(1) One category coniprises the interaction between two a-bond systems as in butadiene or vinyl ketones. Here, the a-orbitals overlap the center C-C single bond and increase its charge density and bond strength. In consequence, both of the adjacent double bonds (or unsaturated groups) lose charge and the bond strengths (and basicities of carbonyl groups) decrease. For conjugated carbonyl compounds, as the polarizability of the adjacent group increases the a-orbital overlap increases and the oxygen basicity also increases due to a greater release of charge to the carbonyl group (or possibly less charge is withdrawn from the carbonyl group since even acetophenone and methyl vinyl ketone are less basic than acetone). ( 2 ) Conjugation, as in amides where an electrondonating atom is attached to a a-electron system: If no unoccupied orbitals are energetically available on this atom, then the only type of a-orbital overlap which can occur is by the donation of the lone pair of electrons into a molecular orbital
[COMIVIVNICATIO~ 5-0.2044 FROM THE
extending over the donating atom and the adjacent unsaturated group. The force constants of the N-C bond and the C=O bond increase as did the central C-C bond in conjugated ketones, but the carbonyl basicity increases. (3) Conjugation, as in thiolesters, where an electron-receiving atom is attached to a a-electron system: In this case, the group molecular orbital is set up by a pa-dn-orbital overlap allowing a certain amount of electron drift from the carbonyl bond into the sulfur orbitals thus decreasing the force constant of C-0, but increasing that of C-S. This markedly lowers the carbonyl basicity but not as effectively as does a single halogen. Acknowledgment.-lye gratefully acknowledge the help of Gil Rerezin in synthesizing some of the sulfur compounds and the help of A h . Ethel Rightmire in preparing the graph and in obtaining spectra. PITTSBURG, CALIF.
KODAKRESEARCH LABORATORIES]
The Introduction of n-Alkyl Groups into Phenols and Hydroquinones BY E. C. ARMSTROSG, R. L. BENT,A.LORIA,J. R. THIRTLE AND A. WEISSBERGER RECEIVED AUGUST10, 1959 Xcylatioii of ~z-alk~’lh~’droquini,iles and n- and sec-alkj Iphenols proceeds in the presence of boron trifluoride & h u t isomerization of t h e alkyl groups. Reduction of the carbonyl groups (or of their Grignard reaction products) furnishes di- and tri- 12- (or sec-)alkyl products.
Dialkylphenols’ and dialkylhydroquinones2-4 with alkyl groups of 3 to 18 carbon atoms are used in color photography. Properties such as melting point, solubility, diffusivity and resistance to aerial oxidation of the side chains vary with the nature of the side chains, and walkyl derivatives could be expected to offer advantages. While the number of known alkylphenols and alkylhydroquinones is considerable, few authentic derivatives with two (or more) n-alkyl groups have been prepared. Direct alkylation has resulted in mixtures of isomers which differ in the location of the aliphatic chain on the ring and in the structurc of the chain itse1f.j Xcylation in the presence of ea talysts such as aluminum chloride5,6 (FriedelCrafts, Fries), followed by reduction of the ketones, yields rriono-n-alkplphe~iols~and mono-n-alkylhydroquiiioiie dialkyl ethers.8-12 (1) I . Ins,Iiic., S e w l 7 < r k ,N. Y., 1942, pp. 342-369. (7) XV. j . Close, B. D. Tiffany and 31. A. Spielman, THISJOUK(1942). N A L , 71, 1265 (1949). G. Sandulesco a n d A. Girard, Bull. SDC. chim. (12) D. U’asserman and C. R. Dawson, THISJ O U R N A L , 72, 4994 (1950). F r a t i c e , [4] 47, 1300 (1830). (13) D. Kastner, “Newer Methods of Preparative Organic Chemis(8) J. H. Cruickshank and R. Robinson, J . Cheiiz. Soc., 2004 (1938). t r y , ” Interscience Publishers, I n c , X e w York, X. Y.,1948, pp. (0) I’. Kurado and 3f. Wada, S‘i. PNPWSI?zsl. Phrs. C h e m Reseavch 2-10-3 13. ( 7 ’ n k y o ) , 34, 1740 (1938). ( I O ) 31. &,aiio ;riilethod
--Carbon, Calcd.
Pd-C 71.1 91.5-92.0* Water 75.7 Dil. acetic acid then petr. ether Pd-C 96.5-98.0 c16H33 58 112.5-113. 5d Ligroin-benzene Pd-C 79.0 Lit. 86"; T. B. Reduction of 2-allylhydroquinone using Raney nickel gave a 90% yield. Preparation described in this paper; see also refs. 3 and 21. THISJOURNAL, 35, 1014 (1913). C3H1 CsHi7"
39"
86
studied in greater detail than that of phenols and is therefore discussed first. The isomeric status of the side chains in the phenols and the hydroquinones was established by the identity of products obtained by alternate routes (see Discussion) and by mass spectrometry. l5 The mass spectrometer was of the 60" sector type18 equipped with a heated inlet system17which operated a t 230". This instrument successfully analyzed di- and trialkylphenols and dialkylhydroquinone ethers; the di-n-alkylhydroquinones were, however, insufficiently volatile. The spectra contain peaks attributable to the parent compound and to the parent minus certain fragments split off in the ionization chamber. Fragmentation of alkylbenzenes is known to occur with greatest ease between the cy- and P-carbon atoms of the alkyl chain,'s so that a molecule containing a n-alkyl chain will reveal a major peak corresponding to loss in the chain of all except the a-CH2. We have confirmed that this is also the pattern in alkylphenols, anisoles and hydroquinone ethers. A molecule containing a secalkyl chain, where R and CHI are attached to the cy-carbon, will give a major peak corresponding to loss of the R group. The peak corresponding to loss of the cy-methyl group is insignificant in size. Thus, 2,4-di-n-amylphenol gives peaks corresponding to mass 234 (the ionized molecule itself), mass 177 (loss of C4H9),mass 120 (loss of two C I H Siragments) and mass 121 (loss of C4H9 and of C4H8, the latter through hydrogen rearrangement). The peak a t mass 191, corresponding to a loss of C3H7, was only 1% in size, compared to the principal peak a t mass 177. 4-n-Amyl-2-sec-amylphenol gives, among others, peaks corresponding to mass 234 (the ionized molecule), mass 191, the largest peak in the spectrum (loss of C3H7) and mass 177 (loss of C4H9 from the n-amyl chain). (15) T h e authors are grateful t o D. W. S t e y a r t and G. P. H a p p f o r this assistance. (16) A. 0. Nier, Rev. Sci. Inst., 18, 398 (1947); R. I,. Graham, A. L. Harkness and H. G. Thode, J. Sci. Instruments, 24, 119 (1947). 117) V . J. Caldecourt, Anal. Chenz., 27, 1670 (195.5). (18) F. H. Field and J. I.. Franklin, "Electron Impact Phenomena and the Properties o f Gxseous Ions," Academic Press, Inc., h-ew York, N. Y . , 1'357, p. 17.5.
%--
Found
-Hydrogen, c/oFound Calcd.
8.7 71.4 7.9 9.9 10 .O 75.5 80.2 11.4 11.2 Johnson and W. )V. Hodge, L k i o 110-111 .
Hydroquinones. 2,5-Di-n-alkylhydroquinones.Cruickshank and Robinson's synthesis of 2-namyl-5-n-octylhydroquinone required eight steps, starting with hydroquinone dimethyl ether, valeryl chloride and aluminum chloride in carbon disulfide,8 and was complicated by ether cleavages in each acylation step (see also refs.gplO),and by a tedious purification of the product. Cook, Heilbron and Lewis,ll and Wasserman and Dawson,12 preparing monoalkylhydroquinones, avoided ether cleavage by working a t lower temperatures and with solvents such as tetrachloroethane. These modifications gave us a 24% yield of 2-n-amyl-5-n-octylhydroquinone in five steps as a waxy solid melting a t 104106" with some prior softening,lg while acylation of hydroquinone with the corresponding acids in the presence of BFs yielded, in four steps, 32y0 of 2-n-amyl-5-lz-octylhydroquinone melting a t 106.5-107". il no-solvent technique developed later in this program would probably increase the yield. 2o
OH
OH
OH
Tables I-IV list the various hydroquinone derivatives prepared.22 Absence of isomerization in the final product was demonstrated by the fact that identical products (19) We first assumed t h e product t o be a mixture attributable t o isomerization of t h e side chains b y aluminum chloride. However, mass spectrometric examination of t h e intermediate, 2-amyl-5-octylhydroquinone dimethyl ether, refutes this assumption. (20) See Experimental-Stearoylhydroquinone. (21) Reductions were catalyzed b y palladium-on-charcoal or b y copper chromite. T h e authors thank J. L. R. Williams for suggesting t h e latter catalyst; see J. L. R. Williams, J Org. Chem., 22, 772 (1957). (22) I n niaily t j f tlic grepardtioiis, no a t t e m p t was niadc t o work o u t iii:rxirnum yields.
E. C. ARMSTRONG, R.L. BENT,A. LORIA,J. K. TIIIRTLE AND A. WEISSBERGEK
1930
VOl. 82
TABLE I11 5-ACYL-2-n-ALKYLHYDROQUlNONES Yield, 2-n-Alkyl
5-Acyl
%
Recrystn. solvent
CdHeCO" 65 C8Hl7 70 CSHI7 C.iHiSC0' 69 ci~3ico CHs 56 CisHaiCO CsH7 CiHsCO 50 Ci&a CiiHzaCO 37 c12H26 Preparation described in this paper;
M.P.,
-Carbon, Calcd.
oc.
59-60 82-83 94-94.5 76.5-77.5 93-94 88-90
Petroleum ether Cyclohexane Dil. ethanol EtOH then ligroin Ligroin then EtOH Ligroin see also ref. 3.
74.5 75.9 76.3 76.9 76.9 78.2
%-
Found
74.8 76.2 76.1 76.9 76.9 77.9
-Hydrogen, Calcd.
9.8 10.3 10.6 10.8 10.8 11.4
%-
Found
10.0 10.6 10.7 10.9 10.6 11.3
TABLE IV 2,6-DI-?Z-ALKYLHYDROQUINONES 2-WAlkyl
5%
Alkyl
Yield,
%
hl.p., o c .
Recrystn. solvent
Method
-Carbon, Calcd.
%-
Found
-Hydrogen, %Calcd. Found
11.0 11.4 82 106.5-107 Ligroin CuCrOl 78.1 78.3 Cd€iIO" CsHiT 11.4 11.5 90 109.5-110.5 Dil. HAC then cyclohexane Pd-C 79.0 79.1 c&7' C8Hl7 11.6 11.4 79.1 83 127-128 Acetic acid Pd-C 79.3 ClsHa: CHI 11.7 11.5 50 110-111 Benzene-heptane 79.8 80.1 Pd-C CieHu' CaH7 CaH7 Ci&Issd 83 110-111 Benzene-cyclohexane CuCrOz .. .. .. .. CizHza CiaHz5 76 108-109.5 Acetic acid Pd-C 80.7 80.3 12.2 11.8 Ref. 8 gave no data, but reported the quinone t o melt a t 65'; Preparation described in this paper; see also ref. 3. the quinone prepared from this material melts a t 65",also. From 2-n-hexadecpl-5-propionylhydroquinone. From 2palmitoyl-5-n-prop ylh ydroquinone.
are obtained if the acyl groups are introduced in the with the product of the sequence reverse order. For example, 2-hexadecyl-&pro0 pylhydroquinone prepared via 2-hexadecyl-5-propionylhydroquinone is identical with that prepared
via 2-palmitoyl-5-propylhydroquinone. A rigorous proof that 2-alkylhydroquinones or their ethers acylate in the 5-position has not been reported. It is given by the fact that the dialkylhydroquinones obtained ultimately, after acylation of monoalkylhydroquinones, differ (see Experimental) from the corresponding 2,G-dialkylhydroquinones and 2,3-dialkylhydroquinones prepared by unequivocal reactions. 2,6-Di-n-alkylhydroquinones.-A synthesis of 2,G-di-n-alkylhydroquinonesis based on observation that acylation of phenol ethers in the o-position, with BF3 as a catalyst, required forcing conditions,l 3 while phenols are more readily acylated to products that include o-derivatives. It is therefore expected that 4-methoxyphenol would undergo acylation preferentially in the 2-position, and that 2-alkyl-4-methoxyphenol should be acylated in the G-po~ition.~ This ~ was confirmed by the identity of the di-n-octylhydroquinone prepared by this sequence O €I
'4 OH This again demonstrates that, under the conditions described, little or no isomerization occurs in boron trifluoride-catalyzed acylations. The substituted 4-methoxyphenols prepared are listed in Table V and 2,6-di-n-alkylhydroquinones . in Table VI.
2,3-Di-n-alkylhydroquinones.-2,3-DialkylhyOCH,
OCHB OH
OCHj OH
droquinones, other -than 2,3-dimethyl- and- 2,3diallylhydroquin~ne,~~ have not been reported in the literature. However, Baker and L ~ t h i a n * ~ prepared a potential intermediate, 2-acetyl-3allylhydroquinone, the structure of which was proved by Cruickshank and Robinson.8 We have made use of Baker and Lothian's method to prepare 2 - n - hexadecyl-3 - n - propylhydroquinone. The product differs from those obtained by procedures chosen to yield the corresponding 2,5and 2,6-isorners. Phenols.-2,4-Di-n-alkylphenols were prepared under conditions similar to those used in the alkyl(24) L. F. Fieser, W. P. Campbell and E. M. Pry, THISJOURNAL,
(23) Cruickshank and R o b i n s o d prepared 0-octanoyl-2-amyl-4inethoxyphenol by an aluminum chloride-catalyzed ncylation.
61, 2206 (1959). (25)
W.n a k e r and
0. h l . Lothian,
J . Chein. Soc., 274 (1030).
April 20, 19GO
n-ALKYL
GROUPSIN
1931
PHENOLS AND HYDROQUINONES
TABLE V
4-METHOXYPHENOLS OCHj Yield, 2-Position
6-Position
HaPb H
%
M.p., ' C .
-Carbon, Calcd.
Recrystn. solvent
70-
-Hydrogen, %Calcd. Found
Found
42.544 Methanol 72.0 71.7 8.8 9.0 57.5-59 Ethanol 76.2 76.2 10.5 10.4 COCnHos H 59.5-61.5" Ethanol 76.9 76.9 10.8 11.0 88 43.5-5. 5d Methanol 76.3 75.7 10.2 10.0 C8Hl7 Ha CieKaa H 60 69.5-70.5 Acetic acid 79.3 79.6 11.5 11.4 C18H37 H 63 72-73.5" Dil. HAC thenligroin 79.8 79.9 11.7 11.6 C8Hl7 C7H1,jCO"" 43 31-32g Ethanol 76.2 76.4 10.5 10.3 c16H81c04 37 66-67 Ethanol 76.6 77.0 10.9 10.9 CH3 11.1 CisHn CzHsCO 54 65.4-66.5 Acetic acid 77.3 77.6 10.9 C8H17 CsHiF 89 39-41h .... 79.3 i9.6 11.5 11.4 CHa Cl5&3' 76 70-71.5 Ethanol 79.5 79.1 11.6 11.2 CisH33 CaH7 59 61-62 Acetic acid 80.0 80.1 11.8 11.2 Also formed by action of diazomethane on 2-caprylylhydroPreparation described in this paper; see also ref. 3. Lit.1o 63-64'. quinone and by BF3-catalyzed Fries rearrangement of p-methoxyphenyl caprylate (see Experimental). Rearrangement of the caprylate of 4-methoxy-2-n-amylphenol using BF3 as the dB.p. 187-191' (10 mm.) e Lit. 73-75'. B.p. 190-200" (1 mm.). catalyst, gave a 59% yield (see Experimental). 0 B.p. 195-205" (1 mm.). COC7His
coc16H31
55 47 46
*
(I
TABLE VI 26-DI-n-ALKYLHYDROQUINONES 2-Position
Yield, 6-Position
%
M.p., O C .
Recrystn. solvent
-Carbon, Calcd.
64 81.5-82.5 1: 1 ligroin-petr. ether GHn" C8H17 CH3 c1&83' 76 93.5-94.5 2 : 1 ligroin-petr. ether 44 74-75 Dil. MeOH CaH7 Ci6Haa Preparation described in this paper; see also ref. 3.
$!Cl5Hd1
OCH,CH=CH,
'0:
::
OH
C-CJLL
OH CH,CH=CH,
+ I
OH
$f;; OH
+l-cc>H81 OH CjH7-1
hydroquinone syntheses but a t somewhat higher acylation temperatures to avoid contamination of the ketones by esters. I n the case of 2,4-di-namylphenol, a repetition of the acylation and reduction yielded 2,4,G-tri-n-amylphenol. The 4-n-alkylphenols used as starting materials were obtained by reduction of the corresponding ketones. The ketones were prepared by acylation of phenol in the presence of aluminum chloride in excess to avoid formation of the 2-i~onier.~An excess of boron trifluoride cannot be maintained since only little more than the theoretical amount is absorbed by the reaction mixture26 and, therefore, more or less of the o-derivatives result. However, 4-decanoylphenol was isolated in fairly good yield from a BF3-catalyzed reaction which most likely also yielded some of the 2-isomer. As with the hydroquinones, the absence of isomerization (26) Boron trifluoride ttherate might aid in maintaining an exces3 of catalyst, b u t we did not examine this possibility.
79.0 79.3 79.8
%-
Found
-Hydrogen, Calcd.
79.1 79.6 79.9
11.4 11.5 11.7
V0Found
11.3 11.2 11.3
by BF3 was confirmed mass spectrometrically and by comparison of products; e.g., 4-n-decyl-2n-propylphenol, obtained from 4-n-decyl-2-propionylphenol, is identical with the material obtained from 4-n-decyl-2-allylphenol. Table VI1 lists n-alkylphenols and their intermediates. The n-alkyl groups, as compared to the t-groups, can have a marked influence on tendency to crystallize and on melting points of derivatives. 2,4Di-n-amylphenol does not freeze a t -40', while its t-isomer freezes a t 25.8'. It gives an cr-naphthylurethan melting a t 104.5" and an aryloxyacetic acid melting a t 65', while the corresponding tisomers melt a t 133.5 and 126") respectively. The failure of boron trifluoride to isomerize nalkyl chains also applies to sec-chains and has made possible the preparation of authentic sec-alkylphenols. Thus, p-sec-butylphenol has yielded 2,4di-sec-butylphenol and 2,4,6-tri-sec-butylphenol, the mass spectra of which follow the pattern predicted for sec-alkyl derivatives and show no evidence
+i;2H5
vHc2H OH
dehvdration reduction
*
('H,C' IIC211.
CH,CHGH,
YH3
( ' 1 Ij("C,Hj
E.
e. ARMSTKUNG,K.L.BENT,A. LOKIA,J . li. THIKTLB AND A. \ T U I S ~ ~ ~ U K G ~l.01. K s2 TABLE VI1
OH ~OLY-?Z-ALKYLPII&.UOLSA N D ISTERMEDIATES
h 1 . p or b.p., "C. (mm.)
R"
H H H H H H H I-I H H
Yield, n /c
145 (1) 145-148 (7) 185-192 (16) 122-127(1) 172-175 (1.5) 143-145(1) 189-194(21 161-165(1)
It'*
--Carbon, Calcd.
i1~6ri
67
'
Y l?
1.5110 1.5249 1.5180 1.5144 1.5067 1.5048 1.5000 1.5072 ....
'lo-
Found
77.9 76.7 76.9 77.4 78.6 78.9
-Hydrogen, %Calcd. Found
'78.3
9.9 9.9 75.8 8.8 8.9 88 76.5 9.4 9.6 77 77 0 9.7 9.3 66 78.1 10.4 10.4 73 79.0 10.6 10.4 66 TY.7 80.3 11.0 11.3 81 78.6 i8.6 10.4 10.8 i2.574." i3 77.8 77.7 10.0 10.0 i2-i3d ... . 80.2 80.6 86 11.3 11.2 H 125-128(1) 88 1.4995 82.2 82.6 11.3 11.4 H 110 ( 0 . 5 ) 82 1.501; 82.0 82.4 11.1 11.3 H i6 150-lSl(0.06) 82.6 82.4 1.4981 11.6 12.0 H 149-151(1) 1.4953 82.7 83.1 11.8 11.4 86 H 138-141(1) 1.5008 82.2 82.1 93 11.3 11.2 H 149-154(1) 11.7 11.6 1.4966 82.5 82.9 83O H 61-62" 88 12.3 12.2 . . .. 83.3 83.3 COCaHs 140-145(1) 91 1.5071 79.2 79.4 10.8 10.7 148-151(1) 85 52.8 82.4 11.9 11.9 1.4945 CE"ih a Preparation described in this paper. * 4-Decaiioylphenol and 4-n-decylpliericjl ai-e described iu the Experimental From ligroin. From n-heptane. e a-Saphthylurethan, m.p. 104-104.5" (see Esperiincntall. 1 a-Saphthylurethan, m.p. 87-88", Hydrogenation of the corresponding allyl intermediate was effected in 81 rL !-ield (see Experimental). a-Kaphthylurethan, m.p. 76-79". Si
TABLE 1'111
BRANCHED-CHAIN ALKYLPHENOLS A X D INTERMEDIATES
Rr+, l
