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Durch Einwirkung von Aryllithiumverbindungen auf Diarylketone wurde eine Anzahl von methylsubstituierten Tripenylcarbinolen erhalten. Wenn im Diarylketon mehr als zwei Orthomethylgruppen vorhanden sind, findet keine Carbinolbildung statt. An deren Stelle wurden in einigen Fallen Stoffe erhalten, denen vermutlich die Struktur eines methylsubstituierten 9,10-Diaryl-9,10-dioxy-9,10-dihydro-phenanthrens oder -anthracens zuerkannt werden muss.

Bei der Elektrolyse von Diphenylessigsaure in methylalkoholischer Kalilauge und Pyridin nach Riccoboni1) wurden als nichtgasformige Reaktionsprodukte identifiziert: Tetraphenylathan, Di-(diphenylmethyl)-ather, Benzophenon, Diphenylmethyl-methylather, Stoffe die, ausgenommen der letztgenannte, auch bei der Halogenentziehung an Diphenylchlormethan mit molekularem Silber unter Sauerstoff gefunden worden sind. Durch diese Ubereinstimmung in den Reaktionsprodukten ist Gleichheit des Reaktionsmechanismus und damit das Auftreten von freien Radikalen bei der Kolbe-Reaktion als feststehend anzusehen.

Our research on the occurrence of free radicals with only two unconnected aromatic groups on the central atom, has now been extended to reactions of molecular silver with: a. bis-phenyl-chloromethane; b. bis-(4-methoxyphenyl)-chloromethane; c. bis-(2:4:6-triethylphenyl)-chloromethane. We always found indications of the occurrence of free radicals. We shall report on these reactions in detail in a subsequent communication. Of the substances required for this investigation, only bis-(2:4:6-triethylphenyl)-chloromethane has not been described in the literature. Therefore in this communication we describe the preparation of this compound.

In guter Ubereinstimmung mit dem fruher fur die Aktivierungsenergie der Dissoziation des sym. Tetra(2,6-dimethylphenyl)athan in ortho-Dichlorbenzen gemessenen Wert von 22.5 kcal wurde in den Losungsmitteln ortho-, meta- und para-Xylen 22.9 bzw. 23.0 bzw. 23.4 kcal gefunden.

The energy of activation (E), the Arrhenius constant (A) and the period of half-life at 80° (t1/2) for the radical-dissociation reactions of the following compounds: pentaphenylethane (I) 1,1,1,2-tetraphenyl-2-(2-methylphenyl)ethane (II) 1,1,1,2-tetraphenyl-2-(3-methylphenyl)ethane (III) 1,1,1,2-tetraphenyl-2-(4-methylphenyl)ethane (IV) 1,1,1-triphenyl-2,2-di-(3-methylphenyl)ethane (V) 1,1,1-triphenyl-2,2-di-(4-methylphenyl)ethane ((VI) have been calculated from the velocity constants for the first-order reactions of the radicals concerned with oxygen in o-dichlorobenzene as a solvent

From this investigation it is concluded that expansine C7H6O4, a substance with bactericidal and fungicidal properties isolated by Oosterhuis and Luyken 1 ) from the culture liquid of Penicillium expansum Westl., very probably has the structure of an anhydro-3-hydroxymethylene-tetrahydro-γ-pyron-2-carboxylic acid. Expansine is probably identical with patulin 1 ), claviformin 2 ) and clavacin 3 ).

Several trans-1-(o-alkylphenyl)decahydro-1-naphthols were synthesised from trans-octahydro-1(2H)-naphthalenone with aryl-lithium. Their conformations were assigned on the ground of the chemical shift of the hydroxyl proton. A comparison was made with the corresponding cyclohexanols.

Several 1-arylisochromans were prepared from 1-bromoisochroman and 1-bromo-4,4-dimethylisochroman by reaction with arylmagnesium bromides. Bromination and heating yielded, presumably via bromo-1-arylisochromans, o-(bromoalkyl)benzophenones. Treatment with lithium aluminium hydride converted the ketones into the corresponding carbinols, the side-chain being simultaneously debrominated if sufficient hydride was used. Reactions of the bromoalkylbenzophenones with hydrazine derivatives yielded benzodiazepines. Treatment with hydriodic acid and red phosphorus converted 1-phenyl-isochroman into o-(2-iodoethyl)diphenylmethane while 4,4-dimethyl-1-phenyl-isochroman yielded 10,11-dihydro-10,10-dimethyl-5H-dibenzo[a,d]cycloheptene and a compound (C13H10)n of unknown structure.

The reaction of tryptamine with some isocoumarins has been studied. From the reaction products hexadehydroyohimbane and a new dimethoxy derivative can be synthesized.

The reaction between an isocyanate and an α-hydroxy-ester leads to the formation of an N-substituted carbamylo-α-hydroxy-ester, which can give an oxazolidinedione-2,4 under the influence of a small amount of metallic sodium by ring closure with the splitting off of alcohol. This ring closure can sometimes be brought about without the use of sodium, by heating the carbamylo-α-hydroxy-ester to a sufficiently high temperature. Whether or not the required ring closure takes place on heating, depends apparently upon the nature of the carbon substituents of the carbamylo-α-hydroxy-ester, since the latter, on heating to a higher temperature, sometimes can give an isocyanate.

From a quantity of ethyl mandelate there separated, after prolonged storage, a crystalline compound, which was found to consist of mandelic acid and ethyl mandelate in a 1 : 1 ratio. This product can also be prepared in situ by mixing equivalent amounts of mandelic acid and ethyl mandelate, the crystalline product separating with generation of heat. This phenomenon did not occur when some other mandelic esters were investigated.

As part of a series of investigations into the relationship between chemical structure and biological activity1 , a number of 3-phenyl-4-hydroxycoumarins with alkylsubstituents in the 3-phenyl group were synthesized.

Two routes for the synthesis of 2,3,5-trimethylterephthalic acid are described, starting from 1,2,4-trimehylbenzene and p-xylene, respectively.

To some of the quinolizine derivatives described earlier (1 and 2) we have been able to assign a cis or trans structure on the strength of a stereoselective synthesis. Infrared spectral data and differences in the rate of dehydrogenation, combined with a study of the conformations possible, allowed such assignment for other compounds in this series.

The preparation of some derivatives of 1,3,4,6,7,1 1b-hexahydro-9,10-dimethoxy-2H-benzo[a]quinolizine and 1,2,3,4,6,7,12,12b-octahydroindolo-[2,3-a]quinolizine substituted with two alkyl groups, either in the 1- or the 3-position is described. Two reaction routes were followed for each of the two types of compounds and some of the numerous intermediates have been isolated.

To aconic acid, first described in literature by Kekule, the structure of a β,γ-butenolide was given by Fittig and Beer. In 1947 Campbell and Hunt put forward arguments for an α,β-butenolide structure. These arguments were based on a new synthesis of the acid and a comparison of the U.V. absorption spectrum of aconic acid with those of mesaconic acid and itaconic acid. Close inspection of the properties of aconic acid shows however that Campbell and Hunt's synthesis of aconic acid is not proving for its structure. Moreover these authors drew their spectral conclusions only from curveshapes, so we found it necessary to repeat the U.V. measurements at lower wave lengths. The rightness of the structure proposed by Campbell and Hunt could be proved.

Controversial structures have been assigned 1,2 to the nitrogen-containing carboxylic acid which is one of the products formed on hydrolysis of N-substituted oxazolidinediones-2,4. The present publication solves the problem in favour of our previous suggestions.

The preparation of a number of 2,8-substituted 1,2,3,4,6,7,8,12c-octahydroindolo[3,2-α]quinolizines, using a 2-(2-aminoethyl)indole derivative and 3-substituted glutaric anhydrides, or 3-substituted 5-bromovalerates, as starting materials, is described.

Several 2-alkyl-1-(ortho-alkyl)phenylcyclohexanols have been synthesized from lithium compounds (obtained from alkylbromobenzenes) and 2-alkyl-cyclohexanones. G.L.C. analysis has shown that only one isomer is formed. The conformation was elucidated with the aid of N.M.R. spectra, which showed that a tert-alkyl group in the ortho position of the aromate gave rise to an axial position of this aromatic group at the cyclohexane ring. In all other cases the phenyl group is equatorial.

The heat of dissociation of hexaphenylethane in m-xylene as a solvent, measured by means of electron spin resonance, amounts to 10.9 ± 0.29 (2.7%) kcal/mol. The ESR method appears to have important advantages over other techniques for this purpose.

The activation energies of the dissociation of some ortho-alkyl-substituted symmetrical tetraphenylethanes were determined by measuring the reaction rates of these compounds with oxygen in m-xylene solutions. The values found are 25.3, 22.9 and 19.6 kcal/mole for symm.tetra(2-tert-butylphenyl)ethane, symm.-tetra(2,6-dimethylphenyl)ethane and symm.tetra(2,6-diethylphenyl)ethane, respectively. The frequency factors and activation entropies of the dissociation reaction were obtained from the same measurements. Using the known data on the dissociation equilibria, we also calculated the relevant kinetic values for the recombination reactions.

Whereas benzoylation of toluene or m-xylene is known to lead to a mixture of 2- and 4-methylbenzophenone and to 2,4-dimethylbenzophenone respectively, the presence of a blocking t.butyl group in the 4- and the 5-positions respectively leads to products which on debutylation yield benzophenones with substituents in the ortho position only.

The synthesis of 2-mercapto-4-aminobenzoic acid, a compound which is the sulphur analogue of p-amino-salicylic acid (2-hydroxy-4-aminobenzoic acid), is described.

The U.V. absorption spectra of p.amino-salicylic acid were measured both in water and in ethanol. The results of these measurements show that there is no discrepancy between the work of Way a.o. and Drain a.o. as was suggested by the latter authors. In addition the U.V. absorption spectra of some related compounds were measured.

The UV absorption spectra of a small series of aromatic tricyclic ketones derived from benzophenone by introduction of an interconnecting -(CH2)n-bridge (n = 1, 2, or 3) are described. The spectra show well-defined steric effects in the 270-nm region and they appear to be related to those of I-indanone, I-tetralone and similar structures with a corresponding band at about 240 nm. The band system is of conjugative origin and shows one single maximum - with one exception: 10.11-dihydro-2,4-dimethyl-5H-dibenzo[a.d]cyclohepten-5-one shows two separate maxima: at about 245 nm and 275 nm.

This article gives the experimental results of UV measurements made on a number of benzophenones with ethyl, isopropyl and tert.butyl groups as substituents. The results are compared with the previously published data on the corresponding methyl-substituted benzophenones1,2,3,4. Our investigation showed that there is no significant difference between the effects of introduction of ortho-methyl, ortho-ethyl or ortho-isopropyl groups into a benzophenone. With a tert.-butyl group, however, the result is somewhat different: in this case a steric effect is observed on the electronic spectra, which is only slightly smaller than that encountered in 2,6-dimethylbenzophenone. When plotting the λC differences between meta/para-substituted derivatives and the unsubstituted benzophenone against the Hammett σ-values the result is a straight line, the Hammett σ-constant being −0.061 for ethanol and −0.050 for isooctane solutions.

The heats of dissociation of some ortho alkyl-substituted tetraphenylethanes which show reversible thermal dissociation in solution at room temperature, were measured by means of ESR. The values found are 22.0, 19.7 and 12.0 kcal/mole for symm.tetra(2,6-dimethylphenyl)ethane, symm.tetra(2-tert-butyl-phenyl)ethane and symm.tetra(2,6-diethylphenyl)ethane, respectively.

Depending on the method of working, alkylation of 5,5-dimethyl-oxazolidinedione-2,4 leads to 3-alkyl-5,5-dimethyl-oxazolidinedione-2,4 or an alkyl derivative of a lactim form of 5,5-dimethyl-oxazolidinedione-2,4. It could be shown that the compound obtained by Spielman, by methylating 5,5-dimethyl-oxazolidinedione-2,4 with dimethyl sulphate, had indeed the structure of 3,5,5,-trimethyl-oxazolidinedione-2,4. Methylation of the silver salt of 5,5-dimethyl-oxazolidinedione-2,4 with methyl iodide on the other hand, leads to the formation of an oxygen-methylated compound. In connection with this matter, several syntheses, which might lead to the formation of 3,5,5-trimethyl-oxazolidinedione-2,4 were submitted to a closer examination.

To investigate possible differences in spasmolytic activity the four isomers of cyclandelate (the DL-mandelate of low melting 3,5,5-trimethylcyclohexanol) as well as the corresponding isomeric esters from high melting 3,5,5-trimethylcyclohexanol were prepared.

The synthesis is described of a number of derivatives of 10,11-dihydro-5H-dibenzo[a,d]cycloheptene, with basic substituents in the ethylene bridge. Moreover, a method is reported for the preparation of amino ethers of 5H-dibenzo-[a,d]cyclohepten-10-ol.

The validity of a superimposability principle for the electronic spectra of disubstituted benzene derivatives, proposed by Doub and Vandenbelt5 to interpret the principal absorption bands of some trisubstituted benzene derivatives is discussed for p-aminosalicylic acid, β-resorcylic acid and 2-amino-5-chlorobenzoic acid.

The synthesis of a number of acids in the 5H-dibenzo[a,d]cycloheptene series is described including the 5-carboxylic acid and its 10,11-dihydro analogue, 5H-dibenzo[a,d]cycloheptene-5-acetic acid and its 10,11-dihydro derivative. The latter acid was prepared by several routes. Treatment of its acid chloride with stannic chloride yielded 2,6,7,1 1b-tetrahydro-1H-dibenzo[c,d,h]azulen-2-one, which by reductive amination with methylamine, dimethylamine and 1-methyl-phenethylamine was converted into the corresponding amines. Several esters with aliphatic and heterocyclic amino alcohols were prepared from the carboxylic acids mentioned. The acids were likewise converted into 1-substituted 4-piperazides which were reduced to the corresponding piperazine derivatives. The acid derivatives were screened for biological activity.

The present investigation deals with the effect of the number of ortho-ethyl and ortho-isopropyl substituents on the stability of diarylmethyl radicals. These diarylmethyls were obtained by halogen abstraction from the correspondingly substituted benzhydryl chlorides. If not all ortho positions of the diarylmethyl carried ethyl or isopropyl groups, complete dimerization led to a symmetrical tetra-arylethane; if all four positions were occupied by ethyl groups an equilibrium was reached between the radical and the dimer, while diarylmethyls with four ortho-isopropyl groups showed no dimerization at all. Radicals of the last type were prone to disproportionation, however.

In the hydrolysis of 5,5-dimethyl-oxazolidinediones-2,4 and 5-phenyl-oxazolidinediones-2,4, with alkali, a carbamylo-α-hydroxy-acid and an α-hydroxy-amide are produced in a constant ratio, independent of the nature of the N-substituent, the decomposition temperature and the concentration of the alkali. For 5,5-dimethyl-oxazolidinediones-2,4 this ratio is 1.66 on the average and for 5-phenyl-oxazolidinediones-2,4 5.2 on the average. Practically the same ratios are found in the hydrolysis of the corresponding carbamylo-α-hydroxy-esters.

The synthesis of 2,2-bis-(2,6-dimethylbenzoyl)-3,3′-dimethylbenzyl is described starting from 2,6-dimethylbenzoic acid. This substance appears to be identical with the condensation product obtained previously from 2.6-dimethylphenyllithium and 2,6-tetramethyl-benzophenone.

The preparation of a number of 2-substituted 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzo[a]quinolizines and 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizines is described. Starting from 3-substituted valerolactones, the preparation required five stages (see Reaction Scheme I). A number of the 3-substituted valerolactones used were conveniently prepared by reduction of the corresponding glutaric acid derivatives, e.g. the anhydrides, with sodium borohydride. The final stage is a stereoselective reduction, leading to cis or trans isomers. The synthesis and data of one of the end-products, 1,3,4,6,7,11b-hexahydro -9,10-dimethoxy-2-phenyl-2H-benzo[a]quinolizine, are compared with those reported for this compound by Tomimatsu.

In an attempt to prepare 4-amino-3,5-dichloro-2-hydroxy-benzoic acid (I) from 4-amino-2-hydroxy-benzoic acid (II) by a chlorination reaction, it was found that the isolated reaction product was identical with 2,4,4,6,6-pentachloro-cyclohexene-1-dione-3,5 (III). Exhaustive chlorination of 2,4-dihydroxy-benzoic acid (IV) led to the same 1,3-dihydroxy-benzene derivative. (I) could be prepared by chlorination of 4-acetylamino-2-hydroxy-benzoic acid (V) to 4-acetylamino-3,5-dichloro-2-hydroxy-benzoic acid (VI) and subsequent saponification of the latter compound. By converting I into 3,5-dichloro-2-hydroxy-benzoic acid (VII) and into 3,5-dichloro-2,4-dihydroxy-benzoic acid (VIII), the 3,5-position of the chlorine atoms in I and VIII could be proved.

The U.V.-absorption spectra of diduryl ketone, diisoduryl ketone and durylisoduryl ketone have been measured and mutually compared. A ketone previously described by Coops et al. as diduryl ketone was definitely established as durylisoduryl ketone.

Three β-amino-dicarboxylic acids were prepared by reduction of the corresponding ethyl β-oxo-dicarboxylate acetylhydrazones. The melting point and the tuberculostatic activity of β-amino-pimelic acid are not in accordance with the data found by Romeo for a compound obtained by hydrogenation of p-amino-salicylic acid, which seemed to be β-amino-pimelic acid.

In contrast with the oxazolidinediones-2,4 which are not substituted on the nitrogen atom, the majority of N-substituted oxazolidinediones-2,4 are sensitive to alkali. With the latter compounds, hydrolysis takes place in two ways, an N-substituted hydroxyamide being produced, along with a substituted carbamylo-α-hydroxy-acid. A different scheme of reactions, which can be shown to be incorrect, has been suggested for this decomposition by Davies and Hook. From a number of oxazolidinediones-2,4 the decomposition products have been isolated. Substituted carbamylo-α-hydroxy-esters on treatment with alkali do not undergo direct hydrolysis, as suggested by Lambling, but ring closure occurs, followed by ring hydrolysis, with the formation of the two decomposition products (α-hydroxyamide and carbamylo-α-hydroxy-acid).

Addition of an organic isocyanate to hydroxy-esters or amino-esters results in attachment of the active H of the OH or NH2 group to the N atom of the isocyanate, the rest of the adding molecule being linked to the C atom of the N = C bond. Though stable in themselves, the resulting products undergo cyclisation in inert media under the catalytic influence of sodium, or in some cases, by simply heating without any medium. The final ring compounds obtained in this way are oxazolidinediones, hydantoins, oxazines, uracils and quinazolidinediones starting with α-hydroxy-esters, α-amino-esters, ortho-hydroxybenzoates, β-amino-esters, and ortho-aminobenzoates, respectively, as the original addition partners. β-Hydroxy-esters with a free H in the α-position give unsaturated amides as final reaction products.