Cyclocondensation aldehyde

In the reverse reaction, thioheteroaryl amides reacted under reflux in alcohol with haloketones or aldehydes to give the corresponding 2-heteroarylthiazole derivatives (238, 271, 482, 550, 751, 765, 776, 781). 2,2 -Bithiazoles (4,4 -disubstituted) have been obtained in 80 to 90% yield by cyclocondensation of 1 mole rubeanic acid with 2 moles of a-bromoketones in polyphosphoric acid at 95 to 135 C (780). Some multiheteroaryl substituted thiazoles have been also reported (704). 

Cyclocondensation of D-homocystine methyl ester hydrochloride (106) and aldehyde 105 in the presence of Ph3P yielded 9-(benzyloxycarbonyla-mino)-6-oxoperhydropyrido[2,l-f ][l,3]thiazine-4-carboxylate (107) and its diastereomer (97MIP4, 98USP5710129). 

The sequential treatment of triazine derivative 990 with acyl chlorides and acetic anhydride and perchloric acid afforded (86H1031) thiadi-azolo[l, 2,4]triazinium perchlorates 991. On the other hand, cyclocondensation of 992 with organic acids gave 993 [82JHC1577 83JAP(K)58/180492] and 994 with aromatic aldehydes (84JIC552) (Scheme 183). 

A new route to 2//-thiopyrans has been found in the cyclocondensation of thioenolates with a./J-unsaturated carbonyl compounds. The starting sulfur component can be methyl thiol-thione-ethanoate (90BSF446) or a /3-thienol-aldehyde (90ZC247) as shown by Eqs. (1) and (2), respectively. 

Lithium catalyzed hetero-Diels-Alder reactions. Cyclocondensation of N-protected ot-amino aldehydes with 1-methoxy-3-fert-butyldimethylsilyloxybutadiene in the presence of lithium perchlorate [104]... 

The cyclocondensation of an aldehyde, CH-acidic ketone and ammonia provides symmetrical l,4-dihydropyridine-3,5-dicarboxylate derivatives of pharmacological importance, often called Hantzsch 1,4-dihydropyridines (1,4-DHPs) following its original invention over a century ago (Scheme 4) [44,45]. The 1,4-DHP motif is found in a number of chemotherapeutic agents for... 

The Pictet-Spengler reaction has mainly been investigated as a potential source of polycyclic heterocycles for combinatorial apphcations or in natural product synthesis [149]. Tryptophan or differently substituted tryptamines are the preferred substrates in a cyclocondensation that involves also aldehydes or activated ketones in the presence of an acid catalyst. Several versions of microwave-assisted Pictet-Spengler reactions have been reported in the hter-ature. Microwave irradiation allowed the use of mild Lewis acid catalysts such as Sc(OTf)3 in the reaction of tryptophan methyl esters 234 with different substituted aldehydes (aliphatic or aromatic) [150]. Under these conditions the reaction was carried out in a one-pot process without initial formation of the imine (Scheme 86). 

A completely different kind of macro cycle, a calix-salen type macrocycle, was obtained in good yield by microwave irradiation of various dialdehydes and diamines [165]. This was the first example of a calix-type synthesis under microwave conditions and without the presence of a metal template. An example of a [3 -1- 3] cyclocondensed macrocycle 265, obtained from a bis aldehyde and a chiral diamine is reported in Scheme 97. 

Tandem cyclization from [5+1,6+0] atom fragments took place when 3-isothiocyanatobutyraldehyde was reacted with 2-aminobenzylamine 228 (X = NH) to give 229. Based on literature analogies the first step involves the attack of the most nucleophilic aliphatic amino group onto the isothiocyanate and then onto the aldehyde carbon to form 1-(n-aminobenzyl)-6-hydroxytetrahydropyrimidine-2-thione, which undergoes intramolecular cyclocondensation to 229 (Scheme 38) <2005BMC3185>. 

In a facile and rapid stereoselective, three-component, one-pot reaction, a series of cis-isoquinolonic acids 132 were synthesized using silica supported sulfuric acid to catalyze the reaction between homophthalic anhydride 133 with different aldehydes 134 and amines 135. This three-component cyclocondensation offers a variety of advantages including high yields, easy experimental work-up, and the use an inexpensive, non-toxic, readily available, and recyclable catalyst <06JHC187>. 

The sodium bromide catalyzed three-component cyclocondensation of aryl aldehydes, CH-acidic nitriles, and dimedone under solvent-free conditions has been studied by Devi and Bhuyan (Scheme 6.245) [429]. Utilizing equimolar amounts of the building blocks and 20 mol% of sodium bromide as catalyst, microwave irradia-... 

Wu and Sun have presented a versatile procedure for the liquid-phase synthesis of 1,2, ,4-tctrahydro-/i-carbolines [77]. After successful esterification of the MeO-PEG-OH utilized with Fmoc-protected tryptophan, one-pot cyclocondensations with various ketones and aldehydes were performed under microwave irradiation (Scheme 7.68). The desired products were released from the soluble support in good yields and high purity. The interest in this particular scaffold is due to the fact that the l,2,3,4-tetrahydro-/f-carboline pharmacophore is known to be an important structural element in several natural alkaloids, and that the template possesses multiple sites for combinatorial modifications. The microwave-assisted liquid-phase protocol furnished purer products than homogeneous protocols and product isolation/ purification was certainly simplified. 

Substantial MW rate enhancements have been reported in the Biginelli synthesis of dihydropyrimidines [50, 51] under homogeneous conditions. The synthesis involves a one-pot cyclocondensation of a /i-ketoester with an aryl aldehyde and urea or thiourea in the presence of a catalytic amount of HC1 in ethanol solution. An example of this synthesis is shown in Scheme 4.17. 

When treated with DBU at elevated temperature, l-[(benzotriazol-l-yl)methyl -2-aminopyridine salts 741 eliminate rather the N-H proton than the C-H one. Intermediates 742 can be trapped with aromatic aldehydes to create betaines 743. The consecutive cyclocondensation and elimination of benzotriazole results in formation of imidazolo[l,2-rz]pyridines 744 in good yields (Scheme 117) <2000JOC9201>. Aldehydes with enolizable a-protons fail to give bicyclic systems 744, producing corresponding enamines instead. 

The synthesis of 4,5-disubstituted triazoles shown in Scheme 208, carried out on a polymer support with microwave assistance, is based on a similar principle. In the first step, sulfinate 1248 is converted to sulfone 1249. Condensation with aldehydes provides vinyl sulfones 1250. Cyclocondensation of sulfones 1250 with sodium azide generates corresponding triazoline intermediates that eliminate sulfinate 1248 to provide triazoles 1251 in moderate to good yield <2006OL3283>. 

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... 

Similarly, Dang and co-workers reported the displacement of one chloride from pyrimidine 44 with various amines to give diaminopyrimidines 45 <00TL6559>. These compounds were then subjected to a FeCb-SiOz-promoted cyclocondensation with various aldehydes to produce trisubstituted purines 46 in moderate to good yields as potential adenosine regulating agents. 

Bis(bromomethyl)quinoxalines 263 was treated with aldehydes 264 to obtain 265 . Macrocyclization to 266 was completed by cyclocondensation of the aldehydes 265 with the appropriate diaminoalkanes. Elwahy used this chemistry to synthesize new macrocyclic ligands containing the quinoxaline subunit. 

A range of l,3-oxazolidin-4-ones (93) have been prepared by cyclocondensation of cyanohydrins, R R C(OH)CN, with aldehydes or ketones, R COR, under anhydrous strong acid conditions. The R groups used are mainly simple alkyl and aryl moieties, and the mechanism is discussed. 

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