2-chloro derivatives, hydrolysis

Direct bromination readily yields the 6-bromo derivative (111), just as with uracil. Analogous chlorination and iodination requires the presence of alkalies and even then proceeds in low yield. The 6-chloro derivative (113) was also obtained by partial hydrolysis of the postulated 3,5,6-trichloro-l,2,4-triazine (e.g.. Section II,B,6). The 6-bromo derivative (5-bromo-6-azauracil) served as the starting substance for several other derivatives. It was converted to the amino derivative (114) by ammonium acetate which, by means of sodium nitrite in hydrochloric acid, yielded a mixture of 6-chloro and 6-hydroxy derivatives. A modified Schiemann reaction was not suitable for preparing the 6-fluoro derivative. The 6-hydroxy derivative (115) (an isomer of cyanuric acid and the most acidic substance of this group, pKa — 2.95) was more conveniently prepared by alkaline hydrolysis of the 6-amino derivative. Further the bromo derivative was reacted with ethanolamine to prepare the 6-(2-hydroxyethyl) derivative however, this could not be converted to the corresponding 2-chloroethyl derivative. Similarly, the dimethylamino, morpholino, and hydrazino derivatives were prepared from the 6-bromo com-pound. ... 

The usual order found with halogenonitrobenzenes is F > Cl Br I, the order of Cl and Br being variable, just as in heteroaromatic reactivity. The position of fluorine is of interest the available data indicate that it is usually the same as for nitrobenzene derivatives. Thus, in acid hydrolysis the order F > Cl for 2-halogeno-quinolines can be deduced beyond doubt since the fluoro derivative appears to react in the non-protonated form and the chloro derivative to resist hydrolytic attack even in the protonated form under appropriate conditions (Section II,D, l,d). Furthermore, in the benzo-thiazole ring, fluorine is displaced by the CHgO reagent at a rate 10 times that for chlorine. ... 

When the cyclization of compound 807 (R = H) was carried out in boiling phosphoryl chloride, the isomeric chloro derivatives (816 and 817) were obtained in 98% yield. They were separated by the use of column chromatography, in which the linear product (816) was prepared in 50% yield, and the angular product (817) was prepared in 27% yield (74GEP2335760). Earlier, 31% offuro[2,3-j ]quinolinecarboxylic acid (814, R = H) and 7% of furo[3,2-/]quinolinecarboxylic acid (815, R = R1 = H) were isolated from the cyclization of compound 807 (R = H) in phosphoryl chloride and after hydrolysis of the reaction product with hydrochloric acid (71GEP2030899). 

Active methylene anions also displace the 5-halogen substituent for example, the 5-chloro derivative (152) (X = Cl) reacts with the sodium salt of ethyl acetoacetate to give (90) (R = Et) which is readily hydrolyzed and decarboxylated (Scheme 22) <82M793>. The 5-chloro substituent in (152) (X = Cl) is also readily displaced by the lithium enolate of 3-(methoxycarbonyl)quinuclidine (153) to give (154) which on hydrolysis with sodium hydroxide and then decarboxylation with hydrochloric... 

Stoichiometry (28) is followed under neutral or in alkaline aqueous conditions and (29) in concentrated mineral acids. In acid solution reaction (28) is powerfully inhibited and in the absence of general acids or bases the rate of hydrolysis is a function of pH. At pH >5.0 the reaction is first-order in OH but below this value there is a region where the rate of hydrolysis is largely independent of pH followed by a region where the rate falls as [H30+] increases. The kinetic data at various temperatures both with pure water and buffer solutions, the solvent isotope effect and the rate increase of the 4-chloro derivative ( 2-fold) are compatible with the interpretation of the hydrolysis in terms of two mechanisms. These are a dominant bimolecular reaction between hydroxide ion and acyl cyanide at pH >5.0 and a dominant water reaction at lower pH, the latter susceptible to general base catalysis and inhibition by acids. The data at pH <5.0 can be rationalised by a carbonyl addition intermediate and are compatible with a two-step, but not one-step, cyclic mechanism for hydration. Benzoyl cyanide is more reactive towards water than benzoyl fluoride, but less reactive than benzoyl chloride and anhydride, an unexpected result since HCN has a smaller dissociation constant than HF or RC02H. There are no grounds, however, to suspect that an ionisation mechanism is involved. 

Conversion of the 3, 5 -diacetyl thymidine 652 (R = Me) to the chloro derivative 653 followed by reaction with sodium azide in anhydrous DMF gave 654, whose hydrolysis gave 655 (86JHC1401). The 2 -deoxy-2, 2 -difluoro analog of 655 was prepared (93EUP576230) (Scheme 132). 

Acylation of the ring nitrogen of fluorinated dibenzoxazepine 13 afforded ring-opened products 53 after addition of chloride anion and hydrolysis (Scheme 5). The hydroxy and chloro derivatives 52 could be isolated and characterized by X-ray crystallography <2003JFC(119)15>. 

The rate constant for the hydrolysis of t-butyl chloride at 298 K decreases as x2 increases in DMSO + water mixtures (Heinonen and Tommila, 1965). A clear-cut contrast between TA and TNAN mixtures is shown by the volumes of activation and related parameters for the solvolysis of benzyl chloride in acetone + water (TA) and DMSO + water mixtures (Fig. 57). Thus, in the latter system, the curves show no marked extrema but there is a shallow minimum in AV near x2 = 0 4. Extrema in Sm AH and T. 5m AS for the hydrolysis of benzyl chloride are also smoothed out when the co-solvent is changed from acetone to DMSO (Tommila, 1966). A similar trend is observed in the kinetic parameters for the hydrolysis of chloromethyl and methyl trifluoroacetates (Cleve, 1972a). For example, in the case of the chloro derivative, 6mACp decreases gradually over the range 0 < x2 < 0-2 for DMSO + water mixtures, whereas a minimum is observed in this range for acetone + water mixtures. 

Three cyanohydrins (la-c) (see Table 16.1) were subjected to hydrolysis in the presence of a number of nitrilases (Figure 16.2). The reactants included the standard substrate mandelonitrile (la) and its o-chloro derivative (lb), which is of... 

Dioxo-5,7-dialkyl-3-oxides of 476 have been synthesized by ring-closure and converted by means of thionyl chloride (20°, 6 hr) into the 6,8-dioxo-5,7-dialkyl-4-chloro derivatives of 1,2,3,5,7-penta-azanaphthalene. The 4-chloro derivative was unstable to acid-catalyzed hydrolysis (20° in moist solvent for several hours or boiling... 

Pepper has briefly reported on their activity vis-a-vis styrene, but has never published a full account of his investigation Asami and Tokura used CISO3H in sulphur dioxide for the polymerisation of the same monomer and found it to be a very efficient initiator. Recently, Masuda et al. published a concise study of the polymerisaticMi of styrene by both acids in various solvents. As expected, the chloro derivative was found to be a weaker promoter than the fluorosulphonic acid. Both systems gave asymptotic yields indicating that fast initiation was followed by an important termination reaction. Incorporation of chlorine into the polystyrenes prepared with chlorosulphonic acid (but absence of sulphur) suggested that this acid decomposes in the polymerisation process (hydrolysis ). On the whole, the limited amount of evidence obtained in this study does not allow any mechanistic conclusion. 

Some of the reactions of coordinated donor atoms are quite unexpected. Thus, coordinated thiol will react with alkyl bromides to form sulfonium salts. Here, there are lone pairs on the donor atom in addition to the one involved in forming the coordinate bond. Their qualitative reactivity is hardly affected by coordination. Ammonia which has been coordinated to platinum (IV) will form iV-chloro derivatives when treated with hypochlorite. This reaction involves an N-H bond rather than the lone pair. Coordinated PCI3 will undergo hydrolysis to give coordinated P(0H)3, a reaction which involves the P-Cl bonds rather than the lone pair. 

Hydrolysis of the 10-chloro derivative 36 in 0.5 M sodium hydroxide solution at 50°C for 6 hr gave the 2,6-diazabicyclo[5.4.0]undecan-l-one (39), probably via the 11-membered azalactam (38) through intramolecular alkylation (84JHC583). 

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