Imidazolidine Derivatives Research Articles

Synthese von Imidazolidin‐Derivaten aus Dicyanessigsäureestern

Synthesis of Imidazolidine Derivatives from DicyanoacetatesBy nucleophilic additions of amino acids to one cyano group of salts of alkyl dicyanoacetates 1 followed by ring‐cyclisation reactions the 4‐imidazolidinone derivatives 3, 5 are obtained.

ChemInform Abstract: Reaction of Oxalic Amidines with Carbonic Acid Derived Heterocumulenes to Imidazolidine Derivatives.

AbstractA useful synthetic route to nonsymmetric imidazolidine derivatives such as (III) or (IV) is described.

Recyclization of enamino ketones that are imidazolidine derivatives to 1-pyrrolin-4-one 1-oxides

The recyclization in an acidic medium of enamino ketones that are imidazolidine derivatives leads to 1-pyrrolin-4-one 1-oxide derivatives, viz., cyclic Β-oxo nitrones, which exist in the form of equilibrium mixtures of the ene hydroxyamino keto and oxo nitrone tautomeric forms, the ratio of which depends on the solvent and the character of the substituent.

Radiation Chemistry of 2 prime -Deoxycytidylyl-(3 prime -5 prime)-2 prime -Deoxyguanosine and Its Sequence Isomer in N 2 O- and O 2 -Saturated Solutions

The radiation chemistry of the dinucleoside monophosphate d(CpG) and its sequence isomer, d(GpC), has been examined in aqueous solutions saturated with either N2O or O2. The products were isolated using HPLC, and the major products were identified using proton NMR spectroscopy and mass spectrometry. The major products include 5,6-dihydroxy-5,6-dihydrouracil (glycol) derivatives, 5- and 6-hydroxycytosine substitution products, 1-carbamoyl-2-oxo-4,5-dihydroxyimidazolidine products, and the 8-hydroxyguanine substitution product. Both trans stereoisomers of the imidazolidine derivatives are obtained from d(CpG) as well as from its sequence isomer. These are prominent products when the irradiation is carried out in the presence of oxygen, but they are not observed in the absence of oxygen.

Formation of imidazolidine derivatives from dimethyl (2,2-dimethylhydrazino)succinate in reactions with allyl and phenyl isothiocyanates

The reaction of (2,2-dimethylhydrazino)succinic acid ester with allyl and phenyl isothiocyanates leads to esters of 1-substituted (3-dimethylamino-5-oxo-2-thioxo-4-imidazolidinyl)acetic acids, which in protic solvents undergo a slight degree of elimination of dimethylamine to give esters of 1-substituted (5-oxo-2-thioxoimidazolidin-4-ylidene)acetic acids. The structure of methyl (1-allyl-5-oxo-2-thioxoimidazolidin-4-ylidene)acetate was proved by x-ray diffraction analysis.

ChemInform Abstract: Chemoselective Protection of Heteroaromatic Aldehydes as Imidazolidine Derivatives. Preparation of 5‐Substituted Furan‐ and Thiophene‐2‐carboxaldehydes via Metallo‐imidazolidine Intermediates.

AbstractDie Aldehydgruppe der Formyl‐heterocyclen (I) kann bequem durch Überführung in die Imidazolidine (III) maskiert werden.

EPR spectroscopic study of the spin-labeled chelating reagent-solvent-neutral electron-donor compound system

Dimerization of spin-labeled hydroxamic acid (I) in aprotic solvents was demonstrated, and the dimerization constants in heptane, toluene, and chloroform were calculated. There is an indirect exchange reaction between the radicals at the bonds in the molecule of the dimer. The effect of the nature of the solvent on the HFI constants of nitroxyl radicals, imidazoline and imidazolidine derivatives, was studied. The distance between the unpaired electrons in the molecule of the dimer in a glassy toluene solution of the reagent was determined. Addition of neutral electron-donor compounds inhibits the dimerization of (I). The constants for the formation of molecular complexes of the reagent with triethylamine, piperidine, triphenylphosphine oxide, tri-n-butyl phosphate, dimethylsulfoxide, ethanol, and acetone were estimated. An increase in the basicity of the additive compounds results in an increase in the constants for the formation of molecular complexes.

Chemoselective protection of heteroaromatic aldehydes as imidazolidine derivatives : Preparation of 5-substituted furan- and thiophene-2-carboxaldehydes via metallo-imidazolidine intermediates

Furan-, thiophene- and N -methylpyrrole-2-carboxaldehydes may be transformed into the corresponding N , N '-dimethylimidazolidines in a reaction not requiring acid catalysis. The resulting furan and thiophene (but not N -methylpyrrole) derivatives may be metallated in high yields [predominantly at the 5 (α-) positions of the heteroaromatic rings] and the carboxaldehyde functionality regenerated under very mild conditions. Treatment of the aldehydoketone 2-acetyl-5-formylthiophene with N , N '-dimethylethylenediamine gives only the product of reaction at the aldehyde function thus establishing this methodology as a potentially valuable method for the protection of an aldehyde in the presence of a ketone.

Reaction of 1,3‐diaryl‐2,3‐dibromo‐1‐propanones with urea in basic and acidic medium. Synthesis of pyrimidine, imidazoline and imidazolidine derivatives

AbstractReaction of 1,3‐diaryl‐2,3‐dibromo‐1‐propanones 1 with urea in basic medium afforded 4,6‐diaryl‐5‐bromo‐5,6‐dihydropyrimidine‐2(1H)‐ones 4. Oxidation of these bromopyrimidines 4 in dimethylsulphoxide gave 4,6‐diaryl‐1,6‐dihydropyrimidine‐2,5‐diones 6, which were further converted to their thione analogues 7. Reaction of 1,3‐diaryl‐2,3‐dibromo‐1‐propanones 1 with urea, phenylurea and sym‐diphenylurea in glacial acetic acid medium gave in appreciable yields 4‐phenyl‐5‐α‐(bromoarylmethyl)imidazolin‐2‐one 8 and 1,3‐diphenyl‐4‐aroyl‐5‐arylimidazolidin‐2‐one 11 respectively.

Studies on the vasoconstrictor activities of imidazolidine derivatives in various vascular beds.

Summary We compared various imidazoline derivatives with noradrenaline and methoxamine for vasoconstrictor activity in several different vascular beds. We used rat autoperfused hindquarters, kidneys, and mesenteric vasculature; rat saline-perfused renal and mesenteric vasculature; rabbit autoperfused kidneys and hindquarters; and pithed rats and autoperfused rabbit kidneys; and we studied the blood pressure of conscious, ganglion-blocked rabbits. Clonidine, oxymetazoline, naphazoline, St 91, St 95, methoxamine, and nor-adrenaline all acted as full pressor agonists in the pithed rat without any sign of α-antagonist effect. St 91 and noradrenaline were the most potent, and clonidine and methoxamine were the weakest agonists. However, while noradrenaline and methoxamine displayed full vasoconstrictor agonist potencies in the rat autoperfused tissues, all the imidazoline derivatives except St 91 acted as partial agonists or antagonists. St 91 in most cases acted as a full agonist, although in the autoperfused hindquarters it was often a partial agonist. Similar effects were seen in rat saline-perfused tissues, except that antagonists activity was even more prominent. pA2 values for several imidazolidine derivatives were calculated in rat saline-perfused mesenteric and renal vascular beds, and it was found that oxymetazoline was a considerably more potent α-antagonist than either piperoxane or yohimbine, while clonidine had a similar potentcy to these drugs. In the conscious, ganglion-blocked rabbit, both clonidine and oxymetazoline acted as fairly weak partial agonists, and in the rabbit autoperfused hindquarters and kidneys, clonidine acted as a pure α-antagonist. These results suggest that vascular α-adrenoceptors comprise an heterogeneous population, but the observations may also be due to low receptor reserves in different tissues.

Isomerization of imidazoline to imidazolidine derivatives under electron impact

AbstractThe electron impact induced fragmentation of some new derivatives of imidazolidin‐2,4‐dione and 4‐imidazoJin‐2‐one has been examined. The main fragmentation pathways have been established with the help of appropriate metastables and high resolution measurements. The effect of isomerization of 4‐aryliminoimidazolidin‐2‐ones to 4‐arylamino‐4‐imidazolin‐2‐ones and conversely, 4‐aryldo‐4‐imidazolin‐2‐ones to 4‐aryliminoimidazolidin‐2‐ones on fragmentation has been investigated by temperature dependence measurements and deuterium labelling.

Displacement of [ 3H]clonidine binding by clonidine analogues in membranes from rat cerebral cortex

[ 3H]Clonidine binds to membranes prepared from rat cerebral cortex by a high affinity saturable process. Using [ 3H]clonidine of specific activity 5.29 Ci/mmol the K d for the binding was 1.7 ± 0.1 nM and the B max 9.4 ± 0.6 pmol/g (n = 5). The Hill coefficient for [ 3H]clonidine binding to rat cerebral cortex membranes was 0.97 ± 0.05 (r > 0.93; n = 5) indicating an absence of +ve or −ve cooperativity. The clonidine metabolites 4-hydroxyclonidine; N(2,6-dichlorophenyl)guanidine; N(2,6-dichloro-4-hydroxyphenyl)guanidine; and 2-(2,6-dichlorophenyl)iminoimidazolidine-4-one and the metabolic intermediate 2-(2,6-dichlorophenylamino)imidazole were less effective displacers of [ 3H]clonidine binding than the parent compound. The first three compounds were more polar and the last two less polar than clonidine as judged by their apparent partition coefficients in octanol/phosphate buffer. Seven imidazolidine derivatives with known α-adrenoceptor activity were potent displacers of [ 3H]clonidine binding: the order of potency being 14,304-18 > naphazoline > clonidine > lofexidine and tiamenidine > CP18,534 > ST600 > ST91. Five ‘clonidine-like’ drugs displaced [ 3H]clonidine binding with an order of potency guanabenz > Bay a 6781 > guanfacine > clonidine > xylazine >> FLA136. Apparent partition coefficients of the displacing agents have been measured in octanol/phosphate buffer and the importance of this factor is discussed with reference to their in vivo antihypertensive potency and potency as displacers of [ 3H]clonidine binding.

Structure-activity relationship of imidazolidine derivatives related to clonidine at histamine H2-receptors in guinea-pig isolated atria.

1 Cumulative concentration-response relationships for the chronotropic effects of histamine, oxymetazoline, clonidine and thirteen clonidine-like imidazolidine derivatives were examined in isolated spontaneously beating guinea-pig atria.2 The following compounds induced positive chronotropic effects: histamine, clonidine (2,6-dichloro-phenyliminoimidazolidine) and the 2,6-dibromo, 2,6-dimethyl, 2,6-diethyl, 2,6-dihydroxy, 2,4,6-trimethyl, 3,4-dihydroxy and 2-methyl-5-fluoro analogues of clonidine. These compounds appeared to act as partial agonists on histamine H(2)-receptors, with potencies ranging from one tenth to one hundredth and intrinsic activities from approximately 20% to 75% of those of histamine.3 The following compounds did not induce positive chronotropic effects but rather decreased the atrial rate, usually at high concentrations: oxymetazoline and the 2,3-dichloro, 4-dichloro, 5-dichloro, 2-chloro-4-methyl, 2-methyl-5-chloro, 2,4,6-trichloro analogues of clonidine.4 The effects of histamine were antagonized by cimetidine, the pA(2) value being 6.68 (s.e. mean = 0.16, n = 3), and also in a concentration-dependent manner by clonidine. Cimetidine antagonized the response to clonidine in a concentration-dependent manner; however, high concentrations of cimetidine depressed the maximal response to clonidine and the slope of the concentration-response curve was no longer parallel to the control curve.5 The effects of the other compounds which induced positive chronotropic effects were also antagonized by cimetidine (1 mumol/l); however, the effect of the 3,4-dihydroxy derivative was unaffected by cimetidine (1 mumol/l) but was abolished by propranolol (0.3 mumol/l).6 In general, phenyliminoimidazolidine derivatives with 2,6-substitution on the phenyl ring are active on histamine H(2)-receptors, whereas derivatives with 2,3-, 2,4- or 2,5-substitutions are weakly active or inactive. Thus the restriction imposed on the free rotation of the phenyl ring about the carbon-imino nitrogen bond by the introduction of two ortho substituents appears to result in increased agonist activity on the histamine H(2)-receptor. The introduction of substituents in the 3, 4 or 5 positions in the phenyl ring may lead to compounds sterically hindered from combining with the histamine H(2)-receptor.7 There is no apparent relationship between the activities of clonidine-like imidazolidine derivatives as agonists on histamine H(2)-receptors and their hypotensive activities (as reported in the literature).

Gas chromatographic identification of aldehydes as their imidazolidine derivatives

A new gas chromatographic method for aldehydes analysis with their imidazolidine derivatives was developed. N, N'-diphenylethylenediamine easily reacts with aldehydes to form the imidazolidine derivative in the presence of acid catalyst. Differing from the peak of 2, 4-dinitrophenylhydrazone on a gas chromatogram, the peak corresponding to the imidazolidine derivative is single because of the absence of geometrical isomers. The gas chromatographic conditions were as follows : column packing, 1% PEG-HT on Chromosorb WAW DMCS; column size, 2 mm i.d. ×2.25 m or 3 m; detector, FID; column temp., (235265)°C (1°C/min); inj. port, 265°C; detector temp., 265°C. The imidazolidine derivatives of formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, iso-butyraldehyde, furfural, benzaldehyde and ο-tolualdehyde were clearly separated by the gas chromatographic conditions presented above. But, when acetaldehyde and butyraldehyde are mixed together, each aldehyde can't be identified because the retention time of both imidazolidine derivatives overlaps each other. In such a case, each aldehyde should be identified by using column packing of both 2% OV-17 and 1% PEG-HT. The relative mole response to anthracene as internal standard substance are as follows: the formaldehyde derivative, 0.85; the acetaldehyde derivative, 0.92; the propionaldehyde derivative, 1.18. The presented method was applied to analyse aldehydes in the cigarette smoke and the exhaust gas of automobiles, and several aldehydes were identified in both cases. The gas chromatographic method presented above can be used for analysis of aldehydes as their imidazolidine derivatives.

Reduction of 4H-imidazole N-oxides with sodium borohydride

The reduction of derivatives of 4H-imidazole N-oxides with sodium borohydride leads, depending on the presence and position of an N-oxide group, to 1-hydroxyimidazoline or imidazolidine derivatives. Under the same conditions 4H-imidazole N,N′-dioxides form 1,3-dihydroxyimidazolidines. The reduction of 1-hydroxy-2,4,5,5-tetramethyl-3-imidazoline 3-oxide leads to N-(3-oximino-2-methyl-2-butyl) ethylhydroxylamine. It was observed by UV spectroscopy that 1-hydroxy-2-imidazolines exist in a tautomeric equilibrium with 2-imidazoline 3-oxides.

Reaction of Group IV Organometallic Compounds. XXXII Modified Synthesis of Imidazolidines with N,N′-Bis(trimethylsilyl)-1,2-diamines

Abstract N,N′-Bis(trimethylsilyl)-1,2-diamines gave imidazolidine derivatives accompanied with the elimination of hexamethyldisiloxane in excellent yields by condensation reactions with carbonyl compounds under mild conditions. These reactions are regarded as the typical addition-elimination reaction of group IV organometallics.

Studies on the heterocyclic compounds. XVIII. Syntheses of imidazo-(1,2-c)-and pyrimido(1,2-c)pyrimidine derivatives

2, 4-Dichloro- (Ia, b) or 4, 6-dichloropyrimidine (II) was treated with aminoalcohols to afford the 4-substituted compounds. When these compounds were treated with thionyl chloride in tetrahydrofuran, cyclized compounds (Va, b, VIb, XIa, b, XIIb, XVa, b, XVII, XIX, and XXI) were obtained. In this reaction, some of the compounds (VIb and XIIb) were substituted by chlorine atom at the 5-position of pyrimidine ring. By the reaction of compound XXI with alkaline solution under a mild condition, ring opening of the pyrimidine occurred to give imidazolidine derivatives (XXII and XXIII). The compounds Ia, b or II was treated with aminoacetal to afford 4-(2, 2-diethoxyethylamino) compounds, which were converted to imidazo[1, 2-c]pyrimidines (XXVIIa, b and XXXII) by the reaction with 6 N hydrochloric acid followed by cone. sulfuric acid. In this case, ring opened compound (XXXIII) was obtained as a minor product.

Extension of sugar chains by enolate addition to methyl 2,3-di- O-acetyl-4-deoxy-β-l- threo-hex-4-enodialdo-1,5-pyranoside

Methyl 2,3-di- O-acetyl-4-deoxy-β- L- threo-hex-4-enodialdo-1,5-pyranoside ( 2) reacts readily with enolate anions by attack at the aldehyde carbonyl group. Nitromethane gives initially the adduct 1, which readily undergoes elimination to afford the conjugated, unsaturated derivative 5; reduction of the latter with borohydride effects selective reduction of the exocyclic double bond to give the nitro sugar derivative 6. The aldehyde 2 undergoes condensation with acetone to give a conjugated, 9-carbon sugar derivative 7, having a carbonyl group at C-8 that can be reduced selectively by borohydride to a secondary alcohol derivative, isolated as its acetate 8. The readily available, unsaturated aldehyde 2, which can be condensed with 1,2-bis(anilino)-ethane to give a stable, crystalline imidazolidine derivative 3, thus provides a useful starting point for synthesis of higher-carbon sugars by chain extension at the ϖ-carbon atom. Addition of dimethylamine at C-4 of 2 was not observed under a variety of experimental conditions.

Über die Struktur von Imidazolin‐ und Imidazolidin‐Derivaten aus 2‐Amino‐2‐desoxy‐hexosen

AbstractIn earlier publications [1] [2] [3] [4] a pyranoid structure has been proposed for the sugar moiety of imidazoline and imidazolidine derivatives from D‐glucosamine. But by NMR.‐spectra and periodate oxidation the sugar moiety of these compounds and of similar derivatives from other 2‐amino‐2‐deoxy‐sugars is now shown to be of furanoid structure.

The Stereochemistry of the Imidazolidine Ring

The electric moments of several imidazolidine derivatives in p-xylene solution have been measured at various temperatures. It is suggested that the substances are mixtures of geometrical isomers which are in thermal equilibrium, the isomerism being due to the pyramidal arrangement of the valencies of the tervalent nitrogen. From the temperature dependence of the moments, the energy difference between the two postulated isomers is calculated to be about 1.6 kcal/mole.