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A convenient method for the synthesis of a novel series of four 5-trilfluoromethyl-1,2,3,4-tetrahydroacridines, by intramolecular cyclization reactions of 2-trifluoroacetyl-1-(arylamino)-cyclohexene using polyphosphoric acid (PPA), is described. The six new enaminoketone intermediates were obtained by an oxygen–nitrogen exchange reaction from 2-trifluoroacetyl-1-methoxycyclohexene with six 4-substituted anilines.

Twelve novel 3-alkyl[aryl]-1-carboxamides-5-trichloromethyl-5-hydroxy-4,5-dihydro-lH-pyrazole have been synthesized in good yields (72–90%) using environmentally benign microwave-induced techniques. The compounds were synthesized from the cyclocondensation of 4-alkoxy-1,1,1-trichloro-3-alkyl[aryl]-2-ones [Cl3CC(O)C(R2) = C(R1)OR, where R = Me, Et; R1 = H, Me, Et, Pr, i-Pr, i-Bu, t-Bu, Ph, Ph-4-NO2, Ph-4-F, Ph-4-Cl, Ph-4-Br; and R2 = H, Me] with semicarbazide hydrochloride in the presence of pyridine and using methanol/water (3:1 v/v) as the solvent. The advantages of using microwave irradiation, rather than a conventional method, were demonstrated.

A series of six (8)‐alkyl‐4‐trifluoromethyl‐5,6,7,8‐tetrahydro‐2(1H)quinazolinones, 4‐trifluoromethyl‐cyclopenta[d]‐2(1H)pyrimidinones, and their thioxo analogs from the reaction of five β‐alkoxyvinyl trifluoromethyl ketones, derived from alkylated cyclohexanones and cyclopentanone with urea and thiourea, is reported. The reactions were carried out in a single step in propan‐2‐ol as solvent and boron trifluoride diethyl etherate as catalyst in 18–65% yield.

A convenient one‐pot synthesis of eight pyrazole‐5(3)‐carboxyamides from the reaction of the 5(3)‐trichloromethylpyrazoles with amines, in good yield, is reported. These reactions show that the trichloromethyl group is a convenient precursor to carboxyamide groups.

The one-pot synthesis of nine 5-trichloromethyl-1,2-dimethyl-1H-pyrazolium chlorides 2 from the cyclocondensation of 4-alkoxy-1,1,1-trichloro-3-alken-2-ones [CCl3C(O)C(R2)= C(R1)OR, where R1 = H, Me, Et, n-Pr, (CH2)5CO2Et, CH2Br, Ph, 4-Br-C6H4; R2 = H, Me; and R = Me, Et] with 1,2-dimethylhydrazine is reported. For Part 16, see Ref. [12].

A series of five N-[1-aryl-3-oxo-4,4,4-trifluoro-1-buten-1-yl]-o-phenylenediamines 2 [CF3COCH=C(R)NH-o-PhNH2], where R=Ph, 4-MePh, 4-BrPh, 4-ClPh, 4-OMePh from the reaction of β-aryl-β-methoxyvinyl trifluoromethyl ketones 1 with o-phenylenediamine was prepared and isolated in good yield (59–71%). Another series of five 4-aryl-2-trifluoromethyl-3H-1,5-benzodiazepines 3, where aryl=Ph, 4-MePh, 4-BrPh, 4-ClPh, 4-OMePh was also obtained in an one-step reaction from ketones 1 by an intramolecular cyclization reaction with o-phenylenediamine under mild acid conditions in good yields (60–77%).

The synthesis of a novel series of N-[1-alkyl(aryl)-3-oxo-4,4,4-trichloro(trifluoro)-1-buten-1-yl]-o-aminophenols and the analogous o-phenylenediamine derivatives [X3CC(O)CH=CR(o-NHC6H4Y), where X = F, Cl; R = H, Me, Et, aryl; and Y = NH2, OH] is reported.

The one-pot synthesis of six 3-methylisoxazole-5-carboxamides 2 [where the N-substituents are R1 = H, Me and R2 = Ph, CH2Ph, n-Bu, C(CH3)2Et, 3-methylisoxazol-5-yl] and twelve 5-[(1H-pyrazol-1-yl)carbonyl]-3-methyl isoxazoles 3 and 4 [where the pyrazole substituents are R3 (C5/C3) = CO2Et, CF3 and R5 (C3/C5) = H, Me, Et, Ph] from the 3-methyl isoxazole-5-carboxylic acid, thionyl chloride and the corresponding amine or pyrazole is reported. In the synthesis of 5-[(1H-pyrazol-1-yl)carbonyl]-3-methylisoxazoles we obtained a mixture of 1,3- and 1,5-isomers 3 and 4 in variable ratios, i.e., the substituent R3 (CO2Et and CF3) are present in position 3 or 5 on the pyrazole ring.

A quantitative relationship between the 17O substituent chemical shifts (SCS) of γ-alkyl substituents and the torsion angles calculated by the AM1 method is reported. A series of 3-alkyl substituted 5-trichloromethyl-5-hydroxy-4,5-dihydroisoxazoles and 5-trichloromethyl isoxazoles [where 3-alkyl substituents are Me, Et, n-Pr, iso-Bu, BrCH2, iso-Pr, Br2CH and tert-Bu] as model compounds were used. †For Parts 1–6, see References 14-15a, 15b-16, [19a], [19b].

A multi-linear-regression analysis using the Kamlet- Abboud-Taft (KAT) solvatochromic parameters in order to elucidate and quantify the solvent effects on the 17O chemical shifts of three 5-trichloromethyl-5-hydroxy-4, 5-dihydroisoxazoles [(1a) non-, (1b) 3-methyl- and (1c) 4-methyl-substituted] are reported. The chemical shifts of ring oxygen atom, O1, of compo- unds 1a, b, c show dependencies (in ppm) on the solvent polarity-polarizability of −2.4π*, −6.9π*, −4.3π*; on the solvent hydrogen-bond-donor (HBD) acidities −0.3α, 0.6α, −2.3α; and the solvent hydrogen-bond-acceptor (HBA) basicities 4.8β, 3.5β, 6.4β, respectively. The chemical shifts of hydroxyl oxygen atom, O5, of compounds 1a, b, c show dependencies (in ppm) on the solvent polarity-polarizability of 26.7π*, 18.3π*, 18.5π*; on the solvent hydrogen-bond-donor (HBD) acidities 2.8α, 2.2α, 1.2α; and the solvent hydrogen-bond-acceptor (HBA) basicities −12.1β, −10.2β, −14.1β, respectively. The net charge and dipole moment data, obtained from MO calcu...

A convenient method for the synthesis of a series of 4-trichloromethyl-pyrimidin-2-ylamines from the reaction of 4-trichloromethyl-2-chloropyrimidine and ammonium hydroxide, primary- and secondary-amines, and guanidine hydrochloride, is reported. This reactions was also extended to obtain 4-trichloromethyl-2-alkoxy-pyrimidines.

A multi-linear-regression analysis using the Kamlet-Abboud-Taft (KAT) solvatochromic parameters in order to elucidate and quantify the solvent effects on the 17O chemical shifts of (E)-1,1,1-trichloro-4-methoxy-3-penten-2-one (1) and (E)-1,1,1-trichloro-4-methoxy-3-methyl-3-buten-2-one (2) are reported. The chemical shifts of carbonyl group of the two molecules show similar dependencies (in ppm) on the solvent polarity-polarizability (-17φ∗, -15φ∗) and the solvent hydrogen-bond-donor (HBD) acidities (-7α, -6α). The influence of the solvent hydrogen-bond-acceptor (HBA) basicities is significant for compound 1 (3β) and small for compound 2 (0.7β).

A new series of trichloromethylated- 4, 5-dihydro-1H-pyrazoles has been studied. The molecular structure of 5-hydroxy-3-phenyl-5-trichloromethyl-4,5-dihydro-7H-pyrazole-1-carboxyamide (2), synthesized from the reaction of 4-methoxy -4-phenyl-1,1,1-trichloro-3-buten-2-one (1) with semicarbazide hydrochloride, was selected and determined by NMR spectroscopy, X-ray diffraction, and semiempirical MO calculations. Proton and carbon-13 NMR data, as one set of signals, shown that only one pair of the enanfiomers was obtained. The AM1 calculations showed that 2a (1S5S/1R5R) is the more stable enantiomers pair. The x-ray diffraction data confirmed that only the structure 2a (1S5S/1R5R) was obtained. This was explained by the existence of an intramolecular hydrogen bond between the hydroxy group at C(5) and the carbonyl group at N(1), with the formation a stable six-membered ring. Compound 2 (C11H10CI3N3O2, Mr = 320.98) crystallizes in the monoclinic space group P21/c with the unit cell dimensions a = 6.49...

The structure of 5-Bromo-4, 6-dimethoxy-4-(trichloromethyl)hexahydro 2-pyrimidinone (3), synthesized from the reaction of 4-methoxy-4-(trichloromethyl)tetrahydro-2-pyrimidinone (2) with bromo and methanol, was determined by nmr spectroscopy, X-ray diffraction, and semiempirical MO calculations. 1H and 13C nmr data shown that only one pair of the diastereoisomers was obtained. The AM1 calculations showed that 3a is the more stable diastereoisomers pair. The x-ray diffraction data confirmed that only the structure 3a (4S5S6R/4R5R6S) of compound 3 was obtained. Compound 3a (C7H10BrCl3N2O3, Mr = 356.43) crystallizes in the orthorhombic space group P212121 with the unit cell dimensions a = 7.112(2), b = 14.719(2) and c = 12.084(3) A, R = 7.32 % and wR2 = 14.92 % for an F 2 refinement on unique data with 2931 reflections collected and 2248 independent (Rint = 4.01%), Flack parameter 0.00(3). #For Part 1, see Ref. 1.

Evaluation by empirically derived equations for the substituent effect (EXn and EYn, n = 1 to 6) on the 13C NMR chemical shifts for C-1, C-2, C-3, C-4, C-5 and C-6 in 1-alkylamino-6-ethoxy-1,5-hexadien-3,4-diones 1a-f and 1,6-bis(alkylamino)-1,5-hexadien-3,4-diones 2a-f [XCH=CHC(O)-C(O)CH=CHY, where X, Y = OEt, NH2, PhCH2NH, n-BuNH, i-PrNH, cyclo-C6H11NH, t-BuNH], taking as reference the 1,6-diethoxy-1,5-hexadien-3,4-dione (3), is reported. From the calculated values for the EXn and EYn effects for each substituent it was possible to estimate the chemical shift of each carbon of the compounds 1,2 with excellent precision: 100% of the calculated chemical shifts are found to be within ±0.5ppm. The carbon-13 chemical shifts of C-1, C-2 and C-3 of compounds 1a,2a,3 led a good correlation with carbon charge densities (qr).

This work presents the evaluation by empirically derived equations for the substituent effect (α, β, γ, δ) on the 13C NMR chemical shifts for C-1, C-2, C-3 and C-4 in β-alcoxyvinylhalomethylketones 1a–h to 3a–h [R3C(O)-C(R2)=C(R1-OR, where R1 = H, alkyl or phenyl, R2 = H, alkyl or hetero-alkyl, and R3 = di- or trihalomethyl], taking as reference the compound la. From the calculated values for the α, β, γ, δ effects for each substituent it was possible to estimate the chemical shift of each carbon of the compounds 1–3. The 13C chemical shifts of the C-1, C-2, C-3, C-4 of these compounds, can be estimated with good to rasoable precision: 93% of the calculated chemical shifts are found to be within ±2.0ppm, and 100% are found to be within ±3.0ppm.

The 1H and 13C NMR chemical shift assignments of a series of (E) - and (Z)-N,N-Dialkylacetamides [CH3C(O)NR1R2, with R1/R2=Me/Et (1), Me/n-Bu (2), Et/n-Bu (3), Et/t-Bu (4), Me/Hydrcxyethyl (5)., Et/Hydroxyethyl (6), Et/Acetylhydroxyethyl (7)] are reported. The 1H chemical shifts for the N-substituents of the amides 1–7 recorded in benzene-d6 and in chloroform-d1 are in agreement with the Hatton and Richards (ASIS) and Paulsen-Todt models, respectively. The 13C chemical shifts for the N-substituents of compounds 1–3 were compared with data of the corresponding symmetrical amides, and the results can be explained by the reciprocal steric compression effect of one N-substituent on the other. The validity of this explanation is confirmed by 13C spin-lattice relaxation time (T1) measurements.

Carbon-13 NMR chemical shifts of a series of (E)- and (Z)-N-ethyl-N-methylamides [RC(O)NEtMe, R=H, Me, Et, i-Pr, t-Bu, CF3, ClCH2, Cl2CH, Cl3C, BrCH2, Br2CH, Br3C and ICH2] are reported. The α-carbon and carbonyl carbon chemical shifts are correlated with the empirical α-substituent effect and Charton's electrical parameter ([sgrave]I), respectively. The N-alkyl carbon resonances were attributed mainly to the γ- and δ-effects of R.