Boban K John

A study of impurities found in methamphetamine synthesized from ephedrine

Abstract The synthesis of methamphetamine from ephedrine via reduction with hydriodic acid is discussed. Impurities which arise from this method are identified and rationalized. The in situ formation of iodoephedrine from ephedrine leads to trace impurities via internal substitution to 1,2-dimethyl-3-phenylaziridine, followed by retro ring-opening and hydrolysis to phenyl-2-propanone (P-2-P). This ketone or the retro ring-opened aziridine further condenses in an aldol condensation followed by dehydration to give 1-benzyl-3-methylnaphthalene and 1,3-dimethyl-2-phenyl-naphthalene. Two-dimensional nuclear magnetic resonance (2-D NMR) was utilized to elucidate the structure of these impurities.

Effective combination of gradients and crafted RF pulses for water suppression in biological samples

The selection of multiple-quantum coherence wiith field gradients has been shown to be an effective method for suppressing the water resonance in aqueous solutions and for reducing t, noise and other artifacts associated with the phase-cycle selection of coherence (l-3). Recently, some of these advantages have been demonstrated for a phase-sensitive, double-quantum-filtered COSY (DQF COSY) experiment (3). However, for large, dilute biomolecules in water, .the gradient pulse durations and amplitudes must be large to eliminate the water signal. In situations where the gradient amplitude is limited, the gradient duration must be increased, which invariably leads to loss of signal due to spin-spin relaxation. The requirement on the gradient duration may be reduced by combining coherence selection with some other technique which achieves partial water suppression. Traditional presaturation methods require irradiation periods on the order of seconds, which may result in the loss or attenuation of a desired signal due to magnetization transfer. A succe:ssful strategy for water elimination in volume-localized spectroscopy has been the use of selective water excitation followed by gradient dephasing (4, 5). The selectivity of water elimination using this approach can be improved by the use of crafted RF pulse design. In this Communication, we have used this selective water-elimination strategy to attenuate the water signal prior to the coherence-selection sequence, thereby allowing the use of shorter gradient pulses. A phase-sensitive, gradient-enhanced, DQF COSY experiment is demonstrated here using a medium-sized protein in water. The pulse sequence and the corresponding coherence-level diagram are shown in Fig. 1. The water resonance is selectively excited, followed by a gradient pulse along the x axis which dephases the transverse magnetization. This is repeated a second time to remove any remaining magnetization with the exception that the dephasing gradient is applied along the y axis to avoid gradient-recalled echoes. The flip angle of the second selective pulse is adjusted so that the water magnetization is partially inverted to allow for T, recovery during the dephase gradients. This delay also allows the fasterrelaxing protein signals at the water chemical shift to recover. The water-elimination sequence is followed by a phase-sensitive, DQF COSY sequence with short, doublequantum, coherence-selection gradients G, and GZ along the x, y, and z axes. Multiplequantum coherence orders labeled by the gradient G, are then converted into observable antiphase magnetization by the last RF pulse. The relative ratios of the gradient pulses

Observation of homonuclear double-quantum correlations in plastic crystals using cross polarization and magic-angle spinning

The homonuclear doublequantum correlation experiment INADEQUATE (I7) represents an important capability for structure determination using NMR. In this experiment, spin-spin (scalar) coupling is used to generate double-quantum coherence between pairs of magnetic nuclei. In the two-dimensional version of this experiment, the double-quantum frequencies are allowed to evolve for a time t, . Then, after an appropriate readout pulse, magnetization is detected during time tz. In the two-dimensional spectrum, coupled nuclei with chemical-shift offsets of 6, and 8* in the F2 dimension are observed in F, at a frequency of 6, + 6z, thus allowing connectivities to be established. Well used and documented in the area of liquid-state NMR, the technique has not yet been applied to problems using cross polarization/magic-angle spinning (CP/MAS) NMR because of the difficulties associated with the observation of scalar coupling in CP/MAS NMR. In usual CP/MAS NMR samples, dipolar coupling usually obscures any scalar coupling which might be present. There are, however, a number of CP/MAS samples where scalar homonuclear couplings can be observed. Plastic crystals are an example of a type of sample which cross polarizes and can still show homonuclear scalar coupling. This note illustrates scalar double-quantum observation using two different plastic crystalline samples. Dipolar double-quantum spectra have been observed using cross polarization with an isotopically enriched single crystal of glycine (8). Although the pulse experiment used in the single crystalline glycine study is very similar to the sequence described in this work, there is a major difference in the experimental details. In the dipolar case, T delays necessary to generate doublequantum coherence are relatively short due to the strong dipolar interaction strength, while in the case of scalar couplings, 7 delay times are relatively long due to the weak interaction of the scalar coupling. The results reported in this paper are more closely related to the liquid-phase INADEQUATE experiment than to the glycine study referenced above. The solids INADEQUATE pulse sequence, illustrated in Fig. 1, was based on a liquid-state experiment which uses a 45” read pulse (6) and requires 128 scans for a complete phase cycle. For the solids experiment, the initial 90” pulse was replaced by a proton decoupler 90” pulse and a Hartmann-Hahn cross-polarization pulse (CP). Spin temperature alternation was also incorporated into the phase cycling to eliminate artifacts. After 128 scans are acquired to complete the phase cycle, the phase of the

Multidimensional nmr spectroscopy using switched acquisition time gradients for multiple coherence transfer pathway detection

A signal function S(t1, t2) is obtained from a plurality of coherence transfer pathways in a single acquisition by preparing a molecular system in a coherent non-equilibrium state, and alternately and sequentially detecting signals at individual sampling points, in t2, from the plurality of coherence transfer pathways by using gradient refocusing of a new pathway after siganl detection at a sampling point in another pathway. The gradient encoding and refocusing of coherence pathways can use inhomogeneous rf-pulses (B1 gradients) or B0 field gradients. The coherence transfer pathways can be sequentially selected in an arbitrary order.

Method and apparatus for obtaining pure-absorption two-dimensional lineshape data for multidimensional NMR spectroscopy using switched acquisition time gradients

A signal function S(t1, t2) is obtained from a plurality of coherence transfer pathways in a single acquisition by preparing a molecular system in a coherent non-equilibrium state, and alternately and sequentially detecting signals at individual sampling points, in t2, from the plurality of coherence transfer pathways by using gradient refocusing of a new pathway after signal detection at a sampling point in another pathway. A frequency domain spectrum S( omega 1, omega 2) is another pathway. A frequency domain spectrum S( omega 1, omega 2) is constructed by first Fourier transforming the time domain signals S(t1, t2) in the t2 dimension and producing real and imaginary components which modulate as sine and cosine signals in t1. The real ( omega 2) cosine (t1) components are combined with the imaginary ( omega 2)sine (t1) components to form a complex data set S(t1, omega 2) that is amplitude modulated in t1. The complex data set is then Fourier transformed in the t1 dimension to construct in frequency domain spectrum S( omega 1, omega 2) which contains construct in frequency domain spectrum S( omega 1, omega 2) which contains pure absorption lineshapes.