Nitriles displacement reactions

Displacement Reactions. The reactions RCl RCN are carried out by heating a threefold excess of concentrated aqueous NaCN solution with the alkyl chloride and 2 mol % tributyUiexadecylphosphonium bromide for 2 h (1) (see Nitriles). 

Because of resonance stabilization of the anion, a tet-nazolyl moiety is often employed successfully as a bioisosteric replacement for a carboxy group. An example in this subclass is provided by azosemide (27). Benzonitrile analogue is prepared by phosphorus oxychloride dehydration of the corresponding benzamide. Next, a nucleophilic aromatic displacement reaction of the fluorine atom leads to The synthesis concludes with the 1,3-dipolar addition of azide to the nitrile liinction to produce the diuretic azosemi de (27). ... 

Carboxylic acids can be prepared from nitriles by reaction with hot aqueous acid or base by a mechanism that we ll see in Section 20.9. Since nitriles themselves are usually made by Sts 2 reaction of a primary or secondary7 alkyl halide with CN , the two-step sequence of cyanide displacement followed by nitiile hydrolysis is a good way to make a carboxylic acid from an alkyl halide (RBr —> RC=N RC02H). 

Lithium salts of resonance-stabilized organic anions have also found a role in carbon-phosphorus bond formation by displacement at phosphorus. The generation of the lithium salt derived from acetonitrile (or other aliphatic nitriles by reaction with butyl lithium or lithium diisopropylamide) provides for carbon-phosphorus bond formation by displacement of halide from phosphorus (Equation 4.24).68... 

BioH14 is a mdo-polyborane, therefore, it is expected that it forms adducts with Lewis bases. This is indeed the case but with concomitant loss of hydrogen as shown in Eq. (51). These adducts of the type BioHi2-2L (L = amines, pyridine, phosphines, nitriles, dialkylsulfides inter alia) proved to be versatile reagents. For instance, when triethylamine is used to replace acetonitrile from the adduct not only does the expected replacement occur but in preference also a proton shift (most likely prior to the base displacement reaction) with cluster closure to the decahydro-doso-decaborate(2—) (Eq. 52) ... 

Nucleophilic displacement reactions have also been reported. When compounds 125 are reacted with CuCN (DMF or N-methylpyrrolidone, heat) nitriles are obtained (83JHC1003 88JOU179, 88ZOR199 90MI3). 

The percent ring substitution (% RS) of the polymer with active sites affects catalytic activity. Polystyrenes with < 25 % RS with lipophilic quarternary onium ions are swollen in triphase mixtures almost entirely by the organic phase. Water reduces the activity of anions by hydrogen bonding. In most triphase nucleophilic displacement reactions onium ion catalysts with <25% RS are highly active, and those with >40% RS, such as most commercial ion exchange resins, are much less active. However, low % RS is not critical for the reactions of hydroxide ion with active methylene compounds, as commericial ion exchange resins work well in alkylation of active nitriles. 

Reaction of several acetylated 1 -bromo-/ -D-glycopyranosyl cyanides with mercury(II) acetate in acetic acid-acetic anhydride gave the peracetyl / -d-ald-2-ulopyranosyl nitriles (for example, compound 148) as the major products.85 From the precursor of compound 148, the thioglycosides 149 and 150 were also obtained by nucleophilic displacement reactions.86... 

Amines are at the same low oxidation level as alcohols and consequently are easily prepared by reduction. Amides and nitriles are reduced efficiently by LAH to amines. Nitriles give only primary amines while amides give 1°, 2°, or 3° amines depending on the number of carbon substituents on the amide nitrogen. The advantage of this method is that amides are easy to prepare from acid chlorides and amines while nitriles are available by displacement reactions. 

This method has been widely used for primary and secondary halides tertiary halides undergo ready elimination under these conditions to yield the alkene and give little or no nitrile. Traces of the corresponding isonitriles (R-NC) may be formed during these displacement reactions but may be removed by virtue of... 

Fig. 5-18. Phase-transfer catalyzed nucleophilic displacement reaction of a haloalkane, R-Cl, with sodium cyanide, Na+CN , to yield a nitrile, R-CN, in the presence of sub-stoichiometric amounts of a quaternary ammonium chloride, Q+CP, as PT catalyst.

Nitrile complexes may be synthesized by the thermal reaction of the parent carbonyl with the appropriate nitrile, but elevated temperatures are required, and this often leads to complications of thermal decomposition and/or further reaction. A more controlled route widely used is the irradiation of the metal carbonyl in a solution of the nitrile, or in a donor solvent capable of forming a labile complex such as Cr(CO),THF. Addition of the nitrile displaces the weakly bound solvent molecule 172, 248). 

The oxidative-displacement reaction of allyl compounds RX (R = C3H5, C4H7, C3H4CI X = I, SCN) with [(MeCN)3M(CO)3] (M = Mo, W) gave the metal(II) complexes [(MeCN)2M(CO)2(Tr-allyl)X], which reacted further with bipy, o-phen, diacetylbis(dimethylhydrazone), and CjHj to displace the remaining nitrile groups 170, 253), and with PPh3 to form... 

Nitriles comprise one of the classical functional groups of organic chemistry. The present review deals with useful preparative methods for the synthesis of nitriles by displacement reactions. In view of the extensive current activity in this area, it is necessary to be selective rather than comprehensive. A series of outstanding review articleswill guarantee rapid acquaintance with the field and some complementary accounts,not repeatedly cited, inform of recent developments. 

The low reactivity of vinyl halides in nucleophilic displacement reactions is well known. For preparative procedures the use of CuCN, sometimes in the presence of bases like pyridine, at temperatures higher than 200 °C (closed vessel) is recommended. This technique may be used to prepare maleo-nitrile and fumaronitrile from cis- and /ranj-l,2-diiodoethylene (equation 1). j 20 h, shaking, 150 °C, 59%... 

The term phase transfer catalysis was coined by Starks to describe the mechanism of catalysis of reactions between water-soluble inorganic salts and water-insoluble organic substrates by lipophilic quaternary ammonium and phosphonium ions Ql). His investigations of nucleophilic displacement reactions, such as that of aqueous sodium cyanide with 1-chlorooctane, and the investigations of Makosza on reactions of aqueous sodium hydroxide with chloroform to generate dichlorocarbene, and with active ketones and nitriles to generate carbanions, pioneered the field in the mid-1960 s. It was nearly fifteen years before many such processes were adopted in industry. Starks now estimates there are about sixty phase transfer catalytic processes in use worldwide, mostly in pharmaceutical and fine chemical manufacturing (32V... 

The standard displacement reactions of the chloro group and the elimination to nitrile oxides have been studied by Werner and his co-workers. Weygand and Bauer in 1927 studied the reaction of hydroxamoyl chlorides with alkali salts of ethyl cyanoacetate they obtained isoxazole derivatives. Likewise, Quilico and his students utilized hydroxamoyl chlorides to synthesize numerous isoxazole derivatives. 

The sodium salt of succinimide reacts with a,o)-dibromide such as 4.93 to give 4.94. In a second step, the enolate of a-phenyl nitrile displaced the bromide moiety in 4.94 to give 4.95. Acid hydrolysis converted the nitrile to an acid and the imide to an amine, leading to 4.96. Reaction of 4.94 (n = 4) with the indicated nitrile (R = H) led to a 57% yield of 2-phenyl-6-aminohexanoic acid (4.96a). Similarly prepared were 2-phenyl-7-aminoheptanoic acid 4.96b) in 68% yield 2-phenyl-8-amino-octanoic acid 4.96c) in 68% yield 2-phenyl-10-aminodecanoic acid 4.96d) in 44% yield and, 2-phenyl-12-aminododecanoic acid 4.96e) in 26% yield, all with R = H.45 Many other nitriles were used in this sequence to give a wide variety of phenyl... 

---