Aldehydes reaction with thiourea

Aromatic halides, conversion to aromatic thiols 182-185 by reaction with thiourea 189-191 Aromatic thiols—see also Thiophenols mass spectra 330 preparation of 167-169 from aldehydes and ketones 251-256... 

Chiral fe-thiourea-type catalysts effectively provide the Baylis Hillman reaction with cyclohexenone and aldehydes.181 In several reactions, thiourea derivatives have been used as significant and specific catalyst because of their intermolecular hydrogen bonding ability (Scheme 74).182 186... 

The cyclizations to obtain cyclic thioureas have been performed using thiocarbonyldiimidazole.232 Reaction of methyl acetoacetate, thiourea and an aliphatic aldehyde in the presence of the zinc iodide (Znl2) was studied. Under the normal pressure, reaction has not been occurred whereas at high pressure (300 MPa) conditions 3,4-dihydropyrimidine-2-thione was obtained only in 10% yield.233 The same one-pot three-component cyclocondensation reaction in the presence of iodide (I2) provides a variety of 3,4-dihydropyrimi-dine-2-thione in high yields.234 Condensation reaction of thioureas with a,p-unsaturated ketones in the presence of the sodium methoxide in methanol affords 3,4-dihydropyrimidine-2-thione derivatives.235,236 Acylation of N,N -disubstituted thioureas with methyl malonyl chloride followed by base-catalysed cyclization leads in the formation of l,3-disubstituted-2-thiobarbituric acids (Scheme 78).237... 

A series of solid-state reactions has been explored by Kaupp et al., in which gaseous amines were reacted with aldehydes to give imines. Analogous reactions with solid anhydrides, imides, lactones or carbonates, and isothiocyanates were used to give, respectively, diamides or amidic carboxylic salts or imides, diamides, carbamic acids, and thioureas [24]. In general the yields were found to be quantitative. Ammonia and other gaseous amines, in particular methyl-amine, have also been shown to aminolyse thermoplastic polycarbonates [25]. 

The authors interpreted the outcome of these Henry reactions with an activation of the aldehyde component through double hydrogen-bonding interactions with the thiourea moiety facilitating the product-forming nucleophilic attack of the in situ generated nitronate (Scheme 6.162) [319]. 

A series of 4-heteroaryl-5,6-di(2,5-dimethyl-3-thienyl)-2-phenyM//-l,6-thiazines 54 with photochromic properties was prepared by reacting 3-(2-(2,5-dimethylthiophen-3-yl)ethynyl)-2,5-di ethylthiophene with thiobenzamide and aldehydes <2005CHE86, 2005PS1503>. The acid-catalyzed cyclocondensation of cyclopentanone, aromatic aldehydes, ArCHO, and thiourea affords the cyclopenta[t ]l,3-thiazines 37 <2006PS1655>. Two equivalents of the aldehyde are required. The same products are isolated when 2,5-dibenzylidenecyclopentanones are treated with thiourea under the same conditions. 2-Amino-4i/-l,3-thiazines 184 are easily synthesized in one pot by the reaction of aromatic alkynes, R feCH, aromatic aldehydes, R CHO, and thiourea in the presence of TFA/acetic acid <2005OL3797>. 

The availability of amino-substituted furazans, both by direct synthesis from aminogly-oximes and via Hofmann degradation of the corresponding carboxamides, allows urea, thiourea, imino and acylamido derivatives, for example, to be prepared by reaction with isocyanates, isothiocyanates, aldehydes and acyl halides, respectively (73JPR791, 77JCS(P1)1616). Alkoxy and acyloxy derivatives are likewise formed from hydroxyfurazans (79JHC689). 

Dehuri and Nayak (83JIC970) reported that 3,4,5,6,7,8-hexahydro-l,3-diazocine-2-thione (213), obtained from 1,5-dibromopentane and thiourea in boiling ethanol, reacts with chloroacetic acid or its ethyl ester followed by basification to give 5//-6,7,8,9-tetrahydrothiazolo[3,2-a]-[ 1,3]diazocin-3(2//)-one (214). The reaction of 213 with ethyl chloroacetate was not smooth and the yield was low. The thione 213, on reaction with ethyl chloroacetate and aromatic aldehydes in the presence of pyridine and piperidine, furnishes the arylidene product 215 which is also obtained from 214 and aromatic aldehydes. No spectral data are cited to confirm the thiazolidinone structures 214 and 215 (Scheme 50). 

Figure 10 Schematic representation of the most common reactions for labeling an amine (a) reaction with isothiocyanate to give a thiourea (b) reaction with a Succinimidil ester to give an amide (c) reaction with a sulfonyl chloride to give a sulfonamide (d) reaction with an aldehyde to give an imine (Schiff s base) and (e) reaction with a carbodiimide-activated carboxylic acid to give an amide.

Condensations. Alumina promotes the formation of a-hydroxyphosphonate esters from aromatic aldehydes and dialkyl phosphonates, and the adducts are converted to a-aminophosphonate esters on reaction with ammonia. A solvent-free synthesis of a-nitro ketones comprises mixing nitroalkanes, aldehydes, and neutral alumina and oxidizing the adducts with wet, alumina-supported CrOj (15 examples, 68-86%). The Knoevenagel reaction, the Michael addition of nitromethane to gcm-diactivated alkenes, and the formation of iminothiazolines from thioureas and a-halo ketones are readily effected with alumina under microwave irradiation. 

Heterocycles. In the presence of Yb(OTf)3 epoxides are readily transformed into oxazolidines and 2-iminothiazolidines by reaction with imines and thioureas, respectively. 2-(2-Aminoxyethyl)cyclopropane-l,l-dicarboxylic esters condense with aldehydes to give bicyclic isoxazolidines. ... 

THIOUREA or 2-THIOUREA (62-56-6) Aqueous solution is a base. Violent reaction with acrolein, strong acids. Incompatible with acrylaldehyde, hydrogen peroxide, metal salts. Aqueous solution incompatible with organic anhydrides, acrylates, alcohols, aldehydes, alkylene oxides, substimted allyls, cresols, caprolactam solution, epichlorohydrin, ethylene dichloride, glycols, hydrogen peroxide, isocyanates, ketones, maleic anhydride, nitrates, nitromethane, phenols, vinyl acetate. 

Supports 3e and 3f derived from a related linker with only one me-thoxy group ortho to the aldehyde have been reported [140] to have a more reactive aldehyde group than 3c or 3d due to lower steric hindrance. Resin 3e was used to synthesize aminothiazoles, which were cleaved under acidic conditions [141]. Thus, amines were anchored reductively to 3e and converted to resin-bound thioureas by reaction with Fmoc-isothiocyanate followed by deprotection. Cyclization by reaction with a-bromomketones gave the desired heterocycles, which were cleaved from the resin by treatment with TFA-H2O (19 1) (Scheme 4). 

Succinimidyl esters are an excellent first choice to activate amine-reactive probes, but their low solubility has led to the alternative use of sulphonyl chlorides (Figure 4.17). The resultant sulphonamide link is extremely stable, even more stable than an amide link, and will survive even complete protein hydrolysis - a property that can be exploited in protein analysis. The disadvantage of sulphonyl chlorides is that they are unstable in aqueous buffers under mildly alkaline conditions (typically the pH required for the reaction with aliphatic amine ). Hence extreme care must be taken to perform bioconjugations with sulphonyl chlorides at low temperatures (approx 4 °C). Alternatively, amine-reactive probes may be equipped with isothiocyanate traps , from which thiourea links are formed post-reaction with amine functional groups, or with aldehydes, from which Schiff sbase links can be formed with amine functional groups (Figure 4.17). 

The classic BigineUi three-component condensation [45,46] of aldehyde, urea or thiourea, and a dicarbonyl compound generating 3,4-dihydropyrimidin 2(lH)-one has been accomplished under solventless conditions to synthesize spiro-fused heterocycles in higher yields with shortened reaction time of a few minutes (Scheme 2.2-11) [47]. Purification was achieved by adding crushed ice to the reaction mixture, separating the solid via filtration and washing with cold water, followed by... 

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