Alfred Fischer

Rates of base-catalysed cleavage of pyridyl-, quinolyl-, picolyl- and (quinolylmethyl)-trimethylsilanes

Abstract Rates of cleavage of some picoyl- and (quinolylmethyl)-trimethylsilanes (RSiMe3, where R = PyCH2 or QnCH2SiMe3) have been measured in “90%” aqueous methanolic sodium methoxide at 50°C. Relative reactivities are: 2-PyCH2, 1.0; 3-PyCH2, 0.030; 4-PyCH2, 8.9; 2-QnCH2, 41; 3-QnCH2, 0.161; 4-QnCH2, 37. The rates correlate well with those for base-catalysed hydrogen-exchange in the parent carbon acids RH. Approximate pKas (based on the scale of ion-pair acidities in CsNHC6H11H2NC6H11, with pKa of 9-phenylfluorene = 18.6) for the carbon acids, RH, can be derived as follows: 2-PyCH3, 29.5; 3-PyCH3, 34; 4-PyCH3, 27; 2-QnCH3, 25; 3-QnCH3, 32; 4-QnCH3, 25. Rates of cleavage of pyridyl- and quinolyl-trimethylsilanes (PySiMe3 and QnSiMe3) by sodium hydroxide in 4 : 1 v/v Me2SO/H2O at 50°C have also been measured; and the relative reactivities are: 2-Py, 1.0; 3-Py, 2.9; 4-Py, 8.4; 2-Qn, 15.9; 3-Qn, 12.7; 4-Qn, 184. The sequence of reactivity differes from that for base-catalysed hydrogen-exchange at the relevant positions of pyridine and quinoline, indicating that the reactivities are not determined in both cases (if in either) solely by the stabilities of the corresponding carbanions.

Reactions of organolithium reagents with p-benzoquinones and cyclohexadienones. Synthesis of 4-alkyl-4-hydroxycyclohexa-2,5-dien-1-ones and 1,4-dialkylcyclohexa-2,5-diene-1,4-diols.

Abstract Addition of organolithium reagents to p -benzoquinones in ether gives the corresponding 4-alkyl-4-hydroxycyclohexa-2,5-dien-1-ones. Addition of excess of the reagent to the p -benzoquinones, or to the 4-alkyl-4-hydroxycyclohexa-2,5-dien-1-ones, in tetrahydrofuran, gives the corresponding dialkylcyclohexa-2,5-diene-1,4-diols.

Addition of functionalized organolithium reagents to p-benzoquinones and cyclohexadienones: synthesis of functionalized cyclohexadienones, dienols and dienediols

Abstract Low temperature addition of functionalized alkyllithium reagents to p-benzoquinones produces 4-alkyl-4-hydroxycyclohexa-2,5-dienones, and reaction of excess of the reagents with quinones yields 1,4-dialkylcyclohexa-2,5-diene-1,4-diols. With 4-acetoxy-, 4-hydroxy-, and 4-methoxy-4-methylcyclohexa-2,5-dienones the corresponding dienols are obtained. A one-step synthesis of the antibiotics 4-acetamido- and 4-[(ethoxycarbonyl)methyl]-2,6-dibromo-4-hydroxycyclohexadienones, and the anti-tumour agent jacaranone is described.

Formation of dienones on the reaction of cresols, xylenols, and 2-naphthol with nitrogen dioxide: Observation of keto tautomers of nitrophenols

Abstract Reaction of o - and p -cresol, the xylenols, and 2-naphthol with nitrogen dioxide gives nitrocyclohexadienones and nitrophenols. Secondary nitrodienones, the keto tautomers of the nitrophenols, have been observed in several cases and are intermediates in the formation of the nitrophenols.

Rate constants and solvent isotope effects in the cleavage of picolyl- and (quinolylmethyl)-trimethylsilanes by sodium methoxide in methanol

Abstract Rate constants have been determined for cleavages of picolyltrimethyl-silanes (PyCH 2 SiMe 3 ) and (quinolylmethyl)trimethylsilanes (QnCH 2 SiMe 3 ) by sodium methoxide in 100% MeOH (at 25°C) and sodium hydroxide in 2/1 v/v MeOH/H 2 O (at 50°C), and used to derive σ − constants for the PyCH 2 and QnCH 2 systems (2-PyCH 2 , 0.85; 3-PyCH 2 , 0.53; 4-PyCH 2 , 1.07; 2-QnCH 2 , 1.14; 3-QnCH 2 , 0.70; 4-QnCH 2 , 1.20) and approximate p K a values for the corresponding carbon acids PyCH 3 and QnCH 3 (2-PyCH 3 , 29.5; 3-PyCH 3 , 33.5; 4-PyCH 2 , 26; 2-QnCH 3 , 25.5; 3-QnCH 3 , 31.5; 4-QnCH 3 , 24.5). Values of the solvent rate isotope effect, the ratio of the rate constant in MeOH to that in MeOD (2-, 3-, and 4-PyCH 2 SiMe 3 , 0.65, 0.49, and 0.54, respectively; 2-, 3-, and 4-QnCH 2 SiMe 3 , 0.56, 0.47, and 0.52, respectively) and of the product isotope effect, the product ratio RH/RD on cleavage of RSiMe 3 in 1/1 MeOH-MeOD (2-, 3-, and 4-PyCH 2 SiMe 3 , 5.6, 1.1, and 2.6, respectively; 2-, 3-, and 4-QnCH 2 SiMe 3 , ca. 5, 1.1, and 3.2, respectively) have also been measured. The rate isotope effects for 2-Py- and 2-Qn-CH 2 SiMe 3 are significantly higher than is usual for cleavages of this type. Except for 2-PyCH 2 SiMe 3 , the product isotope effects are rather smaller than those given by XC 6 H 4 CH 2 SiMe 3 compounds of comparable reactivities.

IPSO nitration: nitration of 2-alkylphenols in acetic anhydride. Formation of 6-alkyl-6-nitrocyclohexa-2,4-dienones

Abstract Low temperature nitration of 2-alkylphenols in acetic anhydride gives 6-alkyl-6-nitrocyclohexa-2,4-dienones. The dienones undergo a regiospecific rearrangement to give o -nitrophenols.

Nitration of 3,4-Dimethylacetophenone and 3,4-Dimethylbenzophenone. Formation and Rearomatization of Adducts

Nitration of 3,4-dimethylacetophenone in acetic anhydride gives a mixture of cis-and trans-2-acetyl-4,5-dimethyl-4-nitro-1,4-dihydrophenyl acetate as the main product, together with 3,4-dimethyl-2-, 3,4-dimethyl-5-, and 3,4-dimethyl-6-nitroacetophenone. Analogous products are obtained from 3,4-dimethylbenzophenone. Rearomatization of the adducts under mildly acidic conditions occurs via 1,4-elimination of nitrous acid to form 2-acetyl- and 2-benzoyl-4,5-dimethylphenyl acetate, respectively. In strongly acidic conditions elimination of acetic acid accompanied by 1,2- and 1,3-shifts of the nitro group occurs to form the 2- and 5-nitro derivatives of the parent ketones. The rearomatization to the nitro derivatives involves the intermediate formation of an ipso-cyclohexadienyl cation which may be trapped by anisole or mesitylene to form biphenyl derivatives.

Formation of 4-Halo-4-nitrocyclohexa-2,5-dienones on nitration of p-halophenols and p-halophenyl acetates

Abstract Nitration of p-chloro-, p-fluoro-, and p-bromo-phenol or the corresponding p-halophenyl acetates at t-40 °C and below gives the 4-halo-4-nitrocyclohexa-2, 5-dienones in addition to the 4-halo-2-nitrophenols. The dienones isomerize to the nitrophenols at temperatures between −40 °C and 0°C. Nitration of 4-chloro-2-methylphenol or its acetate gives both 4-chloro-2-methyl-4-nitrocyclohexa-2, 5-dienone and 4-chloro-6-methyl-6-nitrocyclohexa-2,4-dienone. 4-Chloro -3-methylphenol and its acetate give 4-chloro-3-methyl-4-nitrocyclohexa-2,5-dienone.

Ipso-nitration of p-t-butyltoluene. A 1,2 adduct

Nitration of p-t-butyltoluene in acetic anhydride gives 5-t-butyl-2-methyl-2-nitro- 1,2-dihydrophenyl acetate as the major addition product.

Formation of aryliodine(III) derivatives in the nitration of aryl iodides in acetic anhydride

Nitration of iodobenzene, o-iodotoluene, and p-iodotoluene in acetic anhydride results in reversible oxidation to aryliodine(III) compounds prior to the formation of the expected nitro derivatives. µ-Oxo-[nitrato(phenyl)iodine][phenyl(trifluoroacetato)iodine] has been isolated from nitration of iodobenzene and its crystal structure determined.