Β-carbon Atom Research Articles

The mass spectra of Phenyl-substituted 1,1-Dimethyl-silacyclopentanes and -silacyclopentadienes and of 1,1,4,4Tetramethyl2,3,5,6−Tetraphenyl-1,4-Disilacyclohexadiene

The mass spectra of 1,1-dimethyl-2,5-diphenyl-1-silacyclopentadiene, 1,1-dimethyl-2,5-diphenyl-1-silacyclopentane, 1,1-dimethyl-2,3,4,5-tetraphenyl-1-silacyclopentadiene and 1,1,4,4-tetramethyl-2,3,5,6-tetraphenyl-1,4-disila-2,5-cyclohexadiene were recorded using a 90° magnetic-sector type instrument. From the observed meta-stable peaks, most of the fragmentations giving rise to the more abundant ions have been assigned. For these compounds, up to 30% of the total intensity is carried by ions formed by some type of rearrangement. Specifically, four types of rearrangements are indicated and they involve the migration of: (1) hydrogen atoms from a phenyl group bonded to either an α- or β-carbon atom to the silicon atom of a siliconium ion; (2) a phenyl group from an α-carbon atom to a silicon atom;(3) a methyl group from one silicon atom to a second silicon atom in the 4-position; and (4) hydrogen atoms from silicon methyl groups to silicon with the simultaneous loss of CH 2 or C 2H 4.

Reactions of phosphines with acetylenes. Part XVI. Formation of β-alkoxyphosphonium ylides and vinyl ethers via methanolysis of vinylphosphonium salts

Triphenylphosphine in alcohol reacts (a) with dimethyl acetylenedicarboxylate to give a stabilised β-alkoxy-ylide, (b) with methyl phenylpropiolate to give (Z)-methyl 2-methoxycinnamate, and (c) with methyl propiolate to give a mixture of three isomeric methyl methoxyacrylates. The reactions proceed via nucleophilic attack of the phosphine on the acetylene and then of methoxide on the intermediate vinylphosphonium salt by the pathway which involves least build up of negative charge. Methoxide attacks at the β-carbon atom when the vinyl α-carbon atom which bears the phosphonium group possesses an additional stabilising group, e.g. methoxycarbonyl as in (a), or phenyl as in (b). Methoxide attacks both α- and β-positions when there are balancing α- and β-stabilising groups as in (c). The reactions (b) and (c) involve two trans-addition steps followed by a trans-elimination step.

On the rotatory strength of d-d transitions of copper(II)-bis-α-amino acid complexes

The optical activity of the (2:1) copper(II)-bis-α-(L-aliphatic) amino acid complexes in the visible and the ultraviolet regions has been examined with reference to the symmetry rule for the origin of optical activity. It is concluded that the negative ellipticities above 210 nm, reflecting contributions from the n-π * and possibly the charge-transfer bands, and the negative dichroic band in the visible region, reflections of the d-d transitions, are consistent with the δ-conformation of the complexes. The rotatory strengths of the d-d transitions, as seen in the ellipticities at the negative extrema for the series of aliphatic complexes, exhibit a linear relationship with the inductive electron-withdrawing power of the vicinal groups, the latter being represented by the Taft constant and/or the dipole moment of the side chains. The complexes of aliphatic amino acids containing branching at the α-carbon atom exhibit ellipticities which are significantly larger than those predicted by the above linear relationship, whereas those containing branching at the β-carbon atom conform to the relationship. The higher activities of the complexes with branching at the α-carbon atom hvae been ascribed to the additive conformational selectivity resulting from rotational hindrance. The optical activity of the d-d transitions in bis-α-amino acid complexes, in general, is governed by the electronic characteristics of the vicinal groups.

Electron density distribution in unsaturated ethers and esters, and their reactivity in cationic polymerization

The electron density distribution is calculated by the method of Pople-Santry-Segal for some unsaturated ethers and esters: vinylmethyl ether, propenylmethyl ether, isopropenylmethyl ether, β-fluorovinylmethyl ether, 1,2-dimethoxyethylene, vinyl formate, vinyl acetate, vinylmethylcarbonate. For comparison the electron density distribution is calculated for some saturated ethers and esters: dimethyl ether, methylacetate, dimethylcarbonate, methylcarbamate, and for some olefins: ethylene, propylene, butadiene, isobutylene. The correlation of cationic reactivity of the above monomers with the value of the total charge of the β-carbon atom of double bond and its π-component is established.

Metabolic studies of salbutamol- 3H: A new bronchodilator, in rat, rabbit, dog and man

Salbutamol- 3H, labelled on the β-carbon atom, was rapidly absorbed from the gastro-intestinal tract of rat, rabbit, dog and man. 60–90%, depending upon the species studied, of the administered radioactivity was recovered in the 24 hr urine. 70–90% of the radioactivity present in the dog urine was due to unchanged salbutamol- 3H, whereas 90% in the rabbit and 40% in the rat urine was due to salbutamol- 3H o-phenylglucuronide. The latter has been isolated and shown to be neither a β-stimulant nor a β-blocker. The rat conjugated salbutamol- 3H in the liver, and excreted the glucuronide via the bile. 0–48 hr rat faeces contained 25–40% of the label. Analysis of the tissues from the rat and dog indicated that the drug was completely cleared from the body. Salbutamol- 3H inhaled by dogs and humans as an aerosol was slowly adsorbed from the lung, and excreted via the urine.

Photoinduced reactions—XLVI : Photochemistry of hindered nitrobenzene derivatives

The photochemistry of various types of hindered nitrobenzenes, inparticular 2,6-diakyl-substituted nitrobenzenes, has been investigated. Depending on steric factors, two types of reaction were observed. One, the photochemical reduction and nitro-nitrite rearrangement depending on the solvent employed, and the other, the intramolecular oxygen transfer reaction involving α- and β-carbon atom attack of an alkyl side chain. The former type occurs with 2,6-dimenthy 2,6-dichloronitrobenzenes and the latter type with 2,6-dialkylntrobenzenes having a β-hydrogen atom alkyl substituents. It is suggested that the multiplicity of the excited state responsible for the former type of the reaction is triplet and for the latter singlet.

The isolation of ketocatechols from insect cuticle and their possible rôle in sclerotization

Several catechol-derivatives have been isolated from acid hydrolysates of insect hard cuticle, and the two major compounds were identified as a hydroxy-ketocatechol, 2-hydroxy-3′,4′-dihydroxyacetophenone, and the corresponding aldehyde, 3,4-dihydroxyphenylglyoxal. It is shown that the glyoxal is formed from the former compound during hydrolysis. The ketocatechols cannot be obtained from locust cuticle taken immediately after ecdysis when hardening has not yet taken place, whereas they can be obtained in amounts up to 3 per cent of the dry weight of the cuticle in older animals. The proteins in the endo- as well as in the exocuticle are rendered insoluble during the period where the amount of acid-released ketocatechols increases. The ketocatechols arise from some DOPA-derivative which is firmly linked to the cuticle. It is suggested that this DOPA-derivative constitutes the crosslinks formed during sclerotization of the cuticle, and that the formation of crosslinks involves oxidation of the β-carbon atom in the aliphatic side-chain of dopamine or some metabolite of dopamine. The ketocatechols were obtained from all insect hard cuticles examined whereas they were not obtained from any non-insect hard cuticle. This indicates that the sclerotization mechanism suggested here is restricted to insects.

The separation of polar and steric effects. Part XII. The influence of protic and aprotic solvents on the kinetics of the reactions of benzoic acid with diazodiphenylmethane

Rate coefficients have been determined for the reactions at 30 °C of diazodiphenylmethane with benzoic acid in 10 alcohols so that, with earlier work, results are now available for this reaction in 20 alcohols of very varied structures. The kinetic solvent effect can be interpreted in terms of the dielectric constant of the solvent and the influence of hydrogen bonding (solvent basicity or acidity). Multiple linear correlation of log k with the Kirkwood function of dielectric constant and the Taft σ* value for the alkyl group of the alcohol is highly successful (r= 0·983), but an additional parameter is necessary to express the rate enhancing effect of branching at the β-carbon atom of the alcohol. The most useful third parameter is nγH, the number of γ-hydrogen atoms in the alcohol molecule, giving r= 0·991.Apparent second-order rate coefficients have also been determined for the reactions at 37 °C of diazodiphenylmethane with benzoic acid in 22 aprotic solvents. Values determined for a range of initial concentrations of acid have been extrapolated to obtain values of k0, the rate coefficient at [acid]= 0. The effect of solvent on k0 can be interpreted in terms of the effect of the dielectric constant and the basicity of the solvent, but multiple linear correlation of log k0 with a suitable function of dielectric constant and a measure of solvent basicity (two are available) is only moderately successful (r=ca. 0·91). Attempts to improve the correlations by including the refractive index as a measure of ‘dynamic dielectric constant’ have met with little success. Detailed examination of the pattern of results suggests the relevance of other factors but at present these cannot be incorporated as additional parameters in the correlations.In both protic and aprotic solvents the specific role of the solvent is more important than its general electrostatic effect.

Organic reactions involving transition metals. Part VI. Complexes of unsaturated tertiary phosphines with palladium(II) and platinum(II), and their reactions with nucleophiles

Palladium(II) and platinum(II) complexes of the ligands CH2:CH·[CH2]n·PPh2(n= 1,2,3) have been investigated. The but-3-enylphosphine chelates to palladium or platinum, the pent-4-enylphosphine chelates only to platinum, and the allylphosphine chelates to neither metal. The but-3-enyl complexes of platinum react with methoxide or acetate ion, and the pent-4-enyl complexes react with methoxide ion, to give predominant addition of the nucleophile to the β-carbon atom, [[graphic omitted]tX]2(n= 2,3, X = Cl, R = Me; n= 2, X = CO2Me, R = Ac). Carboxylate ions (CH2Y·CO2–, Y = H, Cl, F) displace the co-ordinate double bond of the pent-4-enyl complex from the metal to give the carboxylate-bridged dimers {CH2:CH·[CH2]3PPh2Pt(O2C·CH2Y)2}2. The complexes are characterised by bridge-splitting reactions and by i.r. and n.m.r. spectroscopy.

Isolation of arterenone (2-amino-3′,4′-dihydroxyacetophenone) from hydrolysates of scleratized insect cuticle

A phenolic compound has been isolated from the sclerotized cuticle of several species of insects. The compound is identified as arterenone, 2-amino-3′,4′-dihydroxyacetophenone, an oxidized derivative of dopamine. The material in the cuticle which gives rise to this compound on hydrolysis appears to be firmly bound to the cuticular proteins. It cannot be removed by extracting the cuticle or by mild acid hydrolysis, whereas digestion by proteolytic enzymes can bring it into solution. The peptide mixture obtained by enzymatic digestion does not give the characteristic ketocatechol spectrum. This spectrum appears first after hydrolysis with strong acid. It is suggested (1) that the compound originates from a derivative of N-acetyldopamine, the sclerotizing agent in many insects, (2) that in the cuticle the compound is bound to proteins by means of a linkage going to the β-carbon atom in the side chain in the compound, and (3) that this linkage gives rise to the keto group of the isolated arterenone on acid hydrolysis.

Structure and Reactivity of α,β-Unsaturated Ethers. X. The Acid-Catalyzed Hydrolysis of Ring-Substituted Styryl Ethyl Ethers

Abstract The acid-catalyzed hydrolysis of cis- and trans-styvyl ethyl ethers (SEE) and several of their ring-substituted derivatives has been kinetically investigated in 80% aqueous dioxane. It has been found that these ethers are less reactive than vinyl ethyl ether by a factor of ca. 500 and that all the cis isomers studied are about twice as reactive as the corresponding trans isomers. The hydrolysis of the substituted ethers at 35°C has proved to obey the Hammett relation with the reaction constants ρ=−1.07 and −0.70 for the cis and the trans isomers, respectively. All these results appear to be interpretable at least qualitatively in terms of the reaction scheme involving the rate-determining protonation to the β-carbon atom.

Folate Metabolism in the X-Irradiated Rat

Tissues from x-irradiated rats have been analysed for changes in folate activity. Blood and liver total folate levels were unaffected. Total folate levels were lowered in the spleen, and the decrease in the conjugated folate levels of the bone marrow from irradiated rats was quite significant. An observed rise in "free" bone marrow conjugase levels in the irradiated animals could be correlated with accumulation of unconjugated tetrahydrofolates in the tissue at the expense of the metabolically more active conjugated derivatives involved in nucleic acid biosynthesis. There was a decrease in the folate-dependent incorporation of the β-carbon atom of serine into bone marrow nucleic acid fractions from irradiated rats. The hydrolytic bone marrow folyl conjugase activity had an acidic pH optimum and in comparative studies was shown to exhibit a structure-linked latency similar to acid phosphatase, a known lysosomal marker enzyme.

Lipolytic activity of structurally related agonists in rat epididymal fat tissue in vitro

Utilizing the rat epididymal fat pad, the rates of free-fatty acid (FFA) release were quantitated in the presence of various concentrations of agonists. The calculation of intrinsic activity and affinity constants from standard dose-response relationships and double reciprocal plots were employed to establish the structure-activity relationships. Marked changes in the affinity, and to a lesser degree, in the intrinsic activity constants of phenethylamines for the adrenergic-adipose tissue receptor system were produced by alterations of the (a) side chain nitrogen, (b) α- and β-carbon substituents and (c) meta- and para-ring positions of the phenyl nucleus. While optimal activity was possessed by all catecholamines, results with certain noncatecholamines indicated that the catechol moiety was not obligatory for FFA mobilization. The presence of a phenolic group in either ring position was sufficient to produce a maximal response when the β-carbon atom was also hydroxylated. In addition to β-hydroxylation, N-substitution of a bulky alkyl or aralkyl group greatly enhanced the lipolytic activity of the phenethylamine molecule. Optimal activity was obtained with either primary or secondary amines, whereas tertiary amines were characterized as having a decreased affinity. Furthermore, the presence of a β-keto or α-ethyl substituent on the ethylamino-side chain decreased the ability of the agonist to release FFA from adipose tissue in vitro.

Acylation. Part XXXII. A comparison of the charge distributions in keten and in dimethylketen and a determination of the relative reactivity of these compounds towards m-chloroaniline

The rate equation for the acylation in ether of m-chloroaniline by keten takes the same form as that found for dimethylketen, viz, Rate =(k1[ArNH2]+ k2[ArNH2]2)[R2CCO]. For keten the values of k1 and k2 are ca. 6 and ca. 9-fold greater respectively than for dimethylketen. Calculations by use of the Huckel method suggest that the main effect on the charge density along the C–C–O skeleton of substitution of Me for H is to reduce the negative charge on the β-carbon atom. It is argued that these results provide further support for the mechanisms of acylation by ketens which we have previously suggested. Our experiments render untenable Svetkin's generalisations about keten aminolyses.

The base-catalyzed isomerization of α-cyano-cis-stilbenes

The rates of the base-catalyzed isomerization of α-cyano-cis-stilbenes were measured in methanolic and ethanolic dimethyl sulphoxide (DMSO) containing the appropriate 0·01 M-alkoxide as base; the logarithms of the first-order rate constants were found to correlate with the HR- acidity function. The slopes range from 0·426 to 0·665 depending on the substituent present in the α-phenyl ring and the solvent system and were shown to be related to the structure of the transition state.The effect of substituents on the rate of isomerization has been examined. Substituents in the α-phenyl ring produce effects on the rates which correlate with σ-values and yield ρ-values of +3·07 in DMSO–ethanol and +2·82 in DMSO–methanol.The activation parameters for the isomerization reaction of three substituted α-cyano-cis-stilbenes were determined in DMSO–methanol solutions. The enthalpies of activation were in the range 14·3–16·7 kcal. mole–1 and the entropies of activation ranged from –9·3 to –13·7 e.u.The mechanism of isomerization is believed to involve rate-controlling attack of alkoxide ion on the β-carbon atom of the cis-stilbene to form a carbanion in which free rotation can occur. Elimination of alkoxide ion gives the trans isomer.

Charge distribution in and dipole moments of some aliphatic alcohols

Using the treatment of Smith, et al.,1 charge distributions in several aliphatic alcohols and consequently their dipole moments have been evaluated. The dipole moments of trichloroethanol (2.04 D) and 1,3-dichloropropan-2-ol (2.11 D) have been measured in benzene solution at 35°. The results of evaluation and measurements are interpreted in terms of the occurrence of intramolecular interaction between the hydroxyl hydrogen and an acceptor atom X (halogen or oxygen) at the β-carbon atom.

One-carbon metabolism in the developing ovary of the housefly Musca domestica

Adult female houseflies incorporate one-carbon units from radioactive formate, glycine, and serine into the purines of ovarian RNA. When RNA was extracted from the ovaries and hydrolysed, the purine bases were labelled in a manner suggesting that radioactive substrates were incorporated into RNA by recognized biosynthetic pathways involving a one-carbon pool. The incorporation reached a maximum value in 12-hr-old flies with formate as substrate and in 48-hr-old flies with glycine and serine as substrates. The metabolism of (2- 14C) glycine and (3- 14C) serine has been compared with that of ( 14C) formate. Formate enters the purines to the greatest extent followed by the α-carbon atom of glycine and the β-carbon atom of serine. The concept of active formate has been established in the developing ovary of the housefly.

Conformation and configuration of some α,β-unsaturated carbonyl compounds from their nuclear magnetic resonance spectra

Nuclear magnetic resonance spectra were recorded for 95 styrenes with two functional groups (A and B) on the β-carbon atom where A, B are COCH3, COCH3; COCH3, CO2C2H5; CO2C2H5, COCH3; CO2C2H5, CO2C2H5; CO2C2H5, CN; and CO2C2H5, H. The chemical shifts of the ethylenic hydrogen and the hydrogens of the functional A and B groups were examined in detail to determine the effects of ring substituents. The configuration of the unsymmetrical styrenes and the conformation of the A and B groups as deduced from the spectra are discussed.

Studies on the biosynthesis of phenols in fungi. Production of 4-methoxytoluquinol, epoxysuccinic acid and a diacetylenic alcohol by surface cultures of Letinus degener I.M.I. 110 525.

1. 4-Methoxytoluquinol was secreted into the medium by surface cultures of the basidiomycete Lentinus degener Kalchbr. (approx. 100mg./l. of medium). In addition, epoxysuccinic acid (150-200mg.) and a long-chain diacetylenic alcohol (3mg.) were also secreted. Epoxysuccinic acid has previously been found in the culture medium of some Fungi Imperfecti. These metabolites were all synthesized during the early phase of growth but maximum production occurred some time later. 2. Supplementation of the medium with cycloheximide or 8-azaguanine inhibited the production of epoxysuccinic acid. 3. Sodium [1-(14)C]acetate and 6-methyl[(14)C]salicylic acid were not incorporated into 4-methoxytoluquinol, but [U-(14)C]tyrosine and [Me-(14)C]methionine were incorporated to the extent of 0.55 and 4.75% respectively (minimum values). Degradation studies established that the aromatic ring and C-methyl group were derived from the ring and beta-carbon atom of tyrosine; the O-methyl group alone was formed from methionine.

A Destructive Ethylation Reaction of Benzene with 3-Methylpentane-1-14C

Abstract The destructive alkylation reaction of benzene with 3-methylpentane to give ethylbenzene in the presence of aluminum chloride was investigated. When 3-methylpentane-1-14C was employed, radioactive ethylbenzene was obtained. A radioassay of radioactive ethylbenzene showed that: a) the specific radioactivity of the ethylbenzene was about one-third that of the starting 3-methylpentane-1-14C, and b) more than 90% of the radioactivity of the ethylbenzene was present on the β-carbon atom of the ethyl group. These findings suggested a preceding equilibrium between 3-methylpentane and 2-methylpentane, which resulted in an equivalent localization of the radioactive label on three methyl groups of these C6-hydrocarbons. A carbonium-ion mechanism including an intermediate ethyl cation was discussed in detail.