Cyclopentanone Ring Research Articles

ChemInform Abstract: SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF 6‐ARYL‐2‐AZABICYCLO(4.2.1)NONANES

A series of 6-phenyl-, 6-(m-methoxyphenyl)-, and 6-(m-hydroxyphenyl)-2-azabicyclo[4.2.1]nonanes was synthesized by a sequence involving alkylation of an appropriate 2-arylcyclopentanone with an aminoalkyl substituent. Subsequent ring closure at the other alpha position on the cyclopentanone ring and Wolff-Kishner reduction afforded the title compound. Several derivatives of these materials showed activity in an antinociceptive assay comparable to codeine. Most analogues were either inactive or toxic.

Synthesis and pharmacological activity of 6-aryl-2-azabicyclo[4.2.1]nonanes.

A series of 6-phenyl-, 6-(m-methoxyphenyl)-, and 6-(m-hydroxyphenyl)-2-azabicyclo[4.2.1]nonanes was synthesized by a sequence involving alkylation of an appropriate 2-arylcyclopentanone with an aminoalkyl substituent. Subsequent ring closure at the other alpha position on the cyclopentanone ring and Wolff-Kishner reduction afforded the title compound. Several derivatives of these materials showed activity in an antinociceptive assay comparable to codeine. Most analogues were either inactive or toxic.

3‐Hydroxy‐4‐nitro‐cyclohexanone aus Ketonen und 4‐Nitrobuttersäurechlorid. Eine ringerweiternde Fünfringanellierung

3‐Hydroxy‐4‐nitro‐cyclohexanones from Ketones and 4‐Nitrobutanoyl Chloride. A Ring Enlarging Five‐Ring AnnulationThe 6‐nitro‐1, 3‐diketones 5, 8, 9, 10, and 11, prepared by a 1:1 acylation at the C‐atom of non‐hindered lithium enolates with 4‐nitrobutanoyl chloride according to equation 3, are cyclized with sodium hydrogen carbonate in aqueous tetrahydrofuran to give the hydroxy‐nitro‐ketones 13–17. Such cyclic nitroaldols are not formed from the cyclopentanone, ‐heptanone, and ‐octanone, nor from the aryl derivatives 4, 6, 7 and 12, respectively. Except for the vicinally trisubstituted compound 14, the cyclization products are isolated in diastereomerically pure form. A crystal structure X‐ray analysis reveals the trans‐decalone and the cisβ‐nitroalcohol configurations of the product 13 from cyclohexanone (see Fig. 1–3). Acetalization to 21–25 and catalytic hydrogenation of the nitro groups furnishes the amino alcohols 27–31 (Table 4) which are substrates for the Tiffeneau‐Demjanow rearrangement (see Schemes 2, 3, 4 and 5), From the stereoelectronic control of this sextett rearrangement we deduce the configurations of the 1, 4‐diketones 35, 36, 39, 40, 43, 44, 46, and 47 formed under kinetic or thermodynamic conditions. The six‐ring annulation with nitrobutanoic acid and the subsequent rearrangement are shown in Scheme 6; the sequence of reactions described here allows to carry out a ring enlargement of a cyclic ketone by one C‐atom, with simultaneous annulation of a cyclopentanone ring.

Chiroptical studies. Part 96. Short wavelength (190 nm) circular dichroism of ketones

C.d. data in the region of 190 nm are analysed for 152 chiral ketones, by the empirical methods used recently in re-evaluating c.d. data for the n→π* transition (ca. 290 nm). The 190-nm c.d. band for compounds of either trans- or cis-decalone type is generally dominated by octant-consignate contributions of any axial alkyl substituents at the ring junction positions ‘α’ or ‘β’ to the carbonyl function. Group increments (δδIµ) derived from this analysis allow the ‘prediction’ of values of ΔIµ, although less accurately than for the n→π* band. Compounds which include a cyclopentanone ring exhibit c.d. behaviour with signs which depend both upon the contributions of any ‘α’- or ‘β’-axial methyl substituents and on the conformation of the cyclopentanone ring itself. The structural information which can be obtained from the ‘190 nm’ c.d. band differs markedly in some respects from that provided by the well known n→π* c.d. band. Some applications are suggested.

ChemInform Abstract: STUDIES OF THE REACTION OF VARIOUS 1,2‐DISUBSTITUTED BENZENES WITH CROTONIC ACID IN POLYPHOSPHORIC ACID

AbstractDie Reaktion mit den 1,2‐disubstituierten Benzolen o‐Kresol, Guajacol, 1,3‐Benzodioxol, 1,4‐Benzodioxan und Dihydrobenzofuran mit Crotonsäure in Polyphosphorsäure führt zu den 5,6‐disubstituierten Indanonen (Ia) (R1: Me, OMe), (II) oder (III).

Studies of the Reaction of Various 1,2-Disubstituted Benzenes with Crotonic Acid in Polyphosphoric Acid

The reaction of several 1,2-disubstituted benzenes with crotonic acid in polyphosphoric acid has provided a number of previously undescribed 5,6-disubstituted indan-1-ones. Guaiacol, o-cresol, 1,3-benzodioxole, 1,4-benzodioxan and dihydrobenzofuran yielded indanones (4-8) in which acylation of the benzene ring occurred exclusively para to the free hydroxyl groups of the first two substrates and para to the ether oxygen in the last. Catechol, salicylaldehyde, o-hydroxy acetophenone and o-chloro phenol yielded no indanones and formed crotonate esters. A further four indanones (9-12) were derived from demethylation and acetylation procedures. Annelation of the methyl cyclopentanone ring occurred acrose the furan ring in benzofuran to provide the new heterocycle 1-methyl benzofurocyclopentan-3-one in moderate yield. The assigned carbon-13 NMR spectral shifts for all indanones are set out in Table II.

Sesquiterpenoids. Part XXIV. X-Ray crystallographic analysis of paucin monohydrate, a pseudoguaianolide glucoside

Paucin (1c), a pseudoguaianolide glucoside, has been studied by X-ray diffraction and the glucose ring shown to be acetylated at position 6′-O. The sesquiterpenoid cycloheptane ring adopts a twist-boat conformation, while the cyclopentanone and α-methylene γ-lactone rings have half-chair and envelope conformations, respectively. The CC–CO and Cα–Cβ–Cγ–O torsion angles of the α-methylene γ-lactone are –10 and –17°. Crystals of paucin monohydrate are monoclinic, space group P21, with a= 18.308(4), b= 6.724(2), c= 9.987(4)A, β= 93.38(4)°, and Z= 2. The crystal structure was elucidated by direct-phasing methods and the atomic parameters were subsequently adjusted by least-squares calculations which converged at R 7.9% over 1 929 diffractometer reflections.

Chiroptical studies. Part LXXXIX. An empirical analysis of the circular dichroism of hexahydroindanones, bicyclo[4.2.0]octan-7-ones, and their polycyclic analogues

An empirical analysis of c.d. data for five-membered ring ketones of the hexahydroindanone type, including androstan-15-ones, -16-ones, and -17-ones and similar compounds, has established the main features of the relationships between Cotton effects and structural and conformational types in this series. The analysis has been extended to a few compounds of steroid-like structure which include a cyclobutanone ring (bicyclo[4.2.0]octan-7-ones). Five stereochemical types of hexahydroindanone are recognised, three for hexahydroindan-1-ones and two for hexahydroindan-2-ones.In the first stage of the analysis, estimates of c.d. contributions (δΔIµ) are obtained from experimental data for the following units: (a) the bicyclic systems, (b) angular methyl groups, and (c)‘third rings’. Estimates of the contribution of the ‘second’(cyclohexane) ring to the total value of ΔIµ for each of the bicyclic systems are then obtained by regarding the effects of individual bonds of the ‘second’ ring as equivalent to those of C–Me bonds at ‘α’ or ‘β’ positions of the cyclopentanone ring. The δΔIµ values obtained in this way for ‘second’ rings are used to derive δΔIµ values for the chiral cyclopentanone rings themselves. The values confirm earlier suggestions that the sign and magnitude of the Cotton effect is controlled largely by the chirality of the cyclopentanone ring itself, although other major contributions may come from any ‘α’-quasi-axial substituents present at the ring junction. Effects of alkyl substituents elsewhere on the cyclopentanone ring are discussed briefly.

Chiroptical studies. Part 90. The circular dichroism of cyclopentanones and related compounds. A proposed octant-dissignate effect of C–H bonds

An analysis of c.d. data (n→π*) for chiral cyclopentanone rings suggests that the Cα–H bonds make the dominant contributions, in the octant-dissignate (‘anti-octant’) sense. The magnitude of a Cα–H contribution is considered to be given approximately by the empirical expression δΔIµ= 6.2 sin2ω, where ω is the torsion angle between the Cα–H and CO bonds. On this basis, all common α-substituents probably contribute in the octant-dissignate sense to the c.d. of a ketone, most appearing to have an octant-consignate effect only because they replace a more dissignate α-hydrogen atom. This new method for calculation of chiroptical effects has been applied to some compounds thought to contain twisted cyclohexanone rings, and to some monocyclic cyclopentanone derivatives.

The structure and stereochemistry of the solution photodimer of 3-phenyl-2-cyclopentenone by X-ray diffraction

Light-induced dimerization of 3-phenyl-2-cyclopentenone in a variety of solvents affords the head-tohead cis-anti-cis stereoisomer, C22H2002. The cyclobutane ring is bent with a dihedral angle of 152.4 °. The cyclopentanone rings have an envelope-like conformation. Crystals are monoclinic, space group C2/c, with four molecules per unit cell of dimensions a= 17.018 (3), b= 10.840 (2), c=9.097 (2) A~, and fl=99-12 (1) °. 1406 independent reflections were collected on an automated diffractometer with Nb-filtered Mo Ke radiation. The structure was solved by the symbolic addition procedure and refined by full-matrix least-squares calculation to R= 0-046. Photodimerization in the solid state of 3-phenyl2-cyclopentenone yields a different dimer whose structure is predicted to have the head-to-tail cisanti-cis arrangement.

LOW‐TEMPERATURE PHOTCOXIDATION OF CHLOROPHYLL‐A*

Abstract— Illumination of chlorophyll at low temperature, in solvents containing organic Lewis bases and oxygen, leads to oxidation of the C‐2 vinyl group. This oxidation proceeds through a series of thermal and photochemical changes, including initial formation of a new compound (I) absorbing at 620 nm. This undergoes further rapid photochemical (or thermal) conversion back to a chlorin‐like substance (II), and much slower phototransformation to a third intermediate (III) absorbing near 500 nm. The reaction requires complexed metal (Mg or Zn), but not an intact cyclopentanone ring. The ‘620’ photoproduct is assigned to a cyclic peroxide involving C‐1 of chlorophyll and the vinyl group.

Crystal and molecular structure of 3,3′-spirobi(bicyclo[3,1,0]hexane)-2,2′-dione

Crystals of the title compound are orthorhombic with a= 25·899(4), b= 11·877(2), c= 5·885(5)Å space group Fdd2, with Z= 8 and molecular symmetry C2-2. Intensity measurements by visual estimation from Weissenberg photographs were of limited accuracy because of inherent crystal distortion and consequently very accurate molecular dimensions could not be obtained. However the results of a three-dimensional structure analysis (R ca. 16% for 326 reflections) show unequivocally that the molecules in the crystal have the same configuration as that proposed for molecules in solution on the basis of n.m.r. measurements (S. Bien and D. Ovadia, J. Org. Chem., 1970, 35, 1028). The cyclopentanone rings are in the envelope conformation. The molecules in the crystal are in stacks extending along the c axis, the stacks being pseudo-hexagonally arranged.

Circular dichroism and optical rotatory dispersion of some hexahydroindanone derivatives; methyl- and methylene-substituted steroid ketones

Circular dichroism and optical rotatory dispersion curves of a number of steroid hexahydroindanones have been measured. The compounds were A-nor-5α-androstan-2-ones and 5α-androstan-16-ones carrying methyl groups in positions adjacent to carbonyl. The curves are discussed in relation to the probable conformations of the cyclopentanone ring. Some data on related αβ-unsaturated ketones are also included.

Optical rotatory dispersion and circular dichroism of prostaglandins

AbstractOptical rotatory dispersion and circular dichroism data are given for eight prostaglandins. An interpretation of the data is given in terms of the conformation of the cyclopentanone ring.

Fungal metabolites. Part VIII. Sesquiterpenoids. Part VII. The structure of fomannosin: X-ray analysis of dihydrofomannosin p-bromobenzoylurethane

X-Ray crystal-structure analysis of dihydrofomannosin p-bromobenzoylurethane has led to the elucidation of the structure of fomannosin, a biologically active sesquiterpenoid metabolite of the fungus Fomes annosus. The p-bromobenzoylurethane derivative crystallizes in the monoclinic system, space group P21, with two molecules of C23H24BrNO6 in a unit cell of dimensions a= 11·57, b= 6·05, c= 15·78 Å, β= 95° 35′. The atomic co-ordinates were determined by Fourier and least-squares calculations, the final value of R being 11·2%. The molecule contains a puckered cyclobutane ring with dihedral angle 22°, and a cyclopentanone ring in an envelope conformation.

CHASMANINE AND ITS STRUCTURE

The alkaloid chasmanine, C25H41O6N, isolated from A. chasmanthum contains four methoxyl and two hydroxyl groups as well as an imino-ethyl. It undergoes the usual pyrolytic reaction and the unsaturated product, pyrochasmanine, C25H39O5N, gives rise to an acid-catalyzed allylic rearrangement product, isopyrochasmanine. Pyrochasmanine, on treatment with lithium aluminium hydride, is demethoxylated. It can be concluded that the base, like bikhaconine, contains the sequence [Formula: see text]. Chasmanine can be oxidized to a compound containing a cyclopentanone ring so that its second hydroxyl must be secondary and located on a five-membered ring. It is possible to benzoylate the secondary hydroxyl and acetylate the tertiary hydroxyl. The n.m.r. characteristics of the resulting double ester determine the location of these two groups and their stereochemistry. The relative position of two of the remaining methoxyl groups is established via a demethylation reaction resulting in the formation of a cyclic ether. All the chemical reactions studied are in agreement with structure IV (R = R′ = H) for chasmanine. There is, however, no positive proof for the location of the fourth methoxyl and it has been placed in ring A by analogy. An attempted correlation with bikhaconine is described.

Substituted Urea Herbicides: Their Electrophoretic Behavior and the Influence of Clay Colloid in Nutrient Solution on Their Phytotoxicity

reported to result in greatest activity followed by meta. An ortho substitution reduced activity to half or less than that of the comparable para substitution. Wessels and Van Der Veen (16) reported that photosynthesis in monuron-sprayed plants was immediately inhibited and suggested that the herbicide is adsorbed to an active site which is essential for photosynthesis. They also studied the effects of a number of substituted ureas on the Hill reaction and the results were compared to those obtained with phenylurethane. They concluded that replacement of the ethoxy group in phenylurethane by the dimethylamino group and the introduction of a chlorine atom, or a nitro or trifluromethyl group into the aromatic nucleus resulted in an enhanced inhibitory action on the Hill reaction. In contrast to Freed's (6) report, substitution of a chlorine atom or a hydroxyl group in the meta position was reported to be more effective than a para substitution. The compounds studied were assumed to be adsorbed to the active cyclopentanone ring of chlorophyll by way of hydrogen bonding. The toxicity of nitrophenylureas to Black Valentine beans (Phaseolus vulgaris) was reported by Anderson et al. (1) to be altered by changing the N-alkyl substitution. The dimethyl derivative was most phytotoxic. Lengthening the chain from one to two carbons or removing the alkyl groups reduced the activity. Moreland and Davis (12) studied the response of an amylase enzyme to five substituted ureas. Maximum inhibition of enzymatic activity was correlated with low water solubility. The authors suggested the possibility that several herbicide molecules, grouped together to form particles of colloidal dimensions, are adsorbed on the enzyme in such a way that its structural configuration is altered and its activity consequently hindered. Sheets and Crafts (14) studied the toxicity of four substituted ureas to oats (Avena sativa) grown in soil or in nutrient solution. They concluded that a shift in the electron balance, caused by the electrophilic chlorine atom, has a profound effect on adsorption of the herbicide on soil colloids. N-alkyl substitutions were considered to

A PROPOSED STRUCTURE FOR CHLOROPHYLL d

Treatment of chlorophyll a or methyl chlorophyllide a with potassium permanganate effected oxidation of the 2-vinyl group without concomitant oxidation of the cyclopentanone ring. One of the products obtained was of especial interest because its visible absorption spectrum was identical with that of a previously known, but chemically uncharacterized, pigment—chlorophyll d. The preparation and identification of this oxidation product as 2-desvinyl-2-formyl-chlorophyll-a is given and its probable identity with chlorophyll d is discussed in detail.

Polymers and group interaction. V. Reaction of diazomethane on polymethacroyl chloride

AbstractIn order to follow the course of the Arndt‐Eistert reaction on a polymeric system, polymethacryol chloride has been reacted with diazomethane in dioxane solution using different molar ratios of diazomethane/acid chloride at different temperatures. The structure of the reaction products has been determined by chemical methods and by infrared spectrometry. The contents of acid chloride and diazoketone units have been evaluated from chlorine and nitrogen analyses, respectively; conductometric and potentiometric titrations allow determination of the percentages of ketene and pseudo‐acid groups. From these data it is concluded that the first reaction products of diazomethane on an acid chloride unit are diazoketone groups, as expected; however, the interaction of these primary groups with the neighboring acid chloride units yields principally β‐ketocycloketene functions. The presence of these groups and their content have been confirmed by a decarboxylation reaction effected by hydrolysis in acidic medium, during which carbon dioxide is evolved, while the acid content decreases and cyclic ketones are formed. Their presence has also been confirmed by oxidation with dilute nitric acid, which transforms the polymer into polymethacrylic acid. These results of decarboxylation and of oxidation are unreconcilable with the formation of the higher homolog of polymethacrylic acid, the polyisopropenylacetic acid, which would be the normal chainlengthening reaction product of the Arndt‐Eistert reaction. Infrared spectrometry shows, in the triple bond region, absorption bands at 4.65 and 4.73 μ, and, in the double bond region, bands at 5.55, 5.70, 5.80, and 6.10 μ. By comparison with the data in the literature, and especially with the spectrum of the glutaric bisdiazoketone, these different bands have been assigned and their relative intensities interpreted. The spectrometric results confirm the presence of diazoketone and β‐ketoketene groups; moreover, they show relatively low amounts of cyclopentanone rings and of ester functions.