Boron and gallium esters derived from 2-(1,3,5-dithiazinan-5-yl)- ethanols

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Introduction
Dithiazinanes are very reactive molecules rich in lone pairs and suitable ligands for elements of group 13.They are used as flavouring agents 1 catalysts, 2 antibiotics 2,3 or reagents in organic synthesis. 4,5The coordinating ability of the simple dithiazinanes was already tested using BX 3 reagents (X = H or halogen), in all cases the nitrogen is the more basic site, [6][7][8][9][10][11][12][13] Scheme 1.An In the past, one of us has investigated the reactions of BH 3 and boric acid with ethanolamines. 14It was found that these reactions give selectively boric or boronic esters, amineboranes, amineboranes-boric esters or amineborane-boronic esters depending on the stoichiometry and the reaction conditions.In the reaction products, the nitrogen lone pair could be intramolecularly coordinated to boron, if the steric demand is not very high.Therefore, our interest was focused in exploring how the combination of dithiazinane and ethanolamine groups in compounds 1-3 could give better ligands for boron or gallium compounds, Scheme 2. The strong intramolecular hydrogen bonds O-H•••N of compounds 1-3 15 are indicative that in the corresponding boron or gallium esters, these atoms would occupy the place of the proton, Scheme 2. This idea is supported by the report that diphenyl borinic esters of 4hydroxypiperidine 7 and 1,4-diethanolpiperazine 24 present strong intramolecular N→B coordination leading to spiro-compounds.
The preparation and the structural analysis of the dithiazinanyl-N-ethanols ligands (1-3) have been reported. 15The solid state structures obtained by X-ray diffraction showed that the ethanol moiety was placed in the axial position with a strong intramolecular hydrogen bond OH•••N, whereas the NMR analyses in CDCl 3 showed a ring conformational equilibrium at room temperature with a preferred conformation for the N-alkyl group in axial position 8 , the latter phenomenon has been attributed to the electronic repulsion between the lone pairs at sulfur and nitrogen atoms. 16The low temperature spectra of compounds 1-3 show that the ring conformation is frozen and different signals for equatorial and axial protons are observed. 15For ligands 2 and 3, the low temperature and the presence of a stereogenic center at C-8 (Scheme 2), make the methylene groups at C4 and C6 diasterotopic, with different 1 H-NMR chemical shifts.
We have already investigated the reaction of the neutral ligands 2 and 3 with organoaluminum compounds. 17Three types of aluminum derivatives were obtained, shown in Scheme 3.  17 These results motivated us to test the reactions of compounds 1-3 with other group 13 elements: boron and gallium.The expected derivatives are interesting because both elements can react with the OH group giving the corresponding esters and forming chelates by coordination to the nitrogen atom.They are also of interest as gallium coordination compounds have been less well investigated than boron derivatives, despite the fact that gallium has a metallic character and that strong and stable derivatives are expected.The structure of the products was determined by NMR and the minimum energy conformations of the boron compounds were calculated by ab initio 6-31G(d,p).The X-ray diffraction analysis of the gallium compound (R = CH 3 , 12) as well as the hydrochloride (15) of compound 1 are also reported.

Boron Compounds
We have reacted 2-(1,3,5-dithiazinan-5-yl)ethanols 1-3 with BF 3 •OEt 2 , BCl 3 •SMe 2 , and 1 and 2 with (Ph 2 B) 2 O. Different products were expected because dithiazinanyl-ethanols present two active sites to boron reagents: the OH group which can form boron esters and the nitrogen that can give N→B coordination compounds.Unfortunately, we were not able to obtain crystals for X-ray diffraction analyses, however we have performed ab initio calculations as an alternative to study the minimum energy structures, and as we will see later, calculations are an excellent tool for the structural analyses of these compounds.

Scheme 5
From the reaction mixture of compound 7, some crystals were obtained which were the hydrochloride (15) of compound 1, its X-ray diffraction structure was determined, and is discussed below.
The 11 B NMR spectra show broad signals for compounds 4-6 (4 +3.7, 5 +3.8, 6 +3.4 ppm) which correspond to OBF 2 ←N groups, 18,19 and for compounds 7-9 (7 +9.9, 8 +10.0, 9 +10.3 ppm) characteristic of OBCl 2 ←N groups. 18,19Reactions between two equivalents of compounds 1 and 2 and (Ph 2 B) 2 O produced esters 10-11, the 11 B signals (10 +44, 11 +43 ppm) were attributed to tricoordinated planar diphenylboronic esters, indicating the absence of nitrogen coordination, however when the 11 B spectra were obtained at -60 o (10 +3.2, 11 +1.0 ppm) the chemical shifts corresponded to diphenylborinic esters coordinated with nitrogen, Scheme 6.Therefore, for diphenylboron compounds, an equilibrium between the open boron esters and the intramolecular coordinated N→B molecules is proposed.The experiment indicated that the dithiazinane ring is a weaker base than piperidine or piperazine because the diphenyl borinic Esters formation (4-11) was also confirmed by their 13 C spectra.Signals for C8 are shifted to high frequencies (∆δ ≈ 6.7 ppm) with respect to the starting ethanol-dithiazinanes 1-3, Table 1.The coupling pattern of the 1 H NMR spectra of 4-9 and of 10-11 at low temperature indicate that the inversion of dithiazinane rings is anchored as a consequence of the N→B coordination.The axial and equatorial protons appear at different chemical shift and are coupled due to the presence of stereogenic carbon atoms (C8 bearing methyl or phenyl groups) in compounds 5, 6, 8, 9 and 11.The C4H 2 and C6H 2 methylene groups are diasterotopic, and the separation of the diasterotopic signals increases with the strength of the N→B coordination bond. 20In Table 1, NMR data are shown.
The difference in the chemical shift of the CH 2 protons is also due to the non symmetric contact of the halogen atoms with the methylenic protons in 4-9.As is shown in the calculated molecules that will be discussed below, one of the halogen atoms adopt a pseudoequatorial position with respect to the five membered ring and is close to the two axial C4H and C6H protons, whereas the second halogen atom is pseudoaxial and lies close to the C6H equatorial proton producing an electronic effect.Figure 1 illustrates these interactions.It is therefore expected that the highest frequency signal belongs to the equatorial C6H proton; from this assumption and using HETCOR and COSY experiments the 1 H and 13 C signals were assigned.
From the NMR experiments the N→B coordination bond energy of 10-11 was calculated and the values are 50.84]    25 The calculated preferred conformations are similar to that found by X-ray diffraction analyses for the aluminium derivatives 17 , and for the gallium compound (12) reported here.For example, the calculated angles around the nitrogen (which can be related to the coordination bond) in compounds 5 (C4-N-C6 112.2;C6-N-C7 113.9 and C4-N-C7 114.9 o ) and 8 (C4-N-C6 110.8;C6-N-C7 112.3 and C4-N-C7 114.A view of compounds 5 and 9 in the C7-C8 bond axis (left in Figures 3 and 4) shows the preferred envelope conformation of the five membered ring, with the nitrogen atom out of the ring plane, and that the phenyl or methyl group is in the equatorial position.The coordinated N→B structures of compounds 10-11 were also calculated.The most stable conformation observed for 11 is shown in Figure 5. Angles around the boron and nitrogen atoms and the N•••B distances (≈ 3.05 Å) indicate a weak interaction, shorter than the sum of the van der Waals radii (3.84 Å). 26 In these molecules, the boron sp 3 hybridization is minimum (≈ 0.4 %) disfavouring the N→B bond coordination as was also deduced from the NMR analysis.In the preferred conformation of 11, it is noted that the plane of the phenyl groups is close to the C4H and C6H equatorial protons, which explains the shielding effect found in the 1

Gallium compounds
The gallium (dithiazinyl)ethanol compounds 12 and 13 were prepared from the reaction of the sodium ethanolate of compounds 2 and 3 and GaCl 3 in toluene, 12 (90 %) and 13 (90 %), Scheme 7.After the reaction they were directly dissolved in dried CDCl 3 and analysed by NMR.Compound 12, crystallized directly from the NMR tube.
Compounds 12-13, show very complex NMR coupling patterns, due to the fact that the gallium is strongly bonded to the ligand and to the stereogenic carbon atoms of the racemic ligands.The behaviour is similar to that found in the boron compounds, and the explanation was confirmed by the X-ray diffraction analyses.The position of the chlorine atoms with respect to the C4 and C6 methylene hydrogen bonds is important.There are four intramolecular Cl•••H bonds with distances between 2.67-3.16Å.These bonds produce a very complex NMR spectrum as we have already discussed for the boron compounds, Figure 7.It is interesting to compare the gallium compound 12 with an analogous reported aluminum compound 17 prepared from ligand 1, 17     Compound 15, the hydrochloride of 1, was obtained as a by-product, from the reaction of 1 with BCl 3 and its solid state structure was determined by X-ray diffraction.Selected bond lengths and angles are presented in Table 3.The ring is a chair with an unusual conformation for a protonated dithiazinane, bearing the N-ethanol group in axial and the N-H proton in equatorial positions.The opposite conformation, with the biggest group in an equatorial position was expected, because the electronic repulsion between the lone pairs of the nitrogen and the sulfur atoms no longer exists, Figure 10.One possible explanation for this unusual conformation could be the presence of two hydrogen bonds formed between the N-CH 2 protons and the sulfur atoms (2.94 and 2.80 Å) [∑ vdw = 3.26 Å]. 26 The NH proton has a hydrogen bond with the oxygen and the OH proton with the chloride (2.22 Å).In the net of compound 15, the chloride ion forms five hydrogen bonds with four molecules of the ligand, Figure 11.There is also an intermolecular bond of a geminal proton to OH with one sulfur atom, as well as S•••S (3.5 Å) and S•••Cl (3.78 Å) short contacts.The oxygen atom has also two cooperative intermolecular hydrogen bonds with one proton of the chain (2.57Å) and one proton of the ring (2.56 Å), Figure 12.

Conclusions
New boron and gallium esters derived from ethanol dithiazinanes were prepared and their structures were studied by NMR and in one gallium compound by X-ray diffraction.The difluoro and dichloroboron compounds gave spiranic compounds formed by the N→B coordination whereas diphenylborinic esters were not coordinated in the same conditions.VT NMR experiments were performed for diphenylboron compounds in order to estimate the N→B energy.The minimum energy conformation for all boron compounds was calculated, and they are similar to the solid state gallium structure.The boron and gallium coordination stops the fluxional behaviour of the dithiazinane and the equatorial hydrogen atoms become different from the axial ones.The presence of a stereogenic center in the ethanol arm, differentiates the C4 and C6 methylene groups upon coordination.Therefore the 1 H spectra are useful tools for the structural study of these interesting ligands.
Internal coordination N→B was found for difluoro, dichloro and diphenylborinic esters, the N→B energy for the latter indicating weak coordination.The X-ray diffraction structure of the gallium compound 12 showed formation of hypervalent tbp gallium atoms by dimeric association.

Experimental Section
General Procedures.All solvents were freshly distilled before use.The 1 H, 13 C and 11 B NMR spectra were recorded with a JEOL GXS-270 ( 1 H 270 MHz) or a JEOL Eclipse ( 1 H 400 MHz). 1 H, 13 C and 11 B δ (ppm) are referenced to TMS and BF 3 •OEt 2 .Melting points were measured on a Gallenkamp apparatus and are uncorrected.Elemental analyses were performed by Oneida Research Services, Whitesboro, New York and at Cinvestav Mexico on an Eager 300.The MS spectra were obtained to 20 eV in a HP 5989 spectrometer.Compounds 1-3 were prepared as reported. 15Compounds 2 and 3 are racemic.For the crystallographic study, data were measured on a Nonius Kappa CCD instrument with area detector using graphite-monochromated Mo Kα radiation.Intensities were measured using ϕ + ω scans.All structures were collected at rt. Crystals of 15 were obtained from CHCl 3 , they are triclinic space group P-1 [a = 6.569( 1 4); R 1 = 0.0666; wR 2 = 0.086].In both structures, all hydrogen atoms were located and their positions were refined and solved by direct methods using SHELX-97, and the refinement (based on F 2 of all data) was performed by full matrix least-squares techniques.All non-hydrogen atoms were refined anisotropically.Crystallographic data have been deposited at the Cambridge Crystallographic Data Centre as numbers: 653943 (15) and 653944 (12).Copies of the data can be obtained, free of charge, on applications to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44-(0)1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].

esters derived from 4 - 11 BScheme 6 .
Scheme 6. Compounds 10-11 are in equilibrium between the open structure and the spirobicyclic compound, N→B bond energies were calculated from VT NMR experiments.

Figure 1 .
Figure 1.Minimum energy structure calculated for compound 8.One chlorine atom is close to equatorial C6-H, whereas the other is close to axial C4-H.
4 o ) are similar to those found in the X-ray analysis of the gallium compound 12 (C4-N-C6 110.6;C6-N-C7 111.6 and C4-N-C7 113.3 o ), see below.The boron atoms are also pyramidal.For example, in compound 5 the angles are: O-B-F A 116.5, O-B-F B 117.5, F A -B-F B 112.1 o and in 8 O-B-Cl A 113.9, O-B-Cl B 115.6, Cl A -B-Cl B 110.0 o .

Figure 3 .
Figure 3. Two views of the calculated preferred conformation of compound 5.

Figure 4 .
Figure 4. Two views of the calculated minimum energy structure of compound 9.

Figure 7 .
Figure 7. Short contacts between the chlorine atoms and the methylene protons found by X-ray diffraction analyses in compound 12.

Figure 8 .
The aluminum oxygen bonds vary between 1.82 to 1.92 Å, the longest bonds are the Al-N (2.47 Å) and the shortest the Al-C 1.96-1.97Å.17The angles N-Al-O are similar to those of the gallium compound (151, 152 o ).The angles C-Al-C (124 o ) are more open than the Cl-Ga-Cl angles.

In the cell of compound 12 ,
the chlorine atoms have intermolecular hydrogen bonds as is shown in Figure9.

Figure 9 .
Figure 9. Compound 12 forms polymers by C-H•••Cl hydrogen bonds and sulfur sulfur weak contacts.

Figure 10 .
Figure 10.Solid state structure of the hydrochloride of compound 14 that shows the hydrogen bonds formed with oxygen sulfur and chloride.

Figure 11 .
Figure 11.Intermolecular chloride connections with different dithiazinanium ions for compound 15.The values of the atomic distances in C-H•••Cl, N-H•••Cl and O-H•••Cl hydrogen bonds are shown.

Table 2 .
Compound 12, selected bond lengths and angles

Table 3 .
Compound 15 selected bond lengths and angles