Properties of 10-Ethynyl-10H-Phenothiazines and

Intermolecular Interaction of

Their Halogen Addition Compounds

March 2018

Graduate School of Systems Engineering

Wakayama University

SATORU UMEZONO

10-エチニル-10H-フェノチアジン誘導体の特性と

ハロゲン付加物における分子間相互作用

平成 30年 3月

和歌山大学大学院

システム工学研究科

梅園 悟

Abstract

In this thesis, the author has carried out a comprehensive study of 10-ethynyl-10H-

phenothiazines such as reactivity toward halogens, crystallographic and spectroscopic

studies. The title compounds are classified into “ynamine”, where an acetylenic group is

connected to the nitrogen atom of phenothiazine moiety.

Anomalous chemical shifts were observed in the sulfones of 10-ethynyl-10H-

phenothiazines. And the shifts were reasonably explained by a transannular effect of the

central six-membered ring of phenothiazines. The acidity of the hydrogen atom in the

acetylenic terminal was found to receive this effect by crystallographic studies.

Halogens and interhalogen compound addition to 10-ethynyl-10H-phenothiazines

afforded interesting regio and stereo selectivity, which could not be explained by normal

bridged halonium ion intermediates. The author explained the experimental results by

assumption of “free carbocation intermediate” stabilized by conjugation of lone pairs of

ynamine nitrogen, which was also supported by theoretical calculations.

The intermolecular interactions of halogen adducts of 10-ethynyl-10H-phenothiazines

were explored crystallographically. The results of structural analyses showed the

importance of halogen bonds for crystal engineering.

The many important findings found in this study should be applied to novel synthetic

strategies, crystal engineering and studies of intermolecular interactions.

概要

本論文では 10-エチニル-10H-フェノチアジン誘導体の結晶学的、分光学的特徴

やハロゲン付加反応性などの広範囲な研究を行った。表題化合物はフェノチア

ジン部位の窒素原子上にアセチレンが結合した化合物であり、「イナミン」と総

称されている。

硫黄上がスルホンである 10-エチニル-10H-フェノチアジン誘導体では NMRス

ペクトルにおいて常識的ではない化学シフトが観測された。この挙動はフェノ

チアジンの中央六員環の渡環相互作用の影響だと説明できた。また、この相互作

用によりアセチレン末端の水素の酸性度は影響を受けることが判明した。

10-エチニル-10H-フェノチアジン誘導体に対してハロゲン付加反応を行った結

果、位置、立体選択性を見出し、反応中間体は橋架けイオン中間体ではないこと

が示唆された。そこで反応中間体はイナミンの孤立電子対の共役により安定化

したカルボカチオン中間体であると想定すると説明がつき、理論計算によって

も支持された。

10-エチニル-10H-フェノチアジン誘導体のハロゲン付加物の分子間相互作用を

結晶学的に解明し、結晶工学においてハロゲン結合の重要性を示した。

本論文での 10-エチニル-10H-フェノチアジン誘導体の研究で得られた知見か

ら新奇な合成戦略、結晶工学や分子間相互作用の研究への応用が見込まれる。

Contents

Chapter 1. General Introduction 1

Chapter 2. Preparation and Properties of 10-Ethynyl-10H-Phenothiazines 17

Chapter 3. Halogen Addition to 10-Ethynyl-10H-Phenothiazines 53

Chapter 4. Crystal Structures of 10-Dihalovinyl-10H-Phenothiazines

and Their Halogen Bonds 79

Chapter 5. Concluding Remarks 115

List of publications 119

Acknowledgement 121

1

Chapter 1. General Introduction

1-1. Chemistry of acetylenes

The organic compounds which have a carbon-carbon triple bond are called “acetylene

compounds”.1,2 The acetylene bond is a common motif in organic chemistry, however, it

has become a mainstay in the toolbox of synthetic organic chemists, biochemists, and

materials scientists. Both as a building block and as a versatile synthon, the fascinating

and sometimes unpredictable chemistry associated with the acetylene moiety has fueled

many of the most recent advances.

The geometries of an acetylene moiety are quite simple. The bond length of

carbon-carbon triple bond, in which the carbon has sp hybridization, is reported to be

almost 1.20 Å. The angle of Csp−Csp−Y (Y: adjacent atom) is almost 180°, giving a

linear structure of the moiety. Further an acetylene moiety has two π-bonds which have

a perpendicular orientation with each other, resulting in a cylindrical π-electron system.

An acetylene bond is known to be reactive toward electrophilic addition, Diels-Alder

addition3 or hydrogenation.4,5 For example, preparation of TTF (tetrathiafulvalene)

molecule, which is one of the most famous organic donor molecule, contains

Diels-Alder addition between carbon disulfide and dimethyl but-2-ynedioate (Figure

2

1-1(a)).6,7

Oligo(ethynylphenylene)s (OEPs) (Figuree 1-1(b)), which attract interest from

application to molecular electronics, have been extensively studied.8,9 While the m- and

o-OEPs may adopt helical conformations, p-OEPs are considered to be rigid rods,

which is suitable for the design of molecular wires with various properties such as

reversible one oxidation/reduction, electroluminescence or non-linear optics.

Figure 1-1. Preparation of tetrathiafulvalene with Diels-Alder addition (a) and the

general structure of OEPs (b).

3

1-2. Heterosubstituted alkynes

Besides aromatic groups, main elements have been tried to connect to acetylene

moiety in order to expand -conjugated system or to prepare for synthetic interest.10

Among the typical elements in the second and the third period of the periodic table, B,

N, O, F, Si, P, S and Cl, substituted acetylenes have been isolated successfully.11-17

Haloacetylenes can be prepared by a hydrogen−halogen exchange reaction of terminal

acetylene compounds (Figure 1-2(a)).17 These compounds are not so stable and

chemical modifications are limited, although a halogenation reaction to give trihalovinyl

compounds is important.

In the case of Y (Y = Si, P and S), whose bonds with an acetylenic carbon are easily

prepared by replacement of Y−halogen bond by metal acetylide (Figure 1-2(b)).14-16 The

Y−acetylene bonds are elongated compared with Z−acetylene bonds (Z = B, N and O)

and these heteroatoms affect little interaction to acetylenic π-system. And Si containing

substituents are frequently used for protection/deprotection of terminal acetylenes.

Since a boron atom has a vacant p-orbital, it shows electron-withdrawing property by

connecting to π-conjugated system. B−acetylene bonds are usually formed by

substitution of B−halogen or B−alkyloxy bonds by metal acetylide (Figure 1-2(c)).11

B−acetylene bonds shrink slightly compared by B−alkyl bonds because of conjugation

4

between π-system and the vacant p-orbital. This conjugation decreases electrophilic

reactivity of the carbon−carbon triple bond and this class of compounds is very sensitive

to moisture on B atom without exception.

Both N and O atoms have the lone pair(s) (Figure 1-2(d) (e)) which increase reactivity

of acetylene, and enhancement by N atom is thought to be higher than that by O atom.

Nitrogen substituted acetylenes, called ynamines,18-21 have three sites for chemical

modification, and the structures are not more flexible than those of O−acetylene

compounds. In these reasons, the author thought to execute fundamental studies on

ynamines, such as crystallographic, spectroscopic, theoretical studies and reactivities.

Figure 1-2. Preparation of haloalkynes (a), Si, P, S-substituted alkynes (b) and

B-substituted alkynes (c). The general structure of ynamines (d) and O-substituted

alkynes (e).

5

1-3. A history of ynamines

“Ynamines” mean a certain class of acetylene compounds which carry amino groups to

sp hybridized carbon. The first ynamine compound,

10-(prop-1-yn-1-yl)-10H-phenothiazine, was synthesized accidently in 1958 as shown

in Figure 1-3,22 whose structure was determined recently.23 Substitution reaction of

3-bromo-1-propyne by sodium phenothiazin-10-ide, which was prepared by treatment

of 10H-phenothiazine with sodium hydride, gave

10-(prop-2-yn-1-yl)-10H-phenothiazine. But following conversion owing to existence

of excess base afforded 10-(prop-1-yn-1-yl)-10H-phenothiazine.

Figure 1-3. Formation of 10-(prop-1-yn-1-yl)-10H-phenothiazine.

Several types of ynamines have been developed such as dialkyl ynamines, diaryl

ynamines or incorporated heterocycles ynamines. For example, 9-ethynyl-9H-carbazole

was prepared by Dellepiane et al.24 and Hay coupling of it gave a symmetric diacetylene

compound by Maverle and Flandera (Figure 1-4).25 N-ethynyl-N-phenylaniline was

6

developed by Tokutome and Okuno, and a symmetric diacetylene compound was also

synthesized (Figure 1-4).26 These two symmetric diacetylenes have a twisted form

because of electrostatic repulsion of both lone pairs of nitrogens through conjugated

π-system. Matsuda et al. and Okuno et al. prepared diacetylene compounds which

incorporated an ynamine moiety.27,28 Solid-state-polymerization of them afforded

heteroatom substituted polydiacetylenes (PDAs) which were classified into a novel

class of functionalized polydiacetylenes. Tabata et al. developed bis-ynamine

compounds based on 1,4-phenylenediamine moiety.29 And a bis(butadiynyl)phenylene

diamine compound gave a conjugated ladder-type PDA by utilizing pheneylene diamine

as a linker. This conjugated ladder PDA afforded good conductivity compared with

classical PDAs.

Figure 1-4. Preparation of diacetylene compounds by Hay coupling.

7

1-4. Characteristics of 10H-phenothiazines

Phenothiazines, which belong to an important class of tricyclic nitrogen-sulfur

heterocycles,30,31 are known as good electron donor molecules and have been used for

formation of charge transfer complexes.32-41 Phenothiazines have also attracted interest

from the viewpoints of photoinduced electron transfer (PET)42 or magnetism,43,44 and a

variety of phenothiazines have been developed so far.45-48

Phenothiazines are known to form a butterfly conformation, and the structures show

little change by oxidation of the sulfur atom, although electronic conditions change

drastically.49-56 Electrostatic potential maps of the three oxidation states, sulfide,

sulfoxide and sulfone, are shown in Figure 1-5. Although little structural change is seen

in molecular structures, polarization of electron density and energy level of the HOMOs

are drastically changed. Therefore this is thought to be an ideal system to discuss an

effect of oxidation on the sulfur atom to interaction through π-conjugated system.

8

HOMO (-5.3 eV) HOMO (-6.0 eV) HOMO (-6.2 eV)

(b) (a) (c)

(d) (e) (d)

Figure 1-5. Electrostatic potential maps (a)-(c) and the molecular orbitals (d)-(f) of

10H-phenothiazines, sulfide (a) (d), sulfoxide (b) (e) and sulfone (c) (f), respectively.

9

1-5. Summary of this thesis

In this thesis, the author has carried out systematic studies on chemistry of

10-ethynyl-10H-phenothiazines such as crystallographic and spectroscopic studies and

reactivity toward halogens. Crystallographic studies on the obtained

dihalovinylphenothiazines showed interesting intermolecular interactions. And all

works are discussed based on theoretical calculations.

In Chapter 2, the author reports preparation, crystallographic and NMR studies of

10-ethynyl-10H-phenothiazines (1a-c, 2a-c) (Figure 1-6). These compounds are

classical and fundamental classes of ynamines. Anomalous chemical shifts observed in

the sulfones (1c, 2c) are discussed in terms.

Figure 1-6. The structural formulas of 10-ethynyl-10H-phenothiazines (1a-3c).

10

In Chapter 3, reactivity of 1a, 1c, 2a, 2c, 3a and 3c toward halogens and an

interhalogen compound is indicated. The addition products (4a-12c) are summarized in

Figure 1-7. The regio or stereo selectivities of the addition are discussed based on the

structure of the reactive intermediates.

Figure 1-7. The structural formulas of 10-(1,2-halovinyl)-10H-phenothiazines (4a-13c).

11

In Chapter 4, intermolecular interactions of the obtained

dihalovinyl-10H-phenothiazines (Z-11a, E-11a, E-13c, E-10c, E-7c) are explored. In

these compounds, halogen bonds played a crucial role for molecular arrangement.

Theoretical calculations of intermolecular interactions are also reported.

In Chapter 5, the author mentions about novel knowledge obtained by the whole

studies of 10-ethynyl-10H-phenothiazines such as transannular interaction, steric effect,

structures of the reactive intermediates and the intermolecular halogen bonds.

12

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17

Chapter 2. Preparation and Properties of 10-Ethynyl-10H-Phenothiazines

2-1. Introduction

As mentioned in Chapter 1, 10-ethynyl-10H-phenothiazines are one of the most

classical ynamines. Several ynamines have been developed, but there are some

advantages for 10-ethynyl-10H-phenothiazines because three different electronic

conditions can be formed without structural change by oxidation of the sulfur atom.1-5

There are a couple of systematic studies on reactivity of

10-ethynyl-10H-phenothiazines and its two oxides. Iwahashi et al. reported

tetracyanoethylene (TCNE) addition to 10-(prop-1-yn-1-yl)-10H-phenothiazine (2a)

afforded 2-methyl-3-(10H-phenothiazin-10-yl)buta-1,3-diene-1,1,4,4-tetracarbonitrile

(Figure 2-1).6 In the course of their study, they also examined TCNE addition to 2b and

2c, but these compounds didn’t show any reactivities. This is presumably because the

HOMOs of 2b and 2c are too low to promote TCNE addition via charge transfer

transition states. Okuno et al. expanded π-system of 10-ethynyl-10H-phenothiazine (1a)

to diacetylenes, 5-(10H-phenothiazin-10-yl)penta-2,4-diyn-1-ol (Figure 2-2), and

executed oxidation reaction to obtain their oxides.7 They examined

solid-state-polymerization of the three compounds, and only the sulfoxide showed the

18

polymerization reactivity. They concluded that intermolecular S-O···S interaction

played an important role for molecular arrangement in the crystal.

Figure 2-1. TCNE addition to 2a.

Figure 2-2. Solid-state-polymerization of 5-(10H-phenothiazin-10-yl)penta-2,4-diyn-1

-ol derivative.

19

Difference in three oxide state of 10-ethynyl-10H-phenothiazines was utilized in

several studies. But the most fundamental studies on 10-ethynyl-10H-phenothiazine and

its oxides have never carried out yet. Therefore, the author wishes to report the

preparation and the crystal structures of 10-ethynyl-10H-phenothiazine (1a), its 5-oxide

(1b) and 5,5-dioxide (1c) in this chapter. In order to compare with them, the author also

prepared 10-(prop-1-yn-1-yl)-10H-phenothiazine (2a), the first ynamine compound, its

5-oxide (2b) and 5,5-dioxide (2c). Besides crystallographic studies of 1a-c and 2a-c,

spectroscopic studies of them were carried out, and anomalous chemical shifts on 1H

NMR spectra of 1c and 2c were discussed by comparison with the crystal structures and

DFT calculations of 1a-c and 2a-c, respectively.

20

2-2. Results and discussion

Compound 1a and 2a were prepared according to literature (Scheme 2-1).8,7

Preparations of compound 1b-c and 2b-c by oxidation with m-chloroperoxybenzoic acid

(m-CPBA) from compound 1a and 2a are shown in Scheme 2-2. Formation of

compound 1b-c and 2b-c are easily controlled by equivalence of m-CPBA.

Scheme 2-1. Preparation of 1a and 2a.8,7

Scheme 2-2. Preparation of 1b-c and 2b-c.

21

1H NMR spectra of 1a-c and 2a-c

Figures 2-3 and 2-4 show 1H NMR spectra of 1a-c and 2a-c, respectively. All protons

of 1b and 2b showed downfield shifts compared with those of 1a and 2a as expected,

because of decrease in π-electron density on phenothiazine and acetylene moieties by

oxidation.

In the spectra of 1c and 2c, three kinds of signals, acetylenic or methyl and

1,9-position of 1c and 2c, showed upfield shifts anomalously compared with 1b and 2b,

although remaining three kinds of protons showed downfield shifts.

22

Figure 2-3. 1H NMR spectra of 1a (a), 1b (b) and 1c (c).

(a)

(b)

(c)

H1 H2 H3 H4 Acetylenic-H

ppm

23

Figure 2-4. 1H NMR spectra of 2a (a), 2b (b) and 2c (c).

(a)

(b)

(c)

H1 H2 H3 H4 Methyl-H

ppm

24

Crystal structures of 1b-1c

In crystal 1b, the phenothiazine moiety has a butterfly structure, as shown in Figure

2-5; the planes of the two benzene rings subtend a dihedral angle of 149.66 (8)°. Crystal

data for 1b and 1c are summarized in Table 2-1. The central six-membered ring adopts

a boat conformation in which the transannular S1···N1 distance is 3.090(2) Å (Table

2-2). The coordination around atom N1 is slightly pyramidal, with the distance of N1

from the C1/C12/C13 plane being 0.113(2) Å. These structural features of 1b are in

good agreement with those in compounds reported earlier.7,9 The acetylenic H atom is

involved in an intermolecular Csp−H···O hydrogen bond (Table 2-3). Several examples

of close Csp−H···O contacts have been documented.10-19 The hydrogen bond in 1b can

be classified as rather strong; it generates a helix along the a axis. Between

neighbouring helices, spatial closeness between the benzene rings of adjacent molecules

is recognized, as shown in Figure 2-5, with a C1···C8iii distance of 3.337(3) Å and a

C8···C8iv distance of 3.321 (3) Å. [Symmetry codes: (iii) -x+2, y, -z+3/2; (iv) -x+1, y,

-z+3/2.]

In crystal 1c, the asymmetric unit comprises half a molecule; a mirror plane passes

through the S atom, the ynamine fragment and the acetylenic H atom. The

phenothiazine moiety adopts a butterfly structure (Figure 2-6), with a dihedral angle of

25

142.67 (10)° between the planes of the C1–C6 and C1i–C6i benzene rings. [Symmetry

code: (i) x, -y+1/2, z.] The central six-membered ring is again in a boat conformation,

with a shorter transannular S1···N1 distance of 2.967(3) Å (Table 2-2). Atom N1 is also

pyramidal, with a distance of 0.098 (3) Å from the C1/C1i/C7 plane. The acetylenic H

atom is engaged in an intermolecular Csp−H···O hydrogen bond (Table 2-3). This

contact gives rise to a chain along the a axis, with a close contact of 3.391(4) Å between

atoms C8 to C1iv or C1v, as depicted in Figure 2-6. [Symmetry codes: (iv) x+1/2, -y+1/2,

-z+1/2; (v) x+1/2, y, -z+1/2.] The central six-membered rings of 1b and 1c in boat

conformations correspond to the usual geometry for phenothiazine 5-oxides and

5,5-dioxides, except for a few examples.20 When one or both benzene rings are removed

or replaced by a heteroaromatic ring, however, the resulting 1,4-thiazine 5,5-dioxides

are planar21-30 because of effective conjugation between the aromatic systems. 1c shows

a shorter transannular S···N contact than 1b, indicating a stronger attractive interaction.

As a result, 1c has a smaller dihedral angle between the planes of the benzene rings than

1b or the compounds reported earlier. As for intermolecular contacts in 1b and 1c, the

hydrogen bonding patterns differ significantly. Almost linear hydrogen bonds are

formed in 1b, with a tendency towards a longer Csp−H bond. The H···O separation of

2.13(3) Å is shorter than average Csp−H···O hydrogen-bond distances [2.44 Å31;

26

obtained from the Cambridge Structural Database, 969 counts for a Csp−H···O distance

within 2.72 Å].32 On the other hand, the hydrogen bond in 1c is considered to be weaker.

In the IR spectrum, a higher value for C−H (3394 cm-1) was observed in 1c than in 1b

(3151 cm-1), also suggesting that the hydrogen bond in 1c is weaker than that in 1b.

27

(a)

(b)

Figure 2-5. The molecular structure (a) and the crystal packing structure (b) of 1b with

atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability

level and H atoms are shown as small spheres. [Symmetry codes: (i) x+1/2, -y+1/2,

-z+1; (ii) x-1/2, -y+1/2, -z+1; (iii) -x+2, y, -z+3/2; (iv) -x+1, y, z+3/2.]

28

(a)

(b)

Figure 2-6. The molecular structure (a) and the crystal packing structure (b) of 1c with

atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability

level and H atoms are shown as small spheres. [Symmetry codes: (i) x, -y+1/2, z; (ii)

x+1, y, z; (iii) x-1, y, z; (iv) x+1/2, -y+1/2, -z+1/2; (v) x+1/2, y, -z+1/2; (vi) x-1/2, -y+1/2,

-z+1/2.]

29

Table 2-1. Crystal data and refinement details for 1b and 1c.

Compounds 1b 1c

Empirical formula C14H9N1O1S1 C14H9N1O2S1

Formula weight 239.29 255.29

Crystal size (mm) 0.10 × 0.05 × 0.05 0.10 × 0.10× 0.10

Crystal system Orthorhombic Orthorhombic

Space group Pbcn Pnma

Unit cell dimensions

a (Å) 7.9006(19) 9.177(3)

b (Å) 16.302(4) 11.520(4)

c (Å) 16.998(5) 10.819(3)

α (°) 90 90

β (°) 90 90

γ (°) 90 90

V (Å3) 2189.3(10) 1143.8(7)

Z 8 4

Dx (Mg/m3) 1.452 1.482

μ (mm-1) 0.274 0.274

θ range (°) 2.4 – 27.5 2.2 – 27.5

Index ranges

-10 ≤ h ≤ 8 -11 ≤ h ≤ 11

-21 ≤ k ≤ 15 -14 ≤ k ≤ 14

-22 ≤ l ≤ 22 -14 ≤ l ≤ 13

Reflections collected 16923 8777

Independent reflections 2516 1375

Reflections with I > 2σ(I) 2029 1297

Rint 0.063 0.050

Refinement method Full-matrix least-squares on I

Goodness of Fit on I 1.109 1.105

R1[I > 2σ(I)], wR2(I) 0.0537, 0.1474 0.0497, 0.1281

Data completeness 1.000 0.999

Refined parameters 158 94

Residual density (eÅ-3) 0.49, -0.47 0.84, -0.49

30

Table 2-2. Selected geometries (Å, °) of 1b and 1c.

Table 2-3. Hydrogen bond geometries (Å, °) of 1b and 1c.

D−H∙∙∙A D−H H∙∙∙A D∙∙∙A D−H∙∙∙A

1b C14−H14∙∙∙O1i 1.02(3) 2.13(3) 3.145(3) 175(2)

1c C8−H8∙∙∙O2ii 0.94(4) 2.56(4) 3.270(4) 133(3)

Symmetry codes: (i) x+1/2, -y+1/2, -z+1; (ii) x+1, -y+1/2, z.

1b 1c

S−O 1.5029(17) 1.435(2), 1.440(2)

S−Csp2 1.760(3), 1.768(3) 1.742(2)

N−C sp2 1.417(3), 1.417(3) 1.420(3)

N−Csp 1.364(3) 1.362(4)

S···N 3.090(2) 2.967(3)

Csp2−S−Csp2 96.09(10) 100.22(10)

Csp2−N−Csp2 121.35(18) 121.2(3)

Csp2−N−Csp 118.21(18), 118.52(18) 118.69(13)

31

Crystal structures of 2a-c

The molecular structures of 2a-c are shown in Figure 2-7. Crystal data for 2a-c are

summarized in Table 2-4. Selected geometries are listed in Table 2-5.

The asymmetric unit comprises one half-molecule in crystal 2a; a mirror plane passes

through the sulfide group, ynamine fragment, one carbon atom and one hydrogen atom

of methyl group. The bond distances and angles are comparable with other reported

ynamines.8,9 The crystal structure is stabilized by van der Waals interactions. The

phenothiazine moiety has a butterfly conformation, and the central six-membered ring

has a boat conformation. The dihedral angle between two benzene rings is 149.40 (4)°.

The structure around the nitrogen atom is pyramidal, where the nitrogen atom locates

upward at 0.1146(13) Å from the plane formed by three adjacent carbon atoms.

Intramolecular S···N distance is 3.0122(18) Å and bond angle of C6−S1−C6i and

C1−N1−C1i [symmetry code: (i) -x, y, z] is 99.81(7)° and 119.14(7)°, respectively.

A half of the molecule is crystallographically independent in crystal 2b. Namely there

is a mirror plane passing through the sulfoxide group, ynamine fragment, methyl carbon

atom and one methyl H atom. The bond distances and angles are almost comparable

with those of 2a as shown in Table 2-5. The phenothiazine moiety has a butterfly

conformation, and the central six-membered ring has a boat conformation. The dihedral

32

angle between two benzene rings is 153.51(4)°. The structure around the nitrogen atom

is pyramidal, where the nitrogen atom locates upward at 0.1420(14) Å from the plane

formed by three adjacent carbon atoms. Intramolecular S···N distance is 3.1219(15) Å,

and the bond angles of C6−S1−C6i and C1−N1−C1i [Symmetry code: (i) x, −y+1/2, z.]

is 96.79(6)° and 121.92(11)°, respectively.

In crystal 2c, the phenothiazine moiety also has a butterfly conformation, and the

central six-membered ring has a boat conformation. The dihedral angle between two

benzene rings is 153.50(6)°. The structure around the nitrogen atom is pyramidal, where

the nitrogen atom locates upward at 0.1146(13) Å from the plane formed by three

adjacent carbon atoms. Intramolecular S···N distance is 3.046(2) Å and bond angle of

C6−S1−C7 and C1−N1−C12 is 101.25(8)° and 122.63(13)°, respectively.

As aforementioned, a phenothiazine moiety keeps almost unchanged regardless of the

oxidation state of sulfur atom.1-5 In compound 2a-c, the phenothiazine moieties have

almost the same structure. However, the central six-membered rings show slight

differences. Compared 2b with 2a, the intramolecular S···N distance becomes elongated

from 3.0112(18) Å to 3.1219(15) Å, suggesting electrostatic repulsion between the

oxygen and the nitrogen atoms. The elongation also causes narrowing of the C−S−C

angle. Alternatively from 2b to 2c, the S···N distance shrinks fairly to 3.046(2) Å

33

accompanied by expansion of both C−S−C and C−N−C angles, which suggests

attractive interaction between the sulfur and the nitrogen atoms. These tendencies are

also observed in the reported compounds.1-5

34

(a)

(b)

(c)

Figure 2-7. The molecular structures of 2a (a), 2b (b) and 2c (c) with atom-numbering

scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are

shown as small spheres.

35

Table 2-4. Crystal data and refinement details for 2a-c.

Compounds 2a 2b 2c

Empirical formula C15H11N1S1 C15H11N1O1S1 C15H11N1O2S1

Formula weight 237.32 253.32 269.32

Crystal size (mm) 0.12 × 0.10 × 0.08 0.15 × 0.10 × 0.08 0.10 × 0.08× 0.05

Crystal system Orthorhombic Orthorhombic Triclinic

Space group Cmc21 Pnma P1_

Unit cell dimensions

a (Å) 14.717(6) 17.368(4) 7.744(4)

b (Å) 10.631(4) 11.488(3) 7.912(4)

c (Å) 7.375(3) 6.0557(15) 10.380(5)

α (°) 90 90 73.81(2)

β (°) 90 90 89.07(3)

γ (°) 90 90 85.32(3)

V (Å3) 1153.9(8) 1208.3(6) 608.7(6)

Z 4 4 2

Dx (Mg/m3) 1.366 1.392 1.469

μ (mm-1) 0.253 0.253 0.261

θ range (°) 2.4 – 28.5 3.5 – 27.5 2.0 – 25.0

Index ranges

-19 ≤ h ≤ 16 -22 ≤ h ≤ 14 -6 ≤ h ≤ 9

-14 ≤ k ≤ 12 -14 ≤ k ≤ 14 -8 ≤ k ≤ 9

-9 ≤ l ≤ 9 -7 ≤ l ≤ 6 -12 ≤ l ≤ 12

Reflections collected 16923 8777 4219

Independent reflections 2516 1375 2116

Reflections with I > 2σ(I) 2029 1297 1767

Rint 0.063 0.050 0.023

Refinement method Full-matrix least-squares on I

Goodness of Fit on I 1.081 1.082 0.967

R1[I > 2σ(I)], wR2(I) 0.0252, 0.0645 0.0338, 0.0911 0.0303, 0.0822

Data completeness 0.991 0.994 0.982

Refined parameters 87 98 184

Residual density (eÅ-3) 0.20, -0.16 0.43, -0.32 0.30, -0.38

Flack parameter -0.01(6) - -

36

Table 2-5. Selected geometries (Å, °) of 2a-c.

2a 2b 2c

S−O 1.4986(13) 1.4444(13), 1.4422(15)

S−Csp2 1.7643(13) 1.7667(12) 1.7481(17), 1.7504(19)

N−Csp2 1.4246(14) 1.4145(14) 1.420(3), 1.4197 (19)

N−Csp 1.358(2) 1.370(3) 1.374(3)

S1···N1 3.0122(18) 3.1219(15) 3.046(2)

Csp2−S1−Csp2 99.84(8) 101.25(8) 101.25(8)

Csp2−N1−Csp2 119.97(14) 122.63(13) 122.63(13)

Csp2−N1−Csp 119.16(7) 116.95(12) 116.95(12), 118.44(14)

37

DFT calculations

DFT calculations of 1a-c and 2a-c were performed on Gaussian09 software33 with

B3LYP 6-311G (d,p) level. The optimized structures are shown in Figure 2-8. The

optimized structures were almost consistent with the observed structures including the

intramolecular S···N distances. The natural atomic charges were also calculated based

on the optimized structures as shown in Figure 2-8. The positive charge on the sulfur

atom increases gradually by oxidation, and the negative charges were found to be

induced on the nitrogen atoms. The attractive interaction of 1c and 2c between the

sulfur and the nitrogen atoms is well explained by electrostatic interaction.

This induced negative charge by oxidation from 1b, 2b to 1c, 2c is thought to make the

acetylenic and the methyl protons shift upfield, respectively. And the upfield shift of

1,9-positions is reasonably explained by the substituent effect of the electron rich

nitrogen, which overcomes the anisotropy of the acetylene group.

Therefore the weakening of the intermolecular hydrogen bond in 1c can be explained

by the transannular S···N interaction in the phenothiazine unit. The higher oxidation

state in 1c results in a more positive charge on the S atom, thus enhancing the

interaction between S and the transannular N-atom donor. This interaction also induces

a more negative charge on the N atom and hence a higher π-electron density on the

38

acetylene group of 1c and lower acidity of the Csp−H atom. In 1H NMR spectroscopy,

this is reflected in a high field shift of Csp−H with respect to the situation in 1b.

39

(a) (d)

(b) (e)

(c) (f)

Figure 2-8. The optimized structures for 1a-c (a)-(c) and 2a-c (d)-(f) with natural

atomic charges of the sulfur, oxygen and nitrogen atoms. The positive and negative

charges are depicted in red and blue, respectively.

1.196 -0.440

-0.919

2.094 -0.793

-0.905

-0.926

-0.469 0.292 -0.476 0.296

1.197 -0.448

-0.916

2.094 -0.455

-0.903

-0.924

40

Transannular S···X (X = N, O) interaction in six-membered rings

Transannular interactions are well-known conception, and may exist across rings from

8- to 11-membered and even larger.34 In the sulfur-containing 6-membered rings, the

reports for the interaction are limited, because a structure of sulfur-containing

6-membered rings, such as thiomorpholines or 4H-1,4-thiazines, usually has a chair

conformation or a planar form where the distance between 1,4-positions is too far to

interact each other. However central six-membered rings of tricyclic sulfur-containing

aromatic compounds, such as phenothiazine, phenoxazine or thianthrene, have a boat

conformation and the distances between the 1,4-positions become shorten in the range

of 2.9 to 3.2 Å, which is close enough to make spatial contact each other.

The systematic studies of dependence on the oxidation state of sulfur atom have not

carried out yet, because the crystal structures for the three kinds of the oxidation states,

sulfide, sulfoxide and sulfone, were not completely solved in almost all compounds. In

the case of N-acetylphenothiazine derivatives,3-5 the three kinds were characterized, but

the position of the oxygen atom is disordered either the axial or the equatorial positions

in the sulfoxide. The S···N distances are 2.942(1) Å, 2.930(2) Å and 2.917(1) Å, with

increase of the oxidation number of the sulfur atoms. This tendency may be explained

by the decrease of the repulsive interaction between the oxygen at the axial position and

the nitrogen atoms owing to the smaller holding angles of phenothiazine moieties

41

compared with 1b, 1c, 2b or 2c. In the case of phenoxazines,35-37 the S···O distances are

3.045(2) Å, 3.1148(4) Å and 3.136(1) Å, with increase of the oxidation number of the

sulfur atoms. The elongation from the sulfide to the sulfoxide is similar to 2a and 2b,

but further elongation in the sulfone owing to its planar structure is not good accordance

with 1c and 2c.

While, in the case of phenyl-phenoxtinium iodide38 in which phenyl group is

substituted on the axial position of the sulfur atom, the S···O distance is close enough to

3.005(6) Å in spite of steric repulsion of the phenyl ring, indicating strong attractive

interaction between the oxygen atom and induced positive charge on the sulfur atom.

The similar shrinkage is also observed at the phenothiazine derivatives39,40 by

complexation with transition metals in the axial position of the sulfur atom. Namely, in

a boat conformation of sulfur-containing six-membered rings, large positive charges on

the sulfur atoms are found to increase transannular S···X interactions in spite of steric

repulsion.

42

2-3. Conclusion

The author has succeeded in preparations and crystallographic analyses of the novel

ynamine compounds, 1b, 1c, 2b and 2c, which were obtained by oxidation reaction

from 10-ethynyl-10H-phenothiazines (sulfide). On the oxidation process from 1a and 2a

to 1b and 2b, 1H NMR signals showed downfield shift as expected. However

anomalous upfield shift was observed at two kinds of hydrogens on the oxidation

process from 1b and 2b to 1c and 2c. Comparison of the structures between 1b and 1c,

2b and 2c, effective closeness between sulfur and nitrogen atoms was recognized, which

was also supported by the DFT calculations. The upfield shift was reasonably explained

by increase of electron density on the nitrogen atom caused by transannular S···N

interaction.

The results obtained in this work indicate that large positive charges on the sulfur

atoms induced by oxidation are found to increase transannular interactions in a boat

conformation of sulfur-containing six-membered rings in spite of steric repulsion. And

the interaction is conducted effectively as electron-donating effect toward the

π-conjugated system connected to the nitrogen atom.

Intermolecular Csp−H···O hydrogen bonds were encountered in 1b and 1c, and

stronger hydrogen bonds were found in 1b. The increase in π-electron density,

43

originating from the transannular S···N interaction, is consistent with a decrease in the

acidity of the Csp−H group in 1c.

44

2-4. Experimental Part

General procedure

All chemicals were purchased from Kanto Chemical Co. Ltd. or Tokyo Chemical

Industry Co. Ltd. and were used without further purification. 1H and 13C NMR spectra

were recorded on a JEOL JNM-ECA-400 spectrometer in a deuterated solvent

(chloroform-d) with tetramethylsilane as an internal standard. All 13C NMR spectra

were obtained with a complete proton decoupling. Elemental analysis was performed on

a J-SCEINCE LAB MICRO CORDER JM10.

Crystallographic analysis

X-ray crystallographic data were collected with a RIGAKU Saturn 724+ CCD device

by using multi-layered mirror monochromatic Mo Kα radiation at -180 °C. The

structures including non-H atoms were solved by a direct method (SIR92)41 and were

refined anisotropically. The C-bound H atoms except Csp-bound H atoms were obtained

by calculation and were refined as riding on their parent C atoms. Uiso(H) values of the

H atoms were set at 1.2Ueq (parent atom for Csp2) and 1.5Ueq (parent atom for Csp3

except for H15 of 2b ). The Csp-bound H atoms were obtained from a difference Fourier

map and were refined isotropically without any restrictions. All structures were refined

45

by full-matrix least squares method (Shelxl97).42

DFT calculations

DFT calculations of 1a-c and 2b-c were performed on the Gaussian 09 software33 with

B3LYP 6-311G (d,p) level. The geometrical optimization was carried out, where the

initial structures for calculations were set at those obtained by crystallographycal

analyses.

Materials

General procedure

A solution of 10-ethynyl-10H-phenothiazines and 1.1 eq. (sulfoxides) or 2.2 eq.

(sulfones) of m-CPBA in dichloromethane (50 mmol/L) was stirred for 2 h at -30 °C

(sulfoxide). In the case of sulfone, the solution was allowed to warm up to 0 °C and

stirred for 5h. The solution was poured into a saturated sodium thiosulfate solution. The

organic layer was washed with a saturated sodium hydrogen carbonate solution. It was

dried over anhydrous magnesium sulfate, and concentrated after filtration. The residue

was purified by recrystallization from acetone to give sulfoxides or sulfones of

10-ethynyl-10H-phenothiazines.

46

10-Ethynyl-10H-phenothiazine 5-oxide (1b)

Yield 93%. 1H NMR (400 MHz, CDCl3): δ 3.60 (s, 1H); 7.35 (dt, 3J = 7.5, 4J = 1.1 Hz,

2H); 7.64 (dt, 3J = 8.0, 4J = 1.6 Hz, 2H); 7.92 (dd, 3J = 7.8, 4J = 1.5 Hz, 2H); 7.95 (dd,

3J = 8.5, 4J = 0.8 Hz, 2H).

10-Ethynyl-10H-phenothiazine 5,5-dioxide (1c)

Yield 36%. 1H NMR (400 MHz, CDCl3): δ 3.57 (s, 1H); 7.43 (ddd, 3J = 8.0 Hz, 7.3 Hz,

4J = 0.9 Hz, 2H); 7.70 (ddd, 3J = 8.6 Hz, 7.3 Hz, 4J = 1.5 Hz, 2H); 7.94 (dd, 3J = 8.6 Hz,

4J = 0.9 Hz, 2H); 8.14(dd, 3J = 8.0 Hz, 4J = 1.5 Hz, 2H).

10-(Prop-1-yn-1-yl)-10H-phenothiazine 5-oxide (2b)

Yield 42%. 1H NMR (400 MHz, CDCl3): 2.25 (s, 3H); 7.35 (ddd, 3J = 8.4 Hz and 4J =

1.0 Hz, 2H); 7.67 (ddd, 3J = 7.6 Hz and 4J = 1.6 Hz, 2H); 7.94 (dd, 3J = 7.6 Hz and 4J =

1.6 Hz, 2H); 7.98 (dd, 3J = 8.4 Hz and 4J = 1.0 Hz, 2H). 13C NMR (100 MHz, CDCl3):

69.68; 73.18; 118.00; 123.98; 124.37; 131.04; 133.03; 136.87. Anal. Calc. for

C15H11N1O1S1: C, 71.12; H, 4.38; N, 5.53. Found; C, 70.88; H, 4.40; N, 5.46.

10-(Prop-1-yn-1-yl)-10H-phenothiazine 5,5-dioxide (2c)

Yield 56%. 1H NMR (400 MHz, CDCl3): 2.24 (s, 3H,); 7.38 (ddd, 3J = 8.4 Hz and 4J =

0.8 Hz, 2H); 7.68 (ddd, 3J = 8.2 Hz and 4J = 1.6 Hz, 2H); 7.91 (dd, 3J = 8.4 Hz and 4J =

0.8 Hz, 2H); 8.11 (dd, 3J = 8.2 Hz and 4J = 1.6 Hz, 2H). 13C NMR (100 MHz, CDCl3):

47

69.37; 72.84; 117.92; 123.30; 123.99; 124.59; 133.36; 138.82. Anal. Calc. for

C15H11N1O1S1: C, 66.89; H, 4.12; N, 5.20. Found; C, 66.71; H, 4.25; N, 5.26.

48

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G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B.

Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox, Gaussian 09, Revision B.1;

Gaussian, Inc.: Wallingford, CT, 2009.

34 C. Cope, M. M. Martin and M. A. McKervey, Q. Rev., Chem. Soc. 1966, 20, 119.

35 L. J. Fitzgerald, J. C. Gallucci and R. E. Gerkin Acta Crystallogr. 1991, C47, 381.

36 J. S. Chen, W. H. Watson, D. Austin and A. L. Ternay Junior, J. Org. Chem. 1979,

44, 1989.

37 A. D. Hendsbee, J. D. Masuda and A. Piorko, Acta Crystallogr. 2011, C67, m351.

52

38 A. I. Gusev and Y. T. Struchkov, Kristallografiya 1973, 18, 525.

39 R. Kroener, M.J. Heeg, E. Deutsch, Inorg. Chem. 1988, 27, 558.

40 B. J. Coe, M. C. Chamberlain, J. P. Essex-Lopresti, S. Gaines, J. C. Jeffery, S.

Houbrechts and A. Persoons, Inorg. Chem. 1997, 36, 3284.

41 A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M. Burla, G. Polidori and

M. Camalli, J. Appl. Crystallogr. 1994, 27, 435.

42 G. M. Sheldrick, Acta Crystallogr. 2008, A64, 112.

53

Chapter 3. Halogen Addition to 10-Ethynyl-10H-Phenothiazines

3-1. Introduction

Chapter 2 treated crystallographic, spectroscopic and theoretical studies for

10-ethynyl-10H-phenothiazines. Substituents of the acetylene terminal and oxidation on

the sulfur atom can afford a suitable perturbation to π-system of the ynamines. In this

chapter, reactivities of 10-ethynyl-10H-phenothiazines will be discussed.

Haloenamines are considered to be a useful precursor for natural and pharmaceutical

products.1-3 There are several synthetic routes for haloalkenes such as coupling of

simple haloalkenes with amines4-11 or halogenation of alkynes (Figure 3-1).12,13 The

former route contains nucleophilic substitution and requires hard condition such as a

presence of Cu or Pd-catalyst, suitable bases and high temperature. This is thought to be

disadvantage for the view of green chemistry. While, the latter one has been attracted

interest from the viewpoint of mild reaction conditions and their costs.

Many textbooks, mention that halogenation of alkenes with halogens such as I2, Br2

proceeds along anti-addition specifically because bridged halonium ion intermidiates

control the stereoselectivity.14-16 However, halogenation to alkyne are known to be lack

in stereoselectivity. Furthermore, reports of halogen addition to hetero acetylenes are

54

very limited.

The previous work of bromine addition to an ynamine was reported in

N-butyl-N-(3,3,3-trifluoroprop-1-yn-1-yl)butan-1-amine, in which two butyl groups

were substituted on the ynamine nitrogen (Figure 3-1(b)).12 In this report, the products

were not determined whether it was E or Z isomer, but the ratio of the isomer was

reported to be 78% and 22% and it showed an appreciable stereoselectivity. While

iodine monoboromide addition to an ynamide, methyl phenyl(phenylethynyl)carbamate,

was reported to give E isomer in a yield of 71% (Figure 3-1(c)).13

Figure 3-1. The previous works of coupling with simple haloalkenes and amines (a),

bromine addition to an ynamine (b) and iodine monoboromide addition to an ynamide

(c).

55

Recently, Sproul and Chalifoux reported stereoselective iodine monochloride addition

to acetylene compounds (Figure 3-2).17 In this paper, Z isomer of dihaloalkenes were

obtained selectively. The reason for the selectivity was concluded to neighboring-group

assistance of the trialkyl silyl group in reactive intermediates. This work inspired the

author to examine halogen addition to 10-ethynyl-10H-phenothiazines. Besides the

results of the halogen addition, the author wishes to mention a mechanism of

stereoselective halogenation reaction based on theoretical calculations.

Figure 3-2. Iodine monochloride addition to trialkyl silyl group substituted alkynes.

56

3-2. Results and Discussion

A general reaction scheme of halogens and interhalogen compound additions to

10-ethynyl-10H-phenothiazines is shown in Scheme 3-1. One equivalent of ICl, I2 or

Br2 was added to 10-ethynyl-10H-phenothiazines in a benzene solution. The structure of

each product was mainly determined by crystallographic analysis (Chapter 4), and the

Z/E ratio was also done by 1H NMR spectrum. The results of the addition are listed in

Table 3-1.

Scheme 3-1. Halogens and interhalogen compound additions to

10-ethynyl-10H-phenothiazines.

57

Table 3-1. Halogens and interhalogen compound addition to

10-ethynyl-10H-phenothiazines.

a The ratio of each isomer was determined by 1H NMR.

ICl addition to 10-ethynyl-10H-phenothiazines is summarized in entries 1-4. ICl

addition to 3c (entry 4), which carried a trimethylsilyl (TMS) group as same as the

literature (Figure 3-2),17 gave Z/E ratio of 85:15. Less stereoselective addition suggested

that explanation by neighboring-group assistance of silyl group was not suitable for the

addition to 3c, although it still had some stereoselectivity. Compared with entries 1 and

entry Ynamine R Y X1 X2 products Z : E ratioa

1 1c H SO2 I Cl 4c 60 : 40

2 2a Me S I Cl 5a 0 : 100

3 2c Me SO2 I Cl 5c 63 : 37

4 3c TMS SO2 I Cl 6c 85 : 15

5 1a H S I I 7a 5 : 95

6 1c H SO2 I I 7c 0 : 100

7 2a Me S I I 8a 7 : 93

8 2c Me SO2 I I 8c 2 : 98

9 1c H SO2 Br Br 10c 80 : 20

10 2a Me S Br Br 11a 40 : 60

11 2c Me SO2 Br Br 11c 75 : 25

12 3c TMS SO2 Br Br 12c 100 : 0

58

4, the selectivity further decreased to 60:40 by decreasing bulkiness of the acetylene

terminal. This tendency is also recognized at entries 9, 11, and 12 (vide infra). Entries 2

and 10 showed opposite selectivity compared with entries 3 and 11, suggesting

oxidation on sulfur atom led to increase Z-selectivity.

In the case of 2a (entry 2), the E isomer was obtained, indicating an intermediate had a

simple bridged form as written in the literature.18,19 I2 addition to 1a, 1c, 2a and 3c

(entries 5-8) showed E-selectivity. These results are reasonable by assuming bridged

iodonium intermediate. But Z-selectivity in entries 1, 3, and 4 cannot be explained by

bridged cation intermediate because both addition are thought to have the same

intermediate.

Entries 9-12 showed the results of Br2 addition in which Z-selectivity is recognized.

Entries 9 and 11 gave almost the same selectivity, suggesting steric effects of methyl

group and hydrogen atom is not so different. Addition to 3c (entry 12), which carries

TMS group at acetylene terminal, gave the Z isomer specifically. Z-selectivities

observed in Br2 addition cannot be also explained by the bridged cation intermediate.

59

DFT calculations

The first step of halogenation to alkyne is addition of halonium ion. In order to

determine a structure of the reactive intermediate, the four possible structures were

selected as an initial structure (Figure 3-3): (A) X+ atom bonds to the carbon atom

adjacent to the nitrogen atom, resulting in localization of positive charge on the remote

trivalent carbon atom (B) X+ atom bonds to the carbon atom remote to the nitrogen

atom, resulting in localization of positive charge on the adjacent carbon atom (C) X+

atom bridges two vinyl carbon atom and positive charge is on the bridged X+ atom. (D)

Silyl atom bridges two vinyl carbon atom and positive charge is on the bridged Si atom

in the presence trimethylsilyl group in the acetylene terminal. In both cases of X=Br, I,

each form A and B was found to be a local minimum structure and form B is fairly

stable than form A, indicating form B is the global minimum structure of the

intermediates (Table 3-2). For instance, in the case of Br2 addition to 1a, form B is

171.7 kJ mol-1 more stable than form A (form B = anti form). While forms C and D

were not the local minimum structures and they converged to form B.

60

Figure 3-3. The structures of reaction intermediates A, B, C and D.

Table 3-2. Energy differences (kJ mol-1) between forms A and Ba of I2 or Br2 addition to

10-ethynyl-10H-phenothiazines.

S SO2

I2

H 179.9 136.0

Me 138.1 109.5

TMS 139.2 128.4

Br2

H 171.7 133.9

Me 134.1 118.7

TMS 134.1 120.1

a: Form B = anti form.

61

Furthermore form B was found to have two conformers, anti and syn forms, where

C-X bond directs downward or upward to the phenothiazine butterfly structure. The

optimized structures and their electrostatic potential maps were shown Figures 3-4 and

3-5, and the energy differences of both intermediates were listed in Table 3-3. In each

intermediate, anti form was found to be more stable structure. The tendency of the

energy differences was summarized as follows: The energy differences between anti and

syn forms increased as bulkiness of substituent in acetylene terminal or as oxidation

state of the sulfur atom increase.

62

Figure 3-4. The optimized intermediate structures and their electrostatic potential maps

for the anti and syn forms of the Br2 addition to 1a (a) (b), 2a (c) (d) and 3a (e) (f).

anti form (0.0 kJ mol-1)

anti form (0.0 kJ mol-1)

anti form (0.0 kJ mol-1)

syn form (1.6 kJ mol-1)

syn form (3.2 kJ mol-1)

syn form (6.7 kJ mol-1)

(a) (b)

(c) (d)

(e) (f)

63

anti form (0.0 kJ mol-1)

anti form (0.0 kJ mol-1)

anti form (0.0 kJ mol-1)

syn form (1.9 kJ mol-1)

syn form (6.1 kJ mol-1)

syn form (10.3 kJ mol-1)

Figure 3-5. The optimized intermediate structures and their electrostatic potential maps

for the anti and syn forms of the Br2 addition to 1c (a) (b), 2c (c) (d) and 3c (e) (f).

(a) (b)

(c) (d)

(e) (f)

64

Table 3-3. The energy differences and the populationsa (kJ mol-1, %) between the anti

and syn forms of I2 or Br2 addition to 10-ethynyl-10H-phenothiazines.

a: In the case of T = 300 K.

The possible routes for formation of Z isomers are that X- attacks from the same side

of C-X bond in each intermediate (Figure 3-6, routes 1 and 4). In anti form, closeness of

X- seems to be prohibited by S=O group sterically and electrostatically (route 2). While,

in syn form, attack of X- is prohibited by R-group sterically (route 3). Also the possible

routes for formation of E-isomer are that X- attacks from the opposite side of C-X bond

in both intermediates (routes 2 and 3). In anti form, attack of X- is prohibited by C-X

bond sterically and electrostatically (route 1) and electrostatically. While, in syn form,

closeness of X- seem to be prohibited by sterically and electrostatically of S=O group

and C-X bond (route 4).

R S SO2

anti syn anti syn

I2

H 1.1 kJ mol-1 0.7 kJ mol-1

61% 39% 57% 43%

Me 2.3 kJ mol-1 4.2 kJ mol-1

71% 29% 84% 16%

TMS 6.6 kJ mol-1 10.7 kJ mol-1

93% 7% 99% 1%

Br2

H 1.6 kJ mol-1 1.9 kJ mol-1

66% 34% 68% 32%

Me 3.2 kJ mol-1 6.1 kJ mol-1

78% 22% 91% 9%

TMS 7.1 kJ mol-1 12.1 kJ mol-1

95% 5% 99% 1%

65

Figure 3-6. The possible reaction routes of halogen addition to

10-ethynyl-10H-phenothiazines.

66

In Br2 addition (entries 9-12), addition to 2a showed little stereoselectivity. This is

presumably because steric repulsion of phenothiazine moiety and methyl group in anti

form did not work effectively. While addition to 2c, in which sulfur atom were oxidized

to sulfone, indicated clear Z-selectivity. The electrostatic and steric repulsion of S=O

group worked effectively. In the bulky TMS group, additive steric repulsion of TMS

prevented formation of the E isomer, showing highly notable Z-selectivity. Addition to

1c (entry 9) and 2c (entry 11) showed little difference in Z-selectivity, suggesting these

steric effects of hydrogen are similar to that of methyl group.

Concerning reactive intermediate of I2 or ICl addition, anti form was found to be more

stable than syn form, but energy differences became smaller than the case of bromine.

This is presumably because steric and electrostatic repulsion decreases owing to long

C−I bond. In I2 addition (entries 5-8), E-selectivity of the addition was clearly

recognized. Steric repulsion between I- and I atom of the intermediate was thought to

work effectively, and I- connected to the carbon from the opposite side of C−I bond to

afford the E isomer. In the case of ICl addition, the intermediate is similar to that of I2

addition, but E-selectivity remarkably decreased. Since Cl- is smaller than I-, repulsion

of I atom of the intermediate does not work effectively and repulsion of S=O works

relatively effective to give the Z isomer.

67

3-3. Conclusion

Halogen addition of ICl, I2 and Br2 to 10-ethynyl-10H-phenothiazines was carried out.

In the case of Br2 and ICl addition, Z-selectivity was recognized in spite of absence of

TMS group. While, in the case of I2 addition, E-selectivity was strongly observed. These

complicated selectivity was well explained by considering reactive intermediates

obtained by theoretical calculations. Surprisingly, the structure of the intermediates was

strongly supported to be open-carbocation structure in all additions nor bridged cation.

The stabilization of free carbocation by conjugation to lone pair of nitrogen was more

effective than expected. And the selectivity was found to be generated by steric

hindrance of the molecule and electrostatic potential.

68

3-4. Experimental Part

General procedure

All chemicals were purchased from Kanto Chemical Co. Ltd. or Tokyo Chemical

Industry Co. Ltd. and were used without further purification. Gel permeation

chromatography (GPC) was performed on a JAI LC-918 equipped with JAIGEL -1H

and -2H columns. 1H and 13C NMR spectra were recorded on a JEOL JNM-ECA-400

spectrometer in a deuterated solvent (chloroform-d) with tetramethylsilane as an internal

standard. All 13C NMR spectra were obtained with a complete proton decoupling.

DFT calculations

DFT calculations were performed on the Gaussian 09 program20 with B3LYP 6-311G

(d,p) level (C, H, O, N, S, Si, Cl, Br) and DGDZVP level (I).

Materials

General halogen or interhalogen addition to 10-ethynyl-10H-phenothiazines.

A halogen or interhalogen solution in benzene (0.10 M) was added dropwise to a

solution of 10-ethynyl-10H-phenothiazines in benzene (0.10 M) at 5-10 °C and the

solution was stirred for an hour. It was poured into a saturated sodium thiosulfate

69

solution and extracted with benzene. The organic layer was washed with water and

dried over anhydrous magnesium sulfate. After removal of magnesium sulfate, it was

concentrated by a rotary evaporator. The residue was purified by GPC to give

10-dihalovinyl-10H-phenothiazine.

10-(1-Chloro-2-iodovinyl)-10H-phenothiazine 5,5-dioxide (4c)

Z-isomer: Yield 29%. 1H NMR (400 MHz, CDCl3): δ 7.36 (d, 3J = 8.6 Hz, 2H); 7.40

(dt, 3J = 7.6 Hz and 4J = 0.9 Hz, 2H); 7.53 (s, 1H); 7.66 (ddd, 3J = 8.6 Hz, 7.4 Hz and 4J

= 1.6 Hz, 2H); 8.15 (dd, 3J = 8.0 Hz, and 4J = 1.5 Hz, 2H). 13C NMR (100 MHz,

CDCl3): δ 90.63; 116.90; 123.89; 123.92; 124.11; 133.63; 136.94; 138.05. Anal. Calc.

for C14H9Cl1I1N1O2S1: C, 40.26; H, 2.17; N, 3.35. Found; C, 40.17; H, 2.08; N, 3.27.

E-isomer: Yield 4%. 1H NMR (400 MHz, CDCl3): δ 1H NMR (400 MHz, CDCl3): δ

7.40-7.44 (m, 4H); 7.46 (s, 1H); 7.68 (ddd, 3J = 8.4 Hz, 7.5 Hz and 4J = 1.6 Hz, 2H);

8.20 (dd, 3J = 7.6 Hz, and 4J = 1.5 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 84.96;

116.18; 123.95; 124.14; 124.20; 130.56; 133.66; 135.86. Anal. Calc. for

C14H9Cl1I1N1O2S1: C, 40.26; H, 2.17; N, 3.35. Found; C, 40.01; H, 2.04; N, 3.11.

10-(1-Chloro-2-iodoprop-1-en-1-yl)-10H-phenothiazine (5a)

E-isomer: Yield 55%. 1H NMR (400 MHz, CDCl3): δ 2.75 (s, 3H); 6.90 (dd, 3J = 8.2

Hz and 4J = 1.6 Hz, 2H); 6.94 (td, 3J = 7.5 Hz and 4J = 1.2 Hz, 2H); 7.02 (dd, 3J = 7.7

70

Hz and 4J = 1.6 Hz, 2H); 7.07 (ddd, 3J = 8.1 Hz, 7.3 Hz and 4J = 1.6 Hz, 2H). 13C NMR

(100 MHz, CDCl3): δ 29.79; 99.18; 115.65; 120.45; 123.93; 126.72; 127.21; 129.15;

138.74.

10-(1-Chloro-2-iodoprop-1-en-1-yl)-10H-phenothiazine 5,5-dioxide (5c)

Z-isomer: Yield 35%. 1H NMR (400 MHz, CDCl3): δ 2.43 (s, 3H); 7.36 (d, 3J = 8.6 Hz,

2H); 7.40 (dt, 3J = 7.6 Hz and 4J = 0.9 Hz, 2H); 7.68 (ddd, 3J = 8.6 Hz, 7.4 Hz and 4J =

1.6 Hz, 2H); 8.16 (dd, 3J = 7.9 Hz, and 4J = 1.6 Hz, 2H). 13C NMR (100 MHz, CDCl3):

δ 29.06; 108.26; 116.5; 123.77; 123.84; 124.17; 130.83; 133.71; 137.33. Anal. Calc. for

C15H11Cl1I1N1O2S1: C, 41.74; H, 2.57; N, 3.24. Found; C, 41.66; H, 2.04; N, 2.99.

E-isomer: Yield 23%. 1H NMR (400 MHz, CDCl3): δ 2.86 (s, 3H); 7.31 (d, 3J = 8.6 Hz,

2H); 7.40 (t, 3J = 7.6 Hz, 2H); 7.66 (ddd, 3J = 8.5 Hz, 7.4 Hz and 4J = 1.4 Hz, 2H); 8.19

(dd, 3J = 8.0 Hz, and 4J = 1.44 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 30.12; 102.15;

116.26; 123.74; 124.07; 125.37; 133.55; 136.40. Anal. Calc. for C15H11Cl1I1N1O2S1: C,

41.74; H, 2.57; N, 3.24. Found; C, 41.98; H, 2.62; N, 3.08.

10-(1-Chloro-2-iodo-2-(trimethylsilyl)vinyl)-10H-phenothiazine 5,5-dioxide (6c)

Z-isomer: Yield 37%. 1H NMR (400 MHz, CDCl3): δ 0.02 (s, 9H); 7.33 (d, 3J = 8.6 Hz,

2H); 7.41 (t, 3J = 7.9 Hz, 2H); 7.68 (ddd, 3J = 8.6 Hz, 7.3 Hz and 4J = 1.6 Hz, 2H); 8.16

(dd, 3J = 7.9 Hz, and 4J = 1.6 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 0.10; 117.04;

71

119.96; 123.81; 123.84; 124.04; 133.46; 136.64; 137.59. Anal. Calc. for

C17H17Cl1I1N1O2S1Si1: C, 41.69; H, 3.50; N, 2.86. Found; C, 41.92; H, 3.36; N, 2.82.

10-(1,2-Diiodovinyl)-10H-phenothiazine (7a)

E-isomer: Yield 40%. 1H NMR (400 MHz, CDCl3): δ 6.98-7.01 (m, 4H); 7.04 (d, 3J =

7.7 Hz, 2H); 7.10 (ddd, 3J = 8.3, 5.9 Hz and 4J = 2.7 Hz, 2H); 7.46 (s, 1H). 13C NMR

(100 MHz, CDCl3): δ 86.45; 102.46; 117.09; 120.26; 124.42; 126.87; 127.38; 136.65.

Anal. Calc. for C14H9I2N1S1: C, 35.24; H, 1.90; N, 2.94.

10-(1,2-Diiodovinyl)-10H-phenothiazine 5,5-dioxide (7c)

E-isomer: Yield 75%. 1H NMR (400 MHz, CDCl3): δ 7.45-7.49 (m, 4H); 7.71 (ddd, 3J

= 8.7 Hz, 7.2 Hz and 4J = 1.6 Hz, 2H); 7.88 (s, 1H); 8.22 (dd, 3J = 7.9 Hz and 4J = 1.6

Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 91.17; 93.35; 117.04; 124.07; 124.37; 133.68;

135.02. IR absorption (KBr, νmax/cm-1): 3066, 1294, 1162. Anal. Calc. for

C14H9I2N1O2S1: C, 33.03; H, 1.78; N, 2.75. Found; C, 33.01; H, 1.91; N, 2.83.

10-(1,2-Diiodoprop-1-en-1-yl)-10H-phenothiazine (8a)

E-isomer: Yield 73%. 1H NMR (400 MHz, CDCl3): δ 2.70 (s, 3H); 6.92 (d, 3J = 8.2 Hz,

2H); 6.94-6.97 (m, 4H); 7.05 (ddd, 3J = 8.3, 5.7 Hz and 4J = 3.3 Hz, 2H). 13C NMR (100

MHz, CDCl3): δ 36.36; 100.91; 102.59; 116.94; 119.80; 124.06; 126.69; 127.18; 137.08.

Anal. Calc. for C15H11I2N1S1: C, 36.68; H, 2.26; N, 2.85. Found; C, 36.81; H, 2.15; N,

72

2.62.

10-(1,2-Diiodoprop-1-en-1-yl)-10H-phenothiazine 5,5-dioxide (8c)

E-isomer: Yield 60%. 1H NMR (400 MHz, CDCl3): δ 2.83 (s, 3H); 7.39 (d, 3J = 8.6 Hz,

2H); 7.45(td, 3J = 7.6 Hz, and 4J = 0.8 Hz, 2H); 7.68 (ddd, 3J = 8.6 Hz, 7.3 Hz and 4J =

1.6 Hz, 2H); 8.21 (dd, 3J = 7.9 Hz and 4J = 1.5 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ

36.75; 93.77; 105.46; 117.23; 123.83; 124.23; 124.30; 133.50; 135.59. Anal. Calc. for

C15H11I2N1O2S1: C, 34.44; H, 2.12; N, 2.65. Found; C, 34.68; H, 2.05; N, 2.53.

10-(1,2-Dibromovinyl)-10H-phenothiazine 5,5-dioxide(10c)

Z-isomer: Yield 55%. 1H NMR (400 MHz, CDCl3): δ 7.40-7.46 (m, 4H); 7.48 (s, 1H);

7.68 (ddd, 3J = 8.6 Hz, 7.3 Hz and 4J = 1.6 Hz, 2H); 8.17 (dd, 3J = 7.9 Hz and 4J = 1.6

Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 117.10; 120.70; 123.86; 123.99; 124.27;

124.99; 133.49; 138.21. Anal. Calc. for C14H9Br2N1O2S1: C, 40.51; H, 2.19; N, 3.37.

Found; C, 40.15; H, 2.43; N, 3.47.

E-isomer: Yield 11%. 1H NMR (400 MHz, CDCl3): δ 7.31 (s, 1H); 7.41-7.46 (m, 4H);

7.69 (ddd, 3J = 8.7 Hz, 7.2 Hz and 4J = 1.6 Hz, 2H); 8.20 (dd, 3J = 7.9 Hz and 4J = 1.6

Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 113.29; 116.52; 118.07; 124.11; 124.18;

124.49; 133.67; 135.75. IR absorption (KBr, νmax/cm-1): 3074, 1298, 1167. Anal. Calc.

for C14H9N1O2S1Br2: C, 40.51; H, 2.19; N, 3.37. Found; C, 40.64; H, 2.19; N, 3.16.

73

10-(1,2-Dibromoprop-1-en-1-yl)-10H-phenothiazine (11a)

Z-isomer: Yield 25%. 1H NMR (400 MHz, CDCl3): δ 2.39 (s, 3H); 6.94 (dt, 3J = 7.4

Hz and 4J = 1.2 Hz, 2H); 6.99 (m, 4H); 7.09 (dt, 3J = 7.7 Hz and 4J = 1.7 Hz, 2H). 13C

NMR (100 MHz, CDCl3): δ 25.01; 116.20; 120.41; 122.85; 124.07; 126.75; 127.39;

132.68; 139.22. Anal. Calc. for C15H11Br2N1S1: C, 45.37; H, 2.79; N, 3.53. Found; C,

45.28; H, 2.68; N, 3.55.

E-isomer: Yield 14%. 1H NMR (400 MHz, CDCl3): δ 2.61 (s, 3H); 6.92-6.96 (m, 4H);

6.99 (dd, 3J = 8.0 Hz and 4J = 1.8 Hz, 2H); 7.07 (dt, 3J = 7.6 Hz and 4J = 1.8 Hz, 2H).

13C NMR (100 MHz, CDCl3): δ 27.59; 116.21; 119.74; 120.50; 123.52; 124.07; 126.71;

127.21; 138.19. Anal. Calc. for C15H11Br2N1S1: C, 45.37; H, 2.79; N, 3.53. Found; C,

45.15; H, 2.80; N, 3.51.

10-(1,2-Dibromoprop-1-en-1-yl)-10H-phenothiazine 5,5-dioxide (11c)

Z-isomer: Yield 35%. 1H NMR (400 MHz, CDCl3): δ 2.24 (s, 3H); 7.42 (td, 3J = 7.6

Hz and 4J = 0.8 Hz, 2H); 7.46 (d, 3J = 8.6 Hz, 2H); 7.69 (ddd, 3J = 8.6 Hz, 7.3 Hz and 4J

= 1.6 Hz, 2H); 8.17 (dd, 3J = 7.9 Hz and 4J = 1.5 Hz, 2H). 13C NMR (100 MHz,

CDCl3): δ 24.80; 116.74; 118.22; 123.89; 123.92; 124.36; 133.68; 134.94; 137.49. Anal.

Calc. for C15H11Br2N1O2S1: C, 41.98; H, 2.58; N, 3.53. Found; C, 41.80; H, 2.85; N,

3.55.

74

10-(1,2-Dibromo-2-(trimethylsilyl)vinyl)-10H-phenothiazine 5,5-dioxide (12c)

Z-isomer: Yield 41%. 1H NMR (400 MHz, CDCl3): δ 0.02 (s, 9H); 7.42-7.45 (m, 2H);

7.70 (ddd, 3J = 8.7 Hz, 7.2 Hz and 4J = 1.5 Hz, 2H); 8.19 (dd, 3J = 8.0 Hz and 4J = 1.5

Hz, 2H). 13C NMR (100 MHz, CDCl3): δ -0.69; 117.39; 124.00; 124.07; 124.08;

126.97; 133.41; 137.87; 142.85. Anal. Calc. for C17H17Br2N1O2S1Si1: C, 41.90; H, 3.52;

N, 2.87. Found; C, 41.86; H, 3.61; N, 2.81.

75

3-5. References

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78

79

Chapter 4. Crystal Structures of 10-Dihalovinyl-10H-Phenothiazines and Their

Halogen Bonds

4-1. Introduction

In Chapter 3, the author mentioned stereo selectivity in addition of halogens and

interhalogen compound to 10-ethynyl-10H-phenothiazines. As the results of the

addition, several classes of 10-dihalovinyl-10H-phenothiazines were obtained. In this

chapter, intermolecular interaction of 10-dihalovinyl-10H-phenothiazines are discussed.

During the last two decades, non-covalent bonds such as hydrogen bonds,1,2 halogen

bonds3-5 and chalcogen bonds6-9 attract interest from viewpoints of crystal engineering,

macromolecular chemistry or pharmacology. Halogen bonds have been thought to be

especially important for crystal engineering because they have a clear directional

property.

Halogen bonds were defined by IUPAC in 201310,11 as “an attractive interaction

between an electrophilic region associated with a halogen atom in a molecular entry and

a nucleophilic region in another, or the same, molecular entry”. And in order to

understand halogen bonds deeply, the concept of σ-hole, proposed by Politzer’s group in

200712-18, is particularly important.

80

A typical halogen bond is denoted by the three dots in R−X···Y (X = halogen atoms).

Many patterns of halogen bonds are possible by combination of Lewis acids and bases.

The strength of halogen bonds is known to increase as the electronegativity of X

decreases, because σ-holes become larger in this order. However systematic studies of

dependence on halogen atoms or complementary works of experimental and theoretical

aspects are limited. In this chapter, the author wishes to report two works. One is the

anomalous planar structure caused by intermolecular halogen bond in E isomer of

10-(1,2-dibromoprop-1-en-1-yl)-10H-phenothiazine (11a). The other is a systematic

study of crystal structures of (E)-10-dihalovinyl-10H-phenothiazine 5,5-dioxides (X =

Cl, Br, I), and the intermolecular halogen bonds in their crystals.

Phenothiazines, which are classified into an important class of tricyclic nitrogen-sulfur

heterocycles,19-20 are known to have good electron donating property, and have been

used to make charge transfer complexes.21-30 Phenothiazines also attracted interest from

the viewpoints of photoinduced electron transfer (PET)31 or pharmacology.32,33 Hence

much attention has been paid to correlation between their properties and structures.

Generally, phenothiazines are known to have a butterfly structure. In contrast, they

have a planar structure when they have positive charges. A recent report also indicated

planarity of phenothiazine rings increases in their excited state.34 According to

81

Cambridge Structural Database (CSD),35 26 structures of planar phenothiazines have

been reported, including those of 22 charged phenothiazines. The remaining four

compounds have no charges on phenothiazine rings,36-38 and the reason for planarity

was interpreted as stabilization by intramolecular charge transfer interaction.

The CSD39 also shows that more than a thousand of crystals are found to have

R−X···O=S halogen bonds, which means importance of the halogen bonds. These

systematic and theoretical studies are required for designs of novel materials or drugs,

but there are only 16 systematic studies for R−X···O=S halogen bonds.40-62 Furthermore

there appears some lack of halogen entries, and there are only three series40-45 which

have more than three kinds of halogen atoms. In the case of studies in molecular

complexes, weak R−Cl···O=S interaction may not promote co-crystallization. Therefore

structural studies on single component is thought to be favorable for this kind of weak

interaction. Recently, a crystal structure of 10-(1,2,2-trichlorovinyl)-10H-phenothiazine

5,5-dioxide was reported.63 In this crystal, trichlorovinyl group twisted perpendicular to

phenothiazine moiety and an intermolecular C−Cl···O=S interaction was recognized.

Because of steric repulsion, vinyl groups on 10-position of phenothiazine derivatives

have a twisted conformation unless there is a geminal hydrogen atom or charge transfer

interaction between phenothiazine moiety and the substituents.64-66 Phenothiazines are

82

known to be oxidized at 5-position to give mono- and di-oxides. By fully oxidized,

charge transfer interaction and structural flexibility owing to ring inversion should be

suppressed. Therefore 10-halovinyl phenothiazine 5,5-dioxides are expected to have

twisted conformation, which leads to little intramolecular interaction between the C−X

and S=O groups.

The author reports herein anomalous planar structure of (E)-

10-(1,2-dibromoprop-1-en-1-yl)-10H-phenothiazine (E-11a), and a systematic study of

(E)-10-dihalovinyl-10H-phenothiazine 5,5-dioxides (X = Cl (E-13c), Br (E-10c), I

(E-7c)) (Scheme 4-1). The intermolecular halogen bonds in their crystals should be

discussed based on DFT calculations.

Scheme 4-1. The structural formulas of E-11a, Z-11a, E-13c, E-10c and E-7c.

83

4-2. Results and discussion

Synthesis

There are two possible routes for preparation of dihalovinyl amines, (1) haloganation

of ynamines67,68 and (2) nucleophilic substitution of trihaloolefines with amines.69-71

Compound Z-11a, E-11a, E-10c and E-7c were obtained by the former route with

10-ethynyl-10H-phenothiazines (2a and 1c) and corresponding halogenes (Chapter 3,

Scheme 3-1). An iodine addition to the ynamine proceeded stereospecifically, while a

bromine addition resulted in poor selectivity. Compound E-10c could be given by the

similar way to E-13c, although the yield was quite low.

Compound E-13c was obtained by the latter route between trichloroethylene and

10H-phenothiazine 5,5-dioxide (Scheme 4-2). The former route was not examined

because of difficulty in reaction control. Compound E-13c was also obtained in low

yield from 10-(1,2,2-trichlorovinyl)-10H-phenothiazine 5,5-dioxide by metal-halogen

exchange reaction followed by immediate quenching with methanol.

Scheme 4-2. Preparation of E-13c.

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Crystal structures of Z and E isomers 11a

Single crystals of the Z and E isomers 11a with sufficient quality for X-ray analysis

were obtained by slow concentration from a toluene solution. Crystal data and

geometric parameters of both isomers are summarized in Tables 4-1 and 4-2,

respectively.

Figure 4-1 shows the crystal structure of Z-11a. In Z-11a, the phenothiazine moiety

has a butterfly structure, and the central six-membered ring has a boat conformation.

The dihedral angle between two benzene rings is 31.11(14)°. The structure around the

nitrogen atom is pyramidal, where the N atom locates upward at 0.128(3) Å from the

plane formed by three adjacent carbon atoms (plane N). The dihedral angle between

plane N and N1/C13/C14/C15/Br1/Br2 (r.m.s. deviation = 0.0206 Å) is 87.88(3)°,

indicating the phenothiazine moiety doesn’t conjugate with the dibromopropenyl group.

Intramolecular contact can be detected at Csp3−H∙∙∙N1 and Br1∙∙∙H11 where the

distances are 2.480(5) Å and 2.7759(9) Å, respectively.

A chain structure along the c axis (Figure 4-1(b)) is formed by C13−Br1···S1i

[Symmetry code: (i) x, -y+2, z+1/2.] halogen bonds whose distance is 3.430(15) Å

(Table 4-3), indicating 6% shrinkage compared with the sum of van der Waals radii of

Br and S atoms. The angle of C13−Br1···S1i is 162.48(9)°.

85

(a)

(b)

Figure 4-1. The molecular structure (a) and the crystal packing structure (b) of Z-11a

with atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability

level and H atoms are shown as small spheres. [Symmetry codes: (i) x, -y+2, z+1/2; (ii)

x, -y+2, z-1/2.]

86

In E-11a, the phenothiazine moiety has an anomalous planar structure (Figure 4-2) in

which the dihedral angle between two benzene rings is 2.40(11)°. The vinylic part is

found to be disordered (Form A and B = 50/50). The structure around the nitrogen atom

is pyramidal, where the N atom locates upward at 0.138(3) Å in disordered form A and

0.123(3) Å in disordered form B from the plane formed by corresponding three adjacent

carbon atoms (plane NA and NB). The dihedral angles of the vinyl plane with the plane

NA and NB are 87.714(12)° and 86.708(13)° respectively, indicating the phenothiazine

moiety doesn’t conjugate with the dibromopropenyl group. The significant differences

in molecular structure between the Z and E isomers 11a are observed in the central

six-membered ring. In comparison with Z-11a, tendency in shrinkage of bond distances

and expansion of C6−S1−C7 and C1−N1−C12 angles of E-11a is recognized in the

central six-membered ring (Table 4-2). Intramolecular Csp3−H∙∙∙N and Br∙∙∙H

interactions become disappeared which were detected in Z-11a.

Figure 4-2 shows the crystal packing structure of E-11a. Intermolecular Br2···C10i

and Br2···H4ii [Symmetry codes: (i) x, -y+3/2; z+1/2 (ii) -x+2, y-1/2, -z+3/2.] distances

are 3.355(4) Å and 2.8588(8) Å, shrinking by 5% and 6% respectively compared with

the sum of van der Waals radii of Br with C or H atoms (Table 4-3). Intermolecular

Br2···C10i contact gives a chain structure along the c axis, and Br2···H4ii affords

87

another chain along the b axis.

(a)

(b)

Figure 4-2. The molecular structure (a) and Crystal packing structure (b) of E-11a with

atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability

level and H atoms are shown as small spheres. Disordered atoms are discriminated with

A/B notation, and the disordered forms are drawn as solid and open bonds, respectively.

[Symmetry codes: (i) x, -y+3/2, z+1/2; (ii) –x+2, y-1/2, -z+3/2; (iii) x, -y+3/2, z-1/2.]

88

Table 4-1. Crystal data and refinement details for the Z and E isomers 11a.