Co-crystals of 3-iodopropynyl butylcarbamate

Abstract

The present invention relates to biocidal agents designed to protect industrial products against microbial, bacterial, fungal and algal infections. In particular, the present invention relates to co-crystals containing 3-iodopropynyl butylcarbamate (IPBC) and to compositions containing said co-crystals which possess improved physical, chemical and workability properties compared with the use of IPBC.

Claims

1. A co-crystal of the compound 3-iodopropynyl butyl carbamate with a co-crystallisation agent, wherein said co-crystal is selected from the group of: co-crystal containing 3-iodopropynyl butyl carbamate and pyridine in a 1:1 molar ratio; co-crystal containing 3-iodopropynyl butyl carbamate and 4-[2-(4-pyridinyl)ethyl]pyridine in a 2:1 molar ratio; co-crystal containing 3-iodopropynyl butyl carbamate and 4,4′-bipyridine in a 2:1 molar ratio; co-crystal containing 3-iodopropynyl butyl carbamate and 1,4-diazabicyclo[2.2.2]octane in a 2:1 molar ratio; co-crystal containing 3-iodopropynyl butyl carbamate and tetrabutylammonium iodide in a 3:1 molar ratio; co-crystal containing 3-iodopropynyl butyl carbamate and tetrabutylammonium chloride in a 2:1 molar ratio; co-crystal containing 3-iodopropynyl butyl carbamate and calcium chloride in a 4:1 molar ratio; co-crystal containing 3-iodopropynyl butyl carbamate and zinc chloride in a 4:1 molar ratio; and co-crystal containing 3-iodopropynyl butyl carbamate and N,N′-bis(4-pyridylcarbonyl)-1,6-hexanediamine in a 2:1 molar ratio.

2. A co-crystal according to claim 1, wherein the co-crystallisation agent is tetrabutylammonium iodide or tetrabutylammonium chloride.

3. A co-crystal according to claim 1, wherein the co-crystallisation agent is calcium chloride or zinc chloride.

4. A composition containing a co-crystal of claim 1, a solvent or diluent and optionally additives and/or a biocidal agent.

5. Industrial products containing a co-crystal as defined in claim 1.

6. A method of protecting and preserving wood, personal care products or cosmetic formulations with the composition according to claim 4, said method comprising adding said composition to industrial formulations selected from the group consisting essentially of paints, coatings and metalworking fluids to provide a biocide, preservative, antibacterial, fungicide or algaecide protection to said paints, coatings and metal working fluids for protecting and preserving said wood, body care products or cosmetic formulations.

7. Process for the preparation of a co-crystal as defined in claim 1, comprising the steps of: a) contacting 3-iodopropynyl butyl carbamate with a co-crystallization agent able to form at least one halogen bond with said 3-iodopropynyl butyl carbamate, under crystallisation conditions able to form a solid phase wherein 3-iodopropynyl butyl carbamate and said co-crystallisation agent are bound to each other through at least one halogen bond; b) optional isolation of the co-crystals formed in step a).

Description

DESCRIPTION OF FIGURES

(1) FIG. 1: Graphical representation of the co-crystal of example 1.

(2) FIG. 2: IR spectrum of the co-crystal of example 1.

(3) FIG. 3: XRPD tracing of the co-crystal of example 1.

(4) FIG. 4: DSC tracing of the co-crystal of example 1.

(5) FIG. 5: Graphical representation of the co-crystal of example 2.

(6) FIG. 6: IR spectrum of the co-crystal of example 2.

(7) FIG. 7: XRPD tracing of the co-crystal of example 2.

(8) FIG. 8: DSC tracing of the co-crystal of example 2.

(9) FIG. 9: Graphical representation of the co-crystal of example 3.

(10) FIG. 10: API IR spectrum of the co-crystal of example 3.

(11) FIG. 11: XRPD tracing of the co-crystal of example 3.

(12) FIG. 12: DSC tracing of the co-crystal of example 3.

(13) FIG. 13: API IR spectrum of the co-crystal of example 4.

(14) FIG. 14: XRPD tracing of the co-crystal of example 4.

(15) FIG. 15: DSC tracing of the co-crystal of example 4.

(16) FIG. 16: Graphical representation of the co-crystal of example 5.

(17) FIG. 17: API IR spectrum of the co-crystal of example 5.

(18) FIG. 18: XRPD tracing of the co-crystal of example 5.

(19) FIG. 19: DSC tracing of the co-crystal of example 5.

(20) FIG. 20: .sup.13C-NMR of the co-crystal of example 6.

(21) FIG. 21: Ball and stick representation from single crystal analysis of the co-crystal of example 7. DABCO hydrogen atoms are omitted for clarity.

(22) FIG. 22: IR spectrum of the co-crystal of example 8.

(23) FIG. 23: DSC plot of the co-crystal of example 9.

(24) FIG. 24: Pictures of cones of pure IPBC (A, C) and co-crystal (IPBC).sub.4:CaCl.sub.2 (B, D) powders, taken after flowing the powders through the funnel.

(25) The invention will now be illustrated by the following examples.

EXAMPLES

(26) Materials and Methods

(27) The IR spectra were obtained with a Nicolet Nexus FTIR spectrophotometer equipped with the U-ATR device. The values are reported as wave numbers, and are rounded to 1 cm.sup.−1 after automatic assignment. The melting points were obtained by differential scanning calorimetry (DSC, Mettler Toledo 823e).

(28) Single-Crystal X-Ray Diffraction

(29) The data were collected at different temperatures with a Bruker KAPPA APEX II diffractometer with Mo-Kα radiation (λ=0.71073) and a CCD detector. The Bruker KRYOFLEX device was used for the low-temperature acquisitions. The structures were resolved and refined with the SIR2004 and SHELXL-97 programs respectively. The refinement was performed by the full-matrix least squares method on F.sup.2. The hydrogen atoms were placed using standard geometric models and with their thermal parameters based on those of their geminal atoms.

(30) X-Ray Powder Diffraction

(31) The X-ray powder diffraction experiments were conducted with a Bruker D8 Advance diffractometer operating in reflection mode with Ge-monochromatic Cu Kα1 radiation (λ=1.5406 Å) and with a position-sensitive linear detector. The powder diffraction data was collected at room temperature with a 20 interval of 5-40°, using increments of 0.016° and an exposure time of 1.5 s per increment.

Example 1

Co-crystal containing 3-iodopropynyl butylcarbamate and 4-[2-(4-pyridinyl)ethyl]pyridine in a 2:1 Molar Ratio (Co-Crystal 1)

(32) ##STR00003##

(33) This example demonstrates the ability of IPBC to co-crystallise with a neutral aromatic amine able to act as halogen bond acceptor, such as 4-[2-(4-pyridinyl)ethyl]pyridine.

(34) Rapid precipitation of the two compounds in a quasi-saturated acetonitrile solution leads to the formation of a solid white powder with a melting point of between 81° C. and 83° C.

(35) Single-crystal X-ray diffraction demonstrates that in the co-crystal, IPBC and 4-[2-(4-pyridinyl)ethyl]pyridine are present in a molar ratio of 2:1, as shown in FIG. 1. The basic structural pattern in the co-crystal is a trimer unit wherein 4-[2-(4-pyridinyl)ethyl]pyridine acts as bridge between two IPBC molecules via two halogen bonds I.sup.- - - N.

(36) The dimensions and angles of the crystallographic unit cell are [a=30.666(3) b=4.9869(4) c=21.068(2)] and [α=90.00 β=92.115(6) γ=90.00] respectively.

(37) The IR spectrum of the co-crystal and its characteristic bands are reported in FIG. 2.

(38) FIG. 3 shows the X-ray powder diffraction (XRPD) of the co-crystal, the main peaks of which, in the 5-40° 2θ value range, are shown in Table 1.

(39) The DSC thermogram of co-crystal 1 is reported in FIG. 4.

(40) TABLE-US-00001 TABLE 1 Angle(2θ)* d (Å) Intensity % 2th = 5.117° 17.25577 2521 51.2 2th = 5.684° 15.53601 4923 100.0 2th = 8.644° 10.22081 1240 25.2 2th = 8.924° 9.90129 1792 36.4 2th = 9.274° 9.52842 907 18.4 2th = 11.445° 7.72521 3010 61.1 2th = 12.225° 7.23443 490 10.0 2th = 14.471° 6.11592 932 18.9 2th = 15.726° 5.63077 310 6.3 2th = 16.087° 5.50517 408 8.3 2th = 16.402° 5.40011 592 12.0 2th = 16.951° 5.22630 2000 40.6 2th = 17.228° 5.14312 872 17.7 2th = 17.997° 4.92493 576 11.7 2th = 18.382° 4.82269 644 13.1 2th = 19.133° 4.63491 368 7.5 2th = 19.692° 4.50459 476 9.7 2th = 20.105° 4.41308 507 10.3 2th = 21.176° 4.19213 350 7.1 2th = 21.524° 4.12518 1449 29.4 2th = 21.800° 4.07364 894 18.2 2th = 22.221° 3.99734 4665 94.8 2th = 22.663° 3.92047 2184 44.4 2th = 23.181° 3.83400 1450 29.5 2th = 24.580° 3.61886 373 7.6 2th = 24.967° 3.56356 2850 57.9 2th = 25.348° 3.51083 400 8.1 2th = 25.876° 3.44043 339 6.9 2th = 26.404° 3.37283 302 6.1 2th = 27.191° 3.27701 783 15.9 2th = 27.882° 3.19725 4091 83.1 2th = 28.258° 3.15564 451 9.2 2th = 28.838° 3.09341 1892 38.4 2th = 29.185° 3.05747 373 7.6 2th = 30.311° 2.94642 344 7.0 2th = 30.988° 2.88354 260 5.3 2th = 32.914° 2.71904 255 5.2 2th = 33.516° 2.67160 361 7.3 2th = 34.345° 2.60901 250 5.1 2th = 34.793° 2.57641 883 17.9 2th = 35.051° 2.55803 443 9.0 2th = 35.850° 2.50285 270 5.5 2th = 36.589° 2.45396 519 10.5 2th = 37.072° 2.42311 464 9.4 2th = 37.905° 2.37175 254 5.2 2th = 38.291° 2.34872 309 6.3 2th = 39.015° 2.30676 228 4.6 2th = 39.738° 2.26645 438 8.9 *Values ± 0.05°

(41) The co-crystal thus obtained has a higher melting point, higher thermal stability, better workability and higher degree of crystallinity than IPBC. It is easily manageable in the operations required to form tablets, such as compression.

Example 2

Co-Crystal Containing 3-iodopropynyl butylcarbamate and 4,4′-bipyridine in a 2:1 Molar Ratio (Co-Crystal 2)

(42) ##STR00004##

(43) This example demonstrates the ability of IPBC to co-crystallise with another neutral aromatic amine able to act as halogen bond acceptor, such as 4,4′-dipyridine.

(44) In this case the formation of the co-crystal was effected by slow precipitation from an ethanol solution, which leads to the formation of a white powder.

(45) The basic structural motif in the co-crystal is a trimeric unit, bonded via halogen bonds, consisting of one molecule of 4,4′-bipyridine and two molecules of IPBC, as shown in FIG. 5.

(46) The co-crystal is a solid crystalline product with a melting point of between 112° C. and 114° C. The dimensions and angles of the crystallographic unit cell are [a=28.683(2) b=4.9270(4) c=21.429(2)] and [α=90.00 β=99.92(2) γ=90.00] respectively.

(47) The IR spectrum of the co-crystal and its characteristic bands are reported in FIG. 6.

(48) FIG. 7 shows the X-ray powder diffraction (XRPD) of the co-crystal, the main peaks of which, in the 5-40° 2θ value range, are shown in Table 2.

(49) The DSC thermogram of co-crystal 2 is reported in FIG. 8.

(50) TABLE-US-00002 TABLE 2 Angle(2θ)* d (Å) Intensity % 2th = 6.234° 14.16728 8558 100.0 2th = 8.358° 10.57069 353 4.1 2th = 9.560° 9.24440 679 7.9 2th = 12.160° 7.27286 269 3.1 2th = 12.521° 7.06371 1737 20.3 2th = 13.187° 6.70850 197 2.3 2th = 13.841° 6.39289 399 4.7 2th = 16.255° 5.44854 2148 25.1 2th = 16.825° 5.26536 663 7.7 2th = 18.651° 4.75371 507 5.9 2th = 18.861° 4.70134 1402 16.4 2th = 19.248° 4.60750 1051 12.3 2th = 19.892° 4.45974 187 2.2 2th = 20.400° 4.34990 797 9.3 2th = 21.931° 4.04952 5931 69.3 2th = 22.695° 3.91488 453 5.3 2th = 23.110° 3.84554 991 11.6 2th = 23.835° 3.73028 1084 12.7 2th = 24.461° 3.63616 319 3.7 2th = 24.826° 3.58348 679 7.9 2th = 25.194° 3.53200 3287 38.4 2th = 26.333° 3.38179 452 5.3 2th = 27.465° 3.24488 325 3.8 2th = 27.980° 3.18637 877 10.2 2th = 28.475° 3.13207 786 9.2 2th = 28.928° 3.08399 349 4.1 2th = 29.463° 3.02919 427 5.0 2th = 29.735° 3.00209 298 3.5 2th = 30.264° 2.95086 255 3.0 2th = 30.571° 2.92189 319 3.7 2th = 31.311° 2.85455 198 2.3 2th = 32.653° 2.74021 176 2.1 2th = 33.314° 2.68732 203 2.4 2th = 33.439° 2.67760 232 2.7 2th = 33.914° 2.64116 241 2.8 2th = 34.205° 2.61934 475 5.6 2th = 34.762° 2.57862 234 2.7 2th = 36.146° 2.48303 206 2.4 2th = 37.672° 2.38589 384 4.5 2th = 38.213° 2.35331 596 7.0 2th = 38.614° 2.32980 258 3.0 *Values ± 0.05°

(51) The co-crystal thus obtained has a higher melting point, higher thermal stability, better workability and higher degree of crystallinity than IPBC. It is easily manageable in the operations required to form tablets, such as compression.

Example 3

Co-Crystal Containing 3-iodopropynyl butylcarbamate and tetrabutyl ammonium iodide in a 3:1 Molar Ratio (Co-Crystal 3)

(52) ##STR00005##

(53) This example demonstrates the ability of IPBC to co-crystallise with a halide deriving from an organic salt such as tetrabutylammonium iodide.

(54) The co-crystal was formed by mechano-chemical synthesis in a ball mill, using a stoichiometric ratio of 1:3 between tetrabutyl ammonium iodide and IPBC.

(55) The co-crystal obtained contains one molecule of tetrabutyl ammonium iodide and three molecules of IPBC, as shown in the graphical representation in FIG. 9.

(56) The co-crystal is a solid crystalline product with a melting point between 42° C. and 47.5° C. The dimensions and angles of the crystallographic unit cell are a=10.7688(9) b=20.204(2) c=23.735(2)] and [α=90.00 β=94.778(2) γ=90.00] respectively.

(57) The IR spectrum of the co-crystal and its characteristic bands are reported in FIG. 10.

(58) FIG. 11 shows the X-ray powder diffraction (XRPD) of the co-crystal, the main peaks of which, in the 5-40° 2θ value range, are shown in Table 3.

(59) The DSC thermogram of co-crystal 3 is reported in FIG. 12.

(60) TABLE-US-00003 TABLE 3 Angle(2θ)* d (Å) Intensity % 2th = 9.285° 9.51690 513 53.5 2th = 14.485° 6.11006 445 46.5 2th = 16.322° 5.42635 469 49.0 2th = 17.432° 5.08330 346 36.1 2th = 17.729° 4.99868 537 56.1 2th = 18.440° 4.80755 373 38.9 2th = 20.246° 4.38272 517 54.0 2th = 20.698° 4.28791 438 45.7 2th = 21.072° 4.21276 423 44.2 2th = 21.331° 4.16217 629 65.7 2th = 22.261° 3.99035 958 100.0 2th = 22.903° 3.87977 590 61.6 2th = 23.605° 3.76596 613 64.0 2th = 23.968° 3.70974 484 50.5 2th = 24.305° 3.65910 616 64.3 2th = 25.009° 3.55775 580 60.5 2th = 25.670° 3.46761 363 37.9 2th = 26.129° 3.40770 406 42.4 2th = 26.507° 3.35996 423 44.2 2th = 26.730° 3.33240 343 35.8 2th = 27.359° 3.25726 326 34.0 2th = 27.893° 3.19608 432 45.1 2th = 28.399° 3.14030 389 40.6 2th = 28.918° 3.08502 372 38.8 2th = 30.514° 2.92722 311 32.5 2th = 31.221° 2.86256 302 31.5 2th = 31.654° 2.82441 322 33.6 2th = 32.085° 2.78741 349 36.4 2th = 32.592° 2.74517 308 32.2 2th = 33.490° 2.67360 323 33.7 2th = 34.033° 2.63217 246 25.7 2th = 34.608° 2.58975 249 26.0 2th = 34.973° 2.56357 314 32.8 2th = 35.533° 2.52440 269 28.1 2th = 36.332° 2.47069 261 27.2 2th = 36.772° 2.44214 278 29.0 2th = 37.328° 2.40703 225 23.5 2th = 38.414° 2.34144 277 28.9 *Values ± 0.1°

(61) The co-crystal thus obtained has a lower melting point, higher solubility and better workability in an aqueous medium than IPBC. In particular, its aqueous solubility is approx. 40% greater than that of IPBC.

Example 4

Co-Crystal Containing 3-iodopropynyl butylcarbamate and calcium chloride in a 4:1 Molar Ratio (Co-Crystal 4)

(62) ##STR00006##

(63) This example demonstrates the ability of IPBC to co-crystallise with a halide deriving from an inorganic salt such as calcium chloride.

(64) The co-crystal was formed by mechano-chemical synthesis in a ball mill, using a stoichiometric ratio of 1:4 between calcium chloride and IPBC.

(65) The composition of the co-crystal was detected by analysing the DSC trace, where the presence of peaks of the starting products was not observed.

(66) The co-crystal is a solid crystalline product with a melting point of 83-86° C.

(67) The IR spectrum of the co-crystal and its characteristic bands are reported in FIG. 13.

(68) FIG. 14 shows the X-ray powder diffraction (XRPD) of the co-crystal, the main peaks of which, in the 5-40° 2θ value range, are shown in Table 4.

(69) The DSC thermogram of co-crystal 4 is reported in FIG. 15.

(70) TABLE-US-00004 TABLE 4 Angle(2θ) d (Å) Intensity % 2th = 6.581° 13.41984 5844 16.2 2th = 7.314° 12.07749 10715 29.7 2th = 8.160° 10.82602 4892 13.6 2th = 9.674° 9.13549 16217 45.0 2th = 11.059° 7.99382 7263 20.1 2th = 11.991° 7.37478 4418 12.3 2th = 13.299° 6.65245 6966 19.3 2th = 15.631° 5.66483 4674 13.0 2th = 15.982° 5.54118 6113 17.0 2th = 17.374° 5.10003 8718 24.2 2th = 18.517° 4.78765 9325 25.9 2th = 19.365° 4.57995 11180 31.0 2th = 20.091° 4.41616 3184 8.8 2th = 21.313° 4.16552 4102 11.4 2th = 22.282° 3.98664 36057 100.0 2th = 23.054° 3.85484 3660 10.2 2th = 23.469° 3.78751 3136 8.7 2th = 24.435° 3.63994 6628 18.4 2th = 24.990° 3.56041 12456 34.5 2th = 26.159° 3.40384 5054 14.0 2th = 26.775° 3.32689 4703 13.0 2th = 27.659° 3.22252 11372 31.5 2th = 28.514° 3.12789 5945 16.5 2th = 29.588° 3.01671 6588 18.3 2th = 30.368° 2.94095 2644 7.3 2th = 31.158° 2.86817 4800 13.3 2th = 31.838° 2.80850 8422 23.4 2th = 32.766° 2.73101 2388 6.6 2th = 33.979° 2.63621 4478 12.4 2th = 34.729° 2.58102 3049 8.5 2th = 35.337° 2.53800 2887 8.0 2th = 36.000° 2.49271 2816 7.8 2th = 36.603° 2.45308 2980 8.3 2th = 37.030° 2.42574 3009 8.3 2th = 37.436° 2.40037 3085 8.6 2th = 38.110° 2.35946 4670 13.0 2th = 38.968° 2.30947 3168 8.8 2th = 39.475° 2.28092 2995 8.3 * Values ± 0.05°

(71) The co-crystal thus obtained has a higher melting point, higher solubility and better workability in an aqueous medium than IPBC. In particular, its aqueous solubility is approx. 50% greater than that of IPBC.

Example 5

Co-Crystal Containing 3-iodopropynyl butylcarbamate and N,N′-bis(4-pyridylcarbonyl)-1,6-hexanediamine in a 2:1 Molar Ratio (Co-Crystal 5)

(72) ##STR00007##

(73) In this example, IPBC was co-crystallised with N,N′-bis(4-pyridylcarbonyl)-1,6-hexanediamine by slow evaporation from alcohol solutions and by mechano-chemical synthesis in a ball mill, using a ratio of 1:2 between the co-crystallisation agent and IPBC.

(74) In the co-crystal obtained there is a ratio of 1:2 between the co-crystallisation agent and IPBC, as shown in the graphical representation in FIG. 16.

(75) The co-crystal is a solid crystalline product with a melting point of 132° C. The dimensions and angles of the crystallographic unit cell are [a=29.4501(18) b=5.1100(3) c=27.9417(17)] and [α=90.00 β=118.566(3) γ=90.00] respectively.

(76) The IR spectrum of the co-crystal and its characteristic bands are reported in FIG. 17.

(77) FIG. 18 shows the X-ray powder diffraction (XRPD) of the co-crystal, the main peaks of which, in the 5-40° 2θ value range, are shown in Table 5.

(78) The DSC thermogram of co-crystal 5 is reported in FIG. 19.

(79) TABLE-US-00005 TABLE 5 Angle(2θ) d (Å) Intensity % 2th = 5.887° 14.99966 1231 18.2 2th = 6.951° 12.70619 545 8.1 2th = 10.380° 8.51551 690 10.2 2th = 11.831° 7.47444 3530 52.3 2th = 13.013° 6.79759 324 4.8 2th = 13.477° 6.56468 591 8.8 2th = 13.961° 6.33814 1111 16.5 2th = 14.270° 6.20161 272 4.0 2th = 15.441° 5.73399 1653 24.5 2th = 16.713° 5.30018 510 7.6 2th = 17.132° 5.17156 244 3.6 2th = 17.945° 4.93909 411 6.1 2th = 18.816° 4.71240 331 4.9 2th = 19.095° 4.64417 378 5.6 2th = 19.516° 4.54479 300 4.4 2th = 20.075° 4.41964 366 5.4 2th = 20.950° 4.23697 1050 15.6 2th = 21.366° 4.15541 563 8.3 2th = 21.916° 4.05229 740 11.0 2th = 22.784° 3.89988 6751 100.0 2th = 23.513° 3.78060 855 12.7 2th = 23.856° 3.72703 939 13.9 2th = 24.326° 3.65609 332 4.9 2th = 25.096° 3.54550 509 7.5 2th = 25.760° 3.45568 376 5.6 2th = 26.944° 3.30641 653 9.7 2th = 27.924° 3.19254 305 4.5 2th = 28.684° 3.10973 548 8.1 2th = 29.094° 3.06678 276 4.1 2th = 29.709° 3.00471 330 4.9 2th = 30.531° 2.92568 430 6.4 2th = 31.214° 2.86315 419 6.2 2th = 31.568° 2.83188 367 5.4 2th = 32.461° 2.75600 241 3.6 2th = 32.802° 2.72810 284 4.2 2th = 34.124° 2.62537 365 5.4 2th = 34.688° 2.58393 478 7.1 2th = 36.154° 2.48246 505 7.5 2th = 36.966° 2.42976 398 5.9 2th = 37.750° 2.38110 561 8.3 2th = 39.102° 2.30185 457 6.8 * Values ± 0.05°

(80) The co-crystal thus obtained has a higher melting point, higher thermal stability, better workability and higher degree of crystallinity than IPBC. It is easily manageable in the operations required to form tablets, such as compression.

Example 6

Co-Crystal Containing 3-iodopropynyl butylcarbamate and pyridine in a 1:1 Molar Ratio (Co-Crystal 6)

(81) In this example, IPBC was co-crystallised with pyridine.

(82) The co-crystal was prepared dissolving in the 1:1 molar ratio IPBC in pyridine.

(83) The cocrystal is liquid at room temperature, but the formation of a halogen bonded system between IPBC and pyridine can be confirmed looking at the chemical shift variation of .sup.13C-NMR for the carbon bound to iodine.

(84) Previous studies have demonstrated that the .sup.13C signals of the iodinated carbons of iodoethynyl moieties undergo major low-field shifts on changing the solvent from chloroform to dimethylsulphoxide as a consequence of the XB occurring with the oxygen atoms of the solvent. [ref. Rege, P. D.; Malkina, O. L.; Goroff, N. S. J. Am. Chem. Soc. 2002, 124, 370-371. Gao, K.; Goroff, N. S. J. Am. Chem. Soc. 2000, 122, 9320-9321.]. The ≡C—I signals of deuterochloroform solutions of pure IPBC is at 3.68 ppm, in the cocrystal with pyridine the ≡C—I chemical shift varies from 4.00 ppm up to 14 ppm depending of the concentration of pyridine used, as shown in FIG. 20.

Example 7

(85) ##STR00008##

Co-Crystal Containing 3-iodopropynyl butylcarbamate and 1,4-diazabicyclo[2.2.2]octane (DABCO) in a 2:1 Molar Ratio (Co-Crystal 7)

(86) In this example, IPBC was co-crystallised with the bicyclic tertiary amine 1,4-diazabicyclo[2.2.2]octane (DABCO), to give a co-crystal IPBC:DABCO with molar ratio 2:1.

(87) IPBC was co-crystallised with DABCO by slow evaporation from alcohol/haloalkane solutions, using a ratio of 1:2 between the co-crystallisation agent and IPBC.

(88) Melting point: 35-38° C.

(89) The structure of the IPBC.DABCO co-crystal from single crystal crystallographic analysis is shown in FIG. 21, wherein DABCO hydrogen atoms are omitted for clarity.

(90) Crystallographic data: orthorhombic, Pccn, a: 9.8955(7); b: 31.623(2); c: 8.9335(6) and V=2795.55 A.sup.3.

Example 8

Co-Crystal Containing 3-iodopropynyl butylcarbamate and tetrabutylammonium chloride (TBACl) in a 2:1 Molar Ratio (Co-Crystal 8)

(91) In this example, IPBC was co-crystallised with tetrabutylammonium chloride (TBACl) to give a IPBC:TBACl co-crystal with molar ratio 2:1.

(92) The co-crystal was formed by heating the two components up to 50° C. using a stoichiometric ratio of 1:2 between tetrabutyl ammonium chloride and IPBC.

(93) The co-crystal is liquid at room temperature.

(94) Melting point −15° C.

(95) The formation of a halogen bonded co-crystal between IPBC and TBACl can be confirmed looking at the IR wave number variation for C≡C group. The triple bond stretching band is at 2198 cm.sup.−1 in the pure IPBC while it is red-shifted at 2181 cm.sup.−1 for the (IPBC).sub.2:TBACl cocrystal, as shown in FIG. 22.

Example 9

Co-Crystal Containing 3-iodopropynyl butylcarbamate and zinc chloride in a 4:1 Molar Ratio (Co-Crystal 9)

(96) This example demonstrates the ability of IPBC to co-crystallise with a halide deriving from a transition metal, such as zinc chloride, to give a IPBC:ZnCl.sub.2 co-crystal with molar ratio 4:1

(97) The co-crystal was prepared using the same procedure employed for example 4.

(98) The formation of a halogen bonded cocrystal between IPBC and ZnCl.sub.2 can be confirmed looking at the DSC plot (FIG. 23) showing two peaks at 118° C. and 139° C. (mixture of polymorphs) and the absence of the IPBC melting peak.

Example 10

Evaluation of Flowing Characteristics of Powders Containing the Halogen Bonded (IPBC)4:CaCl2 Complex or Pure IPBC

(99) In this example the angle of response of powders containing the halogen bonded (IPBC).sub.4:CaCl.sub.2 complex of example 4 was compared to that of powders containing pure IPBC (FIG. 24). The angle of response estimates the flow characteristics of the powders,

(100) The use of pure IPBC in industrial products faces significant manufacturing drawbacks. IPBC is difficult to handle because it tends to be clumpy and sticky, this implies that it cannot be fed easily from the blending equipment and the automatic feeding device.

(101) FIG. 24 shows that the cohesive properties of powder for co-crystal (IPBC).sub.4:CaCl.sub.2 are drastically different compared to the pure IPBC. Co-crystal (IPBC).sub.4:CaCl.sub.2 has values of angle of repose between 13° and 20° which indicates that it has excellent free-flow powder characteristic. On the contrary for the pure IPBC it is impossible to evaluate any angle of repose since the cohesive forces in the powder are too strong and its powder does not form an appropriate cone shape but tends to aggregate in irregular pillared shape. The cylindrical shape of IPBC cones indicates clearly the high cohesion of the powders, while the flat cone shape of co-crystal (IPBC).sub.4:CaCl.sub.2 indicates improved flow powder properties.