Chloro-substituted benzoyl chlorides

Earlier work of this school was concerned to establish heats of formation of halogen-containing organic compounds by measuring heats of hydrolysis. Heats of hydrolysis of acetyl fluoride, chloride, bromide, and iodide402 of the chloro-substituted acetyl chlorides oi of the benzoyl halides and of chloral and bromal 3 have also been made. Comparison with heats of formation derived from heats of combustion is not normally possible, but there is a large discrepancy between the two methods for benzoyl chloride, where an early combustion measurement is available, in the sense that the determined heat of combustion appears to be about 14 kcal low. 

The cr-substituent effects and solvent effects (extended Grunwald-Winstein equation) for solvolyses of / -X-substituted benzoyl chlorides (X = OMe, Me, H, and Cl) in 97% wt/wt hexafluoroisopropanol/water was explained by two competing pathways. Plots of log k versus a were consistent with a cationic path and explained by an 5 n2-5n1 spectrum of mechanism. Electron-donating groups favoured the reaction and values of p increased in the order AcOH < HCO2H < TEE < HFIP. A benzoyl cation intermediate was trapped in hexafluoroisopropanol. Ab initio calculations of heterolytic bond dissociation energies of various chloro- and fluoro-substituted and other benzoyl chlorides were correlated with log k for solvolyses... 

Another approach for anchoring the carboxyl groups to the aromatic ring of PS is to use a two-step method [35]. In this method, first, the reaction of PS with 2-chloro-benzoylchloride is carried out. The product can then be followed as shown in Scheme (8). If chloro atom is as o-position on benzoyl chloride the reaction occurred as (a). If there is no substitute group o-position on benzoyl chloride, the preferred is reaction (b). 

In general, reactive carbon electrophiles have been shown to react preferentially at the nitrogen atoms of the purine bicycle (see Section 10.11.5.2.1). However, 9-(2,3,5-tris-0-/r /T-butyldimethylsilyl)-a-D-ribofuranosyl-6-chloro-2-(tri-butylstannyOpurine reacted with benzoyl chloride to substitute the 2-tributylstannyl group (PhCOCl, pyridine, toluene, 60% yield) <1997JOC6833>. Indirect C-alkylations have been achieved through deprotonation and alkylation see Section 10.11.5.3.4. The major routes to (7-alkyl and (7-aryl substitution are through nucleophilic displacement or transition metal-catalyzed reactions of halopurines see Sections 10.11.7.4.1 and 10.11.7.4.2. 

The cyclic sulfonamide (377) can be prepared by heating 5-aminopentanesulfonyl chloride. 4-Chloro-2-benzoylbenzenesulfonyl chloride reacts with acetamidine to give the o-benzoyl-N-phenylsulfonylamidine which can be cyclized with base to give the fully unsaturated 1,2-benzothiazepine 1,1-dioxide (378 R = R1 = H). Alkyl-substituted amidines give the 3-imino derivatives (66USP3377357). 

Occasionally, the reaction is complex and affords a multitude of products. For example, 2,4-dichloronitrobenzene and benzyl cyanide produce a mixture containing bis(4-chloro-2-benzoyl)azoxybenzene, 2-benzoyl-4-chlo-ronitrobenzene, 5,7-dichloroanthranil, and a-(5-chloro-2-nitrophenyl) benzyl cyanide.180 Using sodium hydride in dimethylsulfoxide as the base, the substituted benzyl cyanide, formed by direct nucleophilic displacement of chloride, becomes the major product (48%), whereas with sodium hydroxide and benzyltriethylammonium chloride the dichloroanthranil (33%) predominates. 

In Eqn. (c) compound (II) is treated with p-chloro-benzoyl chloride in the presence of diy dimethyl formamide and sodium hydride when the corresponding n-substituted ester i.e., terCbutyl-l-p-chlorobenzoyl-2-methyl-5-methoxy-3-indolyl-acetate (III) is formed with the elimination of one mole of HCl. 

When a series of 8-substituted adenosines was treated with thionyl chloride in HMPA, the corresponding 5 -chloro- 5 -deoxy compounds were obtained in moderate to good yields. When 2 -deoxyuridine was treated with benzoyl chloride in DMF, 5 -chloro-2 ,5 -dideoxyuridine was formed slowly, whereas the same reagents in the presence of MCPBA gave rapid chlorination of the heterocycle to give 5-chloro-2 -deo3qruridine. Several other similar cases were also reported. The unsaturated compound (56), and Its (. -isomer. 

Iodine can, however, be displaced cleanly with bromine<150) and with chlorine if iodine monochloride or sulfuryl chloride and benzoyl peroxide are used as chlorinating agents.reactivity ratios for the displacement of bromine by chlorine from substituted bromo-benzenes have been found to be in the order p-phenyl > o-methoxy > p-chloro > un-... 

Among dichloro bis-electrophiles, malonyl chloride with enamine 183b affords pyridone 189, probably resulting from C-alkylation and cyclocondensation followed by aromatization (02T2821). Finally, o-chloro-benzoylchloride leads to C-benzoylation and subsequent intramolecular substitution of the isolable intermediate to yield quinoline 190 (03ARK (is.2)146). 

Several reactive chloro compounds have been used to attempt to effect the controlled monochlorination of aromatic amines. One such reagent is N-chlorosuccinimide, with which the chlorination of aniline, for example, can be largely restricted to monosubstitution, although a mixture of isomers (orthopara, 1.9 1) is obtained.24 One approach to the achievement of specific ortho chlorination is illustrated by the synthesis of o-chlorobenzanilide (Expt 6.61), readily hydrolysable to o-chloroaniline. The anilide is formed, by a type of Swi mechanism indicated below, when AT-phenylhydroxylamine is benzoylated and the product is treated with thionyl chloride.25 The reaction has been successfully applied to several substituted JV-phenylhydroxylamines, prepared by the controlled reduction of the corresponding substituted nitro compounds (cf. Expt 6.87). 

Pyrazolo[3,4-Z)]pyridines, the 7-chloro-6-fluoro-2,4-dimethylquinoline and its mercapto-thiadiazolyl or oxadiazolyl quinolines 21 were prepared via Diels-Alder reaction conversion of methyl 2-(3-oxo-3-phenylpropenylamino)benzoate into 3-benzoyl-l.S -quinolin-4-one 22 . A mixture of aniline derivatives and malonic ester gave a variety of 3-aryl-4-hydroxyquinolin-2(l//)-ones 23. Condensation of isatins with ketones afforded quinoline-4-carboxylic acids. 2-Aryl-l,2,3,4-tetrahydro-4-quinolinones 22 and carbazolylquinolone were also prepared. The substitution of 2-chloroquinoline gave the 2-substituted quinolines. Basic alumina has catalyzed the C-C bond formation between 2-hydroxy-1,4-naphthoquinone and 2-chloroquinoline derivative to give 21. Reaction of organic halides with 8-hydroxyquinolines gave the respective ethers. The azodye derivatives of 21 were prepared in the absence of solvent. Silica gel catalyzed the formation of 2-ketomethylquinolines from reaction of 2-methylquinolines with acyl chlorides. 

Deactivation of C-3 by the carboxyl group at C-2 prevents attack by electrophiles, for example, the Mannich reaction results in substitution at C-3 in many chromones [16] but not with chromone-2-carboxylic acid or ester. Radical (homolytic) chlorination of the ester or nitrile using sulphuryl chloride and a trace of benzoyl peroxide gives the 3-chloro derivative (84) [57, 149, 167]. 

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