Hydrolysis of very reactive methylation agents - a rapid injection N. M. R. investigation.

By use of the recently described Rapid Injection N. M. R. technique it has been possible to measure the hydrolysis rates of $\text{1}$, $\text{2}$, and $\text{3}$ at various temperatures; the activation parameters for these rapid reactions have been determined and discussed.     

Per - bicyclophosphoranylation d'alditols

Reaction of bicyclophosphane $\text{1}$ with glycol $\text{2}$, glycerol $\text{3}$, erythritol $\text{4}$, L(-)arabitol $\text{5}$ and dulcitol $\text{6}$ leads to the corresponding per-alkoxybicyclophosphoranes $\text{2p}$ - $\text{6p}$ which are in tautomeric equilibrium with the phosphates forms $\text{2p}$′ - $\text{6p}$′.The amount of these latters increases regularly from traces to 24%.     

Breakdown of cyclic dithiohemiorthoamide tetrahedral intermediates - RC(SR′)(NR″2)SH - at sub-zero temperatures 1,2

The uslfhydrolyses of thioimidate salts $\text{2a}$–$\text{2d}$, in the presence of anh. NASH in dry 2-butanone at ?82°C, proceed by the preferential cleavage of the CN bond rather than the CS bond.     

N-halogeno-compounds. Part 9 [1]. Azoxy- and azo-arenes derived from 4-(dichloroamino)tetrafluoropyridine; crystal structure of trans-2,3,5,6-tetrafluoro-4-(2,4,6-trimethylphenyl-onn-azoxy)pyridine

The nitrosoarenes ArNO (Ar = C₆H₅, 2-MeC₆H₄, 2,4,6- Me₃C₆H₂ and C₆F₅) have been condensed with 4-(dichloroamino)- tetrafluoropyridine to provide the azoxy-compounds py_FN$\text{N}\text{+}$($\text{N}\text{-}$)Ar (py_F = 2,3,5,6-tetrafluoro-4-pyridyl); de-oxygenation of the first three with triphenylphosphine or triethyl phosphite gave the corresponding azo-compounds, and the reverse reaction was achieved in the case of py_FNNC₆H₂Me₃-2,4,6 using peroxytrifluoroacetic acid. Thermolysis of 4-azidotetrafluoropyridine in the presence of pentafluoronitrosobenzene provided the perfluorinated azoxy-compound py_FN$\text{N}\text{+}$($\text{O}\text{-}$)C₆F₅. X-Ray methods have been used to determine the molecular geometry of py_FN$\text{N}\text{+}$($\text{O}\text{-}$)C₆H₂Me₃-2,4,6.     

Reaction of 5,5-diphenyl-2-thiohydantoin with 1,2-dibromoethane.crystal and molecular structures of 2,3-dihydro-6,6-diphenylimi-dazo-[2,1-b]-thiazol-5(6h)-one and 2,3-dihydro-5,5-diphenylimi-dazo-[2,-1-b]-thiazol-6(5h)-one and their reactivity

The crystal and molecular structures of the title isomeric compounds $\text{1}$ and $\text{2}$, obtained by intramolecular N,S--dialkylation of 5,5-diphenyl-2-thiohydantoin with 1,2-dibro-moethane, have been determined from X-ray diffractometer data. 2,3-Dihydro-6,6-diphenylimidazo-[2,1-b]-thiazol-5(6H)-one $\text{1}$ crystallizes in space group P2₁2₁2₁ with a=11.376(3), b=12,255(5), c=8.434(3) Å and Z=4. Crystals of $\text{2}$, containing one molecule of benzene, are monoclinic,space group P2₁/c with a=11.539(6), b=10.242(3), c=16.353(5) Å, β=95.45(5)° and Z=4. In both cases a planar geometry of the two fused five-membered heterocyclic rings was found. The selected bond lengths in $\text{1}$ and $\text{2}$, as well as those analogous imidazothiazinones $\text{3}$ and $\text{4}$, were used to calculate E_HOSE (Harmonic Oscillation Stabilization Energy). The problem of stability and chemical reactivity of compounds $\text{1}$ to $\text{4}$ is also discussed.     

Kationische cyclisierung von (Z)-und (E)-1,3-dimethyl-2-(3-hexenyl)-2-cyclohexenol

The cationic cyclization of the carbinol $\text{3a}$(Z) occurred stereoselectively and resulted in a mixture of the hydrindane $\text{4a}$ and the octalin $\text{5a}$, both with $\text{trans-}$configuration of side chain and angular methyl group. Cyclization of $\text{3b}$(E) yielded in $\text{4b}$ and $\text{5b}$, both with $\text{cis}$-configuration. The structure of $\text{4a}$,$\text{5a}$ was proved by transformation to the diketones $\text{8}$,$\text{9}$.     

Adenosine cyclic 3′,5′-(RP)- and (SP)-phosphoramidates,the first representatives of nucleoside cyclic 3′,5′-phosphoramidates derived from ammonia

Adenosine cyclic 3′,5′-phosphoramidate $\text{2}$ was synthesized by reacting adenosine cyclic 3′,5′-phosphate $\text{1}$ with POCl₃, in trimethyl phosphate for 1 h at O°C, followed by in situ treatment of the reaction mixture with a suspension of (NH₄)₂CO₃ in anhydrous DMF or pyridine or DMF/pyridine mixture for 30 min at 25° C. Diastereoisomers ($\text{R}$_P)-$\text{2}$ and ($\text{S}$_P)-$\text{2}$ the relative quantities of which depended on the solvent of (NH₄)₂CO₃ treatment, were separated by reversed phase partition chromatography. Hydrolysis of (R_P)-$\text{2}$ and (S_P)-$\text{2}$ proceeded with predominant (90% in 0.1 N HCl, 100% in 0.1 N NaOH) -P-O-C bond breaking.     

Amino substituted 1-oxa-3-azabutatrienium salts: preparation, structure and reaction with carbonyl compounds

N,N-Dimethylformamide ($\text{4a}$) and N,N-dimethylpivalamide ($\text{4b}$) react with carbonyl chloride isocyanate ($\text{5}$) in the presence of antimony pentachloride to afford the amino substituted 1-oxa-3-azabutatrienium hexachloroantimonates $\text{6a}$,$\text{b}$. An X-ray diffraction analysis of $\text{6a}$ confirms the proposed structure. The heterocumulenes $\text{6a}$,$\text{b}$ react with aldehydes, ketones and tertiary carboxamides to give the amino substituted 2-azaallenium salts $\text{13a}$-$\text{O}$ in high yields.     

O-silylated ketene acetal chemistry; β-(alkoxycarbonyl)methyl O-silyl enolates,useful synthons for α-substituted-β-(alkoxycarbonyl)methylalkanones

Conjugate addition of O-silylated ketene acetals $\text{2}$ to α,β-unsaturated carbonyl compounds $\text{1}$ in acetonitrile gave quantitative yields of the corresponding β-(alkoxycarbonyl)methyl O-silyl enolates $\text{4}$. Site specific electrophilic substitutions of $\text{4}$ yielded the corresponding α-substituted β-(alkoxycarbonyl)-methylalkanones $\text{5}$, $\text{7}$, and $\text{8}$.     

Marine natural products: fistularin-1, -2 and -3 from the sponge Aplysina fistularis forma fulva

Three new high molecular weight bromotyrosine-related metabolites, $\text{3a}$, $\text{4a}$ and $\text{5a}$, were isolated from the sponge Aplysina ( Verongia) fistularis forma fulva, and their structures were determined from high resolution ¹H NMR and other spectroscopic data. The new metabolites are formally derived by combination of major segments of two known Aplysina metabolites $\text{1a}$ and $\text{2}$.     

An unusual chlorination of 1-phenyl-4-(2,6-dichlorophenyl)-1,3-butadiene

The diene $\text{1a}$ reacted with CHCl₃/aq. NaOH/PTC in CH₂ Cl₂ unexpectedly to give a mixture of the chlorination products $\text{2}$ and $\text{3a}$. Usual chlorination with Cl₂ yielded similarly $\text{2}$, $\text{3a}$, and $\text{3b}$ dependent on the amount of Cl₂. The formation of $\text{2}$ as well as the reaction of $\text{7}$ to give $\text{9}$ (besides $\text{8}$) shows an unusual Cl-Cl-interaction.     

Terpenes and terpene derivatives - XV. [1 ] Synthesis of 4,8-dimethyl-2-(2-methyl-1-propenyl)--1-oxaspiro(4.5]dec-7-ene (“bisabolene oxide”)

Starting from the ketones $\text{3}$ and $\text{4}$ the synthesis of six spiro ethers with an l-oxaspiro[4.5]decane skeleton is described. Five of them, $\text{9a}$,$\text{b}$, $\text{10a}$,$\text{19}$ and $\text{19}$ represent typical partial structures of the sesquiterpenoid spiro ether $\text{1}$. The unambiguous synthesis of $\text{1}$ shows a previous assignment of “'bisabolene oxide“' to structure $\text{1}$ to be wrong.     

4,6-Thioanhydro-hexopyranosides,synthesis and chemical behaviour of methyl 2-0-p-toluenesulfonyl-4,6-thioanhydro-α-d-gulopyranoside

Methyl 4-0-benzoyl-6-bromo-6-deoxy-α-D-glucopyranoside ($\text{1}$, Figure 1) was converted, via the corresponding ditosylate $\text{2}$, into methyl 2,3-di-0-p-toluenesulfonyl-4-0-benzoyl-6-S-acetyl-6-thio-α-D-glucopyranoside ($\text{3}$) by a selective nucleophilic displacement of 6-bromo-group with thioacetate. Unexpectedly, on treating the compound $\text{3}$ with an excess of sodium methoxide in benzene-methanol (1:1) at room temperature, methyl 2-0-p-toluenesulfonyl-4,6-thioanhydro-α-D-gulopyranoside ($\text{4}$) was obtained in a yield of 84%. In order to determine the structure of the relatively unstable oily product $\text{4}$, some stable crystalline derivatives ($\text{5}$, $\text{6}$ and $\text{7}$) were prepared. Detailed analysis of the ¹H-NMR-spectra (200 MHz) of $\text{6}$ and $\text{7}$ gave the conclusive evidence for the structure of $\text{4}$ A self-imposing mechanism of the clean and smooth transformation of $\text{3}$ to $\text{4}$ is proposed, involving: a) formation of $\text{9}$ (Figure 2) as a crucial intermediate and b) a highly regioselective epoxide opening in $\text{9}$ (at C-4) by an intramolecular nucleophilic attack of the mercaptide anion from C-6.     

Synthesis of optically active pheromones with an epoxy ring, (+)-disparlure and the saltmarsh caterpillar moth pheromone [(Z,Z)-3,6-cis-1-9,10-epoxyheneicosadiene]

(+)-Disparlure $\text{2}$, and the saltmarsh caterpillar moth pheromone enantiomers $\text{1}$ were synthesized and the stereochemistry of the naturally occurring $\text{1}$ was shown to be 9$\text{S}$, 1O$\text{R}$.     

Cycloaddition reactions of 1,3-benzothiazines - 6. Reactions of 1,3-benzothiazine derivatives with substituted acetyl chlorides

6, 7-Dimethoxy-2$\text{H}$-l,3-benzothiazine derivatives ($\text{1}$, $\text{8}$) react with substituted acetyl chlorides to give angularly condensed β -lactams ($\text{3a}$-$\text{d}$, $\text{10}$, $\text{11}$). The $\text{cis}$ compound $\text{11}$ was epimerised to the $\text{trans}$ derivative $\text{12}$. From the interaction of 2-phenyl-6,7-dimethoxy-4$\text{H}$-1,3-benzothiazine ($\text{7}$) and α -chloro-phenylacetyl chloride two stereoisomeric β -lactam derivatives ($\text{9a}$, $\text{b}$) were isolated, whereas in the other cases studied the reactions leading to β -lactams proved to be stereospecific. Analogous reactions of $\text{4}$-methyl-6,7-dimethoxy-2$\text{H}$-l,3-benzothiazine ($\text{5}$) furnished the enamides $\text{6a}$,$\text{c}$, $\text{d}$. Structures of the new compounds and configurations of the diastereomers were elucidated by IR and NMR spectroscopy.     

A facile synthesis of 2-(6-ethoxycarbonyl-2-cis-hexenyl)-4-hydroxy-2-cyclopentenone

The title compound $\text{1b}$, a key intermediate for PGE₂ elaboration, is readily available in nine steps from furfuryl alcohol. The crucial steps include the exclusive formation of $\text{6a}$ from $\text{5}$ and the subsequent intramolecular Aldol condensation to $\text{2b}$.     

Synthesis of (±)-1-desoxy-2-lycorinone and of a possible trans-dihydro-lycoricidine precursor

En-route from the 5-aryl-3-hydroxy-4-nitro-cyclohexanones $\text{1}$ and $\text{2}$, readily available from poly-enolates and 3.4-methylenedioxy-w-nitro-styrene, to dihydro-lycoricidine $\text{3}$ and to lycorine $\text{4}$, respectively, the title compounds $\text{9}$ and $\text{14}$ are prepared in few steps.     

19F-19F Coupling constants in the azole series. Synthesis of 3,4-, 4,5-, and 3,5-difluoropyrazoles

Stepwise syntheses of difluoroazoles $\text{1}$, $\text{2}$, and $\text{3}$ have been performed. The J_FF coupling constants are reported for the first time. Surprisingly, no coupling between F₄ and F₅ is observed.     

Etude des reactions des diazoderives avec les cycloimmonium ylures-I : Action des sels de diazonium sur quelques pyridinium - ylures

The synthesis of cycloimmonium salts of the type $\text{7}$, $\text{8}$ and the corresponding cycloimmonium ylides $\text{9}$, $\text{10}$ are reported. In the reaction with diazonium salts $\text{11}$, $\text{12}$ the pyridinium monosubstituted carbanion ylides $\text{9}$, $\text{10}$ give the pyridinium disubstituted carbanion ylides $\text{17}$ – $\text{20}$. These are new types of isolable stable ylides. The synthesis involves the formation “in situ” of ylides $\text{9}$, $\text{10}$ which are bonded by their nucleophile ylide carbon atom to the nitrogen atom in diazonium salts. The intermediat formation of cycloimmonium salts $\text{13}$ – $\text{16}$ must be accepted. The structures of all compounds presented in this paper have been established by using elementary analysis, IR and ¹H-RMN spectra.     

Formation of benzo[a]phenoxazine derivatives by triethylphosphite-induced deoxygenation of 1-(2-nitrophenoxy) and 2-(2-nitrophenoxy)naphthalenes

Reaction of 1-(2-nitrophenoxy)naphthalene or its β-isomer $\text{7}$ with triethylphosphite produces benzo[a]phenoxazines $\text{8}$ and $\text{10}$, through the intermediate $\text{6}$.