NEW DERIVATXVE~S OF AMINOHYDROXY COMPOUNDS
Sept., 1945
By recrystallization twice from ethyl acetate-ligroin there was obtained one-half gram of 4,6-dichlorodiphenic acid (I) white needles, m. p. 216-217'. Anal. Calcd. for C I ~ H ~ O ~ CC1, l ~ 22.8; : neut. equiv., 155.5. Found: C1, 23.0; neut. equiv., 151. Because of the difficulties in isolating this material the quantitative determination of its formation was carried out by treatment of the original crude with concentrated sulfuric acid (see below). A number of experiments were performed in which mixtures of diazotized anthranilic acid and diazotized 0- or p-nitroanilines were reduced. The only acidic product was pure diphenic acid. 2,4-Dichlorofluorenone-5-carboxylic Acid (In.-Threetenths gram of 4,6-dichlorodiphenic acid was heated wit! 2 cc. of concentrateddulfuric acid for ten minutes at 150 or for two days a t 80 The resulting solution was poured on ice and the yellow solid dissolved in warm dilute bicarbonate solution (in some experiments the sodium salt crystallized if the solution was cooled). After reprecipitation with dilute hydrochloric acid it was recrystallized from benzenealcohol as yellow needles, m.p. 240-242 '. Anal. Calcd. for ClrHaOaCln: C1, 24.2; neut. equiv., 293. Found: C1, 24.2, 24.3; neut. equiv., 293, 294. The formation and isolation of this substance proved to be a convenient method for estimating tlie amount of 4,6dichlorodiphenic acid when the latter was mixed with both diphenic acid and 4,6,4',6'-tetrachlorodiphenic acid as in the crude reduction product. In a typical run 14 g. of crude was heated with 45 cc. of concentrated sulfuric acid at 150' for ten minutes or a t 80' for three days. The sol?tion was cooled and 2.6 g. (28% yield) of d,l-4,6,4',6 tetrachlorodiphenic acid filtered off. The Htrate was poured on ice and the resulting yellow solid dissolved in warm dilute bicarbonate solution and filtered free from a small amount of non-acidic material. Reprecipitation with dilute hydrochloric acid gave 6 g. of mixed fluorenone carboxylic acids. There was evidence for the presence of water soluble sulfonation products which were removed a t this point. Separate experiments showed that they
.
-
[CONTRIBUTION FROM
THE
1515
were derived c h i d y but not entirely from the diphenic acid. The acid mixture was recrystallized from a mixture of nine parts of benzene and one part of alcohol. The first fractions were pure 2,4-dichlorofluorenone5-carboxylic ac'id, m. p. 240-242'. A total of 2.5 g. melting in the range 235-241' was obtained in some runs. A separate experiment showed that when mixtures of diphenic acid and tetrachlorodiphenic acid were heated in concentrated sulfuric acid no dichlorofluorenone carboxylic acid was formed. Thus the 2.5 g. isolated above corresponds t o an 18yoyield of 4,6-dichlorodiphenic acid in the reduction reaction.
Summary 1. By reduction with cupro-ammonia ion in dilute ammonium hydroxide the diazotized forms of the following amines are converted to biaryls in yields of 20-90% : the nitroanilines, the nitrotoluidines, anthranilic acid, a variety of halogenoand nitroanthranilic acids, a number of aminonaphthalene carboxylic acids, o-aminobenzenesulfonic acid. 2. The following yield azo compounds in yields of 2040%: aniline, the toluidines, p aminophenol, p-aminoacetanilide, m- and p aminobenzoic -acids. 3. Reduction of a mixture of diazotized anthranilic and 3,&dichloroS-aminobenzoic acids produces the unsymmetrical biaryl 4,6-dichlorodiphenic acid (I) in addition to the usual symmetrical products. 4. 4,6-Dichlorodiphenic acid is converted to 2,4-dichlorofluorenone-5-carboxylicacid (11) by heating with concentrated sulfuric acid. DURHAM, N. H .
RECEIVED JULY 14, 1945
ICESEARCH AND DEVELOPMENT DEPARTMENT OF THE COMMERCIAL. SOLVENTS CORP. ]
Some New Derivatives of Amino Hydroxy Compounds' By MURRAY SENKUS Amino alcohols which have an amino group or a monosubstituted amino group and an alcohol group attached to adjacent carbon atoms are known to react with aldehydes to form oxazolidines. A large number of new amino alcohols have recently become available from the hydrogenation of nitro alcohols that can be prepared by allowing one mole of a nitroparaffin to react with one mole of an aldehyde.2 Some of these amino alcohols have been converted to oxazolidines and the new compounds are reported herein. A study was also made of the reaction of aldehydes with amino polyhydric alcohols that can be prepared by the hydrogenation of nitro polyhydric alcohols derivable from normal nitroparaffins and formaldehyde.* Two types of products were obtained from the above reactions. (1) T h e portion of this article describing the reactiona of aldehydes with the amino polyhydric alcohols was originally received by us on September 7, 1943.-The Editor. (2) Vanderbilt and Hass, 2nd. Eng. Chcm., 119, 34 (1940).
The reaction of one mole of an aldehyde with one mole of an amino polyhydric alcohol gave an oxazolidine. The reaction of two moles of an aldehyde with one mole of an amino polyhydric alcohol gave substituted l-aza-3,7-dioxabicyclo[3.3.0]octanes according to the scheme CHnOH
I I
R'-C-NHe
+ SRCHO +
CHeOH CHe-+CH-R R"C-
I I
I
N
I
+ 2Hn0
CHn--O-CH-R
The structures chosen for the new compounds are supported by analytical data and by the observation that in each reaction one mole of amino polyhydric alcohol and 2 moles of an aldehyde yielded 2 moles of water and the amount of product calculated according to the above equation.
MCRRAYSENKUS
131(i
Further confirmation of the new structure was obtained by studying the hydrogenation of these compounds as well as their reaction with Grignard reagents. Cope and Hancock3had shown that hydrogenation of oxazolidines derivable from 2-aminoethanol gave 9-alkylaininoethanol~according to the equation H CF12--N/ \C
'
,Ft
12
ckr? NH --a$(
' R CH: -011 \.e studied the hydrogenation of other oxazolidims derived from 2-aminoethanol as well as other amino alcohols atid isolated the expected 5-alkylamino alcohol in each experiment. The N-alkylamino alcohols were allowed to react with ddehydes. This reaction gave N-substituted ouazolidines. The S-substituted oxazolidines were also hydrogenated. These hydrogenations vielded the expected dialkylamino alcohols. .%II examination of the structures of oxazolidines and the l-aza-3,7-dioxabicyclo[;3.3.0]octanes will reveal that the grouping -f H, ----f
i". 0' ? I '
--X-C-O
rN-C--O
-
-.
H2+-=N-CH
f HO-
-4 similar splitting of this grouping in the l-aza-
:I,T-dioxabicyclo[3.3.0]octanes would be expected to take place if these compounds were hydrogenated. The hydrogenation of these compounds wxs tried and the expected dialkylamino polyhydric alcohol was isolated in each experiment. 'I'his reaction is represented by the equation K--CHZ-V-CH2-R
KHC-Z)--.CHR C),'
\
~
>O
-+ 2H2
I
HOCH2-C-CH20H
CH2-C-CIS: , R
I
R
'I'he grniipjng
\\.hick1 is coninioii to oxazolidines and l-aza-3,Sciioxabicyclo[3.3.0]octaiies is also present in conipounds of t h e type K& --CHj - 0 -K
liobirisuli arid Robinson4 had found t h a t these compounds will react with Grignard reagents according to the scheme R2N--CH2-O-R .-
I n view of the above reaction the Grignard reagent would be expected to effect a similar splitting of the
I
===&T--C-O--CI
grouping in the N-substituted oxazolidines and in the 1-aza-S,'i-dioxabicyclo [3,3.O] octanes. These reactions were tried and the expected dialkylamino hydroxy compound was isolated from each experiment. These reactions are set forth in the equations below.
I
-C---O---hIg-
R '
-x
I
R
is coinmon to both structures. During the hydrogenation of the oxazolidines the grouping at hand is split as set forth below
I
Vol. ti7
+ RMgCl+ RzN-CH,----R + K
-O--hlg---CI
t3j Cope and Haucock, 'THxs J O U R N A L , 64, 1503 (1942). i l ) Robinson a n i R o i > i n s i > nJ . Ckcm. .Coc , 113. 532 (1023).
X-hlg-O-CH2-C-CH2ORIgX
I
R
Experimental Preparation of Oxazolidines and l-Aza-3,7-dioxabicyclo [3.3.0 ]octanes.-The oxazolidines were prepared by refluxing mixtures of one mole of aldehyde, one mole of amino alcohol and 150 ml. of benzene in a flask connected t o a Dean and Stark moisture trap6 which was connected t o a condenser. The l-aza-3,7-dioxabicyclo[?,.3.0]octanes were prepared by refluxing mixtures of two moles of aldehyde, one mole of amino polyhydric alcohol and 200 nil. of benzene. After water had ceased separating in the above reactions, the benzene was removed by distillation. The crude products were purified by rectification in placao or by recrystallization from a suitable solvent. The new osazolidines are listed in Table I. The l-aza-3,7-dioxabicyclo[3.3.0]octanesare listed in Table 11. Hydrogenation of Oxazolidines to Alkylamino and Dialkylamino Alcohols.-The procedure for the hydrogenation of oxazolidines and N-monosubstituted oxazolidines to alkylamino alcohols and dialkylamino alcohols, respectively, with the exception of 4,4-dimethyl-2-phenyloxazolidine was as follows: One hundred granis of ail oxazolidine dissolved iii Ill0 nil. of methanol was hydrogenated in the presence of 5 g . of 1:; palladium charcoal at 100" and 1000 Ib./sq. i l l . The mixture was filtered and the filtrate was rectificd through a laboratory column. The conversions of oxazolidines t o alkylamino or dialkylamino alcohols averaged about 90%. The hydrogenation of 4,4-dimethyl-2-phenyloxazolidine according t o the above method gave toluene and Z-amino2-methyl-1-propanol but no 2-benzylamino-2-methyl-lpropanol. Debenzylations of this type have been reported by Peyers and by Baltzly and Buck.' However, at 35(5) Dean and Stark, Znd. Eng. Chem., 12, 486 (1920) (6) Peyer, U. S. Patent 2,243,977. ( 7 ) Raltzly and Ruck, TEISJ O U R K A L , 6 6 , 1!284 (18433
NEW DERIVATIVES OF AMINOHYDROXY COMPOUNDS
Sept., 1945
1517
TABLEI
R3
I
/R*
1
)CH-R1
SOME OXAZOLIDINES OF THE TYPER4-C-N Rs-CH-0 p.,.
H C~HB H CsHsCHa CeHsCHz
14
H
CHI
CHI
15
H
CHs
CHa
H
BO
73.0"
CsHiaNOi
I6
H
CHI
CHzOH
H
80
65.0"
CIHIINO? 8.80 8.64
6
7 8 9
a
RS H H H CsHk C6Hk H H H CsH7 CaH7 CiHr CaHi H
92 80 90 84 79 65 94 99
65
489 87 84
96
OC.
62.0- 62.5 66 - 68 72 -73 99.5a 190 -193 78 - 79 93 - 95 66.0' 80
mm.
30 30 10 0.2 10 10
2.7 5 DO - 92 0.1 111 0.3 110.0-110.5 4 97
llzoD
d%
Formula
Nitrogen, % Calcd. Found
10 11 12 13
1
2 3 4 5
R' H H H H H CHs CHI CHa CHI CHs CHa CHI CHI
Conver- --B. sion
Ra H H H CHa CHI CHs CHa CHa CHI CHa CH3 CHa CH6
No.
1.4463 0 9213 CiHisNO .12.16 12.I5 1,4352 0.9066 c7HikNO 10.84 10.76 1,4358 0 8700 CioHiiNO 8.18 8.10 CisHirNO 5 . 8 5 5.81 1.3873 1.12 C Z I H Z ~ N O4.23 4.29 1.4424 0,8895 CioHziNO 8.18 8.09 1 4464 0.8808 CiiHnrNO 7.56 7.33 CiiHisNO 7.90 7.82 1,4418 0.8884 CiiHzsNO 7.56 7.19 1.4477 0.8829 CizHiaNO 7.03 7.06 1.4515 0,0876 C14HzlNO 6.39 6.15 1.5079 0.9776 CikHzaK\10 6 . 0 0 6.03 1.5166 1.0134 CizHi7NO 7.32 7.30
8.38 8.37
Melting point TABLEI1 K,
7 . -
R
R'
H H H H H H CaH7 CaH7
CsHs CHB Melting point.
Conversion -7-
'C.
B. p..-
97 94 95 90 90 94 81
66.5 60.0 71.5 90--91 84-85 65" 94-95 104.5
70
114-118
95
123.0"
/ I
mm.
n%
,K
--Nitrogen, Calcd.
112020
10 10 10 10 10
1.4715 1.1590 1.4818 1 ,4601 1.4631
1.185U 1.1088 1.0829 1.0522 1.0602
12.17 10.85 9.78 8.91 8.91 9.65
10 10
1.4494 1.4544
0,9594 0.9599
0 , (i0
1.4601
0.9276
0.5
%-
Found
0.lti
12.17 11.05 9.79 8.85 8.92 9.86 6 , 63 0.37
CiaHjeNO?
4.30
4.32
C16H,9N02
4.98
,i.O4
a
45' debenzylation did not occur The solution from the serve as an example. The Grignard reagent was prepared low temperature hydrogenatinii was distilled to remove from 8 g. (0.33 mole) of magnesium turnings and 40 g. (0.31 mole) of methyl iodide iii 300 ml. of ethyl ether the methanol. The residue from this distillation solidified o i l cooling. The crude 2-beuzylainiiio-2-inethyl-1-propa-While this solution was stirred, 51.5 g. (0.31mole) of 3-is0 butyl-2-isopropyloxazolidinein 300 mi. of ether was added 1101 Jvas purified l ~ yrecrystollizatioii from cyclol~exaiic a t such a rate that the mixture in the reaction flask rv'I'he new alkylaiiiiiio and dialkylaniino alcohols arc listed fluxed gently. The mixture was allowed t o stand in t h r i i i Table I l l . Hydrogenation of l-Aza-3,7-dioxabicyclo [3.3.0 ]octanes rooin for twenty-four hours, and then while i t was stirred to Dialkylamino Polyhydric Alcohols.-One hundred grams 20 ml. of water was added dropwise to hydrolyze the Grigof l-aza-3,7-dioxabicyclo[a.8.0]octane dissolved in 400 inl. iiard addition product. A further 130 ml. of water was of methanol was hydrogeiiatcd at 100" and 1000 Ib./sq. in. added and stirring was continued for three hours. Thc in the preseiice of 10 g. of Raney nickel catalyst. 'The mixture was allowed t o settle for fifteen minutes and thc mixture was filtered and the filtrate was distilled to remove top ether layer was separated from the thick aqueous layer by decantation. The aqueous layer was extracted with the methanol. The residue was purified by rectification in E'acuo or by crystallization from a suitable solvent. two 200-ml. portions of ether. The ether solutions were The dielkylamino polyhydric alcohols are listed in Table combined and the composite was rectiged. This distillation yielded 54 g. of N-isobutyl-N-(1,2-dimethylpropyl)IV. Reaction of Grignard Rmgents with N-Substituted 2-aminoethanol, b. p. 104.5-105.0" at 10 mni.; conversion, Oxazolidinei.-The procedures for the reaction of Gri- 96%: It is noteworthy that in one experiment of the above type gnard reagents with N-substituted oxazolidines were all similar. The reaction of methylmagnesium iodide with a side reaction occurred. Hydrolysis of the product from the reaction of isopro~~ylmag~iesiui~~ bromide with 3 3-isobutvl-2-i~oprnpylosazolidine is described below to
MURRAY SENKUS
151s
Vol. 67
TABLE I11 R'
SOMEAMINO ALCOHOLSOF
TYPER L C - N I
THE
-
,4 t a r t i n materials Oxazolidine Reducing reference reagent no.
Conversion
85
H (CH7)ICHMgCl H (CH3)2CHMgBr CH3MgI H CH:?vlgI H CIH,MgBr H H CaH7MgC1 H CHsMgI
1 2
3 3 3 4
5 ij -7
1
8 0 10 11 12
B . p.,--------
7 -
OC.
81 - 82
75 92 35 96 70 90 85 80 85 86 75. 80 86
mm.
10 10 10
89"
1.4370 1.4355
Formula
-Nitrogen, Calcd.
0.8844 .8433
CsHi5KO CioH2aNO
11.95 8.08
11.85 7.96
6.50 7.48 5.80 4.05 8.08 6.50 7.81 7.48 5.75 6.33 5.62
6.40 7.45 5.80 4.21 s. OG 6.48 7.86 7.52 5.79 6.33 5.63
s9b 112.5-113.0 -1 1.4600 .8819 104.5-105,O 10 1.44G2 ,8647 100. .5c 190 -193 0 .2 1.5845 1.06 so - 90 1 1.4526 0.8751 105 4 1.4538 ,8746 67.6' 63 0.3 1.4475 .8685 86.5- 87.0 9 1.4529 .8634 .3 1.5100 ,9733 112 110 -112 .2 1.5082 .9617 Melting points of picrates and of a mixture of these picrates, 122.5'. . L
0.b
%---
dSQm
n%
CI~HZOSO CliHzsNO CiaHioXO C&Z~NO GoHzaNO CiaHigNO CilHirNO CiiH&O CirHasNO QJLNO CisHirNO Melting point.
Found
TABLE IV R3\x/R3 SOME AMINO
POLYIIYDRIC
ALCOIIOLS OF
THE
I
TYPEHOCH2-C-CHzOH
I
R' Starting materials Bicyclic Compound
K'
C d H C
\ /O
o;cH\sI/
CHrC-CHI
-
I
R2 R' H
n1
Reducing reagent CdHiMgCI CdIsMgCl
R'
CiH7
CHI
CtHsMgBr
H CiHi I1
CHI CHI CHI CHIOH
CaH7MsCl If CoJIrhIgBr I1
CaHii CbHii CiH7 )CH CIHK C
