Diastereotopic Protons Research Articles

Reactions of C702– with Organic Halides Revisited: Unusual Magnetic Equivalence for the Diastereotopic Methylene Protons in 2,5-(PhCH2)2C70

The reactions of C70(2-) with organic halides result in several isomeric products. However, the structures of the isomers have not been identified unambiguously and the reactions still remain elusive even though the first report of the reaction appeared more than ten years ago. Herein, the reactions of C70(2-) with ArCH2Br (Ar = Ph, o-, m-, and p-BrC6H4) are revisited. Two types of isomeric para-adducts of 2,5- and 7,23-(ArCH2)2C70 are obtained and characterized with the X-ray single-crystal diffractions, HRMS, (1)H and (13)C NMR, and UV-vis spectroscopies. An unusual singlet resonance instead of the typical AB quartet resonance is shown for the C2 diastereotopic methylene protons in (1)H NMR spectrum of 2,5-(PhCH2)2C70 recorded at ambient temperature. The unexpected magnetic equivalence is studied with the variable-temperature (VT) NMR and density functional theory (DFT) calculations. The results show that the greater local curvature in the C70 polar region is likely responsible for the unusual magnetic equivalence exhibited by the C2 diastereotopic methylene protons of 2,5-(PhCH2)2C70, indicating that under certain cases, it is improbable to elucidate the spectral data of fullerene derivatives with a less symmetrical carbon cage in analogy with those of the C60 derivatives.

Exocyclic Diastereotopic Protons as a Probe for Conformational Bias in Eight-Membered Rings Containing Phosphorus and Titanium

The conformation in solution of eight-membered 12H-dibenzo[d,g][1,3,2]-dioxametallocin rings containing phosphorus and titanium, respectively, were studied by the NMR spectroscopy using ring substituents containing diastereotopic protons as a probe for conformational bias. The results of this study suggest that in addition to steric effects, an electronic effect due to donation of the lone pair of electrons on the ring oxygen atoms to the metal center influences the preferred conformation in solution.

Evaluation of Multisite Polypyridyl Ligands as Platforms for the Synthesis of Rh/Zn, Rh/Pd, and Rh/Pt Heterometallic Complexes

Ligands containing linked dipicolylamine (dpa) and bipyridine (bpy) sites have been utilized in the synthesis of monometallic and heterometallic complexes. The two sites have different selectivities for metal binding, which allows preferential formation of singly metalated complexes. The dpa site of the ligands has been observed to bind selectively to Zn(2+), Pd(2+), and Pt(2+), while the bpy site binds selectively to Rh(+). Addition of a second metal then results in the formation of heterometallic products. In the presence of CD3OD, the heterometallic Rh/Pt and Rh/Pd complexes undergo rapid selective H/D exchange of one of the diastereotopic protons of the dpa methylene group.

New strategy for RDC‐assisted diastereotopic proton assignment using a combination of J‐scaled BIRD HSQC and J‐scaled BIRD HMQC/HSQC

A new strategy to assign diastereotopic protons was developed on the basis of residual dipolar couplings (RDCs) collected in compressed poly(methyl methacrylate) (PMMA) gels. A combination of 2D J-scaled BIRD HSQC and J-scaled BIRD HMQC/HSQC NMR experiments was used to collect the RDC data. In the proposed strategy, the first experiment is used to measure (1)D(CH) for methine groups, the sum of (1)D(CHa) + (1)D(CHb) for methylene groups and the average (1)D(CH3) value for methyl groups. In turn, the small molecule alignment tensor is calculated using these D values without the a priori assignment of CH(2) diastereotopic protons. The D values of each individual CH bond (CHa and CHb) of each methylene group in the molecule are then predicted using the calculated alignment tensor and these values compared with the results from the HMQC/HSQC experiment, leading to their unambiguous assignment. This strategy is demonstrated with the alkaloid strychnine that contains five methylene groups with diastereotopic protons, and our results fully agree with the previously reported assignment using combinations of permutated assignments.

Synthesis of a Bis(thiophenolate)pyridine Ligand and Its Titanium, Zirconium, and Tantalum Complexes

A precursor to a new tridentate LX_2 type ligand, bis(thiophenol)pyridine ((SNS)H_2 = (2-C_6H_4SH)_2-2,6-C_5H_3N), was prepared. Bis(thiophenolate)pyridine complexes of Ti, Zr, and Ta having dialkylamido coligands were synthesized and structurally characterized. The zirconium complex (SNS)Zr(NMe_2)_2 (4) displays C_2 symmetry in the solid state, unlike a related bis(phenolate)pyridine compound, C_s-symmetric (ONO)Ti(NMe_2)_2. This change is likely the result of strain about the sulfur atom in the six-membered chelate with longer metal–sulfur and carbon–sulfur bonds. Solid-state structures of tantalum complexes (SNS)Ta(NMe_2)_3 (5) and (SNS)TaCl(NEt_2)_2 (6) also display pronounced C_2 twisting of the SNS ligand. 1D and 2D NMR experiments show that 5 is fluxional, with rotation about the Ta–N(amide) bonds occurring on the NMR time scale that interchange the equatorial amide methyl groups (ΔG^‡_(393) = 25.0(3) kcal/mol). The fluxional behavior of 6 in solution was also studied by variable-temperature ^1H NMR. Observation of separate signals for the diastereotopic protons of the methylene unit of the diethylamide indicates that the complex remains locked on the NMR time scale in one diastereomeric conformation at temperatures below −50 °C, fast rotation about the equatorial amide Ta–N bonds occurs at higher temperature (ΔG^‡_(393) = 13.4(3) kcal/mol), and exchange of diastereomeric methylene protons occurs via inversion at Ta that interconverts antipodes (ΔG^‡_(393) ≈ 14(1) kcal/mol).

NMR and Computational Studies of the Configurational Properties of Spirodioxyselenuranes. Are Dynamic Exchange Processes or Temperature-Dependent Chemical Shifts Involved?

Spirodioxyselenurane 4a and several substituted analogs revealed unexpected (1)H NMR behavior. The diastereotopic methylene hydrogens of 4a appeared as an AB quartet at low temperature that coalesced to a singlet upon warming to 267 K, suggesting a dynamic exchange process with a relatively low activation energy. However, DFT computational investigations indicated high activation energies for exchange via inversion through the selenium center and for various pseudorotation processes. Moreover, the NMR behavior was unaffected by the presence of water or acid catalysts, thereby ruling out reversible Se-O or benzylic C-O cleavage as possible stereomutation pathways. Remarkably, when 4a was heated beyond 342 K, the singlet was transformed into a new AB quartet. Further computations indicated that a temperature dependence of the chemical shifts of the diastereotopic protons results in convergence upon heating, followed by crossover and divergence at still higher temperatures. The NMR behavior is therefore not due to dynamic exchange processes, but rather to temperature dependence of the chemical shifts of the diastereotopic hydrogens, which are coincidentally equivalent at intermediate temperatures. These results suggest the general need for caution in ascribing the coalescence of variable-temperature NMR signals of diastereotopic protons to dynamic exchange processes that could instead be due to temperature-dependent chemical shifts and highlight the importance of corroborating postulated exchange processes through additional computations or experiments wherever possible.

Conformational analysis of the chemical shifts for molecules containing diastereotopic methylene protons

Quantum chemistry SCF/GIAO calculations were carried out on a set of compounds containing diastereotopic protons. Five molecules, including recently synthesized 1,3-di(2,3-epoxypropoxy)benzene, containing the chiral or pro-chiral center and the neighboring methylene group, were chosen. The rotational averages (i.e. normalized averages with respect to the rotation about the torsional angle τ with the exponential energy weight at temperature T) calculated individually for each of the methylene protons in 1,3-di(2,3-epoxypropoxy)benzene differ by ca. 0.6 ppm, which is significantly less than the value calculated for the lowest energy conformer. This value turned out to be low enough to guarantee the proper ordering of theoretical chemical shifts, supporting the interpretation of the 1H NMR spectrum of this important compound. The rotational averages of chemical shifts for methylene protons for a given type of conformer are shown to be essentially equal to the Boltzmann averages (here, the population-weighted averages for the individual conformers representing minima on the E( τ) cross-section). The calculated Boltzmann averages in the representative conformational space may exhibit completely different ordering as compared to the chemical shifts calculated for the lowest-energy conformer. This is especially true in the case of molecules, for which no significant steric effects are present. In this case, only Boltzmann averages account for the experimental pattern of proton signals. In addition, better overall agreement with experiment (lower value of the root-mean-square deviation between calculated and measured chemical shifts) is typically obtained when Boltzmann averages are used.

Self‐Assembled Capsules of Unprecedented Shapes

Self‐Assembled Capsules of Unprecedented Shapes

X-ray structures and computational studies of several cathinones

2-(Ethylamino)-1-(4-methylphenyl)propan-1-one (shortly named 4-MEC) ( 1a), 1-(1,3-benzodioxol-5-yl)-2-(methylamino)propan-1-one (shortly named methylone or 3,4-methylenedioxymethcathinone) ( 1b), 1-(3,4-dimethylphenyl)-2-(methylamino)propan-1-one ( 1c), 2-methylamino-1-(4-methylphenyl)propan-1-one (shortly named mephedrone; 4-MMC or 4-methylmethcathinone) ( 1d) and 2-(methylamino)-1-phenylbutan-1-one (shortly named buphedrone) ( 1e) and their aminium salts ( 2a–e), are examples of cathinones which were characterized by FTIR, UV–Vis, multinuclear NMR spectroscopy. By single crystal X-ray diffraction method structures of 2a, 2b, 2c and 2d were determined. NMR solution spectra showed readily diagnostic H-1 and C-13 signals from methyl, ethyl, N-methyl or N-ethyl groups. The diastereotopic methylene protons of 1a appear as an ABX 3, and 1e and 2e appear as an ABMX 3 system. The geometries of the studied compounds were optimized in singlet states using the density functional theory (DFT) method with B3LYP functional. Electronic spectra were calculated by TDDFT method. In general, the predicted bond lengths and angles are in good agreement with the values based on the X-ray crystal structure data.

Bis(4‐methylthiazolyl)isoindoline (4‐Mebti) Complexes of Palladium: Cationic [PdII(4‐Mebti)L]+ Species with a L = Neutral Group XIV or Group XV Donor Ligand

AbstractLigand exchange has been studied on the chlorido palladium(II) complex of the bis(4‐methylthiazolylimino)isoindoline ligand, [Pd(4‐Mebti)Cl], with a number of neutral group XIV and group XV donor ligands in the presence of the sodium salt of tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate NaB(ArF)4. Seven new cationic compounds with L = PMe3, tBuNH2, PhNH2, py, 2,6‐Me2py, MeCN and MeNC were obtained as B(ArF)4– salts, and were characterized by analytic, spectroscopic and crystallographic means. Further attempts to observe ligand exchange reactions with either the softer AsMe3 or SbMe3 donor ligands or with different carbenes were unsuccessful and led to decomposed material or to mixtures of different compounds. Most of the crystallographically characterized complexes have been found to reside in a pseudoplanar conformation regardless of the size or cone angle of the external donor ligand. The derivatives carrying an sp2‐type donor atom (L = py, 2,6‐Me2py), however, adopt helical forms in the solid state. 1H NMR and UV/Vis spectroscopic data suggest that this helicity is also present in solution. The expected chirality, however, could not be observed due to the lack of diastereotopic ligand protons.

ChemInform Abstract: An Efficient Synthesis of β‐Acylureas via a Three‐Component, One‐Pot Synthesis Using TCS/ZnCl2.

ChemInformVolume 42, Issue 24 Isocyclic Compounds ChemInform Abstract: An Efficient Synthesis of β-Acylureas via a Three-Component, One-Pot Synthesis Using TCS/ZnCl2. Tamer K. Khatab, Tamer K. Khatab Dep. Organomet. Organometalloid Chem., Natl. Res. Cent., Dokki, Cairo 12622, EgyptSearch for more papers by this authorKhairy A. M. El-Bayouki, Khairy A. M. El-Bayouki Dep. Organomet. Organometalloid Chem., Natl. Res. Cent., Dokki, Cairo 12622, EgyptSearch for more papers by this authorWahid M. Basyouni, Wahid M. Basyouni Dep. Organomet. Organometalloid Chem., Natl. Res. Cent., Dokki, Cairo 12622, EgyptSearch for more papers by this author Tamer K. Khatab, Tamer K. Khatab Dep. Organomet. Organometalloid Chem., Natl. Res. Cent., Dokki, Cairo 12622, EgyptSearch for more papers by this authorKhairy A. M. El-Bayouki, Khairy A. M. El-Bayouki Dep. Organomet. Organometalloid Chem., Natl. Res. Cent., Dokki, Cairo 12622, EgyptSearch for more papers by this authorWahid M. Basyouni, Wahid M. Basyouni Dep. Organomet. Organometalloid Chem., Natl. Res. Cent., Dokki, Cairo 12622, EgyptSearch for more papers by this author First published: 19 May 2011 https://doi.org/10.1002/chin.201124084Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume42, Issue24June 14, 2011 RelatedInformation

An efficient synthesis of β-acylureas via a three-component, one-pot synthesis using TCS/ZnCl2

A simple and efficient one-pot, three-component synthesis of new trisubstituted ureas containing diastereotopic protons is achieved via the reaction of aromatic aldehydes, aromatic ketones, and dimethyl cyanamide using a TCS/ZnCl2 reagent mixture at room temperature.

Synthesis and characterisation of medium-sized ring systems by oxidative cleavage. Part 2: Insights from the study of ring expanded analogues

Variable temperature NMR analysis and computational methods have been used to develop a detailed understanding of the 1H NMR spectra of a family of medium-sized ring containing compounds. The family consists of analogues containing 10-, 11- and 12-membered rings and in all cases the NMR spectra at room temperature showed a series of diastereotopic methylene signals despite the lack of a stereogenic centre in these systems. On repeating the NMR analysis at higher temperatures, all the signals coalesced for the 12-membered ring system consistent with full interconversion of ring conformers. This was not observed in the analogous 10- and 11-membered ring systems with the interchange of conformers remaining slow on the NMR timescale. However, 1D gs-NOESY/EXSY NMR experiments showed that in the smaller ring systems interconversion of diastereotopic protons did occur. Computational studies suggest that the dynamic process observed by NMR for the 10- and 11-membered rings systems is different from that observed in the 12-membered ring containing compound.

Demixing of severely overlapped 1H NMR resonances and interpretation of anomalous intensity pattern of dipolar coupled A3 spins in a weakly aligning medium

We report a single 13C spin edited selective proton–proton correlation experiment to decipher overcrowded 13C coupled proton NMR spectra of weakly dipolar coupled spin systems. The experiment unravels the masked 13C satellites in proton spectrum and permits the measurement of one bond carbon–proton residual dipolar couplings in I 3S and for each diastereotopic proton in I 2S groups. It also provides all the possible homonuclear proton–proton residual couplings which are otherwise difficult to extract from the broad and featureless one dimensional 1H spectrum, in addition to enantiodifferentiation in a chiral molecule. Employment of heteronuclear ( 13C) decoupling in the evolution period results in complete demixing of overlapped signals from enantiomers. The observed anomalous intensity pattern in strongly dipolar coupled methyl protons in methyl selective correlation experiment has been interpreted using polarization operator formalism.

N-2,4-dichlorobenzoyl phosphoric triamides: Synthesis, spectroscopic and X-ray crystallography studies

New phosphoric triamides 1–9 were synthesized by the reaction of N-2,4-dichlorobenzoyl phosphoramidic dichloride with various cyclic aliphatic amines and the products were characterized by 1H, 13C, 31P NMR, IR spectroscopy and elemental analysis. Surprisingly, the 1H NMR spectrum of 2 indicated long range 6 J (P, H) coupling constant = 1.3, 1.4 Hz and those of molecules 3, 4, 6–8 display long-range 4 J (H, H) coupling constants (1.8–1.9 Hz) for the coupling of aromatic protons in 2,4-dichlorophenyl rings. 1H NMR spectra indicated 3 J (PNCH) for enantiotopic and diastereotopic benzylic CH2 protons in compounds 7 and 8. The spectroscopic data of newly synthesized compounds were compared with those related N-benzoyl derivatives. The structures of compounds 5, 8 and 10 (2,4-Cl2-C6H3C(O)NHP(O)[NCH2CH(CH3)2]2) have been determined by X-ray crystallography. The structures form centrosymmetric dimers through intermolecular strong -P=O…H-N-hydrogen bonds. The dimers connect to each other via rather strong and weak C-H…O plus weak C-H…Cl H-bonds to produce a 1-D network for 5 while 3-D polymeric chains for 8 and 10.

Effects of Solvation on the Spin State of Iron(III) in 2,8,12,18-Tetrabutyl-3,7,13,17-tetramethyl-5,10-diazaporphyrinatoiron(III) Chloride

The chloroiron(III) complex of 2,8,12,18-tetrabutyl-3,7,13,17-tetramethyl-5,10-diazaporphyrin, [(Cl)FeMBDAP], was prepared and studied by X-ray crystallography and by solution (1)H NMR and UV-vis measurements. In the crystal structure of hemisolvate [(Cl)FeMBDAP] x 0.5CHCl(3), two nonequivalent [(Cl)FeMBDAP] units containing Fe1 and Fe2 are arranged in pi-dimers with considerable overlap on their concave sides. Axial chloride bonded to Fe2 is solvated by hydrogen bonding with CHCl(3). Parameters of the coordination pyramid have typical values for the spin-mixed (S = 3/2 / 5/2) Fe(III) complexes in the case of Fe1 and are characteristic for the pure intermediate-spin state for Fe2 (displacement from the (N(Pyr))(4) planes - 0.385 and 0.290 A and the average N(Pyr)-Fe bond lengths -1.992 and 1.954 A for Fe1 and Fe2, respectively). Effective magnetic moments in CHCl(3) and CH(2)Cl(2) capable of specific solvation of chloride by hydrogen bonding (4.5-4.6 micro(B) at 298 K) are indicative about mixed intermediate/high-spin state S = 3/2 / 5/2, with the S = 3/2 contribution increasing upon lowering of the temperature (4.02 micro(B) in CD(2)Cl(2) at 193 K). In nonsolvating CCl(4), C(6)D(6), and THF-d(8), the mu(eff) values are consistent with the predominantly high-spin state at ambient temperature (5.5-5.75 micro(B) at 298 K) and almost pure S = 5/2 state at low temperature (ca. 5.9 micro(B) in THF-d(8) below 270 K). Downfield isotropic shifts from 35 to 50 ppm are observed for alpha-alkyl protons and upfield shifts from -5 to -15 ppm for meso-CH protons, which is characteristic for the presence of the intermediate-spin state. The splitting of signals of the diastereotopic alpha-CH(2) protons is increased with growth of the S = 3/2 state contribution from 1.5 to 4 ppm in nonsolvating to 11 ppm in specifically solvating solvents at 298 K and further to 31 ppm at 193 K (in CD(2)Cl(2)). In the presence of DMSO addition and in methanol solution, the single CH(2) signal is observed at 25-28 ppm, and the meso-CH resonance is also shifted downfield to ca. 30 ppm, indicating the formation of six-coordinated complexes [(DMSO)(2)FeMBDAP](+) and [(MeOH)(2)FeMBDAP](+), the latter having the mu(eff) value of 4.92 micro(B) at 291 K is a spin-mixed species. The electron spin resonance spectra recorded at 77 K indicates that in frozen glasses in CD(2)Cl(2) and THF molecules in the high-spin state (g( perpendicular) approximately 6) and the predominantly intermediate-spin state (g( perpendicular) approximately 4.2-4.3) coexist together.

The Conversion of l-Phenylalanine to (S)-2-Hydroxy-3-phenylpropanoic Acid: A Simple, Visual Example of a Stereospecific SN2 Reaction

We report a simple, inexpensive, visual, and environmentally friendly SN2 reaction appropriate for the second-year organic chemistry laboratory that illustrates stereospecificity, dependence of water solubility on the state of ionization, optical activity, and effect of diastereotopic protons in 1H NMR spectroscopy. The reaction converts readily available l-phenylalanine in a double SN2 reaction to enantiomerically pure (S)-2-hydroxy-3-phenylpropanoic acid. The optical purity and absolute stereochemistry are determined by the specific rotation of the product.

Synthesis and Characterization ofanti-bisFe(III) Porphyrins,syn-bisFe(III)-μ-oxo Porphyrin, andsyn-bisFe(III)-μ-oxo Porphyrin Cation Radical

BisFe(III) porphyrins bridged by a highly flexible ethane linker are reported in which the bisporphyrin platform "opens" and "closes" its binding pockets leading to facile syn-anti conformational switching with very high vertical flexibility in a single molecular framework. With axial ligand X (X: Cl, Br, I, ClO(4)), the anti-forms of the molecule are stabilized. The X-ray structure of anti bis perchloratoFe(III)porphyrin is reported, and the molecule is found to be high-spin in nature. In sharp contrast, all other Fe(III) porphyrins with ClO(4) as axial ligands are in an either intermediate or admixed spin state. The very strong Fe-OClO(3) bond and relatively weaker Fe-N(p) bonds are responsible for the high-spin nature of the molecule. Upon treatment with base, bis Fe(III)-mu-oxo porphyrin is generated in which the Fe-O-Fe unit is remarkably bent (with a 147.9(1) degrees angle) and two porphyrin rings in a molecule are so close that at least six carbon atoms from each of the porphyrin macrocycles are driven to be essentially closer than the van der Waals contact distance. Upon manipulating the acidity/basicity of the solution, the facile syn-anti conformational switching takes place that is also reversible in nature. The complex catalyzes the rapid photoinduced oxygenation of phosphites under mild condition using aerial O(2). Electrochemical data reveals that bis Fe(III)-mu-oxo porphyrin undergoes four one electron oxidations and one electron reduction. However, oxidations become easier in syn Fe(III)-mu-oxo dimer rather than the anti-form of the molecule (with axial ligand X). The presence of two porphyrin macrocycles within a short distance in the syn form makes the porphyrin core highly nonplanar and more electron rich, and that might be responsible for easier oxidations compared to [Fe(OEP)](2)O. Oxidations of the mu-oxo complex are performed using both chemical and electrochemical methods. The addition of 1.00 mol equiv of iodine-silver perchlorate generates the singly oxidized product that shows large isotropic shifts in (1)H NMR with eight diastereotopic methylene proton signals (at 295 K) spreading over 8 to 16 ppm, and two meso resonances occurs at -10.2 and -13.7 ppm in 2:1 ratio. However, the addition of less than 1 equiv of oxidizing agent gives an average (1)H NMR signal. This indicates that intra- and intermolecular electron transfer is rapid in the NMR time scale, and no porphyrin structural modification has occurred during oxidation.

Triazene derivatives of (1,x)-diazacycloalkanes — Part IX. Synthesis and characterization of a series of 1,4-di[2-aryl-1-diazenyl]-2,6-dimethylpiperazines

A series of 1,4-di-[2-aryl-1-diazenyl]-2,6-dimethylpiperazines (5a–5l), have been synthesized by the reaction of 2,6-dimethylpiperazine with 2 equiv. of the appropriate diazonium salt. The products have been characterized by IR and NMR spectroscopy, and the molecular composition has been verified by high-resolution EI mass spectrometry with accurate mass measurement of the molecular ion. The presence of stereocenters at C2 and C6 of the piperazine ring in the bis-triazene 5 creates two unique pairs of diastereotopic protons in the methylene groups at positions 3 and 5 of the piperazine ring, as evidenced by the complexity of the NMR spectra, which nevertheless can be fully assigned in most cases. The assignment of the proton and carbon signals in the 1,4-di-[2-aryl-1-diazenyl]-2,6-dimethylpiperazines has been aided by the use of 2D NMR HSQC spectroscopy. These results compare favorably with assignments of proton and carbon signals reported previously for triazenes of type 1 and bis-triazenes of type 3.

Solid state and solution study of some phosphoramidate derivatives containing the P(O)NHC(O) bifunctional group: Crystal structures of CCl 2HC(O)NHP(O)(NCH 3(CH 2C 6H 5)) 2, p-ClC 6H 4C(O)NHP(O)(NCH 3(CH 2C 6H 5)) 2, CCl 2HC(O)NHP(O)(N(CH 2C 6H 5) 2) 2 and p-BrC 6H 4C(O)NHP(O)(N(CH 2C 6H 5) 2) 2

Synthetic methods for several novel phosphoramidate compounds containing the P(O)NHC(O) bifunctional group were developed. These compounds with the general formula R 1C(O)NHP(O)(N(R 2)(CH 2C 6H 5)) 2, where R 1 = CCl 2H, p-ClC 6H 4, p-BrC 6H 4, o-FC 6H 4 and R 2 = hydrogen, methyl, benzyl, were characterized by several spectroscopic methods and analytical techniques. The effects of phosphorus substituents on the rotation rate around the P–N amine bond were also investigated. 1H NMR study of the synthesized compounds demonstrated that the presence of bulky groups attached to the phosphorus center and electron withdrawing groups in the amide moiety lead to large chemical-shift non-equivalence (Δ δ H) of diastereotopic methylene protons. The crystal structures of CCl 2HC(O)NHP(O)(NCH 3(CH 2C 6H 5)) 2, p-ClC 6H 4C(O)NHP(O)(NCH 3(CH 2C 6H 5)) 2, CCl 2HC(O)NHP(O)(N(CH 2C 6H 5) 2) 2 and p-BrC 6H 4C(O)NHP(O)(N(CH 2C 6H 5) 2) 2 were determined by X-ray crystallography using single crystals. The coordination around the phosphorus center in these compounds is best described as distorted tetrahedral and the P(O) and C(O) groups are anti with respect to each other. In the compound Br-C 6H 4C(O)NHP(O)(N(CH 2C 6H 5) 2) 2 (with two independent molecules in the unit cell), two conformers are connected to each other via two different N–H⋯O hydrogen bonds forming a non-centrosymmetric dimer. In the crystalline lattice of other compounds, the molecules form centrosymmetric dimers via pairs of same N–H⋯O hydrogen bonds. The structure of CCl 2HC(O)NHP(O)(N(CH 2C 6H 5) 2) 2 reveals an unusual intramolecular interaction between the oxygen of C O group and amine nitrogen.