Chlorobenzonitriles

Chlorobenzonitrile [873-32-5] M 137.6, m 45-46°. Crystd to constant melting point from benzene/pet ether (b 40-60°). 

Aj Preparation of (2-Amino-5-ChlorophenyljPhenylmethaneimine (4356 CB) A solution of 228.7 g (1.5 mols) of 2-amino-5-chlorobenzonitrile in 1,800 ml of dry ether is added slowly in the course of about 3.5 hours to a solution of phenyl magnesium bromide prepared from 109 g (4.5 g-atoms) of magnesium turnings and 848 g (5.4 mols) of bromobenzene In 3,600 ml of anhydrous ether, and the mixture then heated under reflux for 15 hours. 

Aminocephalosporanic acid Cefazolin sodium Ceftizoxime Cephacetriie sodium Cephalogiycin Cephaloridine Cephalothin sodium Cephapirin sodium 2-Amino-5-chlorobenzonitrile Ciorazepate dipotassium 2-Amino-5-chlorobenzophenone Chlordiazepoxide HCi Pinazepam Prazepam... 

This synthetic process is applicable to the preparation of other aromatic nitriles from aldehydes. The submitters have used it to prepare 5-bromoindole-3-carbonitrile, 7-azaindole-3-carboni-trile, j)-chlorobenzonitrile, 3,4,5-trimethoxybenzonitrile, and p-N,N-dimethylaminobenzonitrile.9 There are several advantages to its use. They include (a) readily available and inexpensive reagents, (b) a simple, time-saving procedure, and (c) fair to good yields of nitrile obtained by a one-step method. 

Chloroanthracene, 43,15 3-ChIorobenzaldehyde, 40,10 -Chlorobenzonitrile, 43, 59 2-ChIoro-6-methylphenyl isocyanide,... 

Chlorobenzonitrile (99%) was purchased from Aldrich Chemical Company and used as received. 

Pd/P(t-Bu)., in the presence of Cy2NMe, is an unusually mild and versatile catalyst for Heck reactions of aryl chlorides (Tables 1 and 2) (as well as for room-temperature reactions of aryl bromides).21 22 23 Example A, the coupling of chlorobenzene with butyl methacrylate, illustrates the application of this method to the stereoselective synthesis of a trisubstituted olefin a-methylcinnamic acid derivatives are an important family of compounds that possess biological activity (e.g., hypolipidemic24 and antibiotic25) and serve as intermediates in the synthesis of pharmaceuticals (e.g., Sulindac, a non-steroidal anti-inflammatory drug26). Example B, the coupling of 4-chlorobenzonitrile with styrene, demonstrates that Pd/P(t-Bu). can catalyze the Heck reaction of activated aryl chlorides at room temperature. 

Lithiomethyl-3-phenylquinoxaline (114) and o-chlorobenzonitrile gave 2-(f>-amino-o-chlorostyryl)-3-phenylquinoxaline (115) (no details 28%).973... 

Reaction of m-chlorobenzonitrile with ethyl Grignard reagent produces ethylarylketone 191. Bromination in methylene chloride followed by displacement of the a-bromoketone moiety with t-butylamine... 

A novel nitrilase was purified from Aspergillus niger K10 cultivated on 2-cyanopyridine. It was found to be homologous to a putative nitrilase from Aspergillus fumigatus Af293. The nitrilase exhibited maximum activity at 45 °C and pH 8.0 with much less activity observed at slightly acid pH. Its substrate preference was for 4-cyanopyridine, benzonitrile, 1,4-dicyanobenzene, thio-phen-2-acetonitrile, 3-chlorobenzonitrile, 3-cyanopyridine, and 4-chlorobenzonitrile. ( )-2-Phenylpropionitrile was only poorly converted by this enzyme and with minimal enantioselectivity. The enzyme was shown to be multimeric (>650 kDa) and be stabilized in the presence of sorbitol and xylitol [57]. 

N-benzyladamantyl-2-imines, and 2-methyleneadamantanes were studied (352, 353). In particular, X-ray single-crystal analysis confirmed the configuration of the oxathiazoline 185, resulting from the favored attack of nitrile oxide on the 5-fluoroadamantane-2-thione. 2-Silyl-substituted oxathiazole 186 was synthesized by the 1,3-dipolar cycloaddition reaction of phenyl triphenylsilyl thioketone with 4-chlorobenzonitrile oxide (354). 

Cations, cyclopropenyl, 54, 97 o-Chlorobenzaldehyde, by reduction of o-chlorobenzonitrile with Raney nickel alloy in formic acid, 51, 23 p-Chlorobenzaldehyde, by redaction of p-chlorobenzonitflle with Raney nickel alloy,1 51, 22... 

FIGURE 2.30. Redox catalysis induction of Srn1 reactions. Cyclic voltammetry in liquid ammonia + 0.1 M KC1 at —40°C of (a) redox catalyis of the reductive cleavage of 2-chlorobenzonitrile, RX, by 4-cyanopyridine, P. The dotted reversible cyclic voltammogram corresponds to P in the absence of RX. The solid line shows the catalytic increase of the current, (b) Transformation of the voltammogram upon addition of the nucleophile PhS. Adapted from Figure 1 in reference 23, with permisison from the American Chemical Society. 

Fig. 16 Examples of current dips (a) 2-iodoquinoline (1.6 mM) with benzenethiolate ions (44 mM) (b) 2-iodoquinoline (5.2 mM) with diethylphosphite ions (100mM). Scan rate, 0.2Vs . Example of trace crossing (c) 4-chlorobenzonitrile (1.55mM) with diethylphosphite ions (663 mM). Scan rate, 0.215 Vs . In liq. NHj/O.l m KBr at — 40°C. (Adapted from Amatore et a ., 1980a,b.)...

Fig. 17 Indirect electrochemical induction of Sr I reactions. Cyclic voltammetry of (a) 4-cyanopyridine (2.2 mM) in the absence (—) and presence (—) of 8.9 mM 2-chlorobenzonitrile (b) 4-cyanopyridine (6.6 mM) in the presence of 8.9 mM 2-chloro-benzonitrile and 35 mM PhS -. (Adapted from Amatore el al., 1984b.)...

Photolytic. When dichlobenil was irradiated in methanol with a 450-W mercury lamp and a Corex filter for 8 h, o-chlorobenzonitrile and benzonitrile formed as the major and minor products, respectively (Plimmer, 1970). 

Chlorobenzonitrile was coupled with p-tolylboronic acid affording the important pharmaceutical intermediate 2-(p-tolyl)benzonitrile in good yield... 

Chorazepate Chorazepate, 7-chloro-2,3-dihydro-2,2-dihydroxy-5-phenyl-1H-1,4-benzo-diazepin-3-carboxylic acid (5.1.34), which is used in the form of a dipotassium salt, is synthesized by yet another interesting synthetic scheme. 2-Amino-5-chlorobenzonitrile is used as the initial compound, which upon reaction with phenyhnagnesiumbromide is transformed into 2-amino-5-chlorbenzophenone imine (5.1.32). Reacting this with amino-malonic ester gives a heterocyclization product, 7-chloro-l,3-dihydro-3-carbethoxy-5-phenyl-2H-benzodiazepin-2-one (5.1.33), which upon hydrolysis using an alcoholic solution of potassium hydroxide forms a dipotassium salt (5.1.34), chlorazepate [30-32]. 

Other products of these rearrangements would be alkoxy- and acyloxynitrenes. In the decomposition of 163g, which afforded acetic benzoic anhydride (175) as the major product, a significant component of the reaction mixture was 4-chlorobenzonitrile (176), the formation of which can be rationalized according to Scheme 28. 

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