Nucleophilic reactions chlorides

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

Using sulfur trioxide plus chlorine, or sulfur dioxide plus chlorine, sulfur monochloride yields thionyl chloride [7719-09-7] SOCI2. Various nucleophilic reactions can displace the chlorine atoms of sulfur monochloride ... 

Nucleophilic Reactions. Useful nucleophilic substitutions of halothiophenes are readily achieved in copper-mediated reactions. Of particular note is the ready conversion of 3-bromoderivatives to the corresponding 3-chloroderivatives with copper(I)chloride in hot /V, /V- dim ethyl form am i de (26). High yields of alkoxythiophenes are obtained from bromo- and iodothiophenes on reaction with sodium alkoxide in the appropriate alcohol, and catalyzed by copper(II) oxide, a trace of potassium iodide, and in more recent years a phase-transfer catalyst (27). 

In the synthesis of carpamic acid (98), Mitsutaka and Ogawa have used 1,2-dihydropyridine as a starting material [80H(14)169]. Photooxygenation of dihydropyridine 8h afforded enr/o-peroxide 96. Subsequent stereoselective nucleophilic reaction of 96 with ethyl vinyl ether in the presence of tin chloride gave tetrahydropyridinol 97, which was then converted into carpamic acid (98) in six more steps. 

Nucleophilic chlorination in the 3-position was observed when the 5,8-dibromo derivative of 200 was heated strongly with phosphorus penta-chloride, a reaction also common to the [3,4-rf] compounds (72MI1). 

Acylation of carbon nucleophiles can also be carried out with more reactive acylating agents such as acid anhydrides and acyl chlorides. These reactions must... 

The compounds referred to as azolides are heterocyclic amides in which the amide nitrogen is part of an azole ring, such as imidazole, pyrazole, triazole, tetrazole, benzimidazole, benzotriazole, and their substituted derivatives. In contrast to normal amides, most of which show particularly low reactivities in such nucleophilic reactions as hydrolysis, alcoholysis, aminolysis, etc., the azolides are characterized by high reactivities in reactions with nucleophiles within the carbonyl group placing these compounds at about the same reactivity level as the corresponding acid chlorides or anhydrides. 11... 

Nucleophilic Reactions of Organozirconocene Chlorides with Epoxides... 

Poirier, Wang and Westaway (1994) also investigated the relationship between transition state structure and the magnitude of the secondary a-deuterium KIE in a theoretical study of the SN2 reactions between methyl and ethyl chlorides and fluorides with several different nucleophiles (reaction (12)). 

Nucleophilic Reactions.—Attack on Saturated Carbon. Selected examples of the Arbusov reaction include phosphorylation of the chloroacetophenones (1) to give phosphonates, which cyclized to (2) in the presence of acid chlorides,1 formation of the azodiphosphonate (3) from 2,2 -dichloro-2,2 -azopropane,2 3 and the reaction of 2-chloro-3,4-dihydro-3-oxo-2//-l,4-benzothiazine (4) with triethyl phosphite to give the 2-phosphonate (5), which is used as an olefin synthon.8 Bis(trimethylsilyl) trimethylsiloxymethylphosphonite (6) has been synthesized by silylation of hydroxy-methylphosphonous acid, and, as expected, undergoes a normal Arbusov reaction with alkyl halides to give the phosphonates (7).4 This series of reactions, followed by... 

A solvent-dependent chemoselectivity, pointing to a dependence of the relative reactivities of the 1,2- and 1,1-disubstituted double bonds on solvent polarity and nucleophilicity, has been observed in the reaction of benzeneselenenyl chloride with 2-methylenebicyclo[2.2.1]hept-5-ene (159) which gives products 160-163140. In methylene chloride the reaction occurs with a moderate chemoselectivity, attack on the endocyclic bond being preferred over that on the exocyclic one in a 60 40 ratio. In methanol, the addition is completely chemoselective and the attack occurs exclusively on the endocyclic double bond (equation 132). It may be further noted that 162 and 163 isomerize and solvolyze at high temperatures, leading to the homoallylic products 160 and 161. 

The synthesis of polyhalide salts, R4NX , used in electrophilic substitution reactions, are described in Chapter 2 and H-bonded complexed salts with the free acid, R4NHX2, which are used for example in acid-catalysed cleavage reactions and in electrophilic addition reactions with alkenes, are often produced in situ [33], although the fluorides are obtained by modification of method I.I.I.B. [19, 34], The in situ formation of such salts can inhibit normal nucleophilic reactions [35, 36]. Quaternary ammonium chlorometallates have been synthesized from quaternary ammonium chlorides and transition metal chlorides, such as IrClj and PtCl4, and are highly efficient catalysts for phase-transfer reactions and for metal complex promoted reactions [37]. 

The nucleophilic property of the encapsulated anion was dramatically changed compared to the free anion. Thus, [2-Ag4(/U-Cl)4(/U4-Cl)] acts as a nucleophile to convert alkyl-iodide to alkyl-chloride in high yield. Puddephatt proposed a mechanism where the [2-Ag4(/U-Cl)4(/U4-Cl)] anion reacts with alkyl-iodide to give [2-Ag4(/z-Cl)4(/U4-I)] and alkyl-chloride. The reaction occurs in high yield with the reactivity sequence tertiary>second-ary>primary alkyl. 

The reaction of a carboxylic acid with sodium hydroxide (NaOH) produces the sodium salt of the carboxylic acid. The sodium salt then reacts with an acid chloride to form the anhydride. Figure 12-16 illustrates the final step in this process. In this reaction, the carboxylate ion behaves as a nucleophile and attacks the carbonyl Ccirbon atom of the acid chloride. The reaction of a carboxylic acid with sodium hydroxide also generates water, which, if not removed, reacts with the acid chloride and lowers the yield of the reaction. 

One of the nitro groups in furazan (78) can be substituted by chloride and azide, and displacement of sulfonyl groups has also been reported. Nucleophilic reactions in the homocyclic ring of benzofuroxans may be accompanied by deoxygenation of the A-oxide 4-nitrobenzofuroxan with dialkyl-amines affords 4-dialkylamino-7-nitrobenzofurazans as the major product. Substitution reactions... 

Dyong and Bendlin52 pointed out the possibility of functionalization of sorbic acid at C-3, -4, and -5 in the desired way. Introduction of two hydroxyl groups, at CA and C-5, may be accomplished stereospecifi-cally by means of cis-hvdroxylation, or by intermediation of an epoxide. Michael-type addition of a nucleophile to C-3 of the conjugated double-bond provides the possibility of obtaining all four diastereo-isomeric products. In this way, N-acetyl-DL-acosamine (137, 3-acet-amido-2,3,6-trideoxy-DL-arabmo-hexopyranose) was synthesized from 133 (obtained from the epoxide 129 in an aluminum chloride-catalyzed reaction with acetone). The amide 134 wasN-acetylated and... 

A poly(arylene ether phenylquinoxaline) of structure 14 was prepared by the aluminum chloride catalyzed reaction of 6,6 -bis[2-(4-phenoxyphenyl)-3-phenylquinoxaline] and isophthaloyl chloride in 1,2-dichloroethane [51]. The polymer had an inherent viscosity of 1.29 dL/g and a Tg of 224 °C. A polymer of the same chemical structure was prepared from the reaction of 3,3, 4,4 -tetraaminobiphenyl with l,3-bis(phenylglyoxalyl-4-phenoxy-4 -benzoyl)-benzene that gave a Tg of 239 °C [16], significantly higher than that prepared by the electrophilic route. In addition, a polymer of the same chemical structure (third polymer in Table 3) prepared via nucleophilic substitution exhibited a Tg of 240 °C. 

Preparation of acid chlorides is one of the easiest methods to activate an acid. Thionyl chloride (SOCh) [12, 13] is used widely to generate acid chlorides. The reaction of SOCb with water or other nucleophiles is extremely exothermic, and generates large quantities of sulfur dioxide and HCI. Nevertheless, acid chlorides (via SOCI2) and mixed anhydrides (via acid chlorides or chloroformates), are the most common reagents used for amide formation in the pharmaceutical industry, with N,N -carbonyldiiniidazole (CDl) growing in popularity[8]. 

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