US009249071B2

(12) United States Patent (10) Patent No.: US 9.249,071 B2 Strauss et al. (45) Date of Patent: Feb. 2, 2016

(54) MODIFIED POLYAROMATIC Bravo, “New Methods of Free-Radical Periluoroalkylation of Aro HYDROCARBONS AND matics and Alkenes. Absolute Rate Constants and Partial Rate Factors POLYHETEROCYCLICS FOR for the Homolytic Aromatic Substitution by n-Perfluorobutyl Radi OPTOELECTRONICS cal”, J. Org. Chem., 21:7128-7136 (1997). Cowell, “Fluoroalkylation of Aromatic Compounds”, Journal of (71) Applicant: Colorado State University Research Fluorine Chemistry, 17:345-356 (1981). Foundation, Fort Collins, CO (US) Freskos, "A Convenient Synthesis of Pentafluoroethyl-substituted Aromatics”, Journal: Synthetic communications, 18(9):965-972 (72) Inventors: Steven H. Strauss, Fort Collins, CO (1988). (US): Olga V. Boltalina, Fort Collins, Hosokawa et al., “Synthesis of Beta-Trifluoromethylnaphthalene CO (US); Igor V. Kuvychko, Fort Derivatives'. Gov't Industrial Research Institute, 2:383-386 (1972). Collins, CO (US) (With English Abstract). Hosokawa et al., “Synthesis of (Trifluoromethyl)', (73) Assignee: Colorado State University Research Gov't Industrial Research Institute, 11:1791-1793 (1976). (With Foundation, Fort Collins, CO (US) English Abstract). Hosokawa et al., “Synthesis Bis(trifluoromethyl)naphthalenes', (*) Notice: Subject to any disclaimer, the term of this Gov't Industrial Research Institute, 8: 1163-1167 (1977). (With patent is extended or adjusted under 35 English Abstract). U.S.C. 154(b) by 0 days. Hosokawa et al., “Synthesis of Substituted (Trifluoromethyl)naphthalenes', Gov't Industrial Research Institute, (21) Appl. No.: 14/174,780 2:294-296 (1979). (With English Abstract). Krespan et al., “Bis-(polyfluoroalkyl)-acetylenes. II. (22) Filed: Feb. 6, 2014 Bicyclooctatrienes Through 1,4-Addition of Bis-(polyfluoroalkyl)- acetylenes to Aromatic Rings'. Synthesis of Bicyclooctatrienes, (65) Prior Publication Data Contribution No. 648 from the Central Research Department, US 2014/0221 655A1 Aug. 7, 2014 Experimental Station, 83:3428-3432 (1961). Klebachet al., “Compounds Containing Localized Carbon-Phospho rus Double Bonds I. Diels-Alder Reaction of 3-Methyl-2- Phosphanaphtahlene with Hexafluorobutyne-2. Pergamon Press, Related U.S. Application Data Tetrahedron Letters 12:1099-1 100 (1978). (60) Provisional application No. 61/761,528, filed on Feb. Kuvychko et al., “Taming Hot CF3 Radicals: Incrementally Tuned 6, 2013. Families of Polyarene Electron Acceptors for Air-Stable Molecular Optoelectronics'. Angew. Chem. Int. Ed, 52:4871-4874 (2013). (51) Int. Cl. (Continued) CO7D 47L/04 (2006.01) C07C 17/32 (2006.01) CD7C 22/08 (2006.01) Primary Examiner — Heidi Reese C07C 22/02 (2006.01) (74) Attorney, Agent, or Firm — Haukaas Fortius PLLC; (52) U.S. Cl. Michael H. Haukaas CPC ...... C07C 17/32 (2013.01); C07C22/02 (2013.01); C07C 22/08 (2013.01); C07C 2102/30 (2013.01); C07C 2103/24 (2013.01); (57) ABSTRACT C07C 2103/26 (2013.01); C07C 2103/42 (2013.01); C07C 2103/52 (2013.01) The invention provides methods for substituting polyaro (58) Field of Classification Search matic hydrocarbons or polyheterocyclic compounds with None perfluoroalkyl groups. The methods can include heating a See application file for complete search history. polyaromatic hydrocarbon Substrate or a polyheterocyclic (56) References Cited compound Substrate in the presence of a perfluoroalkyl iodide, typically in a closed system, wherein the heating is U.S. PATENT DOCUMENTS sufficient to bring both the polyaromatic hydrocarbons or 3,281.426 A * 10/1966 Van Dyke Tiers ...... 540,140 polyheterocyclic compound, and the perfluoroalkyl iodide, 7,390,901 B2 6/2008 Yang into the gas phase, thereby allowing the Substrate to react with 2012/0208989 A1 8, 2012 Sun the perfluoroalkyl iodide in the gas phase to form polyaro FOREIGN PATENT DOCUMENTS matic hydrocarbons or polyheterocyclic compounds having one or more perfluoroalkyl substituents. The methods allow WO 2011/022678 A1 2, 2011 for the creation of versatile libraries of novel perfluoroalkyl OTHER PUBLICATIONS containing derivatives that can serve as important building blocks and active components in biomedical, electronic, and Dunyashev et al., Additivity of Electron-Affinity in a Series of Aro materials applications. matic-Compounds During the Accumulation of Fluoroalkyl Substituents Based on Polarography and Theoretical Calculations of the MNDO Method. 19 Claims, 22 Drawing Sheets US 9.249,071 B2 Page 2

(56) References Cited TunableOptoelectronic and Electron Transfer Properties”. J. Phys. Chem. A., 116:8015-8022 (2012). OTHER PUBLICATIONS Tiers, “Perfluoroalkylation of Aromatic Compounds”. Communica tions to the Editor JACS, Contribution No. 182 from the Central Roy et al., “Tetrahedron report No. 933: Trifluoromethylation of aryl Research Dept of 3M, pp. 5513 (1960). and heteroaryl halides”, Tetrahedron, 67:2161-2195 (2011). Sun et al., “Arene Trifluoromethylation: An Effective Strategy to Obtain Air-Stable n-Type Organic Semiconductors with * cited by examiner U.S. Patent Feb. 2, 2016 Sheet 1 of 22 US 9.249,071 B2

Figure 1 U.S. Patent Feb. 2, 2016 Sheet 2 of 22 US 9.249,071 B2

photoaiector Sg8ia

as TRPH-6-1a

PYRN-6- grger gram binding energy, ev Figure 2

Y-K-8-2

Yrxis.

cycic: woitataragrass

Ev vs, Fe(Cp)." Figure 3 U.S. Patent Feb. 2, 2016 Sheet 3 of 22 US 9.249,071 B2

FERYCF,

8 0 1 2 3 4 5 6 7 number of CF groups, in Figure 4

Aji Cis

s

.38. s 6 -38 (.8 8 . . .3, FA}} or PA-(CF) electron affinity, ev Figure 5 U.S. Patent Feb. 2, 2016 Sheet 4 of 22 US 9.249,071 B2

*::

8 PYRN-5- Y&N.S. U.S. Patent Feb. 2, 2016 Sheet 5 of 22 US 9.249,071 B2 CC

COOee

biphenylene

aS-indacene Figure 7 U.S. Patent Feb. 2, 2016 Sheet 6 of 22 US 9.249,071 B2

S. M FN N N aCridine phenanthroline phenanthridine

N 1. CCO CCON N phenazine phenothiazine

O)N COOH H iminodibenzyl indole (10,11-dihydro-5H-dibenz(b,f)azepine)

isoquinoline N21 N nS1 NS N n

1. N-2 1. N1 N 4H-quinolizine quinoline 1,7-phenanthroline

CON OCN 9H-Carbazole beta-Carboline

Figure 8 U.S. Patent Feb. 2, 2016 Sheet 7 of 22 US 9.249,071 B2

CF C2F5 CF r S of: SrcF, scF. CF NAPH(CFs). C2F5 NAPH (CFs).

CF7 Cafe of, s-s ch s ea re, a\ a Cafg CF7 NAPH(n-CF). Cafs NAPH (n-C4Fo)4

Figure 9 U.S. Patent Feb. 2, 2016 Sheet 8 of 22 US 9.249,071 B2

Figure 9 (cont) U.S. Patent Feb. 2, 2016 Sheet 9 of 22 US 9.249,071 B2

y: 3537; + 337888x Rs: (.3333; y: 0.4743 - 3.3884x R: 3.98888 3,3 a 2.5- AN : &les - YRN is squares 5 2.0 t (3 ... 3 15 1,3- c S 0.5 / ANTH slopes 0.38 ev per CF. group &R is PYRK siege as 3.39 ev per CF group

Faber of CF3 groups, in Figure 10

rworrorM 88 8Si 330 33 s rfg Figure 11 U.S. Patent Feb. 2, 2016 Sheet 10 of 22 US 9.249,071 B2

8A-C,

8.8 3.3 8. 8:88::::::::::::... g.:8: 8:38::::::::::::::::::::::: Figure 12 U.S. Patent Feb. 2, 2016 Sheet 11 of 22 US 9.249,071 B2

6. 33.4. Figure 13 U.S. Patent Feb. 2, 2016 Sheet 12 of 22 US 9.249,071 B2

Figure 14 U.S. Patent Feb. 2, 2016 Sheet 13 of 22 US 9.249,071 B2

Figure 15 U.S. Patent Feb. 2, 2016 Sheet 14 of 22 US 9.249,071 B2

NAPHR), R. A Cas A -/2 -

NA

w3. o-2 -1.0 E, v vs. Fe(Cp)," Figure 16 U.S. Patent Feb. 2, 2016 Sheet 15 of 22 US 9.249,071 B2

*F NMR in CDC, AZ-3-3

AX-3-2

A2-3-

a li zults |

A2.4-2

------Aas -54 -56 -58 -60 -62 -64 -66 ppm Figure 17

R in 3. A s ------H NMR in CDC, A **-tir'------was------A23-3-3 is ; :

------a------a-a-a-a-- '...... non-a-a-a-a------'WA.------a------'aws------Air' real-a------s------it ------9.3 3. S. Q 8.8 88 8.4 8.2 38 7.8 ppi Figure 18 U.S. Patent Feb. 2, 2016 Sheet 16 of 22 US 9.249,071 B2

O 2.0 3.O 4.O binding energy, eV

Figure 19 U.S. Patent Feb. 2, 2016 Sheet 17 of 22 US 9.249,071 B2

5-5, s 3. assa 'tis essa...e. er kgy, &... e-estsa. ... : gy 'ssites ex . . 3.61. A &xxx8c:-3&33 & Espá; : g ho-isfl. y s 8X k “, s' 8. 8. w &

Figure 20 U.S. Pa tent Feb. 2, 2016 Sheet 18 of 22 US 9.249,071 B2

AZULENE(CF3), r C10Hs-n(CFs) it Chemical Name Structure formula AZUL- C3H5Fo i3.5- 3- AZUL(CFs):

3.6- azulene(CF)3

sass2,3- AZUL(CFs).

{3,5,7- AZUL(CF4

2,3,5- AZUL(CF3)4

8,2,3,6-

4-3 AZUL(CFs).

8:

7 AZL- CSHF is 2,3,5,7- 5- AZUL(CFs):

Figure 21

U.S. Patent Feb. 2, 2016 Sheet 21 of 22 US 9.249,071 B2

PHENANTHRENE(CFs). i Molecular Name Structure formula By: 1 PHEN-5-1 C19HsF15 1,3,6,7,9- X-ray FC PHEN(CF3)s ( ) CF3 Fc-() ( ) FC CF3

PYRENE(CFs). hi Molecular Name Structure formula By:

1 PYRN-5-1 C21H5F15 1,3,4,6,8- X-ray CF PYRN(CFs). cuC “rer,CF CF 2 PYRN-5-2 C21H5F15 1,3,4,6,9- X-ray CF3 PYRN(CF).5 FC

CCC.CF3 CF 3 PYRN-5-3 C21Hs F15 NMR 4. PYRN-6-1 1,3,4,6,8,9- X-ray CF3 PYRN(CF). FICCFC CCCF,CF3 CF

Figure 21 (cont.) U.S. Patent Feb. 2, 2016 Sheet 22 of 22 US 9.249,071 B2

TRIPHENYLENE(CFs) Molecular Namc Structure formula By: 1 TREH-5-1 NMR 2 TREH-6-1 1,3,6,7,10,11- X-ray FC CF C24H6F18 TRPH(CF) FC r O CF3 CF 3 TRPH-6-2 1,3,6,8,10,11- NMR FC CF C2H6F18 TRPH(CF) FC r C FC CF

Table F21. Experimental Data for PAH and PAH (CFs). Compounds

compound abbrev, gas-phase Solution E/2 X-ray EA, eV V vs. Fe(Cp)," Structure

pentacene PENT 1.39(4)

PENT(CFs)s mixture of isomers 3.32(2) O perylene PERY 0.973(5) -223

PERY(CF), mixture of isomers 2.91(2) O

Figure 21 (cont) US 9.249,071 B2 1. 2 MODIFIED POLYAROMATIC organic molecules with strong electron-accepting properties, HYDROCARBONS AND for example, for use as organic semiconductors in electronic POLYHETEROCYCLCS FOR devices. OPTOELECTRONICS SUMMARY RELATED APPLICATIONS The invention provides a method for the direct perfluoro This application claims priority under 35 U.S.C. S 119(e) to alkylation of polyaromatic hydrocarbons and polyheterocy U.S. Provisional Patent Application No. 61/761,528, filed clic compounds. The method can be carried out in a single Feb. 6, 2013, which is incorporated herein by reference. 10 step by combining reactants in the gas phase to provide new compounds with unprecedented Substitution patterns. GOVERNMENT SUPPORT Accordingly, the invention provides methods for Substitut ing polyaromatic hydrocarbons or polyheterocyclic com This invention was made with government Support under pounds with perfluoroalkyl groups comprising: heating a pol Grant No. CHE1012468 awarded by the National Science 15 yaromatic hydrocarbon Substrate or a polyheterocyclic Foundation. The government has certain rights in the inven compound Substrate in the presence of a perfluoroalkyl tion. iodide, in an optionally closed reaction system, wherein the BACKGROUND OF THE INVENTION heating is Sufficient to bring both the polyaromatic hydrocar bons or polyheterocyclic compound, and the perfluoroalkyl The renaissance in the synthesis of Small organic mol iodide, into the gas phase, thereby allowing the Substrate to ecules with strong electron-accepting properties (i.e., organic react with the perfluoroalkyl iodide in the gas phase to form semiconductors (OSCs)) during the past decade has been polyaromatic hydrocarbons or polyheterocyclic compounds spurred by the global economic needs of (i) renewable having one or more perfluoroalkyl Substituents. Sources of energy and (ii) more efficient and less expensive 25 In one embodiment, the reaction system is a closed system electronic devices that preferably include earth-abundant ele able to withstand the high temperatures and high pressures of ments. The replacement of silicon- and metal-based elec the reaction conditions described herein. The reaction system tronic components with rationally-designed, finely-tuned contains the Substrate and perfluoroalkyl iodide, and these organic molecules and molecular assemblies should lead to reactants can be heated to about 200° C. to about 550° C., sustainable, lower-cost, lower-weight, flexible, yet robust 30 typically to about 250° C. to about 450° C., to about 300° C. solutions to many 21 century technological problems. Sig to about 400°C., or to about 300° C. to about 360° C. Addi nificant progress in this endeavor requires a deep understand tional pressure can be added to the system. ing of the fundamental relationships between molecular In one embodiment, the reaction system is a closed system structure, Solid-state morphology, and electronic and other that provides an increased atmospheric pressure upon heat physicochemical properties of OSCs. 35 It has long been recognized that the presence of electron ing. In another embodiment, the reaction system is a flowing withdrawing groups (e.g., halogen atoms, cyanide, perfluo bed reactor system having input valves for adding Substrate roalkyl (R), or perfluoroaryl groups) in polycyclic aromatic and the perfluoroalkyl iodide, and an outlet for collecting hydrocarbons (PAHs) results in molecules with enhanced products in the gas or liquid phase. electronacceptor properties, better air stability, and improved 40 In some embodiments, the reaction system does not com Solid-state charge-carrier mobilities. In particular, organic prise a catalyst and/or a reaction promoter compound (e.g., a made with the few available PAH acceptors bear metal or salt to promote the reaction). In various embodi ing R groups have long-term air-stability, which can be cor ments, the reaction system does not comprise a solvent. related with either low LUMO energies (ca. -4 eV; estimated In various embodiments, the perfluoroalkyl iodide is CF by cyclic voltammetry), or with DFT-predicted gas-phase 45 (CF).I., wherein n is 0 to about 12. Thus, in some embodi electron affinities (EAS) above 2.8 eV (believed to be the ments, in can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12. threshold value for n-channel-device air stability. The arsenal In certain specific embodiments, the perfluoroalkyl iodide of synthetic methods used in the past to prepare PAHs with is CFI, CFI, n-CFI, or n-CFI. Other commercially one or more R. Substituents include (i) bottom-up design available or synthetically preparable perfluoroalkyl iodide involving multi-step coupling reactions of smaller precursors 50 can readily be used in the method. already bearing an R group (U.S. Pat. No. 7,390.901 (Yang In one embodiment, the Substrate is a polyaromatic hydro et al.); Geib et al., J. Org. Chem. 2012, 77, 6107-6116), (ii) carbon Substrate. In certain specific embodiments, the pol metal-catalyzed reactions in solution for modification of PAH yaromatic hydrocarbon Substrate is anthracene, azulene, intermediates that have reactive substituents such as C1 or Br , fluorene, fluoranthene, naphthalene, pentacene, atoms, intermediates that are themselves not commercially 55 perylene, phenanthrene, pyrene, tetracene, or triphenylene, or available (Schlosser, Angew. Chem. Int. Ed. 2006, 45,5432 5446; Tomashenko and Grushin, Chem. Rev. 2011, 111, another polyaromatic hydrocarbon described herein. 4475-4521), and (iii) direct perfluoroalkylation of PAHs In one embodiment, the Substrate is a polyheterocyclic (Bravo at al., J. Org. Chem. 1997, 62,7128-7136). However, compound Substrate. In certain specific embodiments, the the latter method has not been extensively studied, possibly 60 polyheterocyclic compound Substrate is acridine, beta-carbo because the low yields and poor regioselectivities reported line, 9H-carbazole, iminodibenzyl, indole, isoquinoline, were not encouraging (Tiers, J. Amer: Chem. Soc. 1960, 82, phenanthridine phenanthroline, phenazine, phenothiazine, 5513-5513; b) Cowell and Tamborski, J. Fluorine Chem. quinazoline, or quinoline, or a polyheterocyclic compound 1981, 17,345-356). described herein. Accordingly, there is a need for new methods for the direct 65 In one embodiment, the polyaromatic hydrocarbon having perfluoroalkylation of PAHs and related aromatic and het one or more perfluoroalkyl Substituents formed is a com eroaromatic compounds. There is also a need for new Small pound of Formula (I): US 9.249,071 B2 3 4

(I) (II) N1 N N2 (Rp), it --(RF): 5 \ M 2n 21 (RP), 4N2SR wherein wherein R is —(CF),CF wherein n is 0 to about 11; and 10 R is —(CF),CF wherein n is 0 to about 11: each m is independently 1 to 3. m is 0 to 3; and In some embodiments, the compound of Formula (I) is: p is 1 to 3. 15 In other embodiments, the compound of Formula (II) is: RE RE RE: RE

RE RE R (15-NAPH) (1,3,5-NAPH) RE Fs RF RE: RF; 2s (1,3,5-AZUL) RF

RF RE R R F F 30 (1,3,6-NAPH) (1,3,7-NAPH) RE: F. RE RE (1,3,6-AZUL) RE RE: RF 35 RF O) R F. RE RE RE ( 14,6-NAPH) ( 1,3,5,7-NAPH) 40 (1,2,3-AZUL) RE R; or RE RF

RF 45 RF (1,3,6,7-NAPH) RE RE: RE RE: (1,3,5,7-AZUL) 50 RF RF RF (2,3,6,7-NAPH) RE:

55 R RE wherein R is —(CF),CF wherein n is 0 to about 11. In F certain specific embodiments, the naphthalene core is Substi- (1,2,3,5-AZUL) tuted with the perfluoroalkyl substituent to provide 1.2-, 1.3-, RF 1,4-, 1.5-, 2.5-, 2,6-, 1.8-, or 2.8-substituted naphthalene com pounds. Combinations of the aforementioned compounds can 60 be prepared, and these compounds can also include a third or RF RE; or fourth perfluoroalkyl Substituent in one of the remaining posi tions. RE In various embodiments, the polyaromatic hydrocarbon 65 having one or more perfluoroalkyl Substituents formed is a (1,2,3,6-AZUL) compound of Formula (II): US 9.249,071 B2 6 -continued -continued RF RF RF

RE RE

(1,2,3,5,7-AZUL) 10 (1,3,6,7,9-PHEN) wherein R is —(CF),CF wherein n is 0 to about 11. In various other embodiments, the polyaromatic hydrocar bonhaving one or more perfluoroalkyl Substituents formed is: 15

RE RE

RE 25

30

RE

35

(1,3,4,6,9-PYRN)

40

45

50 RE (1,3,4,6,8.9-PYRN)

55 RE RE

60 RF

RE RE 65 (1,3,5,7,9,11-PERY) (1,3,6,7,10,11-TRPH) US 9.249,071 B2 7 8 -continued a compound of Formula (VI):

(VI) RE N N (RF) - I --(RF): 10 21 2 RF (1,3,6,8,10,11-TRPH)

O 15 wherein R is —(CF),CF wherein n is 0 to about 11. a compound of Formula (VII): In one embodiment, the polyaromatic hydrocarbon having one or more perfluoroalkyl Substituents formed is a com pound of Formula (III): (VII) RF N N (RF) - --(RF): 21 2 (III) 25 RF RF RE N N (RF), it --(R): wherein 2 21 30 R is —(CF)CF wherein n is 0 to about 11: RE m is 0 to 3: p is 0 to 3; and wherein the sum of m and p is 2, 3, 4, 5, or 6. a compound of Formula (IV): 35 In another embodiment, the polyheterocyclic compound having one or more perfluoroalkyl Substituents formed is a compound of Formula (X):

40 (IV) (X) N1 N1 N. RE (Rf), it --(RF): 2 2n 2 N N N (RF), it --(RF): 45 2 2 a compound of Formula (XI): RF RF (XI) 50 RF a compound of Formula (V): N1 N1 N (RF), it -- (R): 55 21 N2n 2 (V) RE a compound of Formula (XII): N N 60 (XII) (Rp), it --(RF): N 2 21 N N1 N (Rf). --(RF): RE 2 Nan 21 65 US 9.249,071 B2 9 10 a compound of Formula (XIII): depending on the number of aromatic rings in the compound. Accordingly, the invention provides formulas of each pol yaromatic hydrocarbon and polyheterocyclic compound S (XIII) described herein (e.g., Formula (XY wherein N is different for N N each substrate and product) substituted by one or more (RF), it H(RF), —(R), groups. In some embodiments, even non-sp-hy 2 N 21 dribized C H moieties can be substituted by using the meth H ods described herein. In various embodiments, a group of compounds, or a group of compounds prepared by the meth 10 a compound of Formula (XIV): ods described herein, exclude a compound substituted at the polyaromatic hydrocarbon or polyheterocyclic compound 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-position, or a (XIV) combination thereof, from the embodiment. 15 The invention thus provides novel compounds of the for mulas described herein, as well as methods of preparing the compounds. The compounds are useful as intermediates for (R)-(-N N= 7 (Rp. the synthesis of other useful compounds, and the compounds can be used as organic semiconductors in electronic devices.

O BRIEF DESCRIPTION OF THE DRAWINGS a compound of Formula (XV): The following drawings form part of the specification and are included to further demonstrate certain embodiments or (XV) 25 various aspects of the invention. In some instances, embodi RF ments of the invention can be best understood by referring to the accompanying drawings in combination with the detailed description presented herein. The description and accompa nying drawings may highlight a certain specific example, or a 30 certain aspect of the invention. However, one skilled in the art (R)-(-N N= 7 (Rp. will understand that portions of the example or aspect may be used in combination with other examples or aspects of the wherein invention. FIG. 1. Single-crystal X-ray diffraction thermal-ellipsoid each R is independently —(CF), CF wherein n is 0 to 35 about 11: plots of five compounds listed in Table 1 showing IUPAC each m is independently 0 to 3; and locants (50% probability ellipsoids except for Hatoms, which wherein the sum of elements m is 1, 2, 3, 4, or 5. are spheres of arbitrary size; F atoms are dark spheres). Also The invention further provides novel compounds one or shown are IUPAC locants for azulene (AZUL). The other more perfluoroalkyl groups. The compounds can include a 40 abbreviations are defined in Table 1. polyaromatic hydrocarbon core, or a polyheterocyclic core. FIG. 2. Negative-ion photoelectron spectra (12K, 266 mm) In some embodiments, the invention provides a compound of representative PAH (CF), compounds. prepared by a method described above. In certain embodi FIG. 3. Cyclic voltammograms (0.1 M N(n-Bu)ClO in ments, the compound having one or more perfluoroalkyl dimethoxyethane, 500 mVs) of representative PAH(CF), groups is a compound illustrated in FIG. 1, FIG.9, FIG. 13, or 45 compounds. FIG. 21, or described or illustrated herein. FIG. 4. Plot of PES-determined gas-phase EA of perylene When R can be —(CF), CF, where n is 0 to about 11, (PERY: n=0) and PERY(CF), compounds (n=4,5,6,7) vs. n. compounds that include Substituents having an in value of 0, 1, The slope of the least-squares fit to the data is 0.28 eV per CF 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 can readily be prepared by group. The experimental uncertainties for the PAH(CF), employing the appropriate starting material perfluoroalkyl 50 compounds (s0.02V or 0.02 eV) are smaller than the width of iodide. the data points. When a compound is described as having one or more FIG. 5. Plot of E. vs. gas-phase EA for PAH and PAH perfluoroalkyl groups, the compound can have as many per (CF), compounds. The slope of the least-squares fit to the fluoroalkyl groups as there are available sp-hydribized data is 0.73 V eV. The experimental uncertainties for the C—H bonds in the substrate. However, typically fewer than 55 PAH(CF), compounds (s0.02V or 0.02 eV) are smaller than the maximum number of Substitutions are achieve. In some the width of the data points. embodiments, one or more perfluoroalkyl groups refers to 2 FIG. 6. Comparison of portions of the X-ray structures of to about 8 perfluoroalkyl groups, or two, three, four, five, six, ANTH-5-1 and ANTH-6-1 (top) and PYRN-5-1 and PYRN seven, or eight perfluoroalkyl groups. 5-2 (bottom). Both F and H atoms have been omitted for The methods described herein are general for a wide range 60 clarity, and the Catoms are shown as spheres of arbitrary size. of polyaromatic hydrocarbons and polyheterocyclic com The CFC atoms are shaded gray. Each drawing is oriented so pounds. Thus, the invention provides a polyaromatic hydro that the least-squares plane of the lower aromatic core is in the carbon or a polyheterocyclic compound having one or more plane of the page. For ANTH-5-1, ANTH-6-1, and PYRN-5- perfluoroalkyl groups, where a formula can be illustrated as 2, the least-squares planes of the upper aromatic cores are the Substrate with a —(R) group on any of the aryl rings of 65 rigorously parallel to the planes of the lower cores. For the compound, wherein mis 0-3. The Sum of mgroups for any PYRN-5-1, the least-squares plane of the upper aromatic core particular compound can be 2, 3, 4, 5, 6, 7, 8, 9, or about 10, is tilted 5.2° with respect to the plane of the lower core. US 9.249,071 B2 11 12 FIG. 7. Examples of polyaromatic hydrocarbon substrates J. Org. Chem. 2010, 75, 3007). Both methods are not well that can be used in the methods of the invention, according to Suited for a preparation of PAHs carrying a large number of various embodiments. R groups in one selective step. The method described herein FIG. 8. Examples of polyheterocyclic compound sub is well-suited for such applications because PAHs can be strates that can be used in the methods of the invention, 5 perfluoroalkylated directly (without the need to prepare and according to various embodiments. isolate brominated PAHs precursors) and without use of sol FIG. 9. Various specific products and general formulas of vents. The method is solvent-free and therefore very environ products of the methods of the invention, according to various mentally friendly. Additionally, the specialized fullerene embodiments. HPLC column Cosmosil Buckyprep can be used for the FIG. 10. Plots of ANTH(CF), and PYRN(CF), electron 10 analysis and separation of mixtures of derivatized PAH com affinities vs. n, based on experimental gas-phase electron pounds, which allows for the isolation of many different affinities (cf. the corresponding graph for PERY(CF), com poly(perfluoroalkylated) PAH compounds, as described pounds in FIG. 4). herein with poly(trifluoromethylated) , penta FIG. 11. Negative-ion APCI mass spectra of the TDAE cene and perylene derivatives. reduced crude products of naphthalene perfluoroalkylation: 15 The invention thus provides a new method for the prepa A) NAPH(CF); B)NAPH(CFs); C) NAPH(n-CF,); and ration of novel perfluoroalkylated polyaromatic hydrocar D) NAPH(n-CF). Peaks marked with daggers are due to bons (PAH) and new compositions of matter, including fragments resulting from loss of HF from parent ions. C20H12. (CFs), C20Ho(CFs), and C22H14,(CFs), com FIG. 12. Single-crystal X-ray diffraction structure of 1.3, pounds. The method is based on a direct reaction between 5,7-NAPH(CF), 50% probability ellipsoids used for all perfluoroalkyl iodides (RFI) and PAH in gas phase at high non-hydrogen atoms of the ORTEP drawing (top left), NI temperature. A symmetric derivative of corannulene CoHs APCI mass spectrum (TDAE-reduced; top right), 'F NMR (CF)s can be prepared with high selectivity using this tech (bottom left), and HNMR spectra (bottom right) with expan nique. This compound displays a blue fluorescence and a sions of the 95%+ pure 1,3,5,7-NAPH(CF). Peaks marked cathodic shift of about 1 V of its reversible first reduction with asterisks are due to internal standard, and peak at 8 7.26 25 potential relative to underivatized CoHo. Such compounds due to solvent (CDC1). are useful for new photoelectrochemical devices such as FIG. 13. Numbering scheme (1 through 8) and symmetry . The new synthetic methodology has been easily related positions (a and b) for substitutions in NAPH and adapted to other promising PAHs such as pentacene and drawings of the most stable isomers of NAPH(CF), DFT perylene for the modification of their physical and electro calculated relative energies (in kJ/mol) are given under each 30 chemical properties. The high-temperature method ensures Structure. that only the most thermodynamically stable isomers of poly FIG. 14. Crystal packing in 1,3,5,7-NAPH(CF). (perfluoroalkyl)PAHs are produced in abundance, thus lead FIG. 15. (A) Single-crystal X-ray diffraction structure of ing to high selectivity. 1,3,5,7-NAPH(CFs). 50% probability ellipsoids used for Breakthroughs in molecular optoelectronics await the all non-hydrogen atoms of the ORTEP drawing. (B) Crystal 35 availability of new families of air-stable polyaromatic hydro packing in 1,3,5,7-NAPH(CFs). Fluorine and hydrogen carbon (PAH) acceptors with incrementally- and predictably atoms are removed for clarity. tunable electron affinities and structures capable of inducing FIG. 16. Cyclic voltammograms (scan rate 100 mV.'s') of desirable solid-state morphologies in hybrid materials. naphthalene (NAPH) and pure 1,3,5,7-NAPH(R) com Although the addition of electron withdrawing groups to pounds in dimethoxyethane (0.1 M (n-Bu)NCIO). All five 40 PAHs has been studied for decades, producing new com CVs are shown relative to Fe(Cp)" defined as 0.0 V. pounds from time to time, a generic one-step synthetic meth FIG. 17. F NMR spectra (CDC1, 376.5 MHz, odology applicable to potentially all PAH substrates has been, Ö(CF)=-164.9 ppm) showing the CF multiplets and sin until now, unavailable. glets of the seven aZulene derivatives. Regions where peaks A variety of Substrates, including seventeen common are in close proximity are shown as insets for clarity. 45 PAHs and polyheterocyclics, can be trifluoromethylated by FIG. 18. 'H NMR of the seven azulene derivatives in the new procedure to yield families of PAH (CF), acceptors CDC1. *-an impurity in AZUL-3-3 spectrum. with (i) n=1-8, (ii) multiple isomers for particular n values, FIG. 19. The low-temperature (12K) photoelectron spec (iii) gas-phase experimental electron affinities as high as 3.32 trum at 266 mm of AZUL-5-1 (top), AZUL-4-2 (middle), and eV and shifted from the respective PAH precursor as a linear AZUL-4-1 (bottom). 50 function of n, and (iv) various Solid-state morphologies, FIG. 20. Showing the packing of AZUL-5-1/pyrene col including the ability to form alternating It stacked hybrid umns from the top down (A) and a view of two columns from crystals with aromatic donors. Furthermore, six new poly the side (B). Distances between AZUL-5-1 core plane and (trifluoromethyl) prepared in a single high-tempera pyrene core planes are given. ture reaction exhibit strong electron accepting properties in FIG. 21. Compounds of the invention and related data, 55 the gas phase and in Solution and demonstrate propensity to according to various embodiments. form regular t-stacked columns in the donor-acceptor crys tals, when mixed with pyrene as a donor. The methods thus DETAILED DESCRIPTION provide robust, finely-tuned materials for new molecular optoelectronics, pharmaceuticals and agrochemicals, fluo Currently there are only two reported methods for perfluo 60 ropolymers, and catalysts roalkylation of polyaromatic hydrocarbons (PAHs). The first method is based on substitution of bromine for a CF group in DEFINITIONS the presence of CuI and CFCOOH in solution (see for example: Org. Lett. 2009, 11, 2808). The second method uses The following definitions are included to provide a clear a reaction of RI precursors with PAHs (R group substitutes 65 and consistent understanding of the specification and claims. a hydrogen atom, see Org. Lett. 2010, 12, 2374) or with As used herein, the recited terms have the following mean brominated PAHs (R group Substitutes a bromine atom, see ings. All other terms and phrases used in this specification US 9.249,071 B2 13 14 have their ordinary meanings as one of skill in the art would the same range being broken down into at least equal halves, understand. Such ordinary meanings may be obtained by thirds, quarters, fifths, or tenths. As a non-limiting example, reference to technical dictionaries, such as Hawley's Con each range discussed herein can be readily broken down into densed Chemical Dictionary 14" Edition, by R. J. Lewis, a lower third, middle third and upper third, etc. As will also be John Wiley & Sons, New York, N.Y., 2001. understood by one skilled in the art, all language Such as “up References in the specification to “one embodiment”, “an to”, “at least”, “greater than”, “less than”, “more than”, “or embodiment', etc., indicate that the embodiment described more', and the like, include the number recited and such may include a particular aspect, feature, structure, moiety, or terms refer to ranges that can be subsequently broken down characteristic, but not every embodiment necessarily includes into Sub-ranges as discussed above. In the same manner, all that aspect, feature, structure, moiety, or characteristic. More 10 ratios recited herein also include all sub-ratios falling within over, Such phrases may, but do not necessarily, refer to the the broader ratio. Accordingly, specific values recited for same embodiment referred to in other portions of the speci radicals, Substituents, and ranges, are for illustration only; fication. Further, when a particular aspect, feature, structure, they do not exclude other defined values or other values moiety, or characteristic is described in connection with an within defined ranges for radicals and Substituents. embodiment, it is within the knowledge of one skilled in the 15 One skilled in the art will also readily recognize that where art to affect or connect such aspect, feature, structure, moiety, members are grouped together in a common manner, such as or characteristic with other embodiments, whether or not in a Markush group, the invention encompasses not only the explicitly described. entire group listed as a whole, but each member of the group The singular forms “a,” “an and “the include plural individually and all possible subgroups of the main group. reference unless the context clearly dictates otherwise. Thus, Additionally, for all purposes, the invention encompasses not for example, a reference to “a compound includes a plurality only the main group, but also the main group absent one or of such compounds, so that a compound Xincludes a plurality more of the group members. The invention therefore envis of compounds X. It is further noted that the claims may be ages the explicit exclusion of any one or more of members of drafted to exclude any optional element. As such, this state a recited group. Accordingly, provisos may apply to any of the ment is intended to serve as antecedent basis for the use of 25 disclosed categories or embodiments whereby any one or exclusive terminology, such as “solely,” “only, and the like, more of the recited elements, species, or embodiments, may in connection with any element described herein, and/or the be excluded from Such categories or embodiments, for recitation of claim elements or use of “negative' limitations. example, for use in an explicit negative limitation. The term “and/or means any one of the items, any com The term “contacting refers to the act of touching, making bination of the items, or all of the items with which this term 30 contact, or of bringing to immediate or close proximity, is associated. The phrase “one or more' is readily understood including at the cellular or molecular level, for example, to by one of skill in the art, particularly when read in context of bring about a physiological reaction, a chemical reaction, or a its usage. For example, one or more substituents on a phenyl physical change, e.g., in a solution or in a reaction mixture, ring refers to one to five, or one to four, for example if the including in the gas phase. phenyl ring is disubstituted. 35 An “effective amount” refers to an amount effective to The term “about can refer to a variation of +5%, +10%, bring about a recited effect, Such as an amount necessary to +20%, or +25% of the value specified. For example, “about form products in a reaction mixture. Determination of an 50 percent can in some embodiments carry a variation from effective amount is typically within the capacity of persons 45 to 55 percent. For integer ranges, the term “about can skilled in the art, especially in light of the detailed disclosure include one or two integers greater than and/or less than a 40 provided herein. The term “effective amount' is intended to recited integer at each end of the range. Unless indicated include an amount of a compound or reagent described otherwise herein, the term “about is intended to include herein, or an amount of a combination of compounds or values, e.g., weight percentages, proximate to the recited reagents described herein, e.g., that is effective to form prod range that are equivalent in terms of the functionality of the ucts in a reaction mixture. Thus, an “effective amount gen individual ingredient, the composition, or the embodiment. 45 erally means an amount that provides the desired effect, and The term about can also modify the end-points of a recited for Substitution, an effective amount is typically at least one range as discuss above in this paragraph. molar equivalent, but can be as high as hundreds of equiva As will be understood by the skilled artisan, all numbers, lents, depending on the desired outcome of a reaction. including those expressing quantities of ingredients, proper A "polyaromatic hydrocarbon refers to a hydrocarbon ties such as molecular weight, reaction conditions, and so 50 having at least two rings, at least one of which is aromatic. forth, are approximations and are understood as being option Polyaromatic hydrocarbon fall within the class of arene com ally modified in all instances by the term “about.” These pounds. Examples of polyaromatic hydrocarbons include, but values can vary depending upon the desired properties sought are not limited to, , acenaphthylene, to be obtained by those skilled in the art utilizing the teachings , anthracene, aZulene, benzoa anthracene, of the descriptions herein. It is also understood that such 55 benzoafluorine, benzocphenanthrene, , values inherently contain variability necessarily resulting benzoapyrene, benzoepyrene, benzob fluoranthene, from the standard deviations found in their respective testing benZofluoranthene, benzokfluoranthene, benzoghi measurementS. perylene, chrysene, corannulene, coronene, , As will be understood by one skilled in the art, for any and diindenoperylene, fluorene, fluoranthene, fullerene, , all purposes, particularly in terms of providing a written 60 , , indene, , naphthalene, description, all ranges recited herein also encompass any and , pentacene, perylene, phenalene, phenanthrene, all possible Sub-ranges and combinations of Sub-ranges dihydrophenanthrene, picene, pyrene, tetracene, and triph thereof, as well as the individual values making up the range, enylene. particularly integer values. A recited range (e.g., weight per As used herein, a “polyheterocyclic compound” refers to a centages or carbon groups) includes each specific value, inte 65 heterocyclic compound having at least two rings, at least one ger, decimal, oridentity within the range. Any listed range can of which is aromatic. Polyheterocyclic compound can also be be easily recognized as Sufficiently describing and enabling referred to as heteroaromatic compounds. As used herein, a US 9.249,071 B2 15 16 heterocyclic compound is cyclic aromatic compound that PHEN, PYRN, and TRPH have been prepared, isolated in includes at least one heteroatom in an aromatic ring. Typical pure form as single isomers and studied (see Table 1 for heteroatoms include oxygen, nitrogen, and Sulfur. Examples abbreviations). Preliminary results indicate that the method of polyheterocyclic compounds include, but are not limited also works for fluorene, fluoranthene, naphthalene, and tet to, acridine, benzimidazole, 2H-1-benzothine, benzthiazole, racene as well as for PAHs containing heteroatoms, such as benzobfuran, benzobthiophene, benzocthiophene, car phenazine, phenanthroline, phenothiazine, and iminodiben bazole, cinnoline, dibenzothiophene, iminodibenzyl, 1H-in Zyl. The reaction mechanism likely involves the formation of dazole, indole, indolizine, isoindole, isoquinoline, 1.5-naph “hot” CF radicals by thermally-induced dissociation of thyridine, 1.8-naphthyridine, phenanthridine phenanthroline, CFI, removal of a PAH H atom by a CF radical to form phenazine, phenoxazine, phenothiazine, phthalazine, 10 quinazoline, quinoline, 4H-quinolizine, thianthrene, and Xan CHF and a PAH radical, and subsequent reaction of another thene. CF radical with the transient PAH radical to form the new A perfluoroalkyl iodide refers to a perfluorinated alkyl PAH CF bond. This sequence would occur in times for a iodide such as a compound of Formula IR: I—(CF), CF; given PAH (CF) derivative. In one reaction, CHF was posi where n is 0 to about 11. Perfluoroalkyl iodides can be used to 15 tively identified as one of the products along with 12 and the provide perfluoroalkyl Substituents on polyaromatic hydro PAH(CF), derivatives. Numbering schemes for six PAHs are carbons and polyheterocyclic compounds. Examples of per shown in FIG. 1. Also shown are five of the seven X-ray fluoroalkyl substituents include moieties of Formula R: structures that have been deposited with the Cambridge Crys —(CF), CF; where n is 0 to about 11. A perfluoroalkyl tallographic Data Centre. Substituent can also be a branched perfluoroalkyl group Such With one exception, we have not yet endeavored to opti as the Krytox group: CFCF( CFs)(OCF.CF( CF,)).F mize reaction conditions as far as overall yield or product where g is 0, 1, 2, 3, 4, 5, or 6. selectivity is concerned. Instead, two goals included (i) to The following abbreviations may be used for reference to demonstrate that families of PAH (CF), derivatives in pure certain polyaromatic hydrocarbons and polyheterocyclic form as single isomers could be readily prepared in a single compounds: acridine (ACRD); anthraquinone (ANTQ); phe 25 nothiazine (PHTZ); phenanthridine (PHTD); phenanthroline reaction from a variety of parent PAHs and (ii) to examine the (PHTL); tetracyanoquinodimethane (TCNQ); and indole electronic properties and solid-state morphologies of as many (INDL). of the new compounds as possible. Therefore, most reactions Polyarene Acceptors for Air-Stable Molecular Optoelectron were carried out using only 0.10-0.12 mmol portions of the 1CS 30 PAH precursor (Table 2). The one exception is a series of A generic, one-step, solvent-, catalyst-, and promoter-free reactions starting with 1.0 mmol (178 mg) portions of ANTH perfluoroalkylation methodology was developed for the that were shown to produce, predominantly and nearly quan preparation of strong PAH (CF), electron acceptors that is titatively, ANTH(CF)4,5,6 mixtures. Isolated yields of two potentially applicable to any commercially-available and of the HPLC-purified products were 5 mol% for 95+% pure thermally-stable PAH precursor. The methodology involves 35 ANTH-5-1 and 20 mol % for 98+% pure ANTH-6-1 (based an elevated-temperature “one-pot' reaction between the PAH on ANTH). precursor and gaseous CFI or related iodides in which single Table 1 lists EAS and E. values for the new PAH (CF), or multiple CF groups can be added to the PAH core by compounds. The former were determined by low-tempera replacing H atoms. Single reactions with 17 different precur ture photoelectron spectroscopy and the latter by CV. Also sors have provided up to four PAH(CF), compositions as 40 predominant products, in Some cases with up to four isomers listed are the NIST-WebBook EAs of the parent PAHs and of particular compositions. their Evalues; the latter were determined in this work using The method appears to be truly generic. PAH (CF), com the same apparatus, electrodes, electrolyte, and conditions pounds for seven PAHs, ANTH, AZUL, PENT, PERY, used for the PAH (CF), compounds. TABLE 1 Experimental Results and Abbreviations for PAH and PAH(CFa), Compounds isolated purity, yield, gas-phase E2. V vs. X-ray Compound mol% mol% abbrev. EA, eV Fe(Cp)," structure" Anthracene 99 - ANTH 0.53(2) -2.52 1,3,6,8,10 95 S ANTH-5-1 2.40(2) -1.24 Yes ANTH(CF) 2,3,6,7,9,10 98 2O ANTH-6-1 2.81 (2) -O.92 Yes ANTH(CF) AZulene 99 — AZUL 0.790(8) -2.14 — 1,2,3,5,7- 98 25 AZUL-5-1 2.890(5) -0.73 prelim. AZUL(CF)s Naphthalene 99 NAPH -0.2 -3.09 — Pentacene 99 PENT 1.39(4) - / PENT(CF) mixture of <2 3.32(2) 3 O isomers Perylene 99 PERY 0.973(5) -2.23 1,4,7,10 98 <3 PERY-4-1 2.20(2) -1.30 Yes PERY(CF). 1,3,6,8,10 98 <3 PERY-5-1 2.46(2) -1.19 Yes PERY(CF). PERY(CF). 95 <3 PERY-5-2 2.48(2) -1.29 O US 9.249,071 B2 17 18 TABLE 1-continued Experimental Results and Abbreviations for PAH and PAH(CFs), Compounds isolated purity, yield, gas-phase E2. V vs. X-ray Compound mol% mol% abbrev. EA, eV Fe(Cp)," structure" PERY(CF). 95 <3 PERY-5-3 2.49(2) -1.22 O PERY(CF). 90 <3 PERY-5-4 2.45(2) -1.15 O ,3,5,7,9,11- 97 <3 PERY-6-1 2.72(2) -1.01 prelim. PERY(CF) PERY(CF), mixture of <2 2.91 (2) 3 O isomers phenanthrene 98 PHEN 0.04 -3.10 — ,3,6,7,9– 95

TABLE 2 Reaction conditions used for trifluoromethylation of PAH substrates.

PAHsubstrate m(PAH), mg n(CFI) V,npoule' mL. Versace, mL. T. C. reaction time, h ANTH 178 12 250 250 360 24 AZUL 13 2O 50 50 360 O.S PENT 28 36 50 50 360 18 PERY 25 36 50 50 360 24 PHEN 18 2O 50 50 360 24 PYRN 2O 30 50 50 360 24 TRPH 23 30 50 50 360 24 TETR 194 12 314 314 360 7 ACRD 179 9 268 268 330 9 TRPH 228 6 50 50 3OO 4 ANTQ 25 10 40 40 3OO 4 PHNZ 216 10 373 373 330 2O PHTZ 200 10 363 363 330 7 PHTD 193 10 330 330 328 6 PHTL 251 10 390 390 330 14 TCNQ 242 8 290 290 310 6 INDL 177 6 28O 28O 32O 8

Representative photoelectron spectra and CVs are shown parent PAHs in Table 1 is 1.39(4) eV for PENT: all others are in FIG.2 and FIG.3. The PAH(CF), EAs range from 1.95(1) 65 <1 eV. The E values range from -1.73(2) V vs. Fe(Cp)." eV for PHEN-5-1 to 3.32(2) eV for the mixture of PENT for TRPH-6-1 to -0.73(2) V for AZUL-5-1 and, in contrast, (CF) isomers. In contrast, the highest EA for the eight the least negative PAH E value is -2.14(2)V for AZUL: the US 9.249,071 B2 19 20 others range from -2.23(2) V for PERY to less than (i.e., more Finally, we have measured the air stability in the presence negative than) -3 V for NAPH, PHEN, and TRPH. of bright light and the fluorescence quantum yields for A plot of E. vs. EA for all but three of the entries in Table selected compounds (see Example 1). Taken together, the 1 is shown in FIG. 5. The plot is nominally linear with a slope results described here demonstrate that our generic synthetic of 0.73 V eV. This demonstrates, for a broad set of PAHs 5 methodology, coupled with high-efficiency HPLC purifica and PAH (CF), derivatives, that the incremental change in tion, can provide many dozens of new PAH(R), compounds, E. from one compound to the next is, on average, attenuated many of which will be sublimable, freely soluble in a range of by 27% relative to the change in EA from one compound to organic solvents, air-, light-, and thermally-stable, and pow the next. Designers of new electron acceptors with targeted erful electronacceptors available for use in fundamental stud EAs will find this correlation useful, because reduction poten- 10 ies of the correlations between molecular composition/struc tials are much easier to measure than precise values of gas ture and physicochemical properties. When the syntheses are phase electron affinities. Significantly, the 0.73 VeV' slope scaled up, the new compounds will be available for new stands in contrast to the 1.0 V eV' slope for a similar plot for generations of molecular transistors, photovoltaics, ferro aromatic hydrocarbons published by Ruoff et al. in 1994 (J. electrics, non-volatile memory, non-linear optics, fluorescent Phys. Chem. 1995, 99, 8843-8850) (i.e., a 1:1 correlation 15 probes pharmaceuticals, agrochemicals, organometallic cata between E. and gas-phase EA for PAHs and PAH deriva lysts, and composite polymer/PAH blends. tives with multiple CF groups was not confirmed in our General Method for Perfluoroalkylation of Polyaromatic work; the correlation observed is 0.73:1). Hydrocarbons and Polyheterocyclics Our EA results also demonstrate that there is a nearly A polyaromatic hydrocarbon (PAH) sample and an excess linear incremental, and therefore predictable, change in EA 20 of CFI reagent is loaded into a glass ampoule and the for each CF added to PERY. ANTH, and PYRN. A plot of EA ampoule is flame-sealed. The ampoule can be heated in a tube vs. the number of CF groups is shown in FIG. 4 for PERY furnace to about 300-450° C. and then be allowed to cool. (CF), derivatives (n=0, 4, 5 (four isomers), 6 and 7). The Typically, ampules are allowed to slowly cool to room tem slope of this plot is 0.28 eV per CF group. For ANTH(CF), perature in open air, although other embodiments may also and PYRN(CF), which have fewer C atoms than PERY 25 utilize standard techniques to accelerate the cooling process. (CF), the slopes of the corresponding plots are 0.38 and Large-volume Pyrex glass ampoules may be used as reactor 0.39 eV per CF, respectively (see Example 1). The slope for vessels; volumes are limited mostly by the size of the heating the ANTH(CF), plot of our data is similar to the DFT-pre oven available. The ampoules can be charged with solid PAH dicted slope of 0.35 eV per CF recently reported by Sun et al. starting materials and RI reagent and flame-sealed under (J. Phys. Chem. A 2012, 116,8015-8022). In that work, the 30 vacuum. The ampoules can be equipped with a relatively hypothetical isomer chosen for ANTH(CF) is coinciden Small test-tube-like tip for RI reagent freezing using liquid tally the same as our new compound ANTH-6-1 (there is also nitrogen. The quantities of the reagents can be limited to good agreement between Sun's DFT-predicted EA for this about 80-100 mmol of RFI reagent per one liter of ampoule compound, 2.73 eV. and the experimental value reported volume to limit the internal pressure to about 1,500 torr at the here, 2.81 (2) eV). Note that the first prediction of a linear plot 35 reaction temperature (300-450° C., typically about 360° C.). of DFT-predicted EA vs. number of CF groups was for This translates into about 0.01 mole of starting PAH material CoHo (CF), derivatives (CoHocorannulene; the per one liter of ampoule Volume (producing up to several reported slope is 0.20 eV per CFs). grams of crude PAH(R), product per run per one liter of The X-ray structures reported here reveal two interesting ampoule Volume). After heating for 1-24 hours, the ampoule results potentially relevant to the use of PAH(CF), deriva- 40 is cooled down and opened by cutting the sealed glass tip. The tives for optoelectronic applications. The first feature is that products are dissolved in dichloromethane and worked up the number of CF groups attached to ANTH can significantly using standard techniques. After a wash, the ampoule can be affect the extent to which neighboring molecules interact outfitted with a new seal-off neck and a Teflon glass valve and through their at clouds. A comparison of neighboring pairs of reused. molecules of ANTH-5-1 and ANTH-6-1 is shown in FIG. 6. 45 The reaction temperature and pressure may be varied. The Note that the molecules are offset differently along both the perfluoroalkylation reaction described herein may be con long and short molecular axes (i.e., the pitch and roll angles, ducted in the temperature range between about 200 and about respectively, are different). The difference in slippage along 450° C. It is possible that lower temperatures may be used (for the long axis, ca. 0.6 A for ANTH-5-1 and ca. 4.0 A for example, in the presence of a reaction promoters such as ANTH-6-1, is far greater than along the short axis. Note that 50 copper) for preparation of thermally unstable compounds; the long axis of the aromatic core is 7.3. A for ANTH, so the higher temperatures (up to 800° C. or 1000°C.) may be used pitch distance in ANTH-6-1 is more than half a molecule. for preparation of highly perfluoroalkylated products and/or The second structural feature is that the isomers PYRN-5-1 for tandem perfluoroalkylation/geodesic PAH synthesis. The and PYRN-5-2, which have nearly identical EAS and E. pressure of the reaction may also be varied. In the certain values, and which have four of their five CF groups in com- 55 embodiments described herein, the internal pressure was lim mon positions, have very different relative orientations ited to about 1,500 torr due to the safety requirements of the between neighboring molecules in their respective lattices, as equipment available to the inventors. It should be understood shown in FIG. 6. This leads to significant differences in L-L that much higher pressures (tens of bars and potentially stacking. In PYRN-5-1, the aromatic cores of neighboring higher) may be of high value for economical large-scale prod molecules are essentially parallel but are rotated 45° with 60 uct preparation (for example, due to reactor Volume decrease respect to one another, resulting in the near Superposition of and possible yield improvements). three rings in each molecule. In PYRN-5-2, on the other hand, The PAH can be replaced with polyheterocyclic com the closest parallel neighboring aromatic cores are not pounds, and other perfluoroalkyl iodides can be used in place rotated, have essentially Zero roll distance, and have a pitch of CFI. Those skilled in the art will readily recognize that the distance equivalent to one-half of the distance between 65 scale of the reaction can be increased in a straightforward para-C atoms on the hexagonal rings, resulting in a signifi way, without deviating from the essence of the method cantly offset stacking geometry. described herein. Furthermore, other methods of achieving US 9.249,071 B2 21 22 the required temperature and pressure will be recognized as Reagents and Solvents. wholly consistent with this method. HPLC Grade acetonitrile (Fisher Scientific), trifluorom The methods described herein can be used to prepare both ethyl iodide (Synduest Labs), and polycyclic aromatic hydro known compounds and novel compounds. Examples of carbons (Sigma Aldrich) were used as received. known compounds that can be prepared using the methods 5 Instruments. described herein include the perfluoroalkyl substituted pol HPLC analysis and separation was done using Shimadzu yaromatic hydrocarbons and polyheterocyclic compounds liquid chromatography instrument (CBM-20A control mod described in US Patent Publication No. 2012/0208989 (Sunet ule, SPD-20A UV-detector set to 300 nm detection wave al.). length, LC-6AD pump, manual injector valve) equipped with Uses of Polyaromatic Hydrocarbons and Polyheterocyclic 10 semi-preparative 10-mm I.D.x250 mm Cosmosil Buckyprep Compounds Having Perfluorinated Substituents. column with a corresponding semi-preparative guard column The perfluoroalkylated aromatic compounds described (Nacalai Tesque, Inc.). The atmospheric-pressure chemical herein offer many advantages over non-fluorinated materials ionization (APCI) mass spectra were recorded on 2000 Finni in a variety of different optoelectronic devices such as, but not gan LCQ-DUO mass-spectrometer (CHCN carrier solvent, limited to, organic light emitting diodes, organic field-effect 15 0.3 mL/min' flow rate, analyte samples injected as solutions transistors, organic photovoltaics, organic Solar cells, and in CHCl). Proton and fluorine-19 NMR spectra were -sensitized solar cells. The fluorinated compounds have recorded on Varian INOVA 400 instrument in CDC1 solu processing advantages and are thermally and photochemi tion. Cyclic Voltammetry measurements were carried out on cally stable. The fluorinated compounds also have advantages PAR 263 potentiostat/galvanostat. in tuning the electronic and optical properties of electronic NMR Spectra of Purified PAH(CF), Compounds. devices. The compounds described herein can be used to All NMR spectra were recorded with CDC1 solutions produce oxygen stable n-type semiconductors. For example, using a Varian 400-MR NMR spectrometer. The H and 'F aZulene's unique properties have uses in molecular Switches, frequencies were 400 and 376 MHz, respectively. The 'F molecular diodes, organic photovoltaics, and charge transfer 25 chemical shifts were determined using 1,4-CH (CF) as an complexes. Introduction of electron-withdrawing groups to internal standard (8 -66.35). The H chemical shifts were the azulenic core, such as CN, halogens, and CF3, can determined using the resonance of the residual CHCl in enhance certain electrical and photophysical properties. The CDC1 as an internal standard (Ö 7.27). The purity of the perfluoroalkylated cores of other compounds can be similarly compounds was determined by examining the 'F NMR useful. The compounds can be used in devices such as those 30 spectra, which in general have very narrow resonances, and described in US Patent Publication No. 2012/0208989 (Sunet estimating the level of impurities from any observable low al.). intensity resonances near the baseline. Sources of Polyaromatic Hydrocarbons and Polyheterocyclic General Trifluoromethylation Procedure. Compound Substrates A sample of PAH was placed into a glass ampoule and the Commercially available polyaromatic hydrocarbon sub 35 ampoule was evacuated using a vacuum line equipped with a strates, polyheterocyclic compound Substrates, and perfluo pressure gauge and a calibrated Volume. Using the calibrated roalkyl iodides may be obtained from standard commercial Volume and the pressure gauge, CFI reagent was measured, Sources including Acros Organics (Pittsburgh, Pa.), Aldrich then the ampoule was cooled with liquid nitrogen and the Chemical (Milwaukee, Wis., including Sigma Chemical and 40 measured amount of CFI reagent was condensed into it. Fluka), Eastman Organic Chemicals, Eastman Kodak Com Then the ampoule was flame-sealed. Caution was taken pany (Rochester, N.Y.), Fisher Scientific Co. (Pittsburgh, againstampoule explosion by calculating maximum pressure Pa.), ICN Biomedicals, Inc. (Costa Mesa, Calif.), Lancaster thresholds and using appropriate equipment; bench shields Synthesis (Windham, N.H.). Spectrum Quality Product, Inc. and personal protection were used. See Table 2 for specific (New Brunswick, N.J.), TCI America (Portland, Oreg.), and 45 experimental details; the individual yields of different iso Wako Chemicals USA, Inc. (Richmond, Va.). mers are given below in the descriptions of their purification. The following Examples are intended to illustrate the Purification of ANTH-6-1 and ANTH-6-2. above invention and should not be construed as to narrow its The first stage of purification employed a semi-preparative scope. One skilled in the art will readily recognize that the Cosmosil Buckyprep HPLC column and an ACN eluent flow Examples Suggest many other ways in which the invention 50 rate of 5.0 mL/min. The fraction collected between 9.7 and could be practiced. It should be understood that numerous 11.5 min contained 98+% pure ANTH-6-1 (the purity was variations and modifications may be made while remaining calculated based on the H and 'F NMR data for all of the within the scope of the invention. reported compounds), which was isolated in 20 mol % yield based on the amount of ANTH starting material. The fraction EXAMPLES 55 collected between 6.7 and 7.7 min contained impure ANTH 5-1, which was purified by a second stage of purification, Example 1 which employed an analytical FluoroFlash column and an ACN eluent flow rate of 2.0 mL/min. The fraction eluting Trifluoromethylation of Polyaromatic Hydrocarbons between 4.9 and 6.3 min contained ca. 95+% pure ANTH-5-1, 60 which was isolated in 5 mol % yield based on ANTH. Simple and regioselective high-temperature, Solvent-free, Purification of AZUL-5-1. and catalyst-free reactions of various polyarenes with CFI The crude product mixture was purified by HPLC using the yielded new families of air-stable, robust, and soluble organic semi-preparative Cosmosil Buckyprep column and an ACN acceptors that exhibit significant and remarkably-regular eluent flow rate of 5.0 mL/min' flow rate. The fraction col incremental changes in gas-phase electron affinities as a func 65 lected between 4.7 and 5.6 min contained 98+% pure AZUL tion of the number of CF groups and demonstrate a variety of 5-1, which was isolated in 25 mol % yield based on the crystalline morphologies with L-L stacking. amount of AZUL starting material. US 9.249,071 B2 23 24 Purification of TRPH-6-1. 0.08 at wavelengths at and above the excitation wavelength. The crude product mixture was purified by HPLC using the The calculated quantum yields are: PERY 0.58, PERY-4-1 Cosmosil Buckyprep column and an ACN eluent flow rate of 0.52, PERY-6-1 0.27. 5.0 mL/min' flow rate. The fraction collected between 20.7 and 22.7 min contained 98+% pure TRPH-6-1, which was TABLE 1.1 isolated in 25 mol % yield based on the amount of TRPH starting material. PAH Product Data (results based on mass spectral analysis). Separation of PERY(CF), Compounds. maximum value of in value(s) of The first stage of HPLC purification employed the Cosmo PAHSubstrate n for PAH(CF), products' predominant products 10 sil Buckyprep column and an ACN eluent flow rate 5.0 ANTH 7 5, 6 mL min'. The fraction collected between 5.0 and 5.9 min AZUL 5 5 PENT 8 6 contained impure PERY-6-1; the fraction collected between PERY 7 4, 5, 6 6.9 and 8.0 min contained impure PERY-5-2; the fraction PHEN 6 5 collected between 9.0 and 10.1 min contained impure PERY 15 PYRN 7 5, 6 4-1; the fraction collected between 10.1 and 11.3 min con TRPH 7 6, 7 COOlele 7 6 tained a mixture of PERY-5-3 and PERY-5-4; the fraction Otle 5 4 collected between 11.3 and 12.8 min contained impure fluoranthene 6 5 naphthalene 6 6 PERY-5-1. Each of these fractions underwent a second-stage phenanthroline 3 3 of purification using the FluoroFlash column with an ACN phenazine 5 4 flow rate of 2.0 mL/min. The amounts of purified com phenothiazine 7 6 pounds collected were too small for meaningful yields to be etracene 8 5 iminodibenzyl 7 5, 6 determined (but less than 5 mol %; see Table 1 for purity acridine 6 5 data). TCNQ 3 2 Purification of PYRN(CF), Compounds. 25 indole 4 4 The first stage of HPLC purification employed the Cosmo See FIG, 7 for the structures of coronene and the eight PAH substrates listed below it. sil Buckyprep column and an ACN eluent flow rate 5.0 Determined by atmospheric-pressure chemical ionization mass spectrometry, mL min'. The fraction collected between 3.1 and 5.3 min Iminodibenzyl = 10,11-dihydro-5H-dibenz(b,f)azepine contained impure PYRN-6-1; the fraction collected between 13.3 and 15.0 min contained ca. 95% pure PYRN-5-1; the 30 NMR Chemical Shifts and Coupling Constants of Purified fraction collected between 16.0 and 17.9 min contained a ca. PAH(CF), Compounds. ANTH-5-1. 70:30 mixture of PYRN-5-2 and another isomer tentatively 'F NMR: 8 -50.40 (singlet, 1CF): -63.25 (singlet, labeled PYRN-5-3. The PYRN-6-1 fraction underwent a sec 2CF): -66.78 (singlet: 2CF). H NMR: 69.55 (singlet, 1H): ond-stage of purification using the FluoroFlash column with 35 9.11 (singlet, 2H); 8.23 (singlet, 2H). an ACN flow rate of 2.0 mL/min. The amounts of purified ANTH-6-1. compounds collected, including ca. 95% pure PYRN-6-1. 'F NMR: 8 -51.24 (singlet, 2CF): -63.50 (singlet, were too small for meaningful yields to be determined (but 4CF). H NMR: 89.17 (singlet, 4H). less than 5 mol%). AZUL-5-1. Purification of PHEN-5-1. 40 'F NMR: 8 -54.32 (quartet, J=12.0 Hz, 2CF); -57.98 The crude product mixture was purified using the Cosmosil (septet, J=12.0 Hz, 1CF): -65.44 (singlet, 2CF). H NMR: Buckyprep column and an ACN eluent flow rate of 5.0 89.51 (singlet, 2H); 8.64 (singlet, 1H). mL min'. The fraction collected between 9.9 and 10.5 min PERY-4-1. contained ca. 95% pure PHEN-5-1. The amount collected 'F NMR: 8 -58.11 (singlet, 2CF): -62.74 (singlet, was too small to determine a meaningful yield (but less than 45 2CF). "H NMR: 8.39 (apparent doublet, J=9 Hz, 2H); 8.17 5 mol%). (apparent doublet, J=8 Hz, 2H); 8.10 (multiplet, 4H). Photostability Testing. PERY-5-1. Equal 2.0 mLaliquots of 0.2 mM solutions of perylene and 'F NMR: 8 -57.92 (singlet, 1CF); -58.29 (singlet, PERY-6-1 in CDC1s were put into glass scintillation vials 1CF); -62.28 (singlet, 1CF); -63.20 (singlet, 1CF); under air, tightly capped, and irradiated with a 30W halogen 50 –66.20 (singlet, 1CF). H NMR: 88.63 (singlet, 1H); 8.49 lamp (the vials were placed 10 cm away from the “naked' (singlet, 1H); 8.41 (singlet, 1H); -8.4 (multiplet, 2H); 8.19 light bulb). After 30 min of the exposure HPLC analysis (multiplet, 2H). showed that perylene underwent a complete degradation turn PERY-5-2. ing into at least six different products (based on the HPLC 'F NMR: 8 -58.38 (singlet, 1CF); -58.41 (singlet, analysis; no precipitate formation was observed). The Solu 55 1CF); -62.78 (singlet, 1 CF); -62.82 (singlet, 1CF); tion of PERY-6-1 was unchanged even after three days of -66.54 (singlet; 1CF). H NMR: 88.55 (singlet, 1H); 8.43 irradiation (based on HPLC analysis and F and "H NMR (broad multiplet, 2H); 8.39 (possible singlet, 1H); 8.24 (mul spectrometry results). tiplet, 1H); -8.1 (multiplet, 2H). Fluorescence Quantum Yields. PERY-5-3. Fluorescence quantum yields were measured on an AVIV 60 'F NMR: 8-58.09 (apparent singlet, 1CF); -58.11 (ap ATF-105 Auto-Titrating Differential/Ratio Spectrofluorim parent singlet, 1CF); -62.20 (singlet, 1CF); -63.17 (sin eter which has a 90° measurement geometry. The standard glet, 1CF); -66.17 (singlet; 1CF). H NMR: 88.66 (singlet, used was quinine sulfate in 0.105 M HClO with a quantum 1H); 8.50 (singlet, 1H); -8.4 (multiplet, 3H); -8.2 (multiplet, yield of 0.60 (Velapoldi, R. A.; Mielenz, K. D. NBS Special 2H). Publication 260-64; National Bureau of Standards: Washing 65 PERY-5-4. ton, D.C., 1980). PERY, PERY-4-1 and PERY-6-1 were sepa 'F NMR: 8 -57.93 (singlet, 1CF); -58.11 (singlet, rately dissolved in toluene and the absorbance was at or below 1CF); -58.41 (multiplet, 20Fs): -63.16 (singlet, 1CF). H US 9.249,071 B2 25 26 NMR: the spectrum was difficult to assign due to the low designed for medicinal applications such as drug discovery signal/noise ratio and the presence of broad multiplets. and diagnostic imaging. One example of the importance of PERY-6-1. F NMR: 8 -58.66 (singlet, 2CF): -62.70 perfluoroalkyl modification to drug discovery is the CF (singlet, 2CF): -66.57 (singlet, 2CF). H NMR: 88.64 bearing fluoxetine, ((RS) N-methyl-3-phenyl-3-4-(trifluo (singlet, 2H); 8.48 (singlet, 2H); 8.44 (singlet; 2H). romethyl)-phenoxypropan-1-amine) known as Prozac, one PHEN-5-1. of the most common antidepressants. Another recently 'F NMR: 8 -61.96 (singlet, 1CF): -62.31 (quartet, emerged field for applications of organofluorine compounds J=13.0 Hz, 1CF):-62.56 (quartet, J=13.0 Hz, 1CF):-63.66 is molecular electronics. The incorporation of electron with (singlet, 1CF): -65.69 (singlet, 1CF). H NMR: 89.26 drawing perfluoroalkyl groups in polycyclic aromatic hydro (singlet, 1H); 9.23 (singlet, 1H); 8.82 (singlet, 1H); 8.80 10 carbons (PAHs) has been predicted theoretically and demon (singlet, 1H); 8.41 (singlet, 1H). strated experimentally to yield air-stable n-type organic PYRN-5-1. 'F NMR: 8 -57.59 (quartet, J=19 Hz, 1CF); -58.42 semiconductors with potentially higher electron mobility per (quartet, J–19 Hz, 1CF): -60.30 (singlet, 1CF): -60.74 formance than the non-fluorinated State-of-the-art analogs. (singlet, 1CF): -60.86 (singlet, 1CF). H NMR: 89.12 15 Several methodologies for introducing CF groups into (singlet, 1H); 8.83 (multiplet, 2H); 8.80 (multiplet; 2H). aromatics and heterocyclics have been described in the litera PYRN-5-2 ture (see, for example, Schlosser, Angew. Chem. Int. Ed. (contaminated with ca. 30 mol% PYRN-5-3). F NMR: 8 2006, 45,5432-5446). These reactions typically result in one –57.90 (quartet, J=19 Hz, 1CF): -58.42 (quartet, J–19 Hz, or, more rarely, two CF. Substituents attached to the aromatic 1CF): -60.37 (singlet, 1 CF): -60.71 (singlet, 1CF); substrate. A known exception is hexakis(trifluoromethyl) -63.64 (singlet, 1CF). H NMR: it is difficult to distinguish benzene prepared via a cyclization of three bis(trifluorom between the spectra of PYRN-5-2 and PYRN-5-3. ethyl)acetylene molecules or a reaction of hexaiodobenzene PYRN-5-3 with trifluoromethylcopper. (a likely impurity of PYRN-5-2). F NMR: 8 -57.68 For naphthalene, several mono- and bis-substituted CF (quartet, J=19 HZ, 1CF); -58.30 (quartet: J=19 HZ, 1CF): 25 derivatives have been reported 10a) S. Roy, B.T. Gregg, G. -60.57 (singlet, 1CF): -60.94 (singlet, 1CF); -63.51 (sin W. Gribble, V.-D. Le and S. Roy, Tetrahedron 2011, 67, glet, 1CFs). 'HNMR: it is difficult to distinguish between the 2161-2195; b) F. Bailly, F. Cottet and M. Schlosser, Synthesis spectra of PYRN-5-2 and PYRN-5-3. 2005, 791-797; c) K. Hosokawa and K. Inukai, Nippon PYRN-6-1. Kagaku Kaishi 1972, 383-386; d) K. Hosokawa and K. Inu 'F NMR: 8 -58.25 (quartet: J=18 Hz, 2CF); -58.66 30 kai, Nippon Kagaku Kaishi 1976, 1791-1793; e) K. (quartet, J=18 Hz, 2CF), -60.95 (singlet, 2CF). "H NMR: Hosokawa, S. Fujii and K. Inukai, Nippon Kagaku Kaishi H NMR: 89.07 (singlet, 2H); 8.80 (singlet, 2H). 1979, 294-296: f). K. Hosokawa and K. Inukai, Nippon TRPH-6-1. Kagaku Kaishi 1977, 1163-1167; g) T. C. Klebach, L. A. M. 'F NMR: 8 -57.21 (singlet, 1CF): -62.32 (multiplet, Turkenburg and F. Bickelhaupt, Tetrahedron Lett. 1978, 19. 2CF); -62.51 (roofed quartet, J=11 Hz, 1CF); -62.64 35 (roofed quartet, J–11 Hz, 1CF); -65.78 (singlet; 1CFs). H 1099-1 100. while only one highly substituted derivative NMR: 89.19 (singlet, 1H); -9.1 (multiplet, 4H); 8.49 (sin (2,3,6,7-tetrakis-(trifluoromethyl)naphthalene) has been glet, 1H). reported (Krespan et al., J. Am. Chem. Soc. 1961, 83, 3428 X-Ray Structures. 3432). Syntheses of mono- and bis-(trifluoromethyl)naphtha Seven X-ray structures determined in this work have had 40 lenes have been typically accomplished via multi-step reac their.ciffiles deposited with the Cambridge Crystallographic tions: i) “assembly' of the naphthalene core from CF Data Center (CCDC). These seven structures are for pure bearing organic precursor molecules (using Friedel-Crafts compounds and do not contain solvent molecules: ANTH-5- intramolecular cyclization or Diels-Alder cyclization with 1, PERY-4-1, PERY-5-1, PHEN-5-1, PYRN-5-1, PYRN-6-1, CF-carrying benzyne intermediate to form the naphthalene and TRPH-6-1. In addition, five preliminary X-ray structures 45 core); ii) fluorination of naphthalene derivatives bearing Suit have been determined in this work. The data are of sufficient able CF “precursor groups (fluorination of naphthoic acids quality to determine the addition patterns of the molecules by SF or fluorination of (naphthalene)methyldithiocarboxy and the nature of the Solid-state packing, but have R factors lates by H.F. fluorine source and 1,3-dibromo-5,5-dimeth greater than 20% and therefore have not been deposited with ylhydantoin (DBDMH) oxidize); and iii) direct substitution the CCDC. Better data sets are being collected, and these 50 of iodine in various iodonaphthalenes with CF group(s) structures will be deposited with the CCDC in due course. using (trifluoromethyl)copper generated in situ. Plots of ANTH(CF), and PYRN(CF), Electron Affinities In this Example, we report a simple and highly efficient VS. N. alternative approach: Substitution of multiple aromatic The plots in FIG. 7 are based on the experimental gas-phase hydrogen atoms in naphthalene with R. radicals generated electron affinities determined in this work (cf. the corre 55 sponding graph for PERY(CF), compounds in FIG. 4). Note by thermolysis of RI precursors (R—CF, CFs, n-CF7, that the uncertainties for the experimental electron affinities, and n-CF). shown by brackets, are smaller than the data points. Results and Discussion. Synthesis and Characterization. Example 2 60 The perfluoroalkylation reactions were accomplished by reacting eight equivalents of RI (R—CF, CFs, n-CF7, or Single-Step Gas-Phase Polyperfluoroalkylation of n-CF) with one equivalent of naphthalene at 300° C. for 3 Naphthalene hours in sealed Pyrex glass ampoules, as shown in Scheme 2.1. Complete vaporization of naphthalene was observed at Fluorine or perfluoroalkyl Substituents strongly augment 65 ca. 150° C. before any visible formation of iodine due to R.I physicochemical and biological properties of organic dissociation, indicating that the perfluoroalkylation took molecular substrates. Organofluorine compounds have been place fully in the gas phase. US 9.249,071 B2 27 28 yield (calculated relative to the starting naphthalene). The Scheme 2.1. Gas phase perfluoroalkylation of napthalene (n = 1-6). compositional purity was confirmed by NI-APCI mass spec trometry. As mentioned above, isolated low- RFI N samples readily formed molecular anions NAPH(R), when -- --(RF) chemically reduced by TDAE in solution. Notably, partial 300° C. 2 fragmentation due to loss of one and two HF molecules was observed for NAPH(CFs) and NAPH(n-CF) and for NAPH(n-CF). Proton and fluorine-19 NMR spectroscopy revealed the 10 isomeric purity of the isolated compounds, which possess the After the removal of iodine (with an aqueous NaSO idealized C, symmetry, thus allowing for unambiguous wash), the crude off-white solid products were weighed, dis structural assignment for the 1.3.5.7-pattern of R groups for solved in 3.0 mL of 5.3 mM solution of (n-Bu)NBF in all four isolated compounds; see FIG. 12 and for NMR data CDC1s, and analyzed by quantitative Hand 'F NMR spec and FIG. 13 for NAPH core numbering scheme. troscopy. Due to the presence of (n-Bu)NBF internal stan 15 Preliminary studies of the remaining soluble fractions after dard, the relative molar concentrations of aromatic H atoms the extraction of NAPH(R) compounds were carried out, and R groups could be determined via integration of the which determined the presence of several isomers of NAPH NMR spectra (Dolbier, W. R. Guide to Fluorine NMR for (R), where n=2 or 3, in agreement with the NMR data on the Organic Chemists, John Wiley & Sons, Inc., New Jersey, average molecular compositions (see Table 2.1). While the 2009). This information was used to determine the average number of R groups per NAPH core, which, in turn, allowed use of an HPLC method for separation of NAPH(CF) and us to calculate the total molar yield of crude products; see NAPH(n-C.F.), has not yet been optimized, one isomer of Table 2.1. No unreacted naphthalene was detected in any of NAPH(CFs) and one isomer of NAPH(CFs) were isolated the four crude products by H NMR spectroscopy, which with high purity, and tentative structural assignments were demonstrates the completeness of the naphthalene conver proposed for them and for the second identified abundant 25 isomer of NAPH(CFs) based on NMR and DFT data. S1O. DFT Relative Energies of NAPH(R). To determine possible Substitution patterns of R groups TABLE 2.1 for NAPH, we have performed DFT computations for all Molar yields of crude NAPHRF), products. isomers of NAPH(CF), (n=1-4) at the DFT level of theory. 30 Complete list of isomers and their relative energies were molar yield of average prepared. The main trends are as follows. Unsubstituted product R. crude NAPH(RF), 96 n(RF) per NAPH core NAPH has two types of C(H)atoms, C1 and symmetry related A. CF 80 15 2.4 + 0.1 C4, C5, and C8 (designated them as an a-type position) and B C2Fs 701S 23 O.1 position C2 and related C3, C6, and C7 (denoted as b), as C n-CF7 95 - 10 1.90.1 35 shown on FIG. 13. D n-C4Fo 95 - 10 1.90.1 An increase of the number of attached CF groups results in the rich variety of their relative positions and hence possible Negative ion atmospheric pressure chemical ionization isomers. From ten possible isomers of NAPH(CF), the most (NI-APCI) mass spectrometry has been applied to determine stable ones are those which combine two CF groups in dis the maximal Substitution degree in Samples A-D. Earlier, 40 tant b-type positions (isomers 2.6 and 2.7 are isoenergetic NI-APCI mass spectrometry was found to be highly effective within 0.3 kJ/mol). They are followed by three isomers com for the direct analysis of perfluoroalkylation products of bining a and b-type groups (1.3, 1.6, and 1.7 with relative larger PAHs, but the analogous mass spectrometry analysis of energies of 8, 6 and 7 kJ/mol, respectively) and then by two products A-D required use of a reducing agent (tetrakis(dim isomers with only a-type distant positions (1.4 and 1, 5 with ethylamino)ethylene (TDAE) to generate NAPH(R), 45 AE of 16 and 13 kJ/mol). It can be seen that when CF groups anions. Treatment with TDAE, which has an ultra-low ion are at distant positions (i.e., do not interact), relative energies ization potential of 5.3 eV. led to the color change from a very can be roughly rationalized as a number of groups in position pale-yellow color to a pale-green (for R-CF) or to a dark a times an increment of ca.7 kJ/mol. However, when two CF yellow (for R=CFs, n-CF7, and n-CF) color suggesting groups are close enough to interact, such interaction signifi the formation of NAPH(R),. radical anions. Indeed, these 50 cantly destabilized the structures. The isomer 2.3 with two chemically reduced NAPH(R), samples produced mass neighboring CF groups in adjacent b-type positions has an spectra shown on FIG. 11, in which the maximum number of energy of 25 kJ/mol, two CF groups in adjacent a and b R substituents was five for R=CF and four for R, CFs, positions 50 kJ/mol, whereas the least stable isomer has two n-CF7, and n-CF. Lower-mass peaks due to loss of HF CF groups in close a-type position (1.8). In the latter, naph have been observed more prominently for R=CFs. Their 55 thalene framework is non-planar to avoid close CF. . . . CF fragmentation origin was established upon analysis of the COntactS. purified compounds. The lower degree of perfluoroalkylation Three CF groups can be arranged in NAPH(CF) in 13 observed for the longer-chain R groups is consistent with different ways, and the relative energies of these isomer span their larger steric requirements in comparison to CF groups. the range of 106 kJ/mol. Because it is impossible to arrange Perfluoroalkylation resulted in significant changes in 60 all three groups inb-type position and avoid close CF ... CF physical properties compared to the parent naphthalene. For contacts, the lowest energy isomers are those combining one example, solubility of tetra-substituted derivatives NAPH a-type and two b-type groups (1.3.6 and 1.3.7). These isomers (R) in polar solvents was strongly reduced compared to bis are followed by two isomers with two a-sites and one b-site and tris-derivatives. The finding allowed us to develop a (1,3,5 and 1.4.6: AE=8 kJ/mol for both isomers). All other simple and efficient method of isolation of 95+%-pure NAPH 65 isomers have at least one pair of neighboring CF groups and (R) compounds from the crude materials using fast and hence are less stable. From them, the most stable is isomer simple precipitation/wash protocols with ca. 5-10 mol % 2.3.6 with relative energy of 18 kJ/mol followed by the isomer US 9.249,071 B2 29 30 1.2.6 whose relative energy is already 42 kJ/mol. The least TABLE 2.2 stable isomers have three groups in neighboring positions Melting points and Sublimation rates of NAPH, 1,3,5,7- (1.2.3 and 1.2.8). NAPH(CF) and 1357-NAPH(C-Fs) at 25.0°C. The largest number of isomers in the whole NAPH(CF), melting point, Sublimation rate, series, 21, is possible for n=4. However, four CF groups are compound o C. |imol min' already too crowded, and 1,3,5,7-NAPH(CF) is the only NAPH 7S.O-78.O 3.6. 102 isomer without adjacent CF groups. The second most stable 1,3,5,7-NAPH(CF). 99.0-99.8 3.7. 103 isomer with AE of 16 kJ/mol has CF groups in 1.3.6.7 posi 1,3,5,7-NAPH(CFs). 88.S-89.0 7.3. 104 tion, whereas the earlier reported 2,3,6,7-NAPH(CF) is the 10 third most stable isomer with the relative energy of 33 kJ/mol. Cyclic Voltammetry. The energies of other isomers span the range of 41-142 Electrochemical properties of 1,3,5,7-NAPH(R) kJ/mol. It is clear that the 2,3,6,7-isomer was a kinetic product (R=CF, CFs, n-CF7, and n-CF) were studied by cyclic whose structure was directed by the synthetic pathway 15 voltammetry and square-wave voltammetry in 0.1 M solution (Krespan et al., J. Am. Chem. Soc. 1961, 83, 3428-3432). of (n-Bu)NCIO in dry deoxygenated dimethoxyethane Conversely, the high temperature synthetic method used in under inert atmosphere; see FIG. 16. The compounds dis this work tends to give thermodynamic products. played a quasi-reversible first reduction except for 1,3,5,7- X-Ray Structures. NAPH(n-CF) which was difficult to assess due to its low solubility in dimethoxyethane. The first reduction potentials The structures of 1,3,5,7-NAPH(CF) (FIG. 14) and 1.3, 5,7-NAPH(CFs). (FIG. 15) were unambiguously confirmed of 1,3,5,7-NAPH(R) were anodically shifted by 1.46, 1.45, by the single-crystal X-ray diffraction study. The molecular 1.53, and 1.52 V from naphthalene for R=CF, CFs, n-CF7, and n-CF, respectively. It should be noted that the structure of 1,3,5,7-NAPH(CF) is more planar and less dis 25 electron-withdrawing effects of different R groups cannot be torted than expected, and with an interesting packing motif. compared directly using only the data on the first reduction The distances between the closest overlapping parallel planes potentials due to differences in the solvation energies. For of the naphthalene cores of 1,3,5,7-NAPH(CF) are example, our earlier study of 1.7-Co (R) compounds decreased to 3.75 A or 4.23 A from 6.77 A in the parent 30 showed how solvation energy differences can compensate the naphthalene. The addition of the CF groups increases the higher electron affinity of the molecules bearing longer R. intermolecular interactions through a F-H close contact of groups, leading to equalization of the observed solution 2.631 A and a F-to-naphthalene centroid distance of 3,089 A phase first reduction potentials across the series of different which pulls the molecules within a layer of parallel oriented R substituents. It is notable that earlier studies of R-substi naphthalene molecules closer together. 35 tuted perylene diimides and R-substituted nitrobenzenes The overall packing structure of the CF groups in one showed negligible differences in the first reduction potentials layer of molecules point towards each other creating a chan between molecules bearing different R groups, which may nel between layers of 1,3,5,7-NAPH(CF), the rings also be due to the similar “equalizing effect of solvation energy. between layers are rotated 83.6° (increased from 50.7° in 40 naphthalene) from planes of adjacent layers, but the naphtha The overall shift in E of 1,3,5,7-NAPH(R) relative to lene cores are rigorously parallel within their respective lay NAPH (ca. 1.5 V) is surprisingly big, especially when com ers. When rotated 90° about the central horizontal, it exhibits pared to the 0.95 V shift of E observed for the penta(trif the common herringbone pattern. The addition of the CF luoromethyl)corannulene Cs-CoH (CF), or 0.2V shift in 45 tetrakis(trifluoromethyl)fullerene Co(CF), relative to their groups to naphthalene increases intermolecular interactions respective parent molecules. This suggests that the electron between CF groups and naphthalene cores. The increase in withdrawing effect of the R groups may vary greatly for R. moiety length to the NAPH(CFs) compound creates organic substrates of different sizes and structures. Earlier packing with distinct naphthalene regions and perfluoroethyl DFT calculations performed on the series of fluorinated and regions (see FIG. 15). The closest distance between overlap 50 trifluoromethylated agree with these findings: the ping parallel planes of NAPH(CFs) is 10.575A. There are largest incremental shift in reduction potential and electron 3 different orientations of the naphthalene cores in NAPH affinity was found for benzene, followed by naphthalene, and (CFs), and it is evident that the structure is dominated by the then larger acenes. rigid CFs moiety rather than by any other interactions. 55 The observed large enhancement in electron accepting The melting points and the Sublimation rates of naphtha properties of NAPH(R), in solution helps explain the fact lene, 1,3,5,7-NAPH(CF), and 1,3,5,7-NAPH(CFs) were that peaks due to NAPH(R)s were not observed mass spec measured (see Table 2.2 and experimental details below). The trometrically in samples A-D (FIG. 11), despite the “fluoro highest melting point was observed for 1,3,5,7-NAPH(CF), philicity” based HPLC analysis and NMR evidence (Table followed by 1.3.5.7-NAPH(CFs), and then naphthalene. 60 2.1) that they represent the bulk of the crude products. This is The sublimation rates were measured in the TGA instrument likely due to i) their low electron affinity (EA) (or reduction at 25.0° C. under a constant stream of nitrogen, and were potentials in solution) and ii) presence of the species with found to decrease from naphthalene to 1,3,5,7-NAPH(CF). significantly higher EAS in these crude samples (i.e., NAPH to 1,3,5,7-NAPH(CFs), in accord with their molecular 65 (R)). A strong correlation between the EA of an analyte and weights. Volatility of pentafluoroethyl naphthalene deriva its ionization efficiency under NI-APCI conditions as well as tives were reported to contribute to lower isolated yields. the Suppression of the signals from less electronegative mol US 9.249,071 B2 31 32 ecules is well documented in the literature. The results of Conclusions. earlier theoretical and experimental data showed that EAs of An efficient synthetic approach for the preparation of poly(trifluoromethyl)PAHs increase roughly proportionately highly perfluoroalkylated naphthalenes that possess pro to the number of CF substituents. Using the calculated EA nounced electron acceptor properties compared to underiva values of NAPH (-0.511 eV) and hypothetical NAPH(CF). tized naphthalene (which has a negative EA of -0.5 eV) was (3.262 eV), the mean EA increase of 0.47 eV/n(CF) in developed. A non-chromatographic isolation of the new four NAPH(CF), can be calculated. Therefore the estimated symmetric tetrakis-derivatives provides easy access to these EA(NAPH(R)) values for n=2 (0.432 eV) and n=3 (0.904 new molecules for further studies. Additionally, we demon eV) are apparently too low for these species to be observed in 10 NI-APCI mass spectrometry, even with TDAE-assisted strated applicability of the HPLC method developed earlier chemical reduction. At the same time, the peak due to NAPH by us for separation of perfluoroalkyfullerenes, for the isola (CF) (with the estimated EA(NAPH(CF)) of ca. 1.84 tion of high-purity single isomers of NAPH(CFs). Cre eV) is likely to be overrepresented in the mass spectrum ation of versatile libraries of novel naphthalene derivatives in compared to its real content in the crude mixture (FIG. 11, top 15 the wide range of compositions, structures, and electrochemi left). cal properties that will serve as important building blocks and As mentioned above, literature experimental data on the active components in biomedical, electronic, and materials synthesis of polysubstituted perfluoroalkylnaphthalenes are studies is currently underway in our laboratories. This “tour very scarce, even less is known about their electronic prop de force' approach to perfluoroalkylation of naphthalene erties. A thorough literature search resulted in only one rel organically complements existing elaborate and elegant solu evant publication, which, as we found, has never been cited tion chemistry, which is mostly focused on (and capable of) outside Russian-language journals. Twenty-five years ago, regioselective preparations of mono- and/or di-substituted Yagupolsky and coworkers showed that consecutive two, perfluoroalkyl derivatives. three, or four hydrogen substitutions (into 1, 4, 5 and/or 8 25 positions) with 'R-CF and/or —O—CF groups in naph Experimental Section. thalene lead to positive shifts in reduction potentials of 0.77. Perfluoroalkylation of Naphthalene. 1.16, and 1.44V vs. naphthalene, respectively (Dunyashev et A flame-dried reactorampoule made out of Pyrex glass (40 al., Zhurnal Obshchei Khimi 1988, 58, 200-202). This leads 30 mL internal Volume) and equipped with a sealing neck and a to an incremental shift of E/n(R)=0.29 V for 14.5.8- 90-degree Teflon vacuum valve was charged with naphtha NAPHCR), whereas a larger increment E/n(R)-0.37 lene (20 mg, 0.16 mmol). Eight equivalents of a perfluoro 0.38 V was determined in our study for 1,3,5,7-NAPH(R) alkyl iodide reagent R.I was either measured using a PVT isomers. method and condensed into the liquid nitrogen-cooled reactor 35 ampoule (R=CF, n-CFs, gaseous reagents at room tem TABLE 2.3 perature), or measured using a 500 uL gas-tight Syringe First reduction potentials E2 (cyclic voltammetry) (Rin-CF7, n-CF; liquid reagents at room temperature). and peak potentials (square-wave voltammetry) for The E° of naphthalene and 1,3,5,7-NAPH(R) compounds The ampoule was cooled in liquid nitrogen and all non-con relative to Fe(CD)' defined as O.O.V. 40 densable gases were evacuated, then the ampoule was flame Compound E12, V 1 peak potential, V sealed and heated in a tube furnace at 300° C. for 3 hours; see Table 2.4. After heating, the ampoule was cooled to room NAPH -3.08 -3.05 NAPH(CF). -1.62 -1.64 temperature. Each of the experiments A-D (Table 2.4) was NAPH(C2Fs) -1.63 -1.59 45 repeated at least twice, yielding practically identical product NAPH(CF7). -155 -1.56 compositions (as determined by H and 'F NMR spectros NAPH(CF). -1.56 -1.56 copy). Two batches of products underwent different work-up procedures, as described further below. TABLE 2.4

Reaction conditions used for naphthalene perfluoroalkylation and mass of crude NAPH(R), products.

RI reaction reaction n(NAPH), n(RI), m(crude product), eXp. reagent temperature, C. time, min mmol mmol ng

300 18O 0.157 1.36 70 300 18O 0.157 1.34 45 300 18O O.163 1.30 69 300 18O O.16S 1.31 91

The mass was determined upon concentrating the crude product mixture to dryness under a stream of air, US 9.249,071 B2 33 34 Crystallography. (-10° C.260° C.:-0.1° C.) and a heating rate of ca. 1-2 The X-ray quality single crystals of 1,3,5,7-NAPH(CF). C./min: all samples were sealed in 1.0x90 mm melt point and 1,3,5,7-NAPH(CFs) were grown by slow evaporation capillary tubes. Sublimation rate studies were performed of their CS and CDC1 solutions, respectively (at room tem using TA Instruments Series-2950 instrumentation. Prior to perature). Both compounds formed clear colorless crystals. each TGA experiment, the platinum pan was rinsed with ethyl DFT Calculations. alcohol and flamed three times (until dull red glow). Upon Atomic coordinates of all studied molecules were first sample loading, care was taken to distribute the sample optimized at the PBE/TZ2P level using Priroda code then evenly over the aluminum pan Surface. During the Sublima followed by B3LYP-D3/def2-TZVP computations per tion rate experiments, TGA temperatures were set at 25.00° formed using ORCA suite. 10 Abbreviations. C. and held isothermally throughout the experiment. TGA, thermogravimetric analysis; NI-APCI, negative ion The X-ray crystallography data were collected using a atmospheric pressure chemical ionization; PAH, polycyclic Bruker Kappa APEX II CCD diffractometer employing Mo aromatic hydrocarbons; NAPH, naphthalene. KC. radiation and agraphite monochromator. Unit cellparam Experimental Details. 15 eters were obtained from least-squares fits to the angular Reagents and Solvents. coordinates of all reflections, and intensities were integrated Naphthalene (Sigma Aldrich, 99%), iodotrifluoromethane, from a series of frames (up and protation) covering more than iodopentafluoroethane, 1-iodoheptafluoropropane, 1-io a hemisphere of reciprocal space. Absorption and other cor dononafluorobutane (SynOuest Labs), sodium thiosulfate rections were applied using SCALE (G. M. Sheldrick, SAD (NaSO, Fisher Scientific, ACS grade), tetrakis(dimethy ABS, v.2.10 a program for area detector absorption correc lamino)ethylene (TDAE, Sigma-Aldrich), chloroform-d tions, Bruker AXS, Madison, Wis., 2003). The structures (CDC1, Cambridge Isotopes), 1,4-bis-(trifluoromethyl)ben were solved using direct methods and refined (on F, using all Zene (Sigma Aldrich), tetrabutylammonium tetrafluoroborate data) by a full-matrix, weighted least-squares process. Stan ((n-Bu), NBF, Sigma-Aldrich), dichloromethane (Fisher dard Bruker control and integration software (APEXII) was Scientific, ACS grade), carbon disulfide (Alfa Aesar, HPLC 25 employed (G. M. Sheldrick, Crystallography Program grade), acetonitrile (Fisher Scientific, ACS grade), APEX2, v.2.0-2, Bruker AXS, Madison, Wis., 2006), and (technical grade) were used as received. Deionized distilled Bruker SHELXTL software was used for structure solution, water was purified by a Barnstead NANOpure Ultrapure refinement, and molecular graphics (G. M. Sheldrick, Crys Water system (final resistance 18 MS2). Dimethoxyethane tallography Software Package SHELXTL, V, 6.12 UNIX, (Sigma-Aldrich, distilled from CaFI under nitrogen atmo 30 sphere), ferrocene (Acros Organics, 98%), and tetrabutylam Bruker AXS, Madison, Wis., 2001.). monium perchlorate (Sigma-Aldrich, dried at 80° C. under NMR Determination of Mol % Yield of NAPH(R), and dynamic vacuum for 24 hours) were used for electrochemical the Average Number of R. Groups Per Naphthalene Core measurementS. (n(R)). Instrumentation. 35 The ampoules containing products A-D were cooled in HPLC analysis and separation were carried on a Shimadzu acetone/dry ice bath, cut open under air, and quickly evacu instrument (composed of Shimadzu LC-6AD pump, a Shi ated to remove the highly volatile R.I., R.H., and (R) com madzu UV detector SPD-20A set for 300 nm detection wave ponents. Then the ampoules were allowed to warm up, the length, and a communication bus module Shimadzu CBM crude products were dissolved in 3-5 mL of CDC1, and the 20A). The instrument was equipped with a FluoroFlash 40 resulting Solutions were washed with aqueous a 1MNa2SO column (Fluorous Technologies, Inc., PF-C8, 5 um): 90/10 solution to remove 12 (only trace amounts of insoluble black Viv mixture of acetonitrile/water was used as the eluent at a carbonaceous materials were present in each product). The flow rate of 2 mL/min. organic layer (bottom layer) was extracted and the solvent Proton (400MHz) and fluorine-19 (376 MHz) NMR spec was quickly evaporated under a stream of dry air. Despite the tra were recorded on a Varian INOVA instrument in CDC1 45 great care taken to limit the losses of the NAPH(R), products solution using 1,4-bis-(trifluoromethyl)benzene (ö('F)=- due to evaporation at this step, it is virtually certain that some 66.35: 8(H)=7.77) as the internal standard. losses were incurred. The resulting dry products were dis Negative-mode atmospheric pressure chemical ionization solved in 3.0 mL of 5.3 mM solution of (n-Bu)NBF in mass spectrometry analysis was performed on a 2000 Finni CDC1. 750 uL aliquots of these solutions were analyzed by gan LCQ-DUO mass-spectrometer using CHCN carrier sol 50 'Hand 'F NMR spectroscopy using the following acquisi vent at 0.3 mL'min' flow rate. The samples were dissolved in tion parameters: dry deoxygenated acetonitrile in a nitrogen-atmosphere 'F NMR: 25s relaxation delay, 45° flip angle, acquisition glovebox and treated with a small amount (1-2 drops) of time=2.000s, 32 scans tetrakis(dimethylamino)ethylene solution in acetonitrile in H NMR: 25s relaxation delay, 45° flip angle, acquisition order to generate negative ions (a few drops ofTDAE solution 55 time=2.556 s, 32 scans were added to the samples which changed color from color Using the integrated intensity of H and 'F NMR peaks less to pale-yellow). due to (n-Bu)NBF standard and NAPH(R), products, the Cyclic Voltammetry measurements were carried out on a molar concentration of aromatic protons and the molar con PAR 263 potentiostat/galvanostat using an electrochemical centration of R groups of NAPH(R), were calculated. The cell equipped with platinum counter and working electrodes 60 total number of R groups and aromatic protons in any NAPH (0.125 mm diameter) and a silver reference electrode (0.5 mm (R), product is equal to eight; therefore, the combined molar diameter). The samples were dissolved in a 0.1 MTBACIO concentration of all NAPH(R), products is equal to the sum Solution in dimethoxyethane; the cyclic Voltammetry was of the molar concentration of aromatic protons and the molar performed at 500 mV.'s scan rate, unless otherwise indi concentration of R groups divided by eight, which allows to cated, and referenced versus ferrocene internal standard. 65 calculate the total number of moles of NAPH(R), products. Melting points were determined using a Laboratory It is notable that no traces of unreacted naphthalene were Devices MeI-Temp instrument with a mercury thermometer observed in the products A-D by H NMR spectroscopy. US 9.249,071 B2 35 36 Isolation of NAPH(R) Products. Example 3 Separate batches of crude materials prepared under condi tions A-D (see Table 2.4) were used to isolate isomerically Poly(Trifluoromethyl)AZulenes: Structures and pure NAPH(R) materials. In all cases the ampoules were Acceptor Properties open under air, the products were dissolved in 3-5 mL of 5 dichloromethane, and the resulting Solutions were washed Six new poly(trifluoromethyl)aZulenes prepared in a single with 1 M aqueous solution of NaSO, to remove I. The high-temperature reaction exhibit strong electron accepting resulting solution was rapidly concentrated to dryness under properties in the gas phase and in Solution and demonstrate a flow of dry air. propensity to form regular t-stacked columns in the donor 10 acceptor crystals, when mixed with pyrene as a donor. NAPH(CF). AZulene is a non-alternant, non-benzenoid aromatic The concentrated crude material resulting from experiment hydrocarbon with an intense blue colour, a dipole moment of A (see Table 2.4) was dissolved in ca. 2 mL of 90/10 (v/v) 1.0D, positive electron affinity, and an “anomalous' emission acetonitrile/water mixture; NAPH(CF) precipitated out and 15 from the second excited state in violation of Kasha's rule. was filtered through a pipette with a plug made of a glass AZulene's unique properties have potential uses in molecular microfiber filter. The filter was washed with ca. 1 mL of 90/10 Switches, molecular diodes, organic photovoltaics, and (v/v) acetonitrile/water mixture; then the purified NAPH charge transfer complexes. Introduction of electron-with (CF) was dissolved in CDC1, and analyzed by H and 'F drawing groups to the azulenic core, such as CN, halogens, NMR spectroscopy, and NI-APCI mass spectroscopy which and CF, can enhance certain electrical and photophysical demonstrated 95+% molar purity, see below. properties. NAPH(CFs). In this work, we report six new trifluoromethyl derivatives The concentrated crude material resulting from experiment of azulene (AZUL), three isomers of AZUL(CF) and three B (see Table 2.4) was washed several times with 50-100LL of isomers of AZUL(CF), and the first X-ray structure of a dichloromethane. The remaining white CHC1-insoluble 25 IL-Stacked donor-acceptor complex of a trifluoromethyl azu material was dissolved in CDC1 and analyzed by F and "H lene with donor pyrene. NMR spectroscopy, HPLC analysis, and APCI mass spec In sharp contrast to the commonly applied multi-step solu tion-based methods of hydrogen substitutions in AZUL with trometry which showed it to be 95+% pure NAPH(CFs), see electron withdrawing groups such as CN or Hal, in this work, below. 30 we prepared all AZUL(CF), compounds in a rapid single NAPH(n-CF). step reaction carried out in the gas phase. AZulene and CFI The concentrated crude material resulting from experiment gas were loaded into a sealed glass ampoule and heated in a C (see Table 2.4) was mixed with 500-1000 uL of absolute furnace to 300° C. for 15 minutes to produce mostly a mixture ethanol. A system with two immiscible liquid layers was of aZulene(CF), (n=3-5), as shown by negative-ion atmo formed; the yellow oil blob was separated and concentrated to 35 spheric-pressure chemical ionization mass spectrometry dryness under the flow of dry air. The resulting yellow solid (APCI-MS). The crude reaction mixture also contained small was washed three times with 250-500 uLofdichloromethane amounts of CoH2(CFs)6 and dimers (C20H16-1 (CFs), 7. leaving behind a white insoluble material. This material was 8,9). Formation of the thermally stable dimeric AZUL species dissolved in CDC1 and analyzed by F and "H NMR spec 40 in Such high-temperature reactions has not been previously troscopy, and APCI mass spectrometry which showed it to be reported and deserves further studies, particularly due to the 95+% pure NAPH(n-CF), see below. relatively high electrical conductivity observed for polymeric AZUL. Doubling the reaction time resulted in more selective NAPH(n-CF). formation of AZUL-5-1 (see Kuvychko et al., Angew. Chem. The concentrated crude material resulting from experiment 45 Int. Ed. Engl., 2013, 52,4871-4874). D (see Table 2.4) was diluted with 1-2 mL ofdichloromethane The crude reaction mixture of the 15-minute reaction was and filtered through a pipette with a plug made of a glass separated by HPLC, yielding seven pure AZUL(CF), deriva microfiber filter. The insoluble material was washed twice tives, i.e., three isomers of AZUL(CF), three isomers of with a minimum amount of dichloromethane; then it was AZUL(CF) and one isomer of AZUL(CF) (for isomer dissolved in ca. 4 mL of CDC1. The solution was analyzed 50 notations see Scheme 3.1). with F and H NMR spectroscopy, and NI-APCI mass spectrometry which showed that it contained 95+% pure NAPH(n-CF), see Table 2.5 below. Scheme 3.1. Synthesis of AZUL(CF3)3-5.

TABLE 2.5 55 10 CFI, 300° C., 15 min Concentrations of R and hydrogen Substituents for H NAPH(R). Solutions and molar wields of NAPH(R roducts. sealed ampoule R, H, n(NAPH(R).), yield of NAPH(R), eXp. R mM mM Imol mol% 60 R7 R A. CF 98 230 123 79 - 15 B C2Fs 87 210 111 701S C n-CF7 95 310 152 95 - 10 D n-CF 1OO 310 154 96 - 10 R6 O) R 160 umol of naphthalene starting material was used for each perfluoroalkylation experi 65 ment, Rs R3 US 9.249,071 B2 37 38 -continued were grown by slow evaporation from dichloromethane and hexane solutions, respectively. AZUL-4-1 crystallizes in the P-1 space group with three molecules per unit cell. One molecule is ordered while the other two molecules are disor dered, adopting opposite orientations at a given site. This disorder is typical and has been observed for azulene and aZulene derivatives. Disorder in the azulene core is not & 8 observed in the structure of AZUL-4-2; however, the fluorine atoms of the CF group attached to C5are disordered around 10 AZUL-5-1 AZUL-4-1 the attached carbon atom. 1,2,3,5,7-C10H3(CF3)5 1,3,5,7-CoH (CF3)4 The UV-vis absorption spectra of the seven poly(trifluo 9.0% 9.5% romethyl)aZulene derivatives were obtained in hexanes and dichloromethane. Unlike azulene, where the S states become CF3 more refined in hexanes vs. dichloromethane, the solvent 15 choice had little or no effect on the absorption spectra of the trifluoromethyl derivatives. Theoretical and experimental O) CF studies by Liu et. al. showed that electron withdrawing groups on odd-numbered carbon atoms blue-shift the 51 maxima by CF lowering the HOMO energy while the LUMO energy remains relatively unchanged (Shevyakov, et al., J. Phys. Chem. A, AZUL-4-3 2003, 107,3295-3299). AZUL-4-2 1,2,3,6-C10H4 (CF3)4 Indeed, the absorption maxima in the 51 band for all seven 1,2,3,5-C10H4(CF3)4 0.7% 3.1% of the trifluoromethyl azulenes are blue shifted by 26-57 nm CF3 CF (see Table 3.1). All seven derivatives have CF, substituents at 25 the C1 and C3 positions which plays a large part in blue shifting the maxima. Two compounds (AZUL-3-2 and AZUL-4-3) have a CF group bonded to an even-numbered O) FC O) C6 atom, which would likely cause a smaller blue shifts (26 and 27 nm), and is in agreement with the earlier prediction FC CF CF 30 that electron withdrawing groups on even-numbered carbon atoms lower the LUMO energy. Electron withdrawing groups AZUL-3-1 AZUL-3-2 1,3,5-C10Hs (CF) 13,6-C10Hs(CF3)3 should lower the HOMO and LUMO-1 energy by nearly the 1.6% O.6% same amount since the electron distributions of the HOMO CF and LUMO--1 are virtually identical, so shifts in the absorp 35 tion maxima in the S region are not expected to be as pro nounced as the S region. Absorption maxima shifts in the S. regionare, in fact, very minor and even slightly red-shifted for O) CF one compound, AZUL-4-1.

CF 40 TABLE 3.1 AZUL-3-3 Absorption maxina for AZUL derivatives in hexanes (nm). 1,2,3-C10Hs (CF3)3 0.5% Compound via (So-S2) Anax via (So-S1) Anax 45 AZUL 341 579 AZUL-3-1 338 -3 532 -47 Abbreviations, full names, and isolated yields are given. The AZUL-3-2 334 -7 553 -26 X-ray structures of AZUL-5-1, AZUL-4-1, AZUL-4-2, are AZUL-3-3 329 -12 522 -57 shown with thermal ellipsoids at the 50% probability level. AZUL-4-1 342 +1 537 -42 Overall isolated yield=25%. AZUL-4-2 334 -7 531 -48 Structural assignments for the new compounds were done 50 AZUL-4-3 332 -9 552 -27 based on negative-ion APCI-MS and the "H NMR and 'F AZUL-5-1 338 -3 536 -43 NMR spectral analysis (see FIG. 17 and FIG. 18). The 'F NMR spectra were obtained in CDC1 and are shown in FIG. The gas-phase electron affinity (EA) was measured experi 17. Multiplets corresponding to each CF group appearintwo mentally by low-temperature photoelectron spectroscopy for distinct regions consistent to whether they are bonded to the 55 two new isomers of AZUL-4 and compared to electron affin five-membered ring (between -53.5 and -58.5 ppm) or the ity of the parent AZUL, 0.790(8), and AZUL-5-1, 2.850(15) seven-membered ring of azulene (between -64.4 and -66.5 (FIG. 19). ppm). Through-space F F coupling is observed between Two AZUL(CF) isomers exhibit very close EA values, CF groups bonded to adjacent carbon atoms of the azulene 2.495 (10) and 2.485(10). A plot of EA vs. number of CF, core resulting in quartets and apparent Septets and no F-H 60 groups reveals a remarkable linear correlation, with a slope of coupling is observed. In some cases, CF groups occupy all 0.42 eV per CF group. An extrapolation to AZUL-6 (that was three carbon atoms of the five-membered ring, whereas CF observed by mass-spectrometry in the crude product as noted groups bonded to adjacent carbon atoms of the seven-mem above) yields an estimated EA value of 3.3 eV. bered ring were not observed. No experimental data are available in the literature on EA The structures of the two most abundant AZUL(CF). 65 values for any aZulene derivatives for comparison. The elec isomers, AZUL-4-1 and AZUL-4-2 were confirmed by trochemical potentials in Solution were reported for some single-crystal X-ray diffraction (Scheme 3.1); the crystals derivatives. Coincidentally, a similar linear correlation with US 9.249,071 B2 39 40 nearly the same slope was observed in the half-wave reduc PF-C8 100 A 5 um column (Fluorous Technologies, Inc.). tion potentials of a series of cyano azulenes, AZUL(CN), The atmospheric-pressure chemical ionization (APCI) mass where the E(0/-) became more positive by 0.42V per one spectra were recorded on 2000 Finnigan LCQ-DUO mass CN Substitution. Cyclic voltammetry in DME using TBAP spectrometer (acetonitrile carrier solvent, 0.3 mL'min' flow electrolyte has been performed in this work for the most 5 rate, analyte samples injected as solutions in dichlo abundant compounds, and reversible electrochemical behav romethane or acetonitrile). iour was only observed in the case of AZUL-4-1, E(0/-) All NMR spectra were recorded on Varian INOVA 400 =-1.05 V vs. FeCp2(+/0). Comparison with the reduction instrument in CDC1 solution. The H and F frequencies potentials of AZUL(CN) shows the latter to be a stronger were 400 and 376MHz, respectively. The 'F chemical shifts acceptor in Solution than AZUL(CF) in agreement with the 10 were determined using hexafluorobenzene as an internal stan theoretical predictions reported earlier for other polycyclic dard (6-164.9). The H chemical shifts were determined aromatic molecules, including our recent work on the Substi using the resonance of the residual CHCl in CDC1 as an tuted corannulene derivatives. internal standard (8 7.26). UV-Vis absorption spectra were Varying the degree of substitution allows for the selection recorded by using a Cary 500 spectrophotometer with a reso of an azulene derivative to match with a proper donor to form 15 lution of 1 nm. Cyclic Voltammetry measurements were car a charge transfer complex. The increased EA of AZUL-5-1 ried out on PAR 263 potentiostat/galvanostat in anaerobic was utilized to form a charge transfer complex with pyrene as conditions using 0.1 M N(nBu)CIO in dimethoxyethane: the donor molecule. Dark red-purple crystalline rods of the platinum working and counter electrodes; silver wire quasi charge-transfer complex between AZUL-5-1 and pyrene reference electrode: 500 mVs'; ferrocene internal standard. were grown by the slow evaporation from a dichloromethane 20 X-ray diffraction data for a single crystal of AZUL-4-1 were solution at 2° C. Columns of alternating AZUL-5-1 and recorded by using a Bruker Kappa APEX II CCD diffracto pyrene were formed in a pseudo hexagonal close-packed meter at Colorado State University. formation (FIG. 20A) with intermolecular, donor-acceptor Trifluoromethylation of AZulene: distances of 3.58 and 3.61 A (FIG.20B). The charge-transfer AZulene(CF), was prepared according the procedure of between AZUL-5-1 and pyrene possibly prevents AZUL-5-1 25 Example 1, modified as follows. AZulene (50 mg, 0.39 mmol. from adopting opposite orientations within its position and blue Solid) was placed into a glass ampoule (327 mL) and the there was no disorder observed in the azulene core as was ampoule was cooled with liquid nitrogen and evacuated using observed in the structure of AZUL-4-1. Solutions with vary a vacuum line equipped with a pressure gauge and a cali ing amounts of AZUL-5-1:pyrene were made in DCM. All brated volume (51.7 mL). Using the calibrated volume and solutions remained the deep purple colour of AZUL-5-1 and 30 pressure gauge, CFI gas was measured (11.7 mmol. 30 no new absorption bands were observed in UV-vis absorption equiv.), and then the measured CFI gas was condensed into measurements at different concentrations, even when AZUL the cooled ampoule containing azulene. The ampoule was 5-1:pyrene=50:50 (the same ratio that formed the single then flame-sealed and warmed to room temperature. The crystal charge-transfer complex). The absence of charge sealed ampoule was then placed in a heating furnace and transfer bands has also been observed with other azulene 35 heated at 10° C. min' to 300° C. When the formation of charge-transfer complexes, but charge-transfer bands from purple iodine gas was observed at 285°C., the ampoule was pyrene have been observed in other pyrenefoligomer com heated for another 15 minutes up to 300° C. before cooling to plexes. room temperature. In conclusion, we have developed an efficient trifluorom After cooling to room temperature, the ampoule was ethylation method for azulene that yields a mixture of seven 40 cooled in liquid nitrogen and opened (lower than ambient readily separable poly(trifluoromethyl)aZulenes has been pressure inside). Excess CFI gas was boiled off upon warm developed. Low-temperature photoelectron spectroscopy ing to room temperature and then the Soluble products were revealed a linear increase in gas-phase electron affinity of dissolved in dichloromethane. The purple dichloromethane 0.42 eV per CF group. Strong acceptor properties of the new Solution was washed twice with a saturated sodium thiosul compounds were utilized in the first example of a charge- 45 fate solution (aq) to remove 12 until color was no longer transfer complex with pyrene that exhibits a regular columnar observed in the aqueous layer. The dichloromethane was packing and strong pi-pi interactions between the aromatic removed by rotary evaporation and the remaining Solid was cores of the donor and acceptor. Further elucidating oligo dissolved and filtered in acetonitrile (purple solution) for meric poly(trifluoromethyl)aZulene and AZUL(CF) species HPLC separation as described below. Care must be taken will result in even stronger electron acceptors and could lead 50 when rotary evaporating the crude mixture because some of to charge-transfer complexes with unique packing motifs and the products are rather volatile. Total conversion of azulene to unusual electronic properties. isolated products=25 mol%. Experimental Section. HPLC Purifications of AZulene(CF). General Information. The first HPLC separation of the azulene(CF), crude All reagents and solvents were reagent grade or better. ACS 55 samples was done using semi-preparative Cosmosil Buck Grade dichloromethane (Fisher Scientific), HPLC Grade yprep HPLC column, acetonitrile eluent, flow rate of 5.0 acetonitrile (Fisher Scientific). ACS Grade hexanes (Fisher mL min', 300 nm detection. Three different fractions 4.3- Scientific), sodium thiosulfate crystals (Mallinckrodt), trif. 5.0 min (I), 5.0-5.8 min (II), and 5.9-6.7 min (III) were iso luoromethyl iodide (Synguest Labs), Chloroform-D (Cam lated for further separation using analytical FluoroFlash col bridge Isotopes Laboratories), and hexafluorobenzene (Oak- 60 umn, flow rate of 2.0 mL/min. Second stage separation of I wood Products) were used as received. HPLC analysis and (acetonitrile/HO-90:10, 300 nm detection) resulted in two separation was done using Shimadzu liquid chromatography more fractions: 3.4-5 min. (IV) and 5.9-7.3 min (AZUL-4-1). instrument (CBM-20A control module, SPDA UV detector Fraction IV was further separated (acetonitrile/HO=60:40, set to 300 or 275 nm detection wavelength, LC-6AD pump, 275 nm detection) and resulted in two fractions: 20-21.6 min manual injector valve) equipped with semi-preparative 10 65 (AZUL-3-2) and 21.6-24.0 min (AZUL-3-1). Second stage mm I.D.x250 nm Cosmosil Buckyprep column (Nacalai separation of II (acetonitrile/HO=80:20, 275 nm detection) Tesque, Inc.) or analytical 4.6 mm I.D.x150 nm FluoroFlash resulted in one predominant fraction collected from 4.0-6.4 US 9.249,071 B2 41 42 min(AZUL-3-3). Second stage separation of III (acetonitrile/ NMR: 8 8.90 (d. J–10.2 Hz, 2H, H'); 8.40 (s, 1H, H): HO=95:5, 300 nm detection) resulted in two more fractions: 7.95 (d. J–11 Hz, 2H, H7). NI-APCI mass spec: 332.40 3.3-4.6 min (V) and 4.6-6.0 min(AZUL-5-1). Fraction V was m/z. calc.: 332.02. further separated (acetonitrile/HO-80:20, 300 nm detec AZUL-3-3, 1,2,3-aZulene(CF). tion) and resulted in two fractions: 6.8-7.8 min (AZUL-4-3) The solvent could not be simply rotary evaporated due to and 7.8-9.4 min (AZUL-4-2). The solvent was then removed the volatility of the product. The product was precipitated by from the compounds as described below along with further the addition of HO and cooling, filtered through glass characterization. microfibre, and the pink solid was collected with dichlo AZUL-5-1, 1,2,3,5,7-aZulene(CF). romethane. 0.7 mg, 0.5 mol % yield based on azulene. 'F 10 NMR: 8 -53.71 (q, J=11.8 Hz, 2CF, CF'); -57.38 (sept, The solvent was removed by rotary evaporation and the J=12.0, 1CF, CFs). H NMR: 89.17 (d. J–10.2 Hz, 2H, purple solid was collected with dichloromethane. Co-crystals H''); 8.17 (t, J–10.0 Hz, 1H, H); 7.81 (t, J–10.4 Hz, ofAZUL-5-1/pyrene (dark red-purple rods) were grown from 2H, H7). NI-APCI mass spec: 332.27 m/z. calc.: 332.02. the slow evaporation of a dichloromethane solution (AZUL X-Ray Diffraction Study. 5-1:pyrene=1:1) at 2°C. 16.6 mg, 9.0 mol% yield based on 15 The diffraction-quality single crystals of 1,2,3,5-aZulene azulene. 'F NMR: 8 -54.35 (q, J=12.3 Hz, 2CF, CF'); (CF) were mounted in a paratone oil on a glass fiber rods –58.02 (sept, J=12.0 Hz, 1CF, C2);-65.46 (s.2CF, CF7). glued to a small copper wire. X-ray diffraction data were H NMR: & 9.50 (s. 2H, H-8); 8.63 (s, 1H, H). NI-APCI collected at ChemMatCARS (CARS=Consortium for mass spec: 468.41 m/z. Calc. 468.00. Advanced Radiation Sources) sector 15-B at the Advanced AZUL-4-1, 1,3,5,7-aZulene(CF). Photon Source (Argonne National Laboratory). The data sets The majority of the solvent was carefully removed by were collected at 100(2) K using a diamond (111) crystal fractional distillation until a concentrated purple solution monochromator, a wavelength of 0.41328 A and a Bruker remained. Dichloromethane was then added to the purple CCD detector. The structure was solved using direct methods solution and all of the solvent was dried down in air to give and refined (on F2, using all data) by a full-matrix, weighted AZUL-4-1 as a purple solid. Single crystals (purple plates) 25 least squares process. Standard Bruker control and integra were grown by the slow evaporation from a dichloromethane tion software (APEX II) was employed, and Bruker solution. 14.7 mg, 9.5 mol % yield based on azulene. 'F SHELXTL software was used for structure solution, refine NMR: 8 -58.41 (s. 2CF, CF,''): -65.19 (s. 2CF, CF-7). ment, and graphics. "H NMR: & 9.12 (s. 2H, H:); 8.51 (s, 1H, H°); 8.49 (s. Data for 1,3,5,7-aZulene(CF) and 1,2,3,5,7-aZulene 1H, H°). NI-APCI mass spec: 400.40 m/z. Calc.: 400.01. 30 (CF)/pyrene were collected using a Bruker Kappa APEXII AZUL-4-2, 1,2,3,5-aZulene(CF). CCD diffractometer employing Mo KC. radiation and a The solvent was rotary evaporated and the purple solid was graphite monochromator. Unit cell parameters were obtained collected in dichloromethane. Single crystals (thin purple from least-squares fits to the angular coordinates of all reflec plates) were grown by the slow evaporation from a dichlo tions, and intensities were integrated from a series of frames romethane Solution. 4.6 mg, 3.1 mol % yield based on azu 35 (c) and protation) covering more than a hemisphere of recip lene. F NMR: 8 -54.02 (q, J=12.3 Hz, 1CF, CF,' ' ); rocal space. Absorption and other corrections were applied -54.07 (q, J=11.8 Hz, 1CF, CF');-57.71 (sept, J=12.0 using SCALE. The structures were solved using direct meth HZ, 1CF, CFs): -65.20(s, 1CF, CFs). H NMR: 89.41 (s, ods and refined (on F, using all data) by a full-matrix, 1H, H); 9.28 (d. J–10.6 Hz, 1H, H); 8.41 (d. J–10.6 weighted least-squares process. Standard Bruker control and HZ, 1H, H); 7.90 (t, J–10.4 Hz, 1H, H7). NI-APCI mass 40 integration software (APEX II) was employed, and Bruker spec: 400.40 m/z. Calc.: 400.01. SHELXTL software was used for structure solution, refine AZUL-4-3, 1.2.3,6-aZulene(CF). ment, and molecular graphics. The solvent was rotary evaporated and a purple Solid was Crystal data for AZUL-4-1: CHF, M-400.17, tri collected in dichloromethane. 1.1 mg, 0.7 mol % yield based clinic, a=8.9064(4) A, b=9.5245(4) A, c=13.4137(6) A, onaZulene. 'F NMR: 8–54.06 (q, J=11.8 Hz, 20F, CF'); 45 C=105.240(2), B=101.240(2), Y=101.091(2), V=1040.70 –57.82 (sept, J=12.0 Hz, 1CF, CFs): -66.46 (s, 1CF, (8) A, T=120(2)K, space group P-1, Z–3, LL(MoKo.)=0.225 CF). "H NMR: 89.28 (d. J–11 Hz, 2H, H:); 8.05 (d. mm, 22507 reflections measured, 5131 independent reflec J–11 Hz, 2H, H7). NI-APCI mass spec: 400.40 m/z. tions (R-0.0268). The final R values were 0.0497 (D2O Calc.: 400.01. (I)). The final wR(F) values were 0.1173 (D2O(I)). The final AZUL-3-1, 1.3.5-aZulene(CF). 50 R values were 0.0667 (all data). The final wR(F) values The solvent could not be simply rotary evaporated due to were 0.1283 (all data). The goodness of fit on F was 1.045. the volatility of the product. The product was precipitated by CCDC number CCDC 980904. the addition of H2O and cooling, filtered through glass Crystal data for AZUL-4-2: CHF, M=400.17, mono microfibre, and the purple solid was collected with a mixture clinic, a=4.8939(3) A, b=32.3450(18) A, c=8.6013(5) A, of dichloromethane and acetonitrile. 2.1 mg, 1.6 mol% yield 55 c=90°, B=94.4396(10), Y=90°, V=1357.44(14) A, T=100 based on azulene. 'F NMR: 8 -58.17 (s, 1CF, CF'); (2) K, space group Cc, Z 4, Synchrotron radiation at Chem -58.21 (s, 1CF, CF'):-64.89 (s, 1CF, CFs). H NMR: 8 MatCARS Sector 15-B at the Advanced Photon Source at 9.03 (s, 1H, H); 8.91 (d. J–9.8 Hz, 1H, H); 8.37 (s, 1H, Argonne National Laboratory (diamond (111) crystal mono H); 8.27 (d. J–10.6 Hz, 1H, H); 7.77 (t, J–10.4 Hz, chromator u(diamond (111))=0.073 mm; -0.41328 A). 1H, H7). NI-APCI mass spec: 332.40 m/z. calc.: 332.02. 60 17319 reflections measured, 4394 independent reflections AZUL-3-2, 1.3,6-aZulene(CF). (R-0.0457).is The final R values were 0.0369 (D2O(I)). The The solvent could not be simply rotary evaporated due to final wR(F) values were 0.0963 (D2O(I)). The final R val the volatility of the product. The product was precipitated by ues were 0.0499 (all data). The final wR(F) values were the addition of H2O and cooling, filtered through glass 0.1226 (all data). The goodness of fit on F was 1.194. CCDC microfibre, and the purple solid was collected with dichlo 65 number CCDC 980900. romethane. 0.8 mg, 0.6 mol % yield based on azulene. 'F Crystal data for AZUL-5-1/pyrene: CHFs, M=670.41, NMR: 8 -58.21 (s. 2CF, CF'): -65.98 (s, 1CF, CFs). "H monoclinic, a 7.2226(7) A, b=16.1783(17) A, c=21.334(2) US 9.249,071 B2 43 44 A, C =90°, B=92.461(5), Y=90°, V=2490.6(4) A, T=120(2) TABLE 6.1-continued K, space group P21/n, Z-4, u(MoKC)=0.183 mm, 59030 reflections measured, 7578 independent reflections Data for Polyheterocyclic Compound Perfluoroalkylation Products (R0.0293). The final R values were 0.0396 (D2O(I)). The Expected range of n in Expected most abundant final wR(F) values were 0.1056 (D2O(I)). The final R val 5 PHC Substrate PHC(R) n(R) ues were 0.0441 (all data). The final wR(F) values were 1,7-phenanthroline 2-6 5 0.1095 (all data). The goodness of fit on F was 1.024. CCDC 9H-carbazole 2-5 4 number CCDC 980901. beta-carboline 2-5 4

Example 5 10 While specific embodiments have been described above Perfluoroalkylation of Polyaromatic Hydrocarbons with reference to the disclosed embodiments and examples, such embodiments are only illustrative and do not limit the Certain specific examples of polyaromatic hydrocarbons Scope of the invention. Changes and modifications can be (PAH) that can be prepared using the methods described 15 made in accordance with ordinary skill in the art without herein are listed below in Table 5.1. The expected range of departing from the invention in its broader aspects as defined perfluoroalkyl substituents (“n”) is provided (typically 2, 3, 4, in the following claims. or 5 perfluoroalkyl substituents on a bicyclic system; 2-6 for All publications, patents, and patent documents are incor atricyclic system), which can be influenced to greater number porated by reference herein, as though individually incorpo of substituents by increasing pressure, temperature, and reac rated by reference. No limitations inconsistent with this dis tion duration from the standard conditions described in the closure are to be understood therefrom. The invention has examples above. A lesser number of substituents can be been described with reference to various specific and pre obtained by decreasing pressure, temperature, and reaction ferred embodiments and techniques. However, it should be duration from the standard conditions described in the understood that many variations and modifications may be examples above. The table also provides the expected most 25 made while remaining within the spirit and scope of the abundant isomer (number of “R” substituents “n”). invention. What is claimed is: TABLE 5.1 1. A method for preparing a purified polyaromatic hydro carbon or polyheterocyclic compound Substituted with one or Data for Polyheterocyclic Compound Perfluoroalkylation Products 30 more perfluoroalkyl groups comprising: Expected range of n in Expected most abundant heating a polyaromatic hydrocarbon Substrate or a poly PAHsubstrate PAH (RF), n(R) heterocyclic compound substrate in the presence of a chrysene 4-8 6, 7 perfluoroalkyl iodide, in an optionally closed reaction picene 6-12 7, 8 system, wherein the heating is sufficient to bring both as-indacene 3-6 3, 4 35 the polyaromatic hydrocarbons or polyheterocyclic phenalene 2-6 5, 6 compound, and the perfluoroalkyl iodide, into the gas acenaphylene 2-6 4, 5 phase, thereby allowing the substrate to react with the biphenylene 2-6 4, 5 perfluoroalkyl iodide in the gas phase to form polyaro matic hydrocarbons or polyheterocyclic compounds 40 having one or more perfluoroalkyl Substituents; and Example 6 isolating the polyaromatic hydrocarbons or polyheterocy clic compounds having one or more perfluoroalkyl Sub Perfluoroalkylation of Polyheterocyclic Compounds stituents by chromatography performed with an HPLC column that has a stationary phase comprising 3-(1- Certain specific examples of polyheterocyclic compounds 45 prenyl)propyl groups. (PHC) that can be prepared using the methods described 2. The method of claim 1 wherein the reaction system herein are listed below in Table 6.1. The expected range of containing the Substrate and perfluoroalkyl iodide is heated to perfluoroalkyl substituents (“n”) is provided (typically 2, 3, 4, about 200° C. to about 450° C. or 5 perfluoroalkyl substituents on a bicyclic system; 2-6 for 3. The method of claim 1 wherein the reaction system is a atricyclic system), which can be influenced to greater number 50 closed system that provides an increased atmospheric pres of substituents by increasing pressure, temperature, and reac Sure upon heating. tion duration from the standard conditions described in the 4. The method of claim 1 wherein the reaction system does examples above. A lesser number of substituents can be not comprise a catalyst, a reaction promoter, or solvent. obtained by decreasing pressure, temperature, and reaction 5. The method of claim 1 wherein the perfluoroalkyl iodide duration from the standard conditions described in the 55 is CF (CF).I., wherein n is 0 to about 12. examples above. The table also provides the expected most 6. The method of claim 5 wherein the perfluoroalkyl iodide abundant isomer (number of “R” substituents “n”). is CFI, CFI, n-CFI, n-CFI, n-CFI, or n-CFI. 7. The method of claim 1 wherein the substrate is a pol TABLE 6.1 yaromatic hydrocarbon Substrate. 60 8. The method of claim 7 wherein the polyaromatic hydro Data for Polyheterocyclic Compound Perfluoroalkylation Products carbon Substrate is anthracene, aZulene, coronene, fluorene, Expected range of n in Expected most abundant fluoranthene, naphthalene, pentacene, perylene, phenan PHC Substrate PHC(R) n(R) threne, pyrene, tetracene, or triphenylene. isoquinoline 2-5 3 9. The method of claim 1 wherein the substrate is a poly 4H-quinolizine 2-5 4 65 heterocyclic compound Substrate. quinoline 2-4 3 10. The method of claim 9 wherein the polyheterocyclic compound substrate is acridine, beta-carboline, 9H-carba US 9.249,071 B2 45 46 Zole, iminodibenzyl, indole, isoquinoline, phenanthridine wherein phenanthroline, phenazine, phenothiazine, quinazoline, or R is —(CF),CF wherein n is 0 to about 11: quinoline. 11. The method of claim 8 wherein the polyaromatic m is 0 to 3; and hydrocarbon having one or more perfluoroalkyl substituents 5 p is 1 to 3. formed is a compound of Formula (I): 14. The method of claim 13 wherein the compound of Formula (II) is: (I) N N 10 RF RF (R)- - (R): 2n-2 O RE O) wherein 15 R is —(CF),CF wherein n is 0 to about 11; and R RE: RE: each m is independently 1 to 3. (1,3,5-AZUL) (1,3,6-AZUL) 12. The method of claim 11 wherein the compound of RE RF RE Formula (I) is: RE: 3) RF RF 2O O- O) RE RF RE RF (1,2,3-AZUL) (1,3,5,7-AZUL) 25 RE RE RE RE O O) RE: RF O O) RE; or (1,5-NAPH) (1,3,5-NAPH) 30 RE RE: RE: R RE RE (1,2,3,5-AZUL) (1,2,3,6-AZUL) RF RE R. 35 RE RE (1,3,6-NAPH) (1,3,7-NAPH) R R F F RE RF RE RE 40 (1,2,3,5,7-AZUL)

R. wherein R is —(CF), CF, wherein n is 0 to about 11. 15. The method of claim 8 wherein the polyaromatic RE RE 45 hydrocarbon having one or more perfluoroalkyl Substituents (1,4,6-NAPH) (1,3,5,7-NAPH) formed is: RE RF: or RE RE: O RF RF R. R?. RF 50 RE (2,3,6,7-NAPH) (1,3,6,7-NAPH) wherein R is —(CF),CF wherein n is 0 to about 11. 55 RE 13. The method of claim 8 wherein the polyaromatic hydrocarbon having one or more perfluoroalkyl Substituents (1,3,6,8,10-ANTH) formed is a compound of Formula (II): RF RE RF 60 (II)

(RF) in 65 (2,3,6,7,9,10-ANTH) US 9.249,071 B2 47 48 -continued -continued RE RE C C RE: RE 10 RF (1,3,4,6,9-PYRN) RE 15 RE RE O C RE: RE RF (1,3,4,6,8.9-PYRN) 25 RE RE; or

30 RE O R. O RE

35 RE (1,3,6,7,10,11-TRPH) RE RE RE RE: (1,3,5,7,9,11-PERY) 40 RE O

45 R. O R. RF (1,3,6,8,10,11-TRPH)

wherein Reis —(CF), CF, wherein n is 0 to about 11. 16. The method of claim 8 wherein the polyaromatic hydrocarbon having one or more perfluoroalkyl Substituents formed is a compound of Formula (III): 55 (III) RF RF 60 N N (RF) - (RF): 21 21

65 RF (1,3,4,6,8-PYRN) US 9.249,071 B2 49 50 a compound of Formula (IV): (X) N1 N1 N. (IV) (RF), it --(RF): RE 5 21\ 2 2

N N a compound of Formula (XI): (RF), it --(RF): 21 21 10 (XI) RE RE RF N1 N1 N a compound of Formula (V): 15 (R)- -- (RF): 2 % 21

(V) R a compound of Formula (XII): F 2O

N N (XII) (RF), i. 2 8. N N N 25 (RF), it -- (R): 21 2n.2 RE N

a compound of Formula (VI): a compound of Formula (XIII): 30

S (XIII) (VI)VI N N RF (Rp), it H(RF), 35 21 N 21 1N N H (RF), it --(R): 2 2 a compound of Formula (XIV): RE 40 (XIV) O a compound of Formula (VII): 45 / \ (33—N N=7 (Rp. (VII) RE O a compound of Formula (XV): N N (RF), it --(RF): 21 2 (XV) RF CC 55 wherein / \ R is —(CF),CF wherein n is 0 to about 11: 60 (33—N N= S(Rp. m is 0 to 3: p is 0 to 3; and wherein wherein the sum of m and p is 2, 3, 4, 5, or 6. each R is independently —(CF)CF wherein n is 0 to 17. The method of claim 10 wherein the polyheterocyclic 65 about 11; compound having one or more perfluoroalkyl Substituents each m is independently 0 to 3; and formed is a compound of Formula (X): wherein the sum of elements m is 1, 2, 3, 4, or 5. US 9.249,071 B2 51 18. A method for preparing a purified polyaromatic hydro carbon or polyheterocyclic compound Substituted with one or more trifluoromethyl groups comprising: heating a polyaromatic hydrocarbon Substrate or a poly heterocyclic compound Substrate in the presence of a 5 trifluoromethyl iodide, in an optionally closed reaction system, wherein the heating is Sufficient to bring both the polyaromatic hydrocarbons or polyheterocyclic compound, and the perfluoroalkyl iodide, into the gas phase, thereby allowing the substrate to react with the 10 perfluoroalkyl iodide in the gas phase to form polyaro matic hydrocarbons or polyheterocyclic compounds having one or more perfluoroalkyl Substituents; and isolating the polyaromatic hydrocarbons or polyheterocy clic compounds having one or more perfluoroalkyl Sub- 15 stituents by chromatography performed with an HPLC column that has a stationary phase comprising 3-(1- prenyl)propyl groups, wherein the chromatography per formed with an HPLC column provides single isomers of the substituted polyaromatic hydrocarbons or poly- 20 heterocyclic compounds. 19. The method of claim 1, wherein the chromatography performed with an HPLC column provides single isomers of the Substituted polyaromatic hydrocarbons or polyheterocy clic compounds. 25