Thiocyanation of aromatic amines

Thiocarbonates, synthesis of, 17, 3 Thiocyanation of aromatic amines, phenols, and polynuclear hydrocarbons, 3, 6 Thiophenes, synthesis of, 6, 9 Thorpe-Ziegler condensation, 15, 1 31 Tiemann reaction, 3, 9 Tiffeneau-Demjanov reaction, 11, 2 Tin(n) enolates, 46, 1 Tin hydride method to prepare radicals,... 

The procedure given above is a convenient method involving the formation of an active thiocyanogen derivative in the presence of dimethylaniline. Thiocyanation of aromatic amines and phenols has also been accomplished electrochemically. ... 

Type K Syntheses (C—C—N—C—S). The reaction between jS-(ethoxycar-bonyl)acryloyl isothiocyanates (obtained from the acid chloride and lead thiocyanate) and aromatic amines gives the 2-arylamino-A -thiazolin-4-ones (48) in good yield.2-(Substituted amino)-A -thiazolines may also be obtained in high yields by allowing vicinal iodo-isothiocyanates to react with amines e.g. PhCH(NCS)CH2l with amines, in the absence of light, gives (49). ... 

The iminothiazocines (53) were prepared via addition of aromatic amines to 5-bromopentane thiocyanate (prepared in turn from 1,5-dibromopentane via formation of the monophthalimide derivative) the initial adduct undergoes intramolecular alkylation to afford the cyclized products in 85-100% yield (Scheme 17) <7lCJC97l>. 

Selective thiocarbamoylation of aromatic amines by Scheme 5.51 using encapsulated methyl thiocyanate molecules of a host-guest 1 4 cage complex of the metallopolymeric cap-... 

From -Chlorovinylmethine-immonium and Bunte Salts Types C and E). j8-Chloro-vinylmethine-immonium salts (9) react with alkali-metal thiocyanates in the presence of aromatic amines to give isothiazoles (10). The reaction is considered to proceed by a nucleophilic displacement to give eventually the jS-thiocyanovinyl aldehyde anils ArC(SCN)=CHCH=NR, which cyclize in situ. The reaction of (9) with sodium thiosulphate gives Bunte salts, which react with amines (R R NH) to give the stable j8-aminovinyl thioketones (11), and hence, by oxidative cycliza-tion, the isothiazolium salts (10 R = H) (Scheme 1). 

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). 

MPO (Myeloperoxidase) [EC 1.11.1.7] catalyzes the hydrogen peroxide dependent two-electron oxidation of halides (CD, I, Br ) and thiocyanate to the corresponding hypohalous acids and hypothiocyanate which are cytotoxic to invading pathogens. In addition, MPO is capable of the singleelectron oxidation of a wide variety of aromatic alcohols and amines. " ... 

Phenols and aromatic amines are thiocyanated on electrolysis in an aqueous solution of SCN" [13]. The reaction is indirect since there is compelling evidence that the thiocyanat-ing reagent must be (SCN)2, formed by anodic oxidation of SCN"" [156]. In MeCN solution oxidation of SCN"" and SeCN in the presence of phenol of various aromatic amines leads to thiocyanation and selenocyanation in 55-80% yields 157 [109]. 

In its reactions thiocyanogen is somewhat like bromine without a catalyst. Direct replacement of hydrogen by the thiocyano group, thiocyanation, is limited to aromatic amines and phenols, and a few very reactive hydrocarbons. Aniline is converted into 4-thiocyanoaniline in 97% yield, o-toluidine into 4-thiocyano-2-methylaniline in 80% yield, anthranilic acid into 5-thiocyanoanthranilic acid in 80% yield. Phenols likewise are thiocyanated in the para position if available, otherwise in the ortho position. 

Catalysis by other nucleophiles has also been found for secondary aliphatic amines, e. g., by thiocyanate (Fan and Tannenbaum, 1973), and by thiourea and its tetramethyl derivative (Meyer and Williams, 1988, and earlier investigations mentioned there). The results are comparable to those of aromatic diazotizations (Zollinger, 1994, Sect. 3.3). 

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... 

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 full paper detailing the conversion of primary aliphatic and aromatic amines into the corresponding thiocyanates via 5,6-dihydro-2,4-diphenyl-naphtho[l,2- ]pyridinium salts (c/. Vol. 4, p. 193) has appeared. ... 

Amines as Catalysts. Some reports have appeared on the use of amines as catalysts in PTC nucleophilic substitution methods. For example, the preparation of alkyl thiocyanates or nitriles from alkyl bromides in two-phase systems may be assisted by a variety of primary, secondary, or tertiary amines as alternatives to quaternary ions. Efficient catalysis seems to require a sterically unhindered amino group with relatively high basicity (J.e. t-alkyl and aromatic amines are not fully efficient), and a total number of carbon atoms in the amine of greater than six to achieve good phase distribution of the catalysts. A similar study on the alkylation of benzyl methyl ketone reached the same conclusions, and from various observations e.g. that the reaction displayed an induction period at low catalyst concentration) it was postulated that initial alkylation of the amine by the alkylating agent (usually a halide) was essential to provide quaternary ions as the actual catalyst,... 

A new synthesis of thiocyanates from aliphatic amines (Scheme 46) utilizes the readily available 2,4,6-triphenylpyrylium thiocyanate (80). The intermediate l-substituted-2,4,6-triphenylpyridinium thiocyanates (81) are smoothly pyrolysed into the corresponding thiocyanates (82) in excellent yields. These promising syntheses complement those available in the aromatic amine series via diazotization. 

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