Isothiocyanates with alcohols

Synthesis.—A standard method for the preparation of G-alkyl thiocarba-mates and S-alkyl dithiocarbamates depends on the reaction of isothiocyanates with alcohols and thiols, respectively, and several new examples of its applicability have appeared during the past two years (refs. 132, 252, 634, and 635). In special cases the products, either spontaneously or promoted by a catalyst present, underwent a subsequent ring-closure reaction to form heterocycles containing the thionocarbamate or the dithiocarbamate moiety. Phenols and thiophenols reacted with isothiocyanates in a similar way. Some Oethyl selenonocarbamates have been obtained in good yields by ethanolysis of isoselenocyanates, and Mayer and his co-workers have reported on the successful synthesis of the heterocyclic... 

CH rCHCH NHCSNH. Colourless crystalline solid with a faint garlic-like odour m.p. 74 C. Manufactured by treating propenyl isothiocyanate with a solution of ammonia in alcohol. It has been given by injection in the treatment of conditions associated with the formation of excessive fibrous tissue. Toxic side reactions may occur. Propenyl thiourea is a chemical sensitizer for photographic silver halide emulsions. 

Thiophosgene reacts with alcohols and phenols to form chlorothionoformates or thiocarbonates. The most studied reactions of thiophosgene are with primary amines to give isothiocyanates and with secondary amines to give thiocarbamyl chlorides ... 

Secondary butyl isothiocyanate, CH3. CH. CH(CH3). N C S, has been isolated from the oils of Cardamine amara and Cochlearia. It is a liquid with a powerful, irritating sulphur odour, having a specific gravity 0 9415 and boiling at 159° to 160°. Warmed with alcoholic solution of ammonia, it yields a thiourea, melting at 135° to 136°. 

This method was extensively reviewed in <84CHEC-I(4)545> and a brief summary is presented here interestingly, since the mid-1980s, this reaction has become less popular. A(-Aryl benzhydrazonyl chlorides react with thiobenzamides to form trisubstituted thiadiazolines which on treatment with alcohols furnish the 2-alkoxy derivative (Scheme 25). A-Arylbenzhydrazonyl chlorides also react with thioketenes to yield 5-methylene thiadiazolines (Equation (16)). Other examples involve the addition of the nitrileimine generated from A-trifluoroacetobenzhydrazonyl bromide to the 0=S of potassium isothiocyanate and methyl isocyanate <87JHC1391>. 

Methylthiourea has been prepared from methyl isothiocyanate and ammonia in alcoholic 1 or aqueous2 solution, from methylammonium thiocyanate,3 and by heating the methyl or ethyl ester of A-methyldithiocarbamic acid with alcoholic ammonia.4... 

Fluorinated alkylisocyanates and isothiocyanates add alcohols, mercaptans, and amines to yield stable 1 1 adducts [76]. When the reaction is performed with carboxylic acids, the anhydrides first formed decompose to give A -fluoroalky-lated amides [77]... 

One of the most commonly used class of derivatization agents for diasteromer formation are isothiocyanates and isocyanates. Enantiomers of /3-blockers, amphetamine, epinephrine, methamphetamine, and mexiletine have been resolved after derivatization with these agents. Isothiocyanates produce thiourea derivatives upon reaction with primary and secondary amines. Thiourea derivatives also provide a strong UV absorbance for the detection of enantiomers lacking a strong UV chromophore. Isocyanates produce ureas when reacted with amines. The physical properties of these ureas are similar to thiourea derivatives. Isocyanates will also react with alcohols to yield carbamates. 

Azine approach. 3-Amino derivatives are readily prepared by the reaction of a 2-hydroxymethylpiperidine with an isothiocyanate with subsequent acid-catalyzed cyclization of the intermediate thiourea. With an optically active alcohol (520) the cyclization proceeds with inversion of the configuration (78MI42901). 

The isocyanate, SF5NCO, is easily hydrolyzed to SF5NH2 and C02, whereas SF5NCS is hydrolytically very stable. Both compounds undergo addition reactions with substrates containing easily replaceable hydrogen atoms, i.e., alcohols, thiols, and amines. With alcohols (thiols) the isocyanate and isothiocyanate give urethanes and thiourethanes, respectively. 

The isothiocyanates are transformed into thiocarbamates by reaction with alcohols or into the acetamides by reaction with acetic acid or anhydride and sodium acetate. These transformations have also been applied to the preparation of unsaturated aminosugars73,74. Thus, suprafa-cial rearrangement of ethyl 2.3,4-trideoxy-6-0-methanesulfonyl-4-thiocyan ato-a-D-t/ireo-hex-2-enopyranoside to the 2-isothiocyanatc occurs in refluxing toluene (1 h), whereas the erythro-epimer needs to be heated in dimethylformamide for 6 hours73. This difference in reactivity might be due to an unfavorable anomeric effect and C-6 in an axial orientation in the transition state of the errr/iro-epimer, respectively. 

At a pH Mgher than 5.5-6.0, isothiocyanates react in vitro and in vivo with thiol compounds (%), thereby blocking essential HS-containing constituents in the cytoplasm. It is still an open question whether isothiocyanates are group reagents of all the HS-containing enzymes, but they presumably also react with enzymes of other types, because they also react easily with alcohols and amines. 

Thioureas are obtained analogously by boiling an amine hydrochloride and an alkali thiocyanate in aqueous solution66 or an amine and a thioiso-cyanate in alcohol 67 aromatic thioisocyanates generally react even in the cold. Further, aqueous ammonia solutions are converted smoothly into mono-alkylthioureas by isothiocyanates.68 Isothiocyanates can be converted directly into symmetrical thioureas by boiling them in aqueous dimethylformamide or dimethyl sulfoxide the thiocarbamic acids formed as intermediates by partial hydrolysis add to unchanged isothiocyanate with loss of COS.69... 

Acetoxy isothiocyanates. Amino alcohols are converted to isothiocyanatoalkyl acetates on treatment with EtjN, CSj, and then AC2O-DABCO at room temperature. 

On the other hand, isothiocyanates are known to be reactive with a variety of food constituents, such as amines, amino acids, proteins, thiols, and alcohols, due to their electrophilic properties to give a variety of compounds, including thioureas and dithiocarbamates [32]. Despite their chemical nature, only limited information has been made available regarding the stability of isothiocyanates and the biological activity of reaction products of isothiocyanates with food constituents [33-35]. 

Allyl isorhodanide Allyl isosulfocyanate. See Allyl isothiocyanate Allyl isothiocyanate CAS 57-06-7 EINECS/ELINCS 200-309-2 UN 1545 (DOT) FEMA 2034 Synonyms Allyl isorhodanide Allyl isosulfocyanate Allyl mustard oil Allyl thiocarbonimide Artificial mustard oil 3-lsothiocyanato-1-propene Isothiocyanic acid allyl ester Mustard oil 3-Propenyl isothiocyanate Synthetic mustard oil Volatile oil of mustard Empirical C4H5NS Formula CH2=CHCH2NCS Properties Colorless-pale yel. liq., pungent Irritable odor, sharp pungent mustard taste misc. with alcohol, carbon disulfide, ether, mostorg. soivs. ... 

Figure 8.66 Reaction of isothiocyanates with nucleophilic reagents HX = water (H O) - thiocarbamoic acid, alcohol (R -OH) - thiocarbamate, sulfan (H2S) - dithiocarbamoic acid, ammonia (NH3) - A/-alkylthiourea, amine (R -NH2) - N,N -dlalkylthiourea.

Polyphenols Sinapicacid Free and esterified phenolic compounds condensed tannins Dark colour Bitter taste Astringent effects React with fimctional groups at protein, similar to isothiocyanates Use of reducing agents to avoid oxidation Pre-extraction with alcohols Membrane processing Adsorption processing... 

Among the most convenient derivatives of primary and secondary amines are substituted thioureas obtained by the reaction of amines with arylisothiocyanates. As isothiocyanates do not react under normal conditions either with water or with alcohol, it is not necessary to utilize anhydrous amines. This is the great advantage of this method. By-products are formed only to a small extent and can be eliminated easily by crystalliza-... 

A soln. of p-bromophenyl isothiocyanate in alcohol allowed to react gradually with an equimolar amount of aq. NaHS, 3 moles 37%-formalin soln. and aq. benzylamine sulfate added, stirred 0.5 hr. at room temp. 5-benzyl-3-p-bromophenyltetrahydro-l,3,5-thiadiazine-2-thione. Y 85%. P. Kristidn and J. Bernat, Tetrah. Let. 1968, 679. 

Add 0 -5 ml. of phenyl isothiocyanate to the distillate and shake the mixture vigorously for 3-4 minutes. If no derivative separates, crystallisation may be induced by cooling the flask in ice and scratching the walls with a glass rod. Filter off the crude product, wash it with a little 50 per nent. ethanol, and recrystaUise from hot dilute alcohol. (See Table 111,123 for melting points of phenylthiourea derivatives of amines.)... 

Fluotination of aromatic isothiocyanates occurs much more readily than that of alkyl isothiocyanates. Alcohols treated with IF ia DMF give 30—70% yields of their respective formates. 

The flask is immersed in an oil bath heated to 120° and dry steam is then passed through the reaction mixture. The first few cubic centimeters of distillate contain the excess of thiophos-gene and are discarded. The isothiocyanate passes over with the water as an oil that solidifies on cooling. The steam distillation requires about four hours. The crude material is crystallized from two parts of ethyl alcohol at 50°, from which it separates as white needles melting at 44-45°. The yield is 245-275 g. (72-81 per cent of the theoretical amount) (Note 3). 

Chlorophenyl isothiocyanate has also been prepared by treating an alcoholic solution of sym-di-/)-chlorophenyl thiourea with iodine/ from ammonium -chloroplienyldithiocarbamate and lead nitrate/ (p. 72), and from the action of thiophosgene with /)-chloroaniline. ... 

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