A Reversible Single-crystal to Single-crystal Thermal Phase Transformation of 3-(2-bromo-4-(1-methylethyl)phenyl)-1,1-dimethyl Urea

3-(2-Bromo-4-(1-methylethyl)phenyl)-1,1-dimethylurea was synthesized and structurally characterized at 296 K, 200 K and 140 K. A reversible thermal phase transformation was observed at ~170–180 K. On cooling, the structure transforms from a monoclinic to a triclinic crystal system. The isopropyl group is disordered above the phase transition temperature but is ordered below the transition temperature.


Introduction
Urea-containing compounds are established as precursors for several biologically active agents [1][2][3][4].Various efficient procedures have been used for the synthesis of ureas [5][6][7][8][9][10][11][12][13][14].The most recent examples involve reactions of primary amines with S,S-dimethyl dithiocarbonate in water followed by reactions with secondary amines [15]; reactions of aromatic amines with secondary amines in the presence of carbon monoxide, sulfur and oxygen in dimethylformamide [16]; and reactions of benzylamine with secondary amines in the presence of a ruthenium catalyst [17].Other synthetic methods involve the catalytic reaction of carboxylic acids with hydroxylamine hydrochloride followed by reaction with primary amines [18]; conversion of aryl chlorides to the corresponding isocyanates using a palladium catalyst followed by reaction with secondary amines [19]; and conversion of isonitriles to the corresponding isocyanates using dimethyl sulfoxide followed by reaction with tert-butylamine [20].The reaction of aromatic ureas with a lithium reagent followed by electrophiles is one of the most common methods used to produce substituted derivatives [21][22][23][24][25].
Polymorphic phase transformation is an area of continued research interest [26][27][28][29][30][31][32][33][34][35].The transformation process is an indication of the fine balance in the interactions within the crystal that can be tipped by a relatively small change in conditions [36,37].In most cases, such transformations proceed with loss of single-crystal integrity, such that a single crystal of the starting solid phase transforms into a polycrystalline sample of the product.Where the structural reorganization involved is small, transformation of a single crystal of the starting material may produce a single crystal of the product phase.Additionally, the process may be reversible but this is rare in organic crystals [30][31][32][33][34][35].Enantiotropic behavior has been observed unsurprisingly between forms with very similar unit cell parameters [31,32], but transformation more commonly involves larger shifts in the parameters [33][34][35].Polymorphism and polymorphic phase transformations are difficult to predict and are often discovered fortuitously [26].
Notably, the transformation occurs reversibly.Thus, the monoclinic structure (1LT) discussed below was determined after cooling a crystal past the transition temperature to 150 K, before warming it again to 200 K.  Triclinic structure: Structure 2 has two independent molecules in the asymmetric unit (Figure 3a).The angles between the planes through the bromobenzene and dimethylurea groups are Notably, the transformation occurs reversibly.Thus, the monoclinic structure (1LT) discussed below was determined after cooling a crystal past the transition temperature to 150 K, before warming it again to 200 K.  Triclinic structure: Structure 2 has two independent molecules in the asymmetric unit (Figure 3a).The angles between the planes through the bromobenzene and dimethylurea groups are Triclinic structure: Structure 2 has two independent molecules in the asymmetric unit (Figure 3a).The angles between the planes through the bromobenzene and dimethylurea groups are 69.25(9)• and 49.51 (11) • for the two molecules.It is notable that the average of these values for the interplanar angles   On cooling the crystal from 296 K, the structure transforms from a monoclinic to a triclinic crystal system, retaining a similar unit cell volume.The single molecule in the asymmetric unit of the monoclinic structure above the phase transition temperature has a disordered isopropyl group.The refined ratios of the disordered components of the isopropyl group at 296 K and 200 K are 0.645(15)/0.355(15)and 0.725(16)/0.275(16), respectively.The values are significantly different from the 1:1 ratio of the two conformations of the independent molecules observed in the ordered On cooling the crystal from 296 K, the structure transforms from a monoclinic to a triclinic crystal system, retaining a similar unit cell volume.The single molecule in the asymmetric unit of the monoclinic structure above the phase transition temperature has a disordered isopropyl group.The refined ratios of the disordered components of the isopropyl group at 296 K and 200 K are 0.645(15)/0.355(15) and 0.725(16)/0.275(16), respectively.The values are significantly different from the 1:1 ratio of the two conformations of the independent molecules observed in the ordered structure of 2. This suggests that the isopropyl group has some rotational freedom about the C-C(CH 3 ) 2 bond.Disorder in isopropyl groups is common, but significant isopropyl rotation is expected to occur only in exceptional circumstances as, for example, observed in 1-(benzoyl)-3-((5'-isopropyl-2'-methylphenoxy)acetamino) thiourea [30].

General
Melting point determination was performed on a Gallenkamp melting point apparatus. 1H (400 MHz) and 13 C NMR (100 MHz) spectra were recorded on a Bruker AV400 spectrometer.
The chemical ionization (ammonia) mass spectrum was recorded on a Quattro II spectrometer at 50 eV.Accurate mass data were recorded on a MAT900 instrument.

Structure Determination
Single-crystal XRD data were collected on an Agilent SuperNova Dual Atlas diffractometer with a mirror monochromator [Mo (λ = 0.7107 Å)] equipped with a Cryosystems cooling apparatus.The crystal structures were solved and refined using SHELX [38].Non-hydrogen atoms were refined with anisotropic displacement parameters.All hydrogen atoms were placed in calculated positions and refined using a riding model.Methyl C-H bonds were fixed at 0.98 A, with displacement parameters 1.5 times Ueq(C), and were allowed to spin about the C-C bond.Aromatic C-H distances were set to 0.95 A and their U(iso) set to 1.2 times the Ueq for the atoms to which they are bonded.The disordered isopropyl group in 1 was refined with two components and restrained geometry.Crystal data, data collection and structure refinement details are summarized in Table 1.CCDC 1532132-1532134 contain the supplementary crystallographic data for this paper.These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44 1223 336033; E-mail: deposit@ccdc.cam.ac.uk.

Conclusions
3-(2-Bromo-4-(1-methylethyl)phenyl)-1,1-dimethylurea was synthesized and its structure was established at 296 K, 200 K and 140 K.A phase transformation was observed at ~170-180 K on cooling the crystal.The structure transforms from a monoclinic to a triclinic crystal system in a single-crystal to single-crystal manner, retaining a similar unit cell volume.The transformation is reversible on warming.The isopropyl group is disordered above the phase transition temperature but is ordered below the transition temperature.

Figure 1 .
Figure 1.A plot of the unit cell parameters as a function of temperature.The dotted vertical line indicates the phase transition point.

Figure 2 .
Figure 2. (a) An ortep representation of the asymmetric unit of 1LT showing the disordered isopropyl group; (b) Crystal packing viewed down the a axis with hydrogen atoms and one disorder component omitted for clarity.Hydrogen bonds are shown as dashed lines.

Figure 1 .
Figure 1.A plot of the unit cell parameters as a function of temperature.The dotted vertical line indicates the phase transition point.

Figure 1 .
Figure 1.A plot of the unit cell parameters as a function of temperature.The dotted vertical line indicates the phase transition point.

Figure 2 .
Figure 2. (a) An ortep representation of the asymmetric unit of 1LT showing the disordered isopropyl group; (b) Crystal packing viewed down the a axis with hydrogen atoms and one disorder component omitted for clarity.Hydrogen bonds are shown as dashed lines.

Figure 2 .
Figure 2. (a) An ortep representation of the asymmetric unit of 1 LT showing the disordered isopropyl group; (b) Crystal packing viewed down the a axis with hydrogen atoms and one disorder component omitted for clarity.Hydrogen bonds are shown as dashed lines.

Figure 3 .
Figure 3. (a) An ortep representation of the asymmetric unit of 2 showing the two molecules in the asymmetric unit; (b) Crystal packing viewed down the a axis with the hydrogen atoms omitted for clarity.Hydrogen bonds are shown as dashed lines.

Figure 3 . 9 Figure 4 .
Figure 3. (a) An ortep representation of the asymmetric unit of 2 showing the two molecules in the asymmetric unit; (b) Crystal packing viewed down the a axis with the hydrogen atoms omitted for clarity.Hydrogen bonds are shown as dashed lines.Crystals 2017, 7, x FOR PEER REVIEW 5 of 9

Figure 4 .
Figure 4.An overlay of the hydrogen bonded chains from 1 LT (red) and 2 (blue).The minor disorder component in 1 has been omitted clarity.

Table 1 .
Experimental and structure refinement data.