Thiocyanates reaction with aromatic

In organo-fluorine compounds fluorine atoms can be eliminated by nucleophilic sulfur species to form C —S bonds. In principle, the fluorine to be eliminated can be bonded to aliphatic or araliphatic compounds, as well as to aromatic or heterocyclic compounds however, the replacement proceeds more efficiently the more the fluorine is activated. Therefore, the synthetic usefulness of these reactions is the broadest with fluoroaromatic compounds, including heteroaromatics, with which the reactions often proceed smoothly under mild conditions. The nucleophilic sulfur compound to be reacted is. in most cases, an aliphatic or aromatic thiol or a metal sulfide, but reactions with, for example, thiourea or ammonium thiocyanate have also been described. The sulfur introduced this way can be either oxidized or removed by reduction, opening additional possibilities for modifications of the original fluoro compounds. 

Agbalyan et al 9 recently employed this reaction in the synthesis of several 3,4-dihydroisoquinoline derivatives with unsaturated substituents in the 1-position. The Madrid group50 has shown that (with the exception of benzyl thiocyanate) aliphatic and aromatic thiocyanates yield 1-alkylthio- and l-arvlthio-3,4-dihydroisoquinolines as expected (cf. Table V). 

Electrolytic introduction of sulfur-containing substituents may be performed by anodic thiocyanation. The primary anodic process of an aromatic system in such a reaction is the loss of an electron with formation of a cation radical. This radical may lose a proton or react with a nucleophile to give a neutral radical which again may lose an electron to form a carbonium ion loss of a proton or reaction with a nucleophile may complete the reaction. 

Aryl cyanates react with aromatic acid chlorides in the presence of anlimony(V) chloride to give 2-aryl-4,6-bis(aryloxy)oxadiazinium salts 5a, b 62 thiocyanates react analogously giving 5c-n but in this case the reaction is of wider scope as both the thiocyanates and the acid chlorides may be aromatic or aliphatic.63,64... 

For introduction of SCN into aromatic compounds the Sandmeyer reaction or its Gattermann variant is much more widely applicable than direct replacement of H by SCN (see page 202). An aqueous thiocyanate solution and CuSCN are added to a diazonium salt solution prepared in the usual way, or the addition is made gradually in the reverse direction — the diazonium salt to an aqueous solution of K3[Cu(SCN)4] copper powder can also be used.1264-1266 Reaction, with evolution of nitrogen, often occurs at room temperature or on... 

An interesting application of the electrochemical oxidation of thiocyanate ion is the preparation of alkyl and aryl thiocyanates via anodically generated thiocyanogen. Alcohols have been converted to the corresponding thiocyanates by constant current electrolysis of NaSCN in CH2CI2 containing triphenylphosphite and 2,6-lutidinium perchlorate. The yields were fair to good for the primary and secondary alcohols, but no thiocyanate formation was observed with tertiary ones. Similarly, various aromatic amines and phenols were thiocyanated in a two-step procedure, namely electrochemical preparation of (SCN)2 and subsequent reaction with the substrates k... 

Alkylation of metal thiocyanates has been known to produce isothiocyanates, and this can be followed by treatment with carbon nucleophiles to give thioamides. Alternatively, metal thiocyanates can be used in the Friedel-Crafts reactions of aromatic compounds. For example, the reactions of aromatic compounds bearing alkoxy groups and heteroaromatic compounds with potassium thiocyanate under acidic conditions are carried out at 30 °C (Eq. 11) [34]. In the reaction a large excess of methanesulfonic acid is used. 

A standard condition has been optimized for this reaction, in which the aryl amine is diazotized in 10 times its amount of acetic acid, followed by the addition of one equivalent of cuprous halide in hydrohalic acid. Under these conditions, the acetate salt of aryl amine is relatively soluble, and less froth and tarry material are formed during diazo transformation. In addition, chlorination, bromination, and iodonation of p-haloaniline to dihalobenzenes under such standard conditions give almost comparable average yields. Other modifications of this reaction include the formation of phenyl selenocyanate by the reaction with potassium selenocyanate, and aryl nitrile by the reaction with nickel cyanide. Moreover, this reaction has been extended to the preparation of phenyl thiocyanate, phenyl isothiocyanate and aromatic sulfonyl chloride. ... 

The detection of aromatic and aliphatic cyanides can be carried out by heating the solid sample or a dry residue in a micro test tube in admixtiue with elemental sulfur. Thiocyanic acid is formed, and this can be detected on the basis of its reaction with ferric salts (58). 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

It has also been argued10,40 that the second mechanism (rapid, reversible interconversion of II and IV) cannot be general. The basis for this contention is the fact that electrophilic catalysis is rare in nucleophilic aromatic substitution of non-heterocyclic substrates, an exception being the 2000-fold acceleration by thorium ion of the rate of reaction of 2,4-dinitrofluorobenzene with thiocyanate... 

Another important click reaction is the cycloaddition of azides. The addition of sodium azide to nitriles to give l//-tetrazoles is shown to proceed readily in water with zinc salts as catalysts (Eq. 11.71).122 The scope of the reaction is quite broad a variety of aromatic nitriles, activated and nonactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. The reaction of an arylacetylene with an azide in hot water gave 1,4-disubstituted 1,2,3-triazoles in high yields,123 while a similar reaction between a terminal aliphatic alkyne and an azide (except 111 - nitroazidobenzcnc) afforded a mixture of regioisomers with... 

The addition of sodium azide to nitriles to give IH-tetrazoles is shown to proceed readily in water with zinc salts as catalysts. The scope of the reaction is quite broad a variety of aromatic nitriles, activated and unactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. 

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