Halides, aryl reaction with sodium

Primary alkyl chlorides and bromides can be distinguished from aryl and alkenyl halides by reaction with sodium iodide in acetone (Finkelstein reaction) ... 

Aryl and vinyl nitriles have been prepared very efficiently from the corresponding bromides by palladium-catalyzed reactions under microwaves. This energy source has been employed for the conversion of these nitriles into aryl and vinyl tetrazoles by cycloaddition reactions with sodium azide (Scheme 9.66). The direct transformation of aryl halides to the aryl tetrazoles in a one pot procedure could be accomplished both in solution and on a solid support [115], The reactions were complete in a few minutes, a reaction time considerably shorter than those previously reported for the thermal reactions. The cydoadditions were performed with sodium azide and ammonium chloride in DMF and, although no explosion occurred in the development of this work, the authors point out the necessity of taking adequate precautions against this eventuality. 

The low reactivity of aryl halides towards nucleophilic reagents makes their reaction with sodium ditelluride unattractive for the preparation of diaryl ditellurides. Low yields are obtained, like the similar reaction with sodium telluride (see Section 3.1.2.1). 

It has been found that the use, as ligands, of electron-poor phosphines, such as 1,1 -bis(diphenylphosphino)ferrocene, enhances yields in the palladium-catalysed reaction of aryl bromides with sodium phenoxides to yield diaryl ethers.87 Palladium-catalysed coupling of ethynylated derivatives of bipyridine or terpyridine with the corresponding bipyridine or terpyridine halides or triflates has been used in the synthesis of preorganized polytopic ligands.88... 

The ready replacement of the halogen in an alkyl or an aralkyl halide illustrated in Expt 5.157 by reaction with sodium or potassium cyanide is inapplicable in the case of aryl halides wherein the halogen is relatively inert. However, aryl bromides can be converted into nitriles in good yield by heating them for several hours at about 200 °C with copper(i) cyanide in the presence of pyridine (e.g. 1-naphthonitrile, Expt 6.168). This displacement may be achieved more readily by using dimethylformamide as the solvent, when reaction is usually completed in a few hours at reflux temperature.63... 

The coupling of alkyl halides by treatment with sodium to give a symmetrical product is called the Wurtz reaction. Side reactions (elimination and rearrangement) are so common that the reaction is seldom used. Mixed Wurtz reactions of two alkyl halides are even less feasible because of the number of products obtained. A somewhat more useful reaction (though still not very good) takes place when a mixture of an alkyl and an aryl halide is treated with sodium to give an alkylated aromatic compound (the Wurtz-Fittig reaction)... 

Sulfides (thioethers) can be obtained by replacing the halogen of alkyl and suitable aryl halides in a reaction with sodium sulfide, this being analogous to the preparation of thiols and disulfides. The reaction is usually carried out... 

Aryl halides containing less reactive halogen can also be converted into sulfides by thiols if heavy-metal (lead, zinc, mercury) thiols are used at 225-230° 1-naphthyl, 2-naphthyl sulfide,301 1- and 2-naphthyl phenyl sulfide,302 and 1-and 2-naphthyl o-, m-, and p-tolyl sulfide303 have been obtained in this way. When the heavy-metal thiolates are too stable and do not react with aryl bromides even at 240°, the aryl sulfides can nevertheless often be prepared by a generally applicable reaction of aryl iodides with sodium thiolates under the influence of copper as catalyst.304... 

Aryl and vinyl azides can also be accessed in one step from the corresponding halides or triflates via a copper-catalyzed reaction with sodium azide in the presence of a catalytic amount of L-proline (Scheme 7.5C) [104]. In this fashion, a range of 1,4-disubstituted 1,2,3-triazoles can be prepared in excellent yields [105-107]. Anilines can also be converted to aryl azides by the reaction with tert-butyl nitrite and azidotrimethylsilane [108]. The resulting azides can be submitted to the CuAAC conditions without isolation, furnishing triazole products in excellent yields. Microwave heating further improves both reactions, significantly reducing reaction time [56, 62]. 

In the reaction of Q,/3-unsaturated ketones and esters, sometimes simple Michael-type addition (insertion and hydrogenolysis, or hydroarylation, and hydroalkenylation) of alkenes is observed[53,54]. For example, a simple addition product 56 to methyl vinyl ketone was obtained by the reaction of the heteroaromatic iodide 55[S5]. The corresponding bromide affords the usual insertion-elimination product. Saturated ketones are obtained cleanly by hydroarylation of o,/3l-unsaturated ketones with aryl halides in the presence of sodium formate, which hydrogenolyses the R—Pd—I intermediate to R— Pd—H[56]. Intramolecular hydroarylation is a useful reaction. The diiodide 57 reacts smoothly with sodium formate to give a model compound for the afla-toxin 58. (see Section 1.1.6)[57]. Use of triethylammonium formate and BU4NCI gives better results. 

The alkenyloxirane 126 in excess reacts with aryl and alkenyl halides or triflates in the presence of sodium formate to afford the allylic alcohol 127[104], Similarly, the reaction of the alkenyloxetane 128 gives the homo-allylic alcohol 130[105]. These reactions can be explained by insertion of the double bond in the Ar—Pd bond, followed by ring opening (or /3-eliraination) to form the allylic or homoallylic alkoxypalladium 129, which is converted into the allylic 127 or homoallylic alcohol 130 by the reaction of formate. The 3-alkenamide 132 was obtained by the reaction of the 4-alkenyl-2-azetizinone 131 with aryl iodide and sodium formate [106]. 

The terminal diyne 320 is prepared by coupling of the zinc acetylide 318 with /rfln.s-l-iodo-2-chloroethylenc (319), followed by elimination of HCI with sodium amide[231]. Similarly, terminal di- and triynes are prepared by using cw-l,2-dichloroethylene[232]. The 1-alkenyl or l-aryl-2-(perefluoroalkyl) acetylene 321 is prepared by the reaction of a zinc acetylide with halides[233]. 

The generally accepted mechanism for nucleophilic aromatic substitution m nitro substituted aryl halides illustrated for the reaction of p fluoromtrobenzene with sodium methoxide is outlined m Figure 23 3 It is a two step addition-elimination mechanism, m which addition of the nucleophile to the aryl halide is followed by elimination of the halide leaving group Figure 23 4 shows the structure of the key intermediate The mech anism is consistent with the following experimental observations... 

Aryl bromides were also perfluoroethylated under these conditions [205] The key to improved yields was the azeotropic removal of water from the sodium perfluoroalkylcarboxylate [205] Partial success was achieved with sodium hepta-fluorobutyrate [204] Related work with halonaphthalene and anthracenes has been reported [206 207] The main limitation of this sodium perfluoroalkylcarboxylate methodology is the need for 2 to 4 equivalents of the salt to achieve reasonable yields A trifluoromethylcopper solution can be prepared by the reaction of bis(tri-fluoromethyl)mercury with copper powder in /V-methylpyrrolidone (NMP) at 140 °C [208] (equation 138) or by the reaction of N-trifluoromethyl-A-nitro-sotnfluoromethane sulfonamide with activated copper in dipolar aprotic solvents [209] This trifluoromethylcopper solution can be used to trifluoromethylate aro matic [209], benzylic [209], and heterocyclic halides [209]... 

The most common types of aryl halides in nucleophilic aromatic substitutions are those that bear- o- or p-nitro substituents. Among other classes of reactive aryl halides, a few merit special consideration. One class includes highly fluorinated aromatic compounds such as hexafluorobenzene, which undergoes substitution of one of its fluorines on reaction with nucleophiles such as sodium methoxide. 

For the in situ preparation of the required arenediazonium salt from an aryl amine by application of the diazotization reaction, an acid HX is used, that corresponds to the halo substituent X to be introduced onto the aromatic ring. Otherwise—e.g. when using HCl/CuBr—a mixture of aryl chloride and aryl bromide will be obtained. The copper-(l) salt 2 (chloride or bromide) is usually prepared by dissolving the appropriate sodium halide in an aqueous solution of copper-(ll) sulfate and then adding sodium hydrogensulfite to reduce copper-(ll) to copper-(1). Copper-(l) cyanide CuCN can be obtained by treatment of copper-(l) chloride with sodium cyanide. 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

Next to the formation of Grignard reagents, the most important application of this reaction is the conversion of alkyl and aryl halides to organolithium compounds, but it has also been carried out with many other metals, (e.g., Na, Be, Zn, Hg, As, Sb, and Sn). With sodium, the Wurtz reaction (10-93) is an important side reaction. In some cases, where the reaction between a halide and a metal is too slow, an alloy of the metal with potassium or sodium can be used instead. The most important example is the preparation of tetraethyl lead from ethyl bromide and a Pb—Na alloy. 

Substituted phenacyl anthranilates were prepared by reaction of sodium anthranilate with substituted phenacyl halides in DMF. The phenacyl esters were cyclized in polyphosphoric add or by heating to give the respective substituted 2-aryl-3-hydroxyquinoline-4(l. -ones in high yield <95CCC(60)1357>. 

Palladium-catalyzed hydroarylation of sterically hindered PTAD adduct 157 with aryl halides in the presence of triphenylarsine, sodium acetate, and DMSO provides a 1 1 mixture of 170 and 171. The same reaction done with sodium fluoride and formic acid provides mixtures containing 171 as the major product. Apparently, the use of sodium fluoride as a base allows the selective formation of the opening products 171 in good yields (Equation 19). Similarly, the 2,3-phthalazine-l,4-dione adduct 172 provides the corresponding products 173 and 174 (Equation 20) <2002AGE3375>. 

Although sodium sulphide reacts readily with haloalkanes [2] and activated aryl halides (see Chapter 2) [e.g. 3-5] in the presence of a quaternary ammonium catalyst to form symmetrical thioethers (Table 4.1), a major side reaction results in the formation of disulphides owing to the oxidation of the intermediate thiols under the basic conditions. Consequently, little use has been made of this procedure for the synthesis of thioethers [3, 6], but the corresponding reaction of the a,(0-dihaloalkanes to yield cyclic thioethers has proved to be a valuable procedure for the synthesis of thietanes [7] (Table 4.2). The ring closure with the secondary dihaloalkanes is considerably more difficult to effect than is the reaction of the primary dihaloalkanes. 1,3-Dihydrobenzo[c]thiophene (89%) is produced in the reaction of 1,2-bis(bromomethyl)benzene with sodium sulphide (Scheme 4.1) [8]. The direct... 

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