Micellar catalysis of organic reactions. 18. Basic hydrolysis of diazepam and some N-alkyl derivatives of nitrazepam

1986 ◽  
Vol 51 (15) ◽  
pp. 2965-2969 ◽  
Author(s):  
Trevor J. Broxton ◽  
Sallyanne Wright
Keyword(s):  
Micellar Catalysis ◽  
Organic Reactions ◽  
Alkyl Derivatives ◽  
Basic Hydrolysis ◽  
Hydrolysis Of ◽  
Derivatives Of

Micellar catalysis of organic reactions. 22. A comparison of the basic hydrolysis of benzodiazepinones in the presence of reactive counterion micelles and vesicles

1988 ◽  
Vol 66 (7) ◽  
pp. 1566-1570 ◽  
Author(s):  
Trevor J. Broxton ◽  
Xenia Sango ◽  
Sallyanne Wright
Keyword(s):  
Surfactant Concentration ◽  
Biological Membranes ◽  
Micellar Catalysis ◽  
Organic Reactions ◽  
Conductivity Measurements ◽  
Amide Hydrolysis ◽  
Rate Of Hydrolysis ◽  
Basic Hydrolysis ◽  
Hydrolysis Of ◽  
Good Agreement

The basic hydrolysis of diazepam and several N-alkyl nitrazepam derivatives has been studied in the presence of reactive counterion micelles of cetyltrimethylammonium hydroxide (CTAOH) and vesicles of didodecyldimethylammonium hydroxide (DDAOH). In both surfactants, the rate of hydrolysis of all compounds was found to be dependent on the hydroxide concentration at constant surfactant concentration and this was interpreted as evidence for initial amide hydrolysis. The hydrolysis in CTAOH was inhibited by added salts in the order Br− < NO3− < SO42−. At concentrations above 3 mM surfactant, the rate of hydrolysis of each compound was similar in CTAOH and in DDAOH. At lower concentrations of CTAOH, however, the rate of hydrolysis was significantly lower than that in DDAOH. On the basis of this evidence, it was concluded that the cmc of CTAOH was between 2–3 mM, which is in good agreement with the value of 1.8 mM obtained by Zana from conductivity measurements. For diazepam, a mechanistic change is indicated on transfer from water to either micelles or vesicles and since vesicles are considered good models of biological membranes, this suggests that conclusions concerning the bioavailability of diazepam should not be based on studies in water but rather on studies in either micelles or vesicles.

Micellar catalysis of organic reactions. XII. Basic hydrolysis of some alkyl and aryl N-(4-Nitrophenyl)carbamates

1984 ◽  
Vol 37 (1) ◽  
pp. 47 ◽  
Author(s):  
TJ Broxton
Keyword(s):  
Cetyltrimethylammonium Bromide ◽  
Kinetic Studies ◽  
Micellar Catalysis ◽  
Organic Reactions ◽  
Bond Breaking ◽  
Tetrahedral Intermediate ◽  
Stable Product ◽  
Methyl Derivatives ◽  
Basic Hydrolysis ◽  
Hydrolysis Of

The basic hydrolysis of a number of alkyl and aryl N-(4-nitrophenyl)carbamates in the presence and absence of micelles of cetyltrimethylammonium bromide (ctab) are reported. In water the stable product at 26�C was N-(4-nitrophenyl)carbamate ion (3). At higher temperatures this carbamate ion slowly decomposed to 4-nitroaniline. In ctab the decarboxylation of the N-(4-nitrophenyl)carbamate ion was strongly catalysed (× 45) and thus the observed final product even at 26�C was 4-nitroaniline. Kinetic studies in water and in ctab were consistent with decomposition of the methyl carbamate (la) by a BAC2 mechanism and the 2,2,2-trifluoroethyl carbamate (lc) by an E1cB mechanism. The extent of ionization of the substrate carbamates to nitranion (4) was enhanced in ctab as was the rate of spontaneous decomposition of the nitranion. This is in contrast to other E1cB reactions reported in the literature, for which the rate of spontaneous decomposition of the carbanion was inhibited by ctab. For compounds reacting by the BAC2 mechanism, the tetrahedral intermediate (2) partitioned in favour of C-OR bond breaking rather than C-N bond breaking observed previously for some N-methyl derivatives.

Micellar catalysis of the basic hydrolysis of anilides. III. α-Substituted N-methyl-N-p-nitrophenylacetamides

1980 ◽  
Vol 33 (8) ◽  
pp. 1771 ◽  
Author(s):  
TJ Broxton ◽  
NW Duddy
Keyword(s):  
Cetyltrimethylammonium Bromide ◽  
Substituent Effects ◽  
Micellar Catalysis ◽  
Single Parameter ◽  
Parameter Analysis ◽  
Basic Hydrolysis ◽  
Presence And Absence ◽  
Hydrolysis Of ◽  
Acetic Acids

The basic hydrolysis of a number of α-substituted N-methyl-N-p- nitrophenylacetamides has been studied both in the presence and absence of micelles of cetyltrimethylammonium bromide (ctab). Unlike the related p-nitrophenyl esters of a-substituted acetic acids, no evidence for the operation of the E1cb mechanism in the basic hydrolysis has been detected. Reasons for the differences between the amides and esters are discussed. Substituent effects on the hydrolysis of the amides have been studied both by single-parameter and dual-parameter analysis.

Synthesis of Some 2'-C-Alkyl Derivatives of 9-(2-Phosphonomethoxyethyl)adenine and Related Compounds

1994 ◽  
Vol 59 (9) ◽  
pp. 2069-2094 ◽  
Author(s):  
Hana Dvořáková ◽  
Antonín Holý ◽  
Ivan Rosenberg
Keyword(s):  
Reaction Pathway ◽  
Sodium Hydride ◽  
Amino Group ◽  
Trimethylsilyl Derivative ◽  
Phosphonic Acids ◽  
Alkyl Derivatives ◽  
Hydrolysis Of ◽  
Trifluoromethyl Derivative ◽  
Derivatives Of ◽  
Related Compounds

To study the effect of β-substitution in 2'-alkyl derivatives of 9-(2-phosphonomethoxyethyl)adenine (Ia) on the antiviral activity or group specificity, these derivatives were synthesized. 9-(2-Hydroxyalkyl)adenines VIII were prepared by alkylation of adenine with suitably substituted oxiranes XIII or 2-hydroxyalkyl p-toluenesulfonates IV and VI. After protection of the adenine amino group by benzoylation (compounds IX) or amidine formation (compounds X), the intermediates were alkylated with diisopropyl p-toluenesulfonyloxymethanephosphonate (XI) in the presence of sodium hydride. After deprotection, the obtained phosphonate diesters XII were converted into phosphonic acids I by transsilylation and hydrolysis. This synthetic scheme was used for the preparation of ethyl (Ie), propyl (If), 2-propyl (Ig), 2-methylpropyl (Ih), cyclopropyl (Ii), cyclohexyl (Ij), benzyl (Ik) and phenyl (Il) derivatives. The 2'-trifluoromethyl derivative XXIIa was prepared analogously from 9-(2-hydroxy-3,3,3-trifluoropropyl)adenine (XXa), obtained by alkylation of adenine sodium salt with 2-hydroxy-3,3,3-trifluoropropyl bromide. 2'-Trimethylsilyl derivative XIXa was obtained by alkylation of adenine with 2-diisopropylphosphonomethoxy-3-(4-toluenesulfonyloxy)propyltrimethylsilane (XVII) followed by transsilylation and hydrolysis of diester XVIIIa. 2,6-Diaminopurine derivatives XVIIId and XXIIb were obtained analogously. 9-(3-Phosphonomethoxybutyl)adenine (XXVIII) and 9-(2-methyl-2-phosphonomethoxypropyl)adenine (XXXV) were prepared from the corresponding hydroxy derivatives XXVIb and XXXII, respectively, by the same reaction pathway as derivatives I.

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