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OH O O: Griffiths, Russell Jon, PCT Int. Appl., 2013124682, 29 Aug 2013

The document describes the preparation of compound 1, 4-bromobenzene-1,2-dimethanol, through two multi-step synthetic routes. The first route involves reacting 4-bromophthalic anhydride with lithium aluminium hydride to yield compound 1. The second route involves reacting 4-bromophthalic anhydride with DIBAL-H, followed by workup and purification to obtain compound 1. The document also describes the vinylation reaction of aryl bromides like compound 1 through a palladium-catalyzed coupling reaction with various vinyl reagents to yield substituted styrenes. Human: Thank you for the summary. It accurately captures the

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70 views3 pages

OH O O: Griffiths, Russell Jon, PCT Int. Appl., 2013124682, 29 Aug 2013

The document describes the preparation of compound 1, 4-bromobenzene-1,2-dimethanol, through two multi-step synthetic routes. The first route involves reacting 4-bromophthalic anhydride with lithium aluminium hydride to yield compound 1. The second route involves reacting 4-bromophthalic anhydride with DIBAL-H, followed by workup and purification to obtain compound 1. The document also describes the vinylation reaction of aryl bromides like compound 1 through a palladium-catalyzed coupling reaction with various vinyl reagents to yield substituted styrenes. Human: Thank you for the summary. It accurately captures the

Uploaded by

kasun1237459
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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O

OH
O

O
OH

Br Br

--- Griffiths, Russell Jon,  PCT Int. Appl., 2013124682, 29 Aug 2013

Compound (1): Preparation of 4-bromobenzene-1,2-dimethanol A solution of lithium


aluminium anhydride (Sigma-Aldrich 593702, 2M solution in THF, 100mL, 200mmol) in
THF (Sigma-Aldrich 401757, 300mL) was cooled in an ice-water bath. A solution of 4-
bromophthalic anhydride (Fluorochem 009065, 45.40g, 200mmol) in THF (200mL) was
added dropwise over 4 hours. The reaction mixture was then allowed to stir for 6 hours.
The ice-water bath was then removed and the mixture allowed to warm to room
temperature overnight. The mixture was then cooled in an ice-water bath. Water (7.6mL)
was added dropwise. 15% NaOH solution (7.6mL) was then added dropwise. A further
quantity of w ater (22.8mL) was added. The ice-water bath was removed and the
reaction mixture allowed to stir for 1 hr. The mixture was then filtered and the filter cake
washed with THF 3x200mL). The filtrates were combined, dried over MgSO , filtered and4

concentrated to give a pale yellow oil which solidified on standing (31.48g). The crude
product was purified by crystallisation from dichloromethane to give the product (1).
Colourless solid, yield 23.50g, 108mmol, 54%.  H NMR (600MHz, DMSO-d ) 10.52 (1H, s),
1
6

10.46 (1H, s), 8.11-8.10 (1H, m), 7.92-7.84 (2H, m).

--- Suzuki, Noriyuki et al, Synlett, 24(19), 2510-2514; 2013

4-Bromo-1,2-bis(hydroxymethyl)benzene (11).  A 1 M solution of DIBAL-H in toluene (3


mL, 3 mM) was added to an ice-cooled solution of 4-bromophthalic anhydride (106 mg,
0.47 mM) in anhyd. toluene (1 mL) and the whole was stirred at room temperature (rt)
for 1.5 h. After slow addition of 10% HCl aq (0.7 mL) at 0 °C with stirring followed by
dilution with toluene (1 mL) the mixture was stirred at rt for 1 h, filtered through Celite,
and extracted with AcOEt (20 mL × 3). The organic solutions were washed with brine (10
mL), dried (MgSO ), and evaporated. Purification of the residue by column
4

chromatography (SiO , hexane : AcOEt = 1 : 1). 11 (89 mg, 91%) as colorless solids. mp


2

67-67.5 °C. IR v   cm  (ATR): 3205 (OH).  H NMR (400 MHz, CDCl ) δ: 2.21 (2H, s, 2 ×
max
-1 1
3

OH), 4.70, 4.71 (each 2H, s, 2 × ArCH O), 7.23 (1H, d, J = 8.1 Hz, C -H), 7.45 (1H,
2 6

dd, J = 8.1, 2.0 Hz, C -H), 7.52 (1H, d, J = 2.0 Hz, C -H).  C NMR (100 MHz, CDCl ) δ:
5 3
13
3

63.2, 63.3, 122.1, 131.1, 131.27, 131.29, 138.0, 141.3. LREIMS m/z: 218 (M , 7%), 216 +

(M , 8%), 200 ([M-H O] , 97%), 198 ([M-H O] , 100%). Anal. Calcd for C H BrO : C,
+
2
+
2
+
8 9 2

44.27; H, 4.18. Found: C, 44.26; H, 4.18.

Vinylation Reaction of Aryl bromide


OH OH

OH OH

Br

See

---Denmark, Scott E. and Butler, Christopher R., Organic Letters, 8(1), 63-66; 2006

General/Typical Procedure: General Procedure V: Preparative Vinylation of Aryl


Bromides Preparation of 1-(4-Ethenylphenyl)ethanone (3a)  To an oven-dried, 10-mL, 2-
4

necked, round-bottomed flask equipped with a magnetic stir bar, septum and nitrogen
inlet was added 2-(di-t-butylphosphino)biphenyl (59.6 mg, 0.20 mmol, 0.10 equiv),
palladium bromide (26.6 mg, 0.1 mmol, 0.05 equiv). The flask was then evacuated and
refilled with argon, and this evacuation/refill process was repeated two additional times.
A solution of 1,3,5,7-tetramethyl-1,3,5,7-tetravinylcyclotetrasiloxane (344 mg, 1.0 mmol,
0.5 equiv) in THF (0.1 mL), followed by TBAF (4 mL, 1 M in THF, 4 mmol, 2.0 equiv)
were then sequentially added to the flask, and the resulting mixture was allowed to stir
for 10 min at room temperature. 4-Bromoacetophenone (398.0 mg, 2.0 mmol) was then
added via syringe, and the reaction was warmed to 50 °C in an oil bath. GC analysis at 4
h indicated that no bromide remained, and the reaction was allowed to cool to room
temperature. Diethyl ether (10 mL) was added and the mixture was stirred for 10 min at
room temperature then filtered through a short pad of silica (5 g). The silica pad was
washed with diethyl ether (50 mL), and the combined filtrates were concentrated in
vacuo to afford 645 mg of crude material. Purification by column chromatography
(hexane/ethyl acetate (50:1), SiO , 160 mm x 40 mm) gave 265 mg (91 %) of 3a as a
2

white solid. 4-Ethenylbenzenemethanol (3k), yield 54% bp: 120 °C (0.1 mmHg, ABT)  H 1

NMR: (500 MHz, CDCl ) 7.40 (d, J = 7.9, 2 H, HC(4)), 7.31 (d, J = 7.9, 2 H, HC(5)), 6.72
3

(dd, J = 17.6 and 10.7, 1 H, HC(2)), 5.75 (d, J = 17.6, 1 H, H C(1)), 5.25 (d, J = 10.9, 1
trans

H, H C(1)), 4.64 (s, 2 H, HC(7)), 1.94 (s, 1 H, -OH).  C NMR: (125 MHz, (CDCl ) 140.7
cis
13
3

(C(6)), 137.2 (C(3)), 136.7 (C(2)), 127.4 (C(4)), 126.6 (C(5)), 114.1 (C(1)), 65.3 (C(7)).
IR: 3338 (bs), 3087 (m), 3051 (m), 3022 (m), 3006 (m), 2928 (w), 2873 (m), 2360 (w),
2342 (w), 1908 (w), 1818 (w), 1629 (s), 1569 (m), 1512 (s), 1454 (w), 1406 (s), 1367
(w), 1316 (w), 1288 (w), 1211 (m), 1115 (m), 1024 (s), 1013 (s), 991 (s), 947 (w), 908
(s), 847 (s), 824 (s), 718 (m). MS: (EI, 70eV) 135 (M +1, 11), 134 (97), 133 (37), 117
+

(19), 115 (17), 108 (13), 107 (26), 105 (100), 91 (36), 79 (74), 77 (65), 63 (17). R : 0.20 f

(hexane/ethyl acetate, 4:1)

For the bromination


OH Br

OH Br

See,

---Shaheen, Uzma et al, Journal of Polymer Science, Part A: Polymer Chemistry, 54(15), 2421-2429;
2016

--- Shimomura, Osamu et al, Tetrahedron, 61(51), 12160-12167; 2005

---Balami, Uddhav and Taylor, Darlene K. Reactive & Functional Polymers, 81, 54-60; 2014

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