Synthesis of ethyl 8-aryl-8-hydroxy-3-oxo-8H[1,2,4]oxadiazolo-[3,4-c][1,4] thiazine-5-carboxylates by ring-expansion rearrangement

Article abstract of DOI:10.1080/00397910701265945

The title compounds were prepared by the ring-ring interconversion of ethyl 5-nitroso-6-arylimidazo[2,1-b]thiazole-3-carboxylates with hydrochloric acid. The effect of electron-withdrawing substituent in the thiazole ring on the general applicability of t

Full text of DOI:10.1080/00397910701265945

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Synthesis of Ethyl
8‐Aryl‐8‐hydroxy‐3‐oxo‐8H[1,2,4]oxadiazolo‐[3,4
[1,4]thiazine‐5‐carboxylates by
Ring‐Expansion Rearrangement
Rajesh Koti a , Vinayak Hegde a , Gundurao Kolavi, a & Imtiyaz Ahmed Khazi
a
a Department of Chemistry , Karnatak University , Dharwad, India
Published online: 22 May 2007.
To cite this article: Rajesh Koti , Vinayak Hegde , Gundurao Kolavi, & Imtiyaz Ahmed Khazi (2007) Synthesis
of Ethyl 8‐Aryl‐8‐hydroxy‐3‐oxo‐8H[1,2,4]oxadiazolo‐[3,4‐c][1,4]thiazine‐5‐carboxylates by Ring‐Expansion
Rearrangement, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 37:10, 1715-1722, DOI: 10.1080/00397910701265945
To link to this article: http://dx.doi.org/10.1080/00397910701265945
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Synthetic Communicationsw, 37: 1715–1722, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701265945
Synthesis of Ethyl 8-Aryl-8-hydroxy-3-oxo-
8H[1,2,4]oxadiazolo-[3,4-c][1,4]thiazine-5-
carboxylates by Ring-Expansion
Rearrangement
Rajesh Koti, Vinayak Hegde, Gundurao Kolavi, and
Imtiyaz Ahmed Khazi
Department of Chemistry, Karnatak University, Dharwad, India
Abstract: The title compounds were prepared by the ring–ring interconversion of
ethyl 5-nitroso-6-arylimidazo[2,1-b]thiazole-3-carboxylates with hydrochloric acid.
The effect of electron-withdrawing substituent in the thiazole ring on the general appli-
cability of the ring–ring interconversion has been also evaluated.
Keywords: imidazo[2,1-b]thiazole, oxazolothiazines, ring–ring interconversion
INTRODUCTION
A literature survey reveals that both oxadiazole and thiazine derivatives
exhibit pharmacological activities wherein oxadiazoles displayed antibacter-
ial, antitubercular, anticancer, anti-inflammatory, and anti-HIV activities[1,2]
and thiazines showed fungicidal[3] activity and are a constituent of cephalos-
porine antibiotics.[3] Oxadiazolothiazines are known to act as myocardial
calcium channel modulators.[4] They exhibited potential antitumor and fungi-
cidal action also. In view of this and in continuation of our work on fused
heterocyclic systems containing nitrogen and sulfur,[5,6] we are reporting a
new simple route for the synthesis of novel oxadiazolothiazines. The
present work also explains the reactivity of 3-ethoxycarbonyl-5-nitroso-6-
arylimidazo[2,1-b]thiazoles with hydrochloric acid in ethanol.
Received in India February 7, 2007
Address correspondence to Imtiyaz Ahmed Khazi, Department of Chemistry,
Karnatak University, Dharwad, India. E-mail: drimkorgchem@gmail.com
1715

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R. Koti et al.
DISCUSSION
The reaction of 2-aminothiazole-4-carboxylate with a-haloketones in boiling
ethanol for 14 h afforded the desired 3-ethoxycarbonyl-6-arylimidazo[2,1-
b]thiazolium bromide in good yields, which on neutralization gave correspond-
ing free bases (3a–g). The p electron charge data of imidazothiazole system
clearly tells us that all electrophilic substitution reactions take place at
C-5 and not at C-2. These findings prompted us to study the effect of the
ethoxycarbonyl group during ring–ring interconversion of 3-ethoxycarbonyl-
5-nitroso-6-arylimidazo[2,1-b]thiazoles (4a–g) into ethyl 8-aryl-8-hydroxy-
3-oxo-8H[1,2,4]oxadiazolo[3,4-c][1,4]thiazine-5-carboxylates (5a–g).
The required 3-ethoxycarbonyl-5-nitroso-6-aryl-imidazo[2,1-b]thiazoles
(4a–g) were prepared by nitrosation of corresponding imidazothiazoles
(3a–g). The IR spectrum of nitroso compound showed nC55O for ester in the
range 1720–1710 cm21 along with nNO in the range of 1540–1530 cm21
The H NMR spectra showed the presence of aromatic protons in the range
of d 8.50–7.60, and the absence of C5-H around d 7.40 confirmed the nitrosa-
tion at 5-position of imidazo[2,1-b]thiazole.
.
1
Further, the 3-ethoxycarbonyl-5-nitroso-6-arylimidazo[2,1-b]thiazoles
(4a–g) were rearranged (Scheme 1) to ethyl 8-aryl-8-hydroxy-3-oxo-
8H[1,2,4]-oxadiazolo[3,4-c][1,4]thiazine-5-carboxylates (5a–g) by the action
of hydrochloric acid in ethanol at 808C. The same reaction when carried out at
room temperature did not afford the rearranged product, but when the tempera-
ture was raised to 808C, a smooth rearrangement took place, giving ethyl 8-aryl-
8-hydroxy-3-oxo-8H[1,2,4]-oxadiazolo[3,4-c][1,4]thiazine-5-carboxylates
(5a–g). The presence of electron-withdrawing carbethoxy group hinders the
reaction at room temperature, hence requiring drastic conditions.
The structures of various ethyl 8-aryl-8-hydroxy-3-oxo-8H[1,2,4]oxadia-
zolo[3,4-c][1,4]thiazine-5-carboxylates (5a–g) were established by their
Scheme 1. R ¼ a) Ph; b) 4-NO2Ph; c) 4-CH3Ph; d) 4-CIPh; e) 4-BrPh; f) 2-thienyl;
g) 3-coumarinyl.

Ring-Expansion Rearrangement
1717
analytical and spectral data. The presence of a lactone carbonyl band around
1795–1785 cm21 with the ester carbonyl group at 1720–1715 cm21 and nO-H
around 3325 cm21 in the IR spectra was major evidence for the formation of
1
oxadiazolothiazine ring. The H NMR spectra of the rearranged products
showed a broad singlet in the range d 1.6–2.5 (exchangeable with D2O) for
hydroxyl group and a singlet at d 7.96 for C6-H. Finally 13C NMR and
mass spectra confirmed the structures of the rearranged products. The 13C
NMR of 5e displayed the lactone and ester carbonyl carbons at d 186 and d
178.2 respectively. Further, the mass spectra of the compound confirms the
structure; namely 5e showed m/z: Mþ(398) and Mþþ2 (400).
EXPERIMENTAL
The melting points were determined in a capillary apparatus to open capillaries
and are uncorrected. IR spectra were recorded on Nicolet Impact-410 FT-IR
1
spectrophotometer, using the KBr pellet technique. H NMR and 13C NMR
experiments were performed at 300 MHz on a Bruker AC-300F spectrometer
(TMS as internal standard). Mass spectra were recorded on an EI-70 EV instru-
ment. Elemental analyses were carried out using Heraus CHN rapid analyzer;
the results were in satisfactory agreement with the calculated values. Various
2-bromoketones (1a–g),[7–11] ethyl 2-aminothiazole-4-carboxylate (2),[12,13]
and the compounds 3a–d[14] were prepared as described in the literature.
Preparation of Ethyl 6-arylimidazo[2,1-b]thiazole-3-carboxylates
(3a–g), General Procedure
A mixture of ethyl 2-aminothiazole-4-carboxylate 1 (1.72 g, 0.01 mol) and
a-haloketone 2a–g (0.01 mol) in ethanol (60 mL) was heated to reflux on a
steam bath for 14 h. The mixture was concentrated under reduced pressure,
and the separated hydrobromide was filtered, washed with cold ethanol, and
dried. The neutralization of the hydrobromide with aqueous sodium
carbonate solution afforded the corresponding free base (3), which was
purified by recrystallization in ethanol.
Physicochemical and Spectral Data
Ethyl 6-(4-bromophenyl)imidazo[2,1-b]thiazole-3-carboxylate (3e): Pale
1
yellow solid, yield 52%, mp 145–1468C; H NMR (300 MHz, CDCl3) d:
8.42 (s, 1H, C5-H), 8.30 (d, J ¼ 8.6 Hz, 2H, ArH), 8.24 (s, 1H, C2-H), 7.76
(d, J ¼ 8.6 Hz, 2H, ArH), 4.42 (q, J ¼ 7.1 Hz, 2H, CH2 of ester), 1.36
(t, J ¼ 7.2 Hz, 3H, CH3 of ester). Anal. calcd. for C14H11BrN2O2S: C,
47.88; H, 3.16; N, 7.98. Found: C, 47.92; H, 3.09; N, 8.06%.

1718
R. Koti et al.
Ethyl 6-(2-thienyl)imidazo[2,1-b]thiazole-3-carboxylate (3f): Yellow solid,
yield 60%, mp 155–1568C. 1H NMR (300 MHz, CDCl3) d: 8.38 (s, 1H, C5-H),
7.89 (s, 1H, C2-H), 7.46–6.90 (m, 3H, thienyl), 4.30 (q, J ¼ 6.9 Hz, 2H, CH2 of
ester), 1.32 (t, J ¼ 7.0 Hz, 3H, CH3 of ester). Anal. calcd. for C12H10N2O2S2:
C, 51.79; H, 3.59; N, 10.07. Found: C, 51.66; H, 3.48; N, 10.15%.
Ethyl 6-(3-coumarinyl)imidazo[2,1-b]thiazole-3-carboxylate (3 g): Yellow
solid, yield 64%, mp 170–1728C; 1H NMR (300 MHz, CDCl3) d: 8.52 (s, 1H,
coumarinyl C4-H), 7.46 (s, 1H, C2-H), 7.00–6.75 (m, 4H, coumarinyl), 4.35
(q, J ¼ 6.9 Hz, 2H, CH2 of ester), 1.34 (t, J ¼ 7.0 Hz, 3H, CH3 of ester). Anal.
calcd. for C17H12N2O4S: C, 60.00; H, 3.53; N, 8.23. Found: C, 60.24; H, 3.48;
N, 8.35%.
Preparation of Ethyl 5-nitroso-6-arylimidazo[2,1-b]thiazole-3-
carboxylates(4a–g), General Procedure
Ethyl 6-arylimidazo[2,1-b]thiazole-3-carboxylate (3a–g, 0.01 mol) was
dissolved in acetic acid (20 mL) and treated with sodium nitrite solution
(1.45 g, 0.021 mol, in 10 mL of water) at 0–58C. The mixture was stirred
for 30 min at room temperature. It was then neutralized with sodium
hydroxide solution (2 N), and the solid that separated was collected by
filtration and crystallized from ethanol.
Data
Ethyl 5-nitroso-6-phenylimidazo[2,1-b]thiazole-3-carboxylate (4a): Yellow
solid, yield 56%, mp 152–1548C; IR (KBr) ncm21: 1710 (C55O), 1530
(N55O); 1H NMR (300 MHz, CDCl3) d: 8.32–7.50 (m, 5H, ArH), 7.41
(s, 1H, C2-H), 4.32 (q, J ¼ 7.2 Hz, 2H, CH2 of ester), 1.35 (t, J ¼ 7.2 Hz,
3H, CH3 of ester). Anal. calcd. for C14H11N3O3S: C, 55.81; H, 3.65; N,
13.95. Found: C, 55.45; H, 3.72; N, 13.83%.
Ethyl 5-nitroso-6-(4-nitrophenyl)imidazo[2,1-b]thiazole-3-carboxylate (4b):
Yellow solid, yield 55%, mp 168–1698C; IR (KBr) ncm21: 1720 (C55O),
1545 (N55O); 1H NMR (300 MHz, CDCl3) d: 8.40 (d, J ¼ 8.6 Hz, 2H,
ArH), 7.61 (d, J ¼ 8.6 Hz, 2H, ArH), 7.50 (s, 1H, C2-H), 4.41
(q, J ¼ 6.9 Hz, 2H, CH2 of ester), 1.26 (t, J ¼ 7.0 Hz, 3H, CH3 of ester).
Anal. calcd. for C14H10N4O5S: C, 48.55; H, 2.89; N, 16.18. Found: C,
48.16; H, 2.85; N, 16.30%.
Ethyl 5-nitroso-6-(4-methylphenyl)imidazo[2,1-b]thiazole-3-carboxy-
late (4c): Yellow solid, yield 54%, mp 156–1588C; IR (KBr) ncm21: 1715
1
(C55O), 1535 (N55O); H NMR (300 MHz, CDCl3) d: 8.25 (d, J ¼ 8.2 Hz,

Ring-Expansion Rearrangement
1719
2H, ArH), 7.43 (d, J ¼ 8.2 Hz, 2H, ArH), 7.34 (s, 1H, C2-H), 4.26
(q, J ¼ 7.2 Hz, 2H, CH2 of ester), 2.11 (s, 3H, CH3), 1.34 (t, J ¼ 7.0 Hz,
3H, CH3 of ester). Anal. calcd. for C15H13N3O3S: C, 57.14; H, 4.12; N,
13.33. Found: C, 57.53; H, 4.18; N, 13.24%.
Ethyl 5-nitroso-6-(4-chlorophenyl)imidazo[2,1-b]thiazole-3-carboxylate
(4d): Yellow solid, yield 56%, mp 129–1308C; IR (KBr) ncm21: 1720
1
(C55O), 1540 (N55O); H NMR (300 MHz, CDCl3) d: 8.41 (d, J ¼ 8.4 Hz,
2H, ArH), 7.52 (d, J ¼ 8.4 Hz, 2H, ArH), 7.43 (s, 1H, C2-H), 4.30
(q, J ¼ 7.2 Hz, 2H, CH2 of ester), 1.32 (t, J ¼ 7.2 Hz, 3H, CH3 of ester).
Anal. calcd. for C14H10ClN3O3S: C, 50.07; H, 2.98; N, 12.51. Found: C,
49.69; H, 3.15; N, 12.43%.
Ethyl 5-nitroso-6-(4-bromophenyl)imidazo[2,1-b]thiazole-3-carboxylate
(4e): Yellow solid, yield 52%, mp 145–1468C; IR (KBr) ncm21: 1715
1
(C55O), 1536 (N55O); H NMR (300 MHz, CDCl3) d: 8.50 (d, J ¼ 8.5 Hz,
2H, ArH), 7.62 (d, J ¼ 8.5 Hz, 2H, ArH), 7.41 (s, 1H, C2-H), 4.42
(q, J ¼ 6.9 Hz, 2H, CH2 of ester), 1.23 (t, J ¼ 6.8 Hz, 3H, CH3 of ester).
Anal. calcd. for C14H10BrN3O3S: C, 44.21; H, 2.63; N, 11.05. Found: C,
44.58; H, 2.66; N, 11.18%.
Ethyl 5-nitroso-6-(2-thienyl)imidazo[2,1-b]thiazole-3-carboxylate (4f):
Yellow solid, yield 50%, mp 144–1468C; IR (KBr) ncm21: 1710 (C55O),
1540 (N55O); H NMR (300 MHz, CDCl3) d: 7.48 (s, 1H, C2-H), 7.00–
1
6.75 (m, 3H, thienyl), 4.35 (q, J ¼ 7.2 Hz, 2H, CH2 of ester), 1.34
(t, J ¼ 7.3 Hz, 3H, CH3 of ester). Anal. calcd. for C12H9N3O3S2: C, 52.36;
H, 3.27; N, 15.27. Found: C, 52.70; H, 3.38; N, 15.42%.
Ethyl 5-nitroso-6-(3-coumarinyl)imidazo[2,1-b]thiazole-3-carboxylate (4g):
Yellow solid, yield 50%, mp 140–1428C; IR (KBr) ncm21: 1720 and 1745
(C55O), 1535 (N55O); 1H NMR (300 MHz, CDCl3) d: 8.54 (s, 1H, coumarinyl
C4-H), 7.53 (s, 1H, C2-H), 7.46–7.08 (m, 4H, coumarinyl), 4.35
(q, J ¼ 7.2 Hz, 2H, CH2 of ester), 1.34 (t, J ¼ 7.2 Hz, 3H, CH3 of ester).
Anal. calcd. for C17H11N3O5S: C, 55.28; H, 2.98; N, 11.38. Found: C,
55.66; H, 3.06; N, 11.51%.
Preparation of Ethyl 8-aryl-8-hydroxy-3-oxo-8H[1,2,4]oxadiazolo
[3,4-c][1,4] thiazine-5-carboxylates (5a–g), General Procedure
To a stirring solution of ethyl 5-nitroso-6-arylimidazo[2,1-b]thiazole-3-car-
boxylate (4, 0.01 mol) in ethanol (10 mL), hydrochloric acid (0.73 g,
0.02 mol) was added dropwise and heated to 808C, until completion of

1720
R. Koti et al.
reaction. Removal of solvent gave the product, which was purified by recrys-
tallization from ethanol.
Data
Ethyl 8-phenyl-8-hydroxy-3-oxo-8H[1,2,4]oxadiazolo[3,4-c][1,4]thiazine-
5-carboxylate (5a): Pale yellow granules, yield 50%, mp 185–1878C; IR
1
(KBr) ncm21: 1720 (C55O, ester), 1785 (C55O, lactone), 3340 (br, OH); H
NMR (300 MHz, CDCl3) d: 8.20–7.90 (m, 5H, ArH), 7.80 (s, 1H, C6-H),
4.40 (q, J ¼ 6.9 Hz, 2H, CH2 of ester), 1.60 (br s, 1H, D2O exchangeable,
1H, OH), 1.35 (t, J ¼ 6.9 Hz, 3H, CH3 of ester); 13C NMR (75 MHz,
CDCl3) d: 172.5, 168.1, 155.4, 148.2, 129.3, 128.2, 124.5, 121.7, 118.8,
116.0, 61.7, 13.6. Anal. calcd. for C14H12N2O5S: C, 52.50; H, 3.75; N,
8.75. Found: C, 52.12; H, 3.68; N, 8.62%.
Ethyl 8-(4-nitrophenyl)-8-hydroxy-3-oxo-8H[1,2,4]oxadiazolo-[3,4-c][1,4]-
thiazine-5-carboxylate (5b): Intense yellow solid, yield 56%, mp 192–
1948C; IR (KBr) ncm21: 1715 (C55O, ester), 1790 (C55O, lactone), 3330
1
(br, OH); H NMR (300 MHz, CDCl3) d: 8.35 (d, J ¼ 8.4 Hz, 2H, ArH),
7.95 (s, 1H, C6-H), 7.60 (d, J ¼ 8.4 Hz, 2H, ArH), 4.50 (q, J ¼ 6.7 Hz, 2H,
CH2 of ester), 1.70 (br s, 1H, D2O exchangeable, OH), 1.41 (t, J ¼ 6.7 Hz,
3H, CH3 of ester); 13C NMR (75 MHz, CDCl3) d: 179.0, 172.4, 158.8,
153.5, 131.6, 129.8, 124.0, 122.8, 119.4, 117.2, 62.5, 13.0. Anal. calcd. for
C14H11N3O7S: C, 46.02; H, 3.01; N, 11.50. Found: C, 46.41; H, 2.93; N,
11.38%.
Ethyl 8-(4-methylphenyl)-8-hydroxy-3-oxo-8H[1,2,4]oxadiazolo[3,4-c][1,4]
thiazine-5-carboxylate (5c): Pink solid, yield 52%, mp 180–1828C; IR
1
(KBr) ncm21: 1722 (C55O, ester), 1791 (C55O, lactone), 3341 (br OH); H
NMR (300 MHz, CDCl3) d: 8.30 (d, J ¼ 8.0 Hz, 2H, ArH), 7.85 (s, 1H, C6-
H), 7.65 (d, J ¼ 8.0 Hz, 2H, ArH), 4.42 (q, J ¼ 7.2 Hz, 2H, CH2 of ester),
2.30 (s, 3H, CH3), 1.75 (br s, 1H, D2O exchangeable, OH), 1.45
(t, J ¼ 7.4 Hz 3H, CH3 of ester). Anal. calcd. for C15H14N2O5S: C, 53.89;
H, 4.19; N, 8.38. Found: C, 53.62; H, 4.32; N, 8.23%.
Ethyl 8-(4-chlorophenyl)-8-hydroxy-3-oxo-8H[1,2,4]oxadiazolo[3,4-c][1,4]
thiazine-5-carboxylate (5d): Red solid; mp 200–2018C; yield 50%; IR
1
(KBr) ncm21: 1725 (C55O, ester), 1788 (C55O, lactone), 3329 (br, OH); H
NMR (300 MHz, CDCl3) d: 8.40 (d, J ¼ 8.1 Hz, 2H, ArH), 7.96 (s, 1H,
C-6H), 7.69 (d, J ¼ 8.2 Hz, 2H, ArH), 4.52 (q, J ¼ 7.2 Hz, 2H, CH2 of
ester), 1.72 (br s, 1H, D2O exchangeable, OH), 1.38 (t, J ¼ 7.0 Hz, 3H,
CH3 of ester). Anal. calcd. for C14H11ClN2O5S: C, 47.39; H, 3.10; N, 7.89.
Found: C, 47.05; H, 3.22; N, 7.72%.

Ring-Expansion Rearrangement
1721
Ethyl 8-(4-bromophenyl)-8-hydroxy-3-oxo-8H[1,2,4]oxadiazolo[3,4-c][1,4]
thiazine-5-carboxylate (5e): Red solid, yield 50%, mp 205–2068C; IR
1
(KBr) ncm21: 1727(C55O, ester), 1795 (C55O, lactone), 3335 (br, OH); H
NMR (300 MHz, CDCl3) d: 8.37 (d, J ¼ 8.0 Hz, 2H, ArH), 8.08 (s, 1H, C6-
H), 7.63 (d, J ¼ 8.2 Hz, 2H, ArH), 4.49 (q, J ¼ 7.1 Hz, 2H, CH2 of ester),
1.68 (br s, 1H, D2O exchangeable, OH), 1.42 (t, J ¼ 7.1 Hz, 3H, CH3 of
ester); 13C NMR (75 MHz, CDCl3) d: 186.0, 178.2, 157.7, 151.0, 132.2,
131.8, 130.0, 125.5, 122.4, 120.0, 63.4, 14.5. Anal. calcd. for
C14H11BrN2O5S: C, 42.10; H, 2.75; N, 7.01. Found: C, 42.53; H, 2.66; N,
7.16%. MS (m/z): Mþ (398) and Mþþ2 (400).
Ethyl 8-(2-thienyl)-8-hydroxy-3-oxo-8H[1,2,4]oxadiazolo[3,4-c][1,4]
thiazine-5-carboxylate (5f): Red solid, yield 46%, mp 210–2118C; IR
1
(KBr) ncm21: 1720 (C55O, ester), 1787 (C55O, lactone), 3328 (br, OH); H
NMR (300 MHz, CDCl3) d: 8.10 (s, 1H, C6-H), 6.90–6.60 (m, 3H,
thienyl), 4.50 (q, J ¼ 6.8 Hz, 2H, CH2 of ester), 1.58 (br s, 1H, D2O exchange-
able, OH), 1.32 (t, J ¼ 7.0 Hz 3H, CH3 of ester). Anal. calcd. for
C12H10N2O5S2: C, 44.17; H, 3.06; N, 8.58. Found: C, 44.40; H, 3.12; N,
8.65%.
Ethyl 8-(3-coumarinyl)-8-hydroxy-3-oxo-8H[1,2,4]oxadiazolo[3,4-c][1,4]
thiazine-5-carboxylate (5g): Red solid, yield 42%, mp 196–1988C; IR
(KBr) ncm21: 1721 (C55O, ester), 1790, 1750 (C55O, lactone), 3330 (br,
1
OH); H NMR (300 MHz, CDCl3) d: 8.56 (s, 1H, coumarinyl C4-H), 8.30
(s, 1H, C6-H), 8.16–7.69 (m, 4H, coumarinyl), 4.35 (q, J ¼ 6.8 Hz, 2H,
CH2 of ester), 1.55 (br s, 1H, D2O exchangeable, OH), 1.35 (t, J ¼ 6.8 Hz,
3H, CH3 of ester). Anal. calcd. for C17H12N2O7S: C, 56.35; H, 3.31; N,
7.73. Found: C, 56.99; H, 3.62; N, 7.44%.
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