NN-Dimethyl tertiary amines undergo oxidative dealkylation on anodic oxidation in aqueous alkaline solution at glassy-carbon electrode, and the major products are secondary amines and the appropriate aldehydes. On prolonged electrolysis the secondary amines produced undergo partial oxidative dealkylation to give primary amines and the appropriate aldehydes. The relative amount of dealkylation in unsymmetrical amines is predominantly governed by the acidity and the number of α-protons, but is also affected by the ease of oxidation of the radical R12NCHR2. Decarboxylation of the cation radical Me2N + CH2CO2– is involved in the anodic oxidation of NN-dimethylglycine.
A comparison is made of the effects of substituents on the proton and carbon basicities of thiophenoxide ions. The carbon basicities were determined by measurements of the equilibrium constants for formation of 1 : 1 covalently bound addition complexes of the thiophenoxides with 1,3,5-trinitrobenzene. They show a somewhat greater susceptibility to change in substituent than do the proton basicities although the general behaviour pattern is similar. The correlation of the substituent effects by σ° values is discussed.
The rates of quaternization of a number of substituted NN-dimethylcyclohexylamines with methyl iodide in methanol have been measured at 30 and 40°C, and the conformations of these compounds are analysed from the kinetic data. The conformational free-energy difference for the dimethylamino-group is found to be –2·3 kcal mol–1 at 30°C and that for the phenyl group –3·0 kcal mol–1. The kinetic data indicate that trans-3,3,5-trimethyl- and 3,3,5,5-tetramethyl-NN-dimethylcyclohexylamine exist in the non-chair conformation.
The structures of two isomers of 1,3-diphenyl-2-(phenylazo)propene have been determined by X-ray crystallography. The trans-isomer (I) has Z= 4, a= 27·50, b= 5·62, c= 11·16 Å, β= 90° 30′, space group P21/a. The cis-isomer (II) has Z= 2, a= 12·33, b= 8·03, c= 8·45 Å, β= 92° 6′, space group P21. The structures were refined to R 0·122 [(I), 2036 reflections] and 0·113 [(II), 1732 reflections]. Slight difference in molecular conformation and crystal packing are discussed.
The crystal and molecular structure of the p-iodobenzenesulphonate of fusicoccin A (C42H59IO14S) has been determined by three-dimensional X-ray analysis. The crystals are orthorhombic, space group P212121, with Z= 4 in a unit cell of dimensions: a= 10·32, b= 12·89, c= 35·14 Å. The structure was solved by the heavy-atom technique and refined to a final R of 0·116, using 1706 observed reflections.Fusicoccin A, a phytotoxic metabolite of Fusicoccum amygdali, is a glycoside in which the sugar is D-glucose acetylated at C-3′ and etherified by 1,1-dimethylallyl alcohol at C-6′, and the aglycone is a tricyclic system formed by the fusion of one eight and two five membered rings. The absolute configuration is also given.
Specific alkyl radicals for e.s.r. studies can be prepared conveniently in the cavity of an e.s.r. spectrometer by photolysis of a mixture of the appropriate alkyl bromide (or chloride) with triethylsilane and t-butyl peroxide. The triethylsilyl radical, produced as an intermediate, will abstract chlorine or bromine from alkyl halides, but abstraction of fluorine has not been observed. Although ketones and esters react with triethylsilyl radicals by addition to the oxygen atom of the carbonyl group, halogeno-ketones and halogeno-esters react preferentially by abstraction of the halogen atom. Bromobenzene, 1-bromohex-1-yne, and cyclopropyl bromide do not give e.s.r. spectra corresponding to the organic radicals: it appears that these reactive radicals react further with triethylsilane to give the observed Et2SiHĊHCH3 radical, but the cyclopropyl radical could be detected when trimethylsilane was used instead of triethylsilane in the reaction mixture. Competition experiments show that ease of removal of halogen atoms increases in the order primary alkyl < secondary < tertiary < acetonyl ≈·CH2·CO2Et < allyl ≈ propargyl ≈ benzyl < cyanomethyl.
The autoxidation of ketones and esters in aprotic solvents containing strong bases such as alkoxides was investigated extensively. Attention was paid to the autoxidation of other weakly acidic substrates such as nitriles, Schiff bases, and phenylhydrazones. The primary products are the α-hydroperoxides, which can be isolated in high yields when the oxidation is carried out at low temperatures, thus preventing their decomposition.The first step of the reaction is ionization of the substrate to yield a resonance-stabilized anion, which subsequently reacts with oxygen.A kinetic study showed that in some cases the oxidation is of the first order in anion and in oxygen, whereas in other cases (e.g., aliphatic esters) the ionization is the rate-determining step. Both oxidation and ionization show low activation energies (<10 kcal mol–1) in aprotic systems. Arguments are advanced for a non-radical mechanism involving interaction of anion and O2 to yield the hydroperoxide anion in one step. By considering the energies of the different steps involved it is shown that the autoxidation is favoured by the substrate being a weak acid as well as having a low C–H bond strength.
Michaelis–Menten parameters have been measured for a series of alkyl-, aryl-, and arylamido-phosphates as substrates of alkaline phosphatase. Kinetic parameters for p-bromophenylamido-phosphate were measured over a pH-range and the results, including inhibition by inorganic phosphate indicated the amides to be normal substrates of the enzyme. Little variation in the parameter k0 was observed for all substrates; the parameter k0/Km which is a measure of the rate constant for phosphorylation of the free enzyme by free substrate showed a high selectivity to steric factor in the alkyl phosphate series. The amido-phosphates were more than ten-fold less reactive than the aryl phosphates in the k0/Km parameter and were calculated to be 60,000-fold too small for the SN1 (P) mechanism. Both these results together with arguments taken from the literature point to an SN2(P) mechanism for phosphorylation involving direct nucleophilic attack at phosphorus. The substituted arylamido-phosphates show a decreasing reactivity with electron-withdrawing substituent indicating acid catalysis. The zinc(II) necessary for phosphatase action is suggested to promote an SN2(P) mechanism at phosphorus by complexing with the substrate and neutralising the negative charge on the oxygen thus activating the phosphorus to nucleophilic attack.
The interactions between potassium methoxide and compounds of the type 2,6-dinitro-4-substituted anilinopropionamides (I) have been studied kinetically over a range of temperatures in methanol. The formation of a Meisenheimer complex is shown to occur with σ-bond formation at the 1-position of the aniline and the reasons for the observation of this path rather than anilino N–H ionization or 3-σ complex formation are discussed.
The rate law for the title process in water at pH > 11 has the form v=k[CH][OH–][OX–] where CH represents a weak carbon acid and X a halogen. The rate constants for hypobromite and hypochlorite ions at 25·3°C are 19·4 and 0·061 l2 mol–2 s–1, respectively. The concept of an equipartition concentration, [OX–]ec, for equal second- and third-order rates is developed and used to clarify problems and discrepancies in the literature.
The mass spectral fragmentation of 1-methyl-4-phosphorinanone was found to follow two major pathways, each involving intial cleavage of a C–P bond. In addition, fragments were detected which resulted from transfer of oxygen to phosphorus. The pattern was quite different from that of N-methyl-4-piperidone, the spectrum of which resembled that of N-methylpiperidine, with initial cleavage occurring at the 2,3-bond.
In aqueous dioxan or acetone, N-aryl-hydrazidic bromides (α-bromoarylidenehydrazines) are converted into the corresponding benzhydrazides. The kinetics of the conversion have been studied in dioxan–water (4 : 1) at 25° and a Hammett ρ value of –0·63 was obtained for variation of the N-aryl substituent. The observation of a primary salt effect, a large common-ion effect, and an m value of 0·89 for solvent variation support a mechanism involving rate-determining ionization (azocarbonium ion formation). The solvolysis of an NN-disubstituted hydrazidic bromide (which unlike the mono-substituted analogues cannot form a 1,3-dipolar ion) was studied in buffered solution; its reactivity paralleled that of the mono-substituted compounds. Steric inhibition of azocarbonium ion formation is marked since cyclic hydrazidic bromides (e.g. 3-bromo-2-pyrazoline) failed to react in aqueous solvents even under forcing conditions.
The crystal structures of the dihydrobromide and dihydroiodide of the novel Buxus alkaloid buxenine-G, C25H42N2, have been determined, and the results establish that ring A of the steroidal alkaloid adopts the chair conformation of a cyclohexane and ring C the half-chair conformation characteristic of a cyclohexene. The dihydroiodide crystallizes in the orthorhombic space group P212121 with a= 13·32 ± 0·02, b= 30·65 ± 0·03, c= 6·96 ± 0·01 Å, and Z= 4, and the dihydrobromide crystallizes in the monoclinic space group P21, with a= 11·012 ± 0·005, b= 7·556 ± 0·004, c= 32·816 ± 0·013 Å, β= 89·8 ± 0·1°, and Z= 4.
An examination of solvent effects on the fluorescence characteristics of a series of 2-(2-quinolyl)thiophen derivatives has shown that these compounds normally fluoresce from an excited state which is mainly π–π* in character. Under acid conditions, the fluorescence quantum yield of 5-(2-quinolyl)-2,2′-bithienyl is anomalously decreased; this effect has been ascribed to a large decrease in the energy difference between the triplet n–π* and singlet π–π* levels resulting in an increased degree of intersystem crossing. The other 2-(2-quinolyl)thiophen derivatives show enhanced fluorescence in acid solution owing to elimination of n–π* character from the excited singlet state or, in the case of two formyl derivatives, possibly because of an inversion of excited energy levels to allow fluorescence from a singlet charge-transfer level.
The phenylation of [ββ-2H2]styrenes with benzene was carried out in the presence of palladium(II) acetate and acetic acid. From the deuterium analyses of the trans-stilbenes formed, it was confirmed that no hydride shift takes place in the reaction.
2-Fluorotropone reacts with piperidine in benzene to give 2-piperidinotropone quantitatively. Experiments with 2-fluoro[3,5,7-2H3]tropone show normal substitution of fluorine by the nitrogen atom of piperidine. A kinetic investigation shows (i) that this reaction is of overall second-order (first-order with respect to both reagents) and (ii) that the free energy of activation is 4–5 kcal mol–1 lower than the corresponding values found for 2-chloro-, 2-bromo-, 2-iodo-, and 2-methoxy-tropone. Clearly, the reaction does not follow the isokinetic relationship observed for the other tropones. The behaviour of 2-fluorotropone towards quinuclidine depends on the solvent; in dimethyl sulphoxide, substitution of fluorine by quinuclidine gives 1-{2-[N-oxocyclohepta-1,3,5-trien-1-yl)-piperidin-4-yl]ethyl}-1-azoniabicyclo[2,2,2]octane fluoride at a rate comparable to that for similar reaction of 2-iodo- or 2-chloro-tropone, but in benzene at room temperature 2-fluorotropone does not react with quinuclidine unlike the chloro- or iodo-compound. Under reflux, only intractable tars are obtained.1-Halogeno-2,4-dinitrobenzenes behave similarly; they undergo clean substitution of the halogen atom by protic amines in both dimethyl sulphoxide and benzene. However, the fluoro-compound is unreactive towards quinuclidine whereas under similar conditions the chloro-compound gives 1-{2-[N-(2,4-dinitrophenyl)piperidin-4-yl]ethyl}-1-azoniabicyclo[2,2,2]octane chloride. Under forcing conditions piperidinium 2,4-dinitrophenolate is formed by hydrolysis (due to moisture) of 1-fluoro-2,4-dinitrobenzene. Intramolecular base catalysis by the 'carbonyl' oxygen atom is suggested as the basis of the isokinetic relationship in the reactions of the troponoid system with protic amines, and the observed data are consistent with this hypothesis.
The naphthoquinone acceptors form stable charge-transfer complexes in solutions of aprotic solvents with aromatic hydrocarbons as donors. From the charge-transfer transition energies of the complexes as well as from the polarographic half-wave reduction potentials of the acceptors relative electron affinities of the acceptors are determined. In addition, the association constant, molar extinction coefficients, oscillator strengths, and enthalpies of formation of the complexes were obtained from charge-transfer spectral studies with hexamethylbenzene as donor. The average electron affinities of 2,3-dichloro-(0·90 eV), 2,3-dichloro-5-nitro-(1·18 eV), 2,3,5,6-tetrachloro-7-nitro-(1·30 eV), 2,3-dicyano-(1·53 eV), 2,3-dicyano-5-nitro-(1·68 eV), and 2,3-dicyano-5,6-dichloro-7-nitro-1,4-naphthoquinone (1·75 eV) obtained from the charge-transfer spectral studies clearly show the cumulative effects of electron-withdrawing substituents on the naphthoquinone π-system. The π-acid character of 1,4-naphtho-quinone aceptors are also correlated with the calculated molecular orbital energies and with the experimental polarographic half-wave reduction potential.
Partial rate factors for protodesilylation of some aromatic compounds Me3Si·C6H4X in methanol–perchloric acid at 50 °C have been determined as: (X =)2-OH, 3720; 2-SH, 4·42; 4-SH, 11·3; 2-SMe, 18·4; 4-SMe, 65·2; 2-CH2Ph, 3·75, and for detritiation of the 2-position of thioanisole in trifluoroacetic acid at 70 °C, 21,500. The relative reactivity of thioanisole and thiophenol is in the inductive order, i.e., SMe activates more than SH in contrast to the results for the oxygen and carbon analogues and this is interpreted as constituting impressive evidence for hyperconjugation in the latter compounds. The ortho:para ratio decreases along the series CH2Y, OY, SY, (where Y = H, Me, or Ph) and ZMe, ZH, ZPh (where Z = CH2, O, or S) apparently through the increasing importance of the inductive effect at the ortho-position; the previously observed low reactivity of the 2-position of diphenyl sulphide in protodesilylation is confirmed and shown not to be anomalous.Application of the Yukawa–Tsuno equation to the desilylation data yields a value for σ+4-SH of –0·365; a value for ƒ4MeO of 1270 is argued to be more accurate than the literature value of 1520.Metallation of diphenyl sulphide produces a mixture of ortho- and meta-derivatives, not merely the former as stated in the literature, and this parallels a recent report on metallation of thiophenetole. The reported rearrangement of 4-LiC6H4·S·SiMe3 to 4-SiMe3·C6H4·SLi is shown to be almost certainly an intermolecular reaction.
The deuterium fractionation factors [(D/H)solute/(D/H)solvent] for hydroxylic positions have been determined by the n.m.r. method for the methanolic hydrogen ion (0·625) and the methanolic methoxide ion (0·74). The effect of counterions has been taken into account in the evaluation of fractionation factors. The existence of significant hydrogen isotope fractionation involving distinguishable hydroxylic positions created by the dissolution of sodium methoxide in methanol is consistent with other evidence for hydrogen-bonding solvation of lyate ions. The deuterium isotope effect on the ionic product of methanol (KH/KD) is calculated to be ca. 6·3.
The reaction between N-benzyl-N-phenylhydroxylamine and para-substituted nitrosobenzenes has been investigated and the products have been identified. Kinetic studies show that the reaction is bimolecular in the early stages and that this initial rate is profoundly influenced by the nature of the para-substituent. A reaction mechanism involving an initial electron-transfer step within a cyclic assembly is proposed.
