Synthesis of 1,1,5,6-tetramethyl-and 7-isopropyl-1,1-dimethyl-1,2,3,4-tetrahydronaphthalene

Article abstract of DOI:10.1135/cccc19990527

4-(2,3-Dimethylphenyl)butanoic acid (4) was treated with excess of methyllithium to yield 5-(2,3-dimethylphenyl)-2-methylpentan-2-ol (6) which was cyclodehydrated using Dowex 50W-X8 resin, trifluoroacetic acid or polyphosphoric acid (PPA) to furnish 1,1,5,6-tetramethyl-1,2,3,4-tetrahydronaphthalene (1). The acid 4 was cyclized with PPA to furnish 5,6-dimethyl-3,4-dihydronaphthalen-1(2H)-one (5) which was converted into 1 by reaction with dimethylzinc and titanium tetrachloride. 4-(4-Isopropylphenyl)butanoic acid (7) on esterification followed by Grignard reaction with methylmagnesium iodide furnished 5-(4-isopropylphenyl)-2-methylpentan-2-ol (9), which was cyclodehydrated as above to yield 7-isopropyl-1,1-dimethyl-1,2,3,4-tetrahydronaphthalene (2).

Full text of DOI:10.1135/cccc19990527

1,2,3,4-Tetrahydronaphthalenes
527
SYNTHESIS OF 1,1,5,6-TETRAMETHYL- AND 7-ISOPROPYL-1,1-
DIMETHYL-1,2,3,4-TETRAHYDRONAPHTHALENE
Ramchandra Bhimrao MANE*, Abhijit Jaysingrao KADAM
and Rajashree Sandeep SALUNKHE
Department of Chemistry, Shivaji University, Kolhapur-416004, India
Received August 11, 1998
Accepted Novem ber 11, 1998
4-(2,3-Dim eth ylph en yl)butan oic acid (4) was treated with excess of m eth yllith ium to yield
5-(2,3-dim eth ylph en yl)-2-m eth ylpen tan -2-ol (6) wh ich was cyclodeh ydrated usin g Dowex
50W -X8 resin , trifluoroacetic acid or polyph osph oric acid (PPA) to furn ish
1,1,5,6-tetram eth yl-1,2,3,4-tetrah ydron aph th alen e (1). Th e acid 4 was cyclized with PPA to
furn ish 5,6-dim eth yl-3,4-dih ydron aph th alen -1(2H)-on e (5) wh ich was con verted in to 1 by
reaction with dim eth ylzin c an d titan ium tetrach loride. 4-(4-Isopropylph en yl)butan oic acid
(7) on esterification followed by Grign ard reaction with m eth ylm agn esium iodide furn ish ed
5-(4-isopropylph en yl)-2-m eth ylpen tan -2-ol (9), wh ich was cyclodeh ydrated as above to yield
7-isopropyl-1,1-dim eth yl-1,2,3,4-tetrah ydron aph th alen e (2).
Key w ord s: 1,2,3,4-Tetrah ydron aph th alen es; Friedel–Crafts reaction ; Alkylation ; Cyclization ;
Sesquiterpen oids.
Several sesquiterpen oids of in terestin g types h ave been discovered1 in th e
steam -volatile oil of Isocoma wrightii alon g with 1,1,5,6-tetram eth yl-
1,2,3,4-tetrah ydron aph th alen e (1), a n ovel n ordrim an e sesquiterpen e.
Com poun d 1 h as been obtain ed earlier from th e degradative rearran gem en t
of n aturally occurin g sesquiterpen e, avarol2. An an alogous 1,2,3,4-
tetrah ydron aph th alen e system h as been obtain ed recen tly from som e
diterpen e derivatives3. Th e 7-isopropyl-1,1-dim eth yl-1,2,3,4-tetrah ydro-
n aph th alen e (2) with th e rearran ged isolon gifolen e skeleton 4,5 is an oth er
1,1-dim eth yl-1,2,3,4-tetrah ydron aph th alen e type kn own in th e literature.
Ion en e (1,1,6-trim eth yl-1,2,3,4-tetrah ydron aph th alen e) an d its 3,4-deh ydro
derivative, a con stituen t of Passiflora edulis (ref.6) can also be regarded as
m em bers of th e 1,1-dim eth yl-1,2,3,4-tetrah ydron aph th alen e fam ily of
sesquiterpen es.
Murali an d Krish n a Rao7 reported th e first syn th esis of
1,1,5,6-tetram eth yl-1,2,3,4-tetrah ydron aph th alen e. We n ow report a sh ort
syn th esis of th is com poun d. Th e Friedel–Crafts reaction of o-xylen e with
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528
Mane, Kadam, Salunkhe:
butan o-4-lacton e8 at 0–5 °C yielded 4-(2,3-dim eth ylph en yl)butan oic acid
(4) as a m ajor product an d 4-(3,4-dim eth ylph en yl)butan oic acid (3) as a m i-
n or product. Th e products were separated by fraction al crystallization an d
th e m ajor product 4 was treated with excess of m eth yllith ium 4 to yield
5-(2,3-dim eth ylph en yl)-2-m eth ylpen tan -2-ol (6). Th is alcoh ol was
cyclodeh ydrated usin g th ree differen t reagen ts, Dowex 50W-X8 resin ,
trifluoroacetic acid or polyph osph oric acid (PPA), to furn ish 1,1,5,6-
tetram eth yl-1,2,3,4-tetrah ydron aph th alen e (1). Th e acid 4 was cyclized
with PPA to furn ish 5,6-dim eth yl-3,4-dih ydron aph th alen -1(2H)-on e (5).
Treatm en t of 5 with excess of dim eth ylzin c an d titan ium tetrach loride9
(Reetz reagen t) yielded 1 (Sch em e 1).
O
(i)
+
+
COOH
COOH
O
4, major
3, minor
(iii)
(ii)
(iv) or (v) or (vi)
(vii)
OH
O
1
6
5
o
(i) AlCl , 0-5 C; (ii) PPA; (iii) MeLi, Et O, r.t.; (iv) Dowex 50W-X8, benzene, reflux; (v) TFA, reflux;
3
2
o
o
(vi) PPA, 90-95 C; (vii) Me Zn, TiCl , CH Cl , -30 C to r.t.
2
4
2
2
SCHEME 1
Th e first syn th esis of 7-isopropyl-1,1-dim eth yl-1,2,3,4-tetrah ydro-
n aph th alen e (2) was reported by Farn um et al.4. Th ere are also several re-
ports10–15 in th e literature on th e form ation of th is com poun d by
rearran gem en t of lon gifolen e or isolon gifolen e. We n ow report an oth er
syn th esis of 7-isopropyl-1,1-dim eth yl-1,2,3,4-tetrah ydron aph th alen e (2).
Th e Friedel–Crafts reaction of isopropylben zen e with butan o-4-lacton e at
10 °C yielded 4-(4-isopropylph en yl)butan oic acid (7), wh ich was con verted
in to its m eth yl ester 8 usin g m eth an ol an d sulfuric acid. Th e ester 8 on
Grign ard reaction with m eth ylm agn esium iodide furn ish ed 5-(4-isopropyl-
ph en yl)-2-m eth ylpen tan -2-ol (9) wh ich was cyclodeh ydrated usin g th ree
differen t reagen ts, Dowex 50W-X8 resin , trifluoroacetic acid or
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1,2,3,4-Tetrahydronaphthalenes
529
polyph osph oric acid to yield 7-isopropyl-1,1-dim eth yl-1,2,3,4-tetrah ydro-
n aph th alen e 2 (Sch em e 2).
O
O
(i)
+
COOH
7
(ii)
(iv) or (v) or (vi)
(iii)
COOMe
OH
9
8
2
+
(i) AlCl , r.t.; (ii) MeOH, H , reflux; (iii) MeMgI, Et O, reflux;
3
2
o
C
(iv) Dowex 50W-X8, benzene, reflux; (v) TFA, reflux; (vi) PPA, 90-95
SCHEME 2
EXPERIMENTAL
Meltin g an d boilin g poin ts are un corrected. Preparative th in -layer ch rom atograph y (PLC)
was carried out on glass plate precoated (2.0 m m ) with silica gel G (Merck). Materials were
detected by visualization un der an iodin e ch am ber. Colum n ch rom atograph y was perform ed
with silica gel (Merck) (60–120 m esh ). Th e IR spectra (waven um bers in cm –1) were recorded
on a Perkin –Elm er 783 spectroph otom eter eith er as n eat (liquids) or in KBr pellets (solids).
1H NMR spectra were recorded on a JEOL spectrom eter FX 90Q (90 MHz) in CDCl3 solution s
an d ch em ical sh ifts were given in ppm (δ-scale).
4-(3,4-Dim eth ylph en yl)butan oic Acid (3) an d 4-(2,3-Dim eth ylph en yl)butan oic Acid (4)
To a m ech an ically stirred solution of o-xylen e (53 g, 0.5 m ol) an d butan o-4-lacton e (21.5 g,
0.25 m ol), an h ydrous alum in um ch loride (85 g, 0.625 m ol) was added at 0–5 °C durin g 2 h .
Th e reaction m ixture was stirred at room tem perature for addition al 5 h an d decom posed
with 15% ice-cold con cen trated h ydroch loric acid. Th e organ ic layer was separated an d th e
aqueous layer was extracted with a sodium h ydrogen carbon ate solution . Acidification of th e
alkalin e extract with con cen trated h ydroch loric acid gave a m ixture of acids 3 an d 4. Yield
24.5 g (54%). Th e m ixture of acids upon fraction al crystallization from petroleum eth er gave
4-(2,3-dim eth ylph en yl)butan oic acid (4), yield 8.6 g (35%), m .p. 99–100 °C (ref.8 gives m .p.
102 °C) an d 4-(3,4-dim eth ylph en yl)butan oic acid (3), yield 1.7 g (7%), m .p. 54–55 °C (ref.8
gives m .p. 56 °C).
5,6-Dim eth yl-3,4-dih ydron aph th alen -1(2H)-on e (5)
To a well stirred polyph osph oric acid, prepared from ph osph orus pen toxide (90 g) an d
orth oph osph oric acid (55 m l), was added 4-(2,3-dim eth ylph en yl)butan oic acid (4; 9.0 g, 46.9
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530
Mane, Kadam, Salunkhe:
m m ol) an d th e reaction m ixture was h eated at 90–95 °C for 1.5 h . Th e cool reaction m ixture
was decom posed by pourin g on to crush ed ice (90 g) an d extracted with dieth yl eth er. Th e
eth er extract was successively wash ed with water, a 10% sodium h ydroxide solution , water
an d th en dried with an h ydrous sodium sufate. Th e residue after evaporation was
ch rom atograph ed on silica gel (80 g). Slow elution with ben zen e gave pure 5, yield 6.85 g
(84%), b.p. 171–175 °C/1 595 Pa (ref.16 gives b.t. 154–158 °C/1 064 Pa). IR (neat): 1 674. 1H NMR
(CDCl3): 2.07 quin tet, 2 H (CH2); 2.22 s, 3 H (CH3); 2.35 s, 3 H (CH3); 2.6 t, 2 H (CH2); 2.9 t,
2 H (CH2); 7.1 d, 1 H, J = 8 (Ar-H); 7.75 d, 1 H, J = 8 (Ar-H).
5-(2,3-Dim eth ylph en yl)-2-m eth ylpen tan -2-ol (6)
To a stirred solution of m eth yllith ium , prepared from lith ium (1.18 g, 170 m m ol) an d
m eth yl iodide (5.6 m l, 90 m m ol) in dry eth er (180 m l), a solution of 4-(2,3-dim eth yl-
ph en yl)butan oic acid (4; 2.3 g, 12 m m ol) in dieth yl eth er (20 m l) was added durin g 15 m in .
Th e reaction m ixture was stirred at room tem perature for 4 h an d th en kept overn igh t. It
was decom posed by pourin g in to a cold saturated am m on ium ch loride solution (70 m l) an d
extracted with dieth yl eth er. Th e eth er extract was successively wash ed with a saturated so-
dium h ydrogen carbon ate solution , water an d th en dried with an h ydrous sodium sulfate. Re-
m oval of th e solven t yielded 6 (2.1 g, 85%), b.t. 132–137 °C/1 064 Pa (ref.7 gives b.t.
112–117 °C/665 Pa). IR (n eat): 3 365 (broad, OH).
1,1,5,6-Tetram eth yl-1,2,3,4-tetrah ydron aph th alen e (1)
A) Cyclodehydration of 6 with Dowex 50W-X8 resin. A m ixture of 6 (0.3 g, 1.45 m m ol) an d
Dowex 50W-X8 resin (1.0 g) in dry ben zen e (10 m l) was refluxed for 4 h . Th e cool reaction
m ixture was filtered off an d th e solven t was rem oved. Th e crude product was purified by
preparative TLC (silica gel G, h exan e) to give pure 1 (0.2 g, 73%), b.t. 100–105 °C/665 Pa
(ref.7 gives 125–130 °C/1 595 Pa). IR (n eat): 810. 1H NMR (CDCl3): 1.25 s, 6 H (CH3); 1.7 m ,
4 H (CH2); 2.1 s, 3 H (Ar-CH3); 2.22 s, 3 H (Ar-CH3); 2.63 t, 2 H (CH2); 7.03 an d 7.08 AB
quartet, 2 H, J = 8.5 (Ar-H). For C14H20 (188.3) calculated: 89.30% C, 10.70% H; foun d:
89.14% C, 10.46% H.
B) Cyclodehydration of 6 with trifluoroacetic acid. A m ixture of 6 (0.2 g, 1 m m ol) an d
trifluoroacetic acid (2 m l) was refluxed for 3 h , cooled, poured in to water an d extracted with
dieth yl eth er. Th e eth er extract was successively wash ed with water, a 5% aqueous sodium
carbon ate solution , water an d th en dried with an h ydrous sodium sulfate. Rem oval of th e
solven t gave a crude product wh ich was purified by preparative TLC (silica gel G, h exan e) to
give pure 1 (0.17 g, 93%).
C) Cyclodehydration of 6 with polyphosphoric acid. Com poun d 6 (0.17 g, 0.8 m m ol) was
added to a well stirred polyph osph oric acid, prepared from ph osph orus pen toxide (0.4 g)
an d orth oph osph oric acid (1.2 m l), an d th e reaction m ixture was h eated at 90–95 °C for 2 h ,
th en cooled, poured on to crush ed ice an d extracted with dieth yl eth er. Th e extract was
wash ed with water an d dried with an h ydrous sodium sulfate. Rem oval of th e solven t gave a
crude product wh ich was purified by preparative TLC (silica gel G, h exan e) to give pure 1
(0.135 g, 88%).
D) Com poun d 5 (1.76 g, 0.01 m ol) was added at –30 °C un der n itrogen atm osph ere to th e
stirred Reetz reagen t, prepared from dim eth ylzin c (1.9 g, 0.02 m ol) an d titan ium tetrach lo-
ride (3.76 g, 0.02 m ol) in dry m eth ylen e ch loride (100 m l). Th e reaction m ixture was stirred
at –30 °C for 30 m in an d allowed to reach room tem perature. Th e product was h ydrolyzed
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1,2,3,4-Tetrahydronaphthalenes
531
by a saturated sodium h ydrogen carbon ate solution (100 m l) an d extracted with dieth yl
eth er. Th e eth er extract was wash ed with water an d dried with an h ydrous sodium sulfate.
Th e residue after evaporation (1.3 g) was ch rom atograph ed on silica gel (20 g). Slow elution
with h exan e gave 1 (1.6 g, 85%).
4-(4-Isopropylph en yl)butan oic Acid (7)
To a m ech an ically stirred solution of isopropylben zen e (60 g, 0.5 m ol) an d butan o-4-lacton e
(21.5 g, 0.25 m ol), an h ydrous alum in um ch loride (85 g, 0.625 m ol) was added at 10 °C dur-
in g 2 h . Th e reaction m ixture was stirred at th is tem perature for 5 h an d decom posed with
15% ice-cold con cen trated h ydroch loric acid. Th e organ ic layer was separated an d th e aque-
ous layer extracted with dieth yl eth er. Th e com bin ed organ ic extracts were wash ed with a
sodium h ydrogen carbon ate solution . Acidification of th e alkalin e extract with con cen trated
h ydroch loric acid gave 4-(4-isopropylph en yl)butan oic acid (7), yield 25.0 g (49%), b.p.
162–165 °C/1 064 Pa (ref.17 gives b.p. 186 °C/1 595 Pa). IR (n eat): 3 700–2 500.
Meth yl 4-(4-Isopropylph en yl)butan oate (8)
To a solution of 7 (6.0 g, 29 m m ol) in m eth an ol (25 m l) was added con cen trated sulfuric
acid (1.5 m l) an d th e reaction m ixture was refluxed for 6 h . Meth an ol was distilled off an d
th e product poured in to water, th e m ixture was extracted with dieth yl eth er an d th e eth er
extract was wash ed with a saturated sodium h ydrogen carbon ate solution , water an d th en
dried with an h ydrous sodium sulfate. Th e residue after evaporation was distilled to give 8
(5.3 g, 83%), b.p. 115–117 °C/266 Pa. IR (n eat): 1 740. For C14H20O2 (220.3) calculated:
76.33% C, 9.15% H; foun d: 76.10% C, 8.92% H.
5-(4-Isopropylph en yl)-2-m eth ylpen tan -2-ol (9)
A solution of 8 (2.16 g, 9.8 m m ol) in dieth yl eth er (15 m l) was added durin g 30 m in to a
stirred solution of m eth ylm agn esium iodide prepared from m agn esium (1.28 g, 53 m m ol)
an d m eth yl iodide (5.1 m l, 82 m m ol) in dry eth er (70 m l). Th e reaction m ixture was stirred
for 6 h an d fin ally refluxed for 1 h . Th e reaction m ixture was cooled to 0 °C an d decom -
posed with a saturated am m on ium ch loride solution (50 m l). Th e product was extracted
with dieth yl eth er an d th e extract was wash ed with water an d dried with an h ydrous sodium
sulfate. Rem oval of solven t furn ish ed 9 (1.9 g, 88%), b.t. 129–131 °C/665 Pa. IR (n eat): 3 385
(broad, OH).
7-Isopropyl-1,1-dim eth yl-1,2,3,4-tetrah ydron aph th alen e (2)
A) Cyclodehydration of 9 with Dowex 50W-X8 resin. A m ixture of 9 (0.5 g, 2.3 m m ol) an d
Dowex 50W-X8 resin (1.5 g) in dry ben zen e (15 m l) was refluxed for 4 h . Th e ben zen e
solution was filtered and the residue after evaporation was purified by preparative TLC (silica gel G,
hexane) to give pure 2 (0.44 g, 95%), b.t. 124–125 °C/665 Pa (ref.5 gives b.p. 90–92 °C/133 Pa). IR
(neat): 1 610, 890, 815. 1H NMR (CDCl3): 1.27 s, 6 H (CH3); 1.22 d, 6 H, J = 7 (CH3CH); 1.65 m ,
4 H (CH2); 2.65 m , 3 H (Ar-CH2, Ar-CH); 6.81 s, 2 H (Ar-H); 7.0 bs, 1 H (Ar-H). For C15H22
(202.3) calculated: 89.05% C, 10.96% H; foun d: 88.85% C, 10.64% H.
B) Cyclodehydration of 9 with trifluoroacetic acid. A m ixture of 9 (0.3 g, 1.36 m m ol) an d
trifluoroacetic acid (2.5 m l) was refluxed for 3 h , th en cooled, poured in to water an d ex-
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Mane, Kadam, Salunkhe:
tracted with dieth yl eth er. Th e eth er extract was successively wash ed with water, a 5% aque-
ous sodium carbon ate solution , water an d th en dried with an h ydrous sodium sulfate. Th e
residue after evaporation was purified by preparative TLC (silica gel G, h exan e) to yield 2
(0.26 g, 95%).
C) Cyclodehydration of 9 with polyphosphoric acid. Com poun d 9 (0.15 g, 0.68 m m ol) was
added to a well stirred polyph osph oric acid, prepared from ph osph orus pen toxide (0.3 g) an d
orth oph osph oric acid (1.0 m l), an d th e reaction m ixture was h eated at 90–95 °C for 2 h . Th e
m ixture was cooled, poured on to crush ed ice an d extracted with dieth yl eth er. Th e eth er ex-
tract was wash ed with water an d dried with an h ydrous sodium sulfate. Th e crude product af-
ter evaporation was purified by preparative TLC (silica gel G, h exan e) to give 2 (0.12 g, 88%).
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