Isothiocyanates with amines

Since chiral amines are much more available than chiral isocyanates, ureas have often been obtained from reaction of an amine used as the chiral source with a stoichiometric amount of a non-chiral isocyanate [41]. Similarly, thioureas are obtained by reacting isothiocyanates with amines. The corresponding ureas and thioureas (examples in the following sections) are... 

Thioureas are most commonly prepared from reaction of isothiocyanates with amines. Also there are some reports on reactions of anime or carbodiimides with several thionating reagents. AA -Disubstituted thioureas bearing double NH groups have been developed as sensors, and as catalysts because of their hydrogen bonding ability. A,A -Disubstituted thiourea-linked sugar chains have been prepared by the reaction of isothiocyanate with amine. 

Reaction of isothiocyanate with amine gives the corresponding thioureas. Many reports are appeared.102 111 The thiourea derivatives have been prepared by reactions of isothiocyanates with arylamines (Scheme 39) and reacted with some substrates to afford heterocyclic compounds, such as 2-amino-4//-ben-zothiazine, 1,3-thiazine, 1,3-thiazinone and l,3-thiazolidin-4-one.112 115... 

Cyclic thiourea derivatives having three different types of cyclophane structure (ortho-meta, meta-meta and meta-para) and a lariat-type thiourea have been synthesized, using reaction of isothiocyanate with amine.230 Cyclic thioureas have been obtained from formaldehyde aminals and sulfur (Sg) (Scheme 77).231... 

In a series of publications and patents,63 64 66"79 Wieniawski and coworkers reported the results of investigations of the reaction of sugar isothiocyanates with amines and various substituted hydrazides of heterocyclic acids. The reaction of isothiocyanate 2 with 2,6-diaminopyridine 81 was described,63 and the formation of dithioureide 82 as the sole product was observed. The... 

Syntheses of heterocycles by reactions of 3-oxobutyl isothiocyanate with amines 03EJO415. 

Coupling of Sugar Isothiocyanates with Amine Nucleophiles... 

In this extensive study of thiourea synthesis by coupling isothiocyanates with amines under mechanochemical conditions of neat and LAG, a total of 49 different thiourea derivatives were prepared. Since the supramolecular chemistry of simple synunetrical and nonsymmetrical diarylthiouieas had not previously been studied in detail, the information from the PXRD patterns of the milling products in this work also allowed for a systematic analysis of structural features of diarylthio-ureas. The three main self-assembly motifs were identified. A characteristic supramolecular synthon based on bifurcated N—H - S hydrogen bonds was found in most cases, whereby the individual thiourea molecules were assembled into chains aligned in a head-to-head (parallel molecular dipoles) or head-to-tail (antiparallel molecular dipoles) manner. In the case of slerically hindered thioureas, such as A -(2,6-dimethylphenyl)-A -phenylthiourea, the third motif arising from discrete cen-trosymmetric dimers based on rI(S) supramolecular synthon was found. A detailed look at the measured PXRD patterns for aU diarylthioureas revealed that solid-state structures of these compounds could be classified into two structural families, denoted as family I and family II (Fig. 1.11). 

Reaction of isothiocyanate with amine gives the corresponding thioureas. 

A -Aroyl-A -substituted thiourea derivatives have been prepared from reaction of aroyl isothiocyanate with amines under solid-liquid phase transfer catalysis condition using polyethylene glycol-400 (PEG-400) as catalyst. Reaction of isothiocyanates with lithiated chiral secondary amines has provided chiral thioureas (Scheme 40). °... 

The most common method for the preparation of thioureas is, however, based on the reaction of isothiocyanates with amines, and, not unexpectedly, the majority of papers deal with this particular reaction. 6-2 1 Among the N-substituent groups thus introduced into thiourea are 3-cyclo-pentenyl, 1-adamantyl, furfuryl, diphenylphosphinoyl, diphenyl-phosphinothioyl, AW-9,10-diacetyldihydro-2-phena2inyl, and variously substituted aryls. - If the isothiocyanate or the amine contains other reactive groups, cyclization to heterocyclic compounds containing the thiourea grouping may occur, either spontaneously or promoted by external influence, as recently demonstrated in the synthesis of thiones derived from imidazoline, pyrimidine, - and j-triazine. - ... 

Synthesis.—The most common method for the preparation of thioureas is based on the reaction of isothiocyanates with amines, and, not unexpectedly, the majority of the papers dealing with the preparation of new... 

Aminopyridotriazinones 123 were obtained from guanidines 122 in hot hydrochloric acid-dioxane solution however, yields were moderate. The intermediates 122 could be obtained from the reaction of 2-aminopyridine 120 with ethoxycarbonyl isothiocyanate, followed by treatment of thioureas 121 with amines in the presence of HgCl2 (Scheme 12) <2002JHC1061>. 

Figure 7.23 Chelating groups such as the isothiocyanate derivative of DTPA can be used to create multivalent chelating complexes with amine-dendrimers. Such complexes are able to coordinate multiple metal ions for detection, imaging, or radioimmunotherapy purposes.

Figure 10.2 The isothiocyanate group of DTTA can react with amine-containing molecules to form isothiourea bonds.

Bromo- or -hydroxy-isothiocyanates react with amines to give 2-amino- or 2-imino-l,3-thiazepines depending on the nature of the amine (710PP27,71CJC971). 

A comparatively large selection of thioureas can be formed from the reaction of amines with isothiocyanates, hence they are attractive starting materials for formation of guanidines. A common solution-phase approach to this reaction involves abstraction of the sulfur via a thiophillic metal salt, like mercuric chloride.10 For solid-phase syntheses, however, formation of insoluble heavy-metal sulfides can have undesirable effects on resin properties and on biological assays that may be performed on the product. A more relevant strategy, with respect to this chapter, is S-alkylation of thioureas and then reaction of the methyl carbamimidothioates formed (e.g., 5, Scheme 6) with amines. This type of process has been used extensively in solution-phase syntheses.1 Ul4 Two examples are shown in Scheme 6 11 the second is an intramolecular variant, which involves concomitant detrity-lation.15... 

Scheme 14 shows a typical example in a series of reactions in which a supported amino acid reacted with fluorenylmethoxycarbonyl isothiocyanate to give a supported (on Rink s amide)35 thiourea.36 Removal of the protection followed by 5-alkylation gave supported isothioureas. Reaction of these with amines, then cleavage from the resin, afforded substituted guanidines. For 10 examples the purities were between 40 and 92%. An aryl group separates the resin from the guanidine, just as in the sequences shown in Schemes 11 and 12. 

The mechanism of these reactions has been suggested to involve initial decomposition of the thiourea to isothiocyanate and amine, and the latter reacts with the carbonyl compound to form a Schiff s base. Condensation of the Schiff s base with the isothiocyanate present, followed by loss of H2S gives the observed products.336-338-340... 

Isothiocyanates can be prepared from support-bound primary amines by treatment with thiophosgene [14] or synthetic analogs thereof (Entry 5, Table 14.2). In an alternative two-step procedure, the amine is first treated with CS2 and a tertiary amine to yield an ammonium dithiocarbamate, which is subsequently desulfurized with TsCl or a chloroformate (Entry 6, Table 14.2 Experimental Procedure 14.1). Highly reactive acyl isothiocyanates have been prepared from support-bound acyl chlorides and tetra-butylammonium thiocyanate (Entry 7, Table 14.2). These acyl isothiocyanates react with amines to give the corresponding 7V-acylthiourcas, which can be used to prepare guanidines on insoluble supports (Entry 6, Table 14.3). 

Ogura and Takahashi18,19 detailed the reaction of the sugar isothiocyanates 2, 30, 31, and 32 with ammonia and amines, as well as with various classes of hydrazines. The reaction of sugar isothiocyanates with various classes of amines,44"62 hydrazines,63 72 and hydrazides has been reported by... 

Isatoic anhydride can be used as a versatile synthon for the synthesis of a diverse set of molecules. The isatoic anhydride can be reacted with amines, amides, hydrazides, isothiocyanates, diketo substrates, aminoacids, amino-, thio or hydroxy anilines, as well as in a three-component reaction with aldehydes and amines to form a large set of diverse pharmacophores. 

Isothiocyanates react with many nucleophiles, but only the products with amines (thiocarbamoyl derivatives) are stable.16 Although the increased specificity is desirable, the reaction with the amino group changes the charge on the protein, and this may be needed in order to maintain the activity or the conformation, or both. The linkage formed is alkali-labile, and, as with the azo derivatives, the aromatic ring is a liability. 

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