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The homolytic benzoylation (benzoyl radical) of 5-tert-butylcarbonylaminopyrimidine (6, 1 equiv.) in the presence of benzaldehyde (3 equiv.), water, sulfuric acid, and acetic acid, upon treatment with FeSO4·7H2O (3 equiv.) and 70% t-BuOOH (3 equiv.) at 5-10°C for 10 min afforded a mixture of 4-benzoyl-5-tert-butylcarbonylaminopyrimidine (7, 23%), 4,6-dibenzoyl-5-tert-butylcarbonylaminopyrimidine (8, 44%), and 4-benzoyl-5-tert-butylcarbonylamino-6- methyl pyrimidine (9, 10%). When a similar reaction was performed using 1 equiv. each of PhCHO, FeSO4·7H2O, and t-BuOOH, to prevent formation of the 4,6-dibenzoyl product 8, the monobenzoyl (7, 38%) and 4-benzoyl-6-methyl (9, 6%) products were obtained. A similar homolytic benzoylation of 5-bromopyrimidine (10) using 1.5 equiv. of reagents to generate the benzoyl radical afforded 4-benzoyl-5-bromopyrimidine (11, 61%) as the predominant product. Elaboration of 11via a six-step reaction sequence afforded 2-hydrazino-5-phenyl-3H-pyrimido[5,4-e][1,4]diazepine (17) in 5.2% overall yield. The acid-catalyzed reaction of 17with triethyl orthoacetate gave the title compound 5-phenyl-10-methyl-7H-pyrimido[4,5-f][1,2,4]triazolo[4,3-a][1,4]diazepine (18, 62%). The triazolo compound 18was more potent than valproic acid (Depakene(r)) in both the subcutaneous metrazol (scMet) and maximal electroshock (MES) anticonvulsant screens, and more potent than clonazepam in the MES anticonvulsant screen but less potent than clonazepam in the scMet anticonvulsant screen.Key words: homolytic benzoylation, pyrimidines, pyrimidodiazepines, anticonvulsants.

A group of 52chlorophenyl10substituted7Hpyrido4,3f1,2,4triazolo4,3a1,4diazepines 7acwere synthesized by the acid catalyzed reaction of 52chlorophenyl2hydrazino3Hpyrido3,4e1,4diazepine 6 with either trimethyl orthoformate, triethyl orthoacetate or triethyl orthobenzoate, respectively. 52Chlorophenyl7Hpyrido4,3f1,2,4triazolo4,3a1,4diazepine 7a and 52chlorophenyl10methyl7Hpyrido4,3f1,2,4triazolo4,3a1,4diazepine 7b exhibited good anticonvulsant activity in the subcutaneous metrazol anticonvulsant screen which serves as a model for absence petit mal epilepsy.

The presence of different amounts of added LiClO4in the solvolysis of triphenyl[2-14C]vinyl bromide (1-Br-2-14C) or trianisyl[2-14C]vinyl bromide (2-Br-2-14C) in 70% HOAc did not materially affect the extent of scrambling of the label arising from 1,2-aryl shifts in the triarylvinyl cation or kr, the rate constant for the 1,2-aryl shift. Solvolysis of a 2:3 mixture of (E)- and (Z)-1,2-diphenyl-2-tolylvinyl bromide ((E,Z)-3-Br) in 70% HOAc gave an 85:15 mixture of 1,2-diphenyl-2-tolylethanone (5) and 2,2-diphenyl-1-tolylethanone (6), the latter product, 6, being derived from a 1,2-phenyl shift in the 1,2-diphenyl-2-tolylvinyl cation to the more stable 2,2-diphenyl-1-tolylvinyl cation. With (E,Z)-3-Br-2-13C as substrate and analysis by gc–ms, about 26–27% scrambling of the 13C label was found in both products, 5-1,2-13C and 6-1,2-13C. Solvolyses of (E,Z)-3-Br-2-13C in 50% and 70% HOAc showed that the extent of scrambling in the major products, 5-1,2-13C, was lower in 50% HOAc than in 70% HOAc, similar to a trend previously observed for solvolyses of 1-Br-2-14C. In contrast, solvolyses of 2-Br-2-14C in 50, 70, or 90% HOAc gave essentially the same extent of scrambling. Mechanistic implications of these results are discussed.

Solvolyses were carried out with 6.0 mMdoubly labeled 1,2-dianisyl-2-p-(2H3)methoxyphenyl[2-13C]vinyl bromide in 70% HOAc – 30% H2O in the presence of 0, 1, 5, 10, or 400 molar equivalents of added NaOAc. The distributions of products derived from the 4 possible isotopomeric trianisylvinyl cationic intermediates were determined from the mass spectra of the isotopomeric dianisyl ketones obtained from degradation of the reaction products, the spectra being obtained by the chemical ionization technique in order to minimize possible complications by multiple fragmentations. The mass spectrometrie results obtained showed agreement with previously obtained 14C scrambling data and with the 13C scramblings obtained in the present study using 13C nmr. Increasing amounts of added NaOAc had the effect of decreasing the extents of scrambling from 1,2-anisyl shifts as previously observed. However, the formation of products from all 4 possible doubly labeled isotopomeric trianisylvinyl cations definitely demonstrated the occurrence of successive 1,2-anisyl shifts in the trianisylvinyl cation, and the detection of such successive shifts was not possible in previous work using a singly labeled substrate. The observed distribution of products derived from the 4 isotopomeric cations could be calculated assuming various contributions from equilibrations among these isotopomeric cations, and the mechanistic implications of the results are discussed.

The acetolysis of trans-1,2-diphenyl-2-phenylthiol[1-13C]vinyl tosylate (2-OTs-1-13C) under anhydrous conditions (HOAc–Ac2O–NaOAc) gave trans-1,2-diphenyl-2-phenylthio[1,2-13C]vinyl acetate (2-OAc-1,2-13C) as product. The label was scrambled equally over C-1 and C-2 and there was no detectable amount of cis-product. These results are consistent with the involvement of an intermediate sulfur-bridged thiirenium ion in the reaction. Soivolysis of 2-OTs-1-13C in 70% HOAc – 30% H2O containing 3 equiv. of NaOAc gave 1,2-diphenyl-2-phenylthio[1,2-13C]ethanone (α-phenyl-α-(phenylthio)acetophenone) (5-1,2-13C) and 1,2-diphenyl[1,2-13C]ethanone (desoxybenzoin) (6-1,2-13C) as major and minor products, respectively. The 13C-label in both of these ketones was again equally distributed over C-1 and C-2. Further studies with unlabeled 2-OTs showed that its soivolysis in aqueous HOAc gave, besides ketones 5and 6, some benzil and diphenyl disulfide. It was also found that 6, benzil, and diphenyl disulfide were derived from the initial product 5. A possible mechanism for these conversions is proposed.

The solvolysis of triphenyl[2-14C]vinyl bromide (1-Br-2-14C) in 70% HOAc – 30% H2O or in 2,2,2-trifluoroethanol (TFE) carried out in the presence of an excess of p-CH3C6H4SNa gave the triphenylvinyl p-tolyl thioether (1-STol) with a greatly decreased extent of scrambling of the 14C-label from C-2 to C-1 when compared with analogous reactions without the presence of the p-toluenethiolate anion. For example, the 1-STol product from the reaction of 1-Br-2-14C in 70% HOAc – p-CH3C6H4SNa showed only 0.5–0.9% scrambling, while previous studies on the reaction of 1-Br-2-14C in 70% HOAc – NaOAc gave 14.7 ± 0.7% scrambling. Previous work on the solvolysis of 1,2-diphenyl-2-[2H5]phenyl[2-13C]vinyl bromide (1-Br-2-13C-2-Ph-d5in 70% HOAc, as well as the present results from the solvolysis of 1-Br-2-13C-2-Ph-d5in TFE – 2,6-lutidine, gave products derived from all 4 possible isotopomeric triphenylvinyi cations 3, 4, 5, and 6arising from successive 1,2-phenyl shifts. On the other hand, solvolysis of 1-Br-2-13C-2-Ph-d5in 70% HOAc or TFE containing an excess of p-CH3C6H4SNa gave 1-STol in which the isotopically rearranged product was derived only from ion 5arising from a 1,2-shift of the unlabeled phenyl group with no detectable amount of production derived from a 1,2-shift of the perdeuterophenyl group. These results are interpreted by the rapid trapping of the triphenylvinyi cation by the highly nucleophilic p-toluenethiolate anion.

The ortho-directed lithiation of 3-tert-butyl- or 3-tert-butoxycarbonylaminopyridines (3) with alkyllithiums and reaction with N,N-diethylbenzamide followed by acid hydrolysis gave 3-amino-4-benzoylpyridine (6) in good yield. Reaction of BTBO with the glycine derivatives 7a, band then reaction with 6afforded 3-alkoxycarbonylaminomethylcarbonylamino-4-benzoylpyridines 8a, b. Acid-catalyzed hydrolysis and cyclization of 8a, byielded 9, which on methylation gave 1,3-dihydro-1-methyl-5-phenyl-2H-pyrido[3,4-e]-1,4-diazepin-2-one (10) in 36% overall yield from 3a.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.