in intramolecular cyclization involving the exocyclic double bonds and one benzene ring to give exo-7endo-10-dihydroxy-2-phenyl-3,4-benzotetracyclo[4.3.3.18,11.01,6]tridecane.     

Chemistry of 1,2,3-thiadiazole. IV. Synthesis of [1]benzoxepino-[3,4-d][1,2,3]thiadiazole, [1]benzothiepino-[3,4-d][1,2,3]thiadiazole, [1]benzoxepino[4,3-d][1,2,3]thiadiazole, [1]benzoxepino[4,3-d]oxazole and [1]benzoxepino[4,3-d]oxazole. Four novel heterocycles

Starting from the readily available 4-bromomethy-5-carbethoxy 1,2,3-thiadiazole (V), 5-bromomethy-4-carbethoxy-1,2,3-thiadiazole (IX) and ethyl 2-aryl-5-bromomethyloxazole-4-carboxylate (XIV), 4,10-dihydro-10-oxo[1]benzoxepino[3,4-d][1,2,3]thiadiazole (Ia), 4,10-dihydro-10-oxo[1]benzothiepino[3,4-d][1,2,3]thiadiazole (Ib), 4,10-dihydro-4-oxo[1]benzothiepino[4,3-d] [1,2,3]thiazole (II), 2-aryl-4,10-dihydro-4-oxo[1]benzoxepino[4,3-d]oxazoles (XIXa-XIXc) and 2-aryl-4,10-dihydro-4-oxo[1]benzothiepino[4,3-d]oxazoles (XIXd-XIXf) were prepared.