IL36836A - Preparation of phenylaminoethanol derivatives - Google Patents

Preparation of phenylaminoethanol derivatives

Info

Publication number
IL36836A
IL36836A IL36836A IL3683671A IL36836A IL 36836 A IL36836 A IL 36836A IL 36836 A IL36836 A IL 36836A IL 3683671 A IL3683671 A IL 3683671A IL 36836 A IL36836 A IL 36836A
Authority
IL
Israel
Prior art keywords
benzyl
formaldehyde
preparation
hydroxy
formula
Prior art date
Application number
IL36836A
Other versions
IL36836A0 (en
Original Assignee
Allen & Hanburys Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Allen & Hanburys Ltd filed Critical Allen & Hanburys Ltd
Publication of IL36836A0 publication Critical patent/IL36836A0/en
Publication of IL36836A publication Critical patent/IL36836A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/10—Separation; Purification; Stabilisation; Use of additives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/82—Purification; Separation; Stabilisation; Use of additives
    • C07C209/84—Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C215/56—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by hydroxy groups
    • C07C215/58—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by hydroxy groups with hydroxy groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
    • C07C215/60—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by hydroxy groups with hydroxy groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain the chain having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

The preparation of phenylamino- ethanol derivatives ALLEIT & HANBURYS LIMITED C: 35052 This invention relates to a process for the preparation of certain phenylaminoethanol derivatives.
We have found that phenylaminoethanol derivatives of the formula I may he prepared from compounds of the formula II in whic R^ and have the meanings given by treatment with formaldehyde in the presence of a strong base and an alkali metal borate.
The invention therefore provides a process for the preparation of phenylaminoethanol derivatives of the formula I: in which R^ represents a hydrogen atom or a benzyl group; and R2 represents a hydrogen atom or a straight or branched chain alkyl radical containing from 1 to 6 carbon atoms or an arylalkyl radical; which comprises treating a compound of the formula II: in which R^ and ll^ have the meanings given with formaldehyd or a formaldehyde yielding compound in the presence of a strong base and an alkali metal borate.
The presence of an alkali metal borate unexpected leads to selective monohydroxymethylation in the 2 position rather than hydroxymethylation in both the 2 and 6 position In carrying out the reaction formaldehyde itself or any suitable source of formaldehyde such as paraformaldehyde may be used. An aqueous solution of formaldehyde, for example 0 Formalin is preferred. The reaction is carried out in the presence of a strong base, preferably an alkali metal hydroxide such as sodium hydroxide, and an alkali metal borate, in particular sodium borate. The reaction is preferably carried out at ambient temperature in aqueous solution.
The compounds of formula I are described in our Patent Specification No. 1,200^886 as intermediates in the preparation of phenylaminoethanols of formula III which are β-adr nergic stimulants and useful as bronchodilators.
The catalytic hydrogenolysis of compounds (l) (R- = PhCIIg, R2 = tert. butyl or PhCHg) to give compounds (III) (ll^ = tert. butyl or H) and the reductive alkylation the latter with aldehydes or ketones to products (ill) in which R-j can have a variety of meanings e.g. p-methoxy-cc-methylphenethyl are described therein.
The process according to the invention has the advantage over the known processes for the preparation of these compounds (see Example 16 of United Kingdom Patent Specification No. 1,200,886) in that the introduction of the hydroxyinethyl group takes place in a single step.
The following Examples illustrate the invention : EXAMPLE 1 q 1-( Bcnzyl-tert-butylaminoniethyl )- -hydroxy-m-xylene-q1" , a -diol q-(Benzyl-tert-butylaminomethyl alcohol, hydrochloride (l.O g) was added to a solution of sodium hydroxide (0.24 g) in water (50 ml) and dioxan (20 ml) and the mixture stirred until a clear solution was obtained.
A solution of sodium borate (2.3 g) in water (50 ml) and 36 formaldehyde (5 ml) was added and the solution kept at room temperature until all the substrate had reacted (7 - 25 iays).
The reaction mixture was acidified by the addition of 2N hydrochloric acid and then basified with an excess of 8% sodium bicarbonate. The product was extracted into ethyl acetate, washed with brine, and dried Concentratio gave a clear oil, which slowly crystallised. Recrystallisation ether , from ethyl acetate - petroleum/(b. 0 60-80°) gave a -benzyl-tert-butylaminomethyl- -hydroxy-m-xylene-a 1 , a3-diol (0.35 g; 3 ^) m.p. 118-119°. Melting point was not depressed when mixed with an authentic sample isolated from the procedure described in Example l6 of United Kingdom Patent Specification r No. 1,200,886.
EXAMPLE 2 q 1-(Pibenzylaminomethyl )-¾-hydroxy-in-xylene-a1 , a -diol Sodium hydroxide (IN) (2 ml) and dioxan (15 ml) were added to a suspension of q^-idibenzylaminomethylJ-^-hydroxy-benzyl-alcohol (0.666 g) in water (15 ml) and the mixture. was stirred until a clear solution was obtained. A solution of sodium borate (0.76 g) in water (10 ml) and 3 $ formaldehyde (5 ml) was added and the solution kept at room temperature until all the substrate had reacted (7 - 25 days). The reaction mixture was acidified by the addition of 2N hydrochloric acid and then basified with excess 8o sodium bicarbonate. After dilution with an equal volume of water the white precipitate was filtered off and air dried. The solid was dissolved in ethyl acetate, filtered through a short column of silica and the filtrate and washings were combined and dried (NapSO^). Concentration of the solution gave a white solid which was crystallised from ethyl acetate-cyclohexane to yield a -dibeiizylaminomethyl-'i-hydroxy-m-xylene-a 1 , a3-diol (0.3 g) m.p. 108-110°. Melting point was not depressed when mixed with an authentic sample, prepared according to Example 33 of United Kingdom Patent Specification No. 1,200,886. This may then be debenzylated by the procedure described in Example 21 of said United Kingdom Patent Specification to give o^-amino-methyl-½-hydroxy-1m1™-xylene-oc 1 , a -diol This compound may" then be reductively alkylated according to the procedure described in Examples 28, 29, 30, 31 and 32 of the said United Kingdom Specification.

Claims (13)

' HAVING NOW particularly described and ascertained the nature of our said invention and in what manner the same is to be performed, we declare that what we claim is:
1. A process for the preparation of phenylaminoethanol derivatives of the formula I: in which R^ represents a hydrogen atom or a benzyl group;, and RQ represents a hydrogen atom or a straight or branched chain alkyl i-adical containing from 1 to 6 carbon atoms or an arylalkyl radical which comprises treating a compound of the formula II: in which R^ and Rg have therieanings given above with formaldehyde or a formaldehyde yielding compound in the presence of a strong base and an alkali metal borate.
2. A process as claimed in claim 1 in which an aqueous solution of formaldehyde is used.
3. A process as claimed in claim 1 or claim 2 in which the strong base is an alkali metal hydroxide. it .
4. A process as claimed in claim 1 or claim 2 in which the alkali metal borate is sodium borate.
5. A process as claimed in any of claims 1 to effected in aqueous solution at, ambient temperature.
6. A process as claimed in any of claims i to 5 for the production of compounds in which is hydrogen which includes the step of debenzylating the compound in which is benzyl.
7. A process as claimed in claim 6 in which the debenzylation is effected by catalytic hydrogenolysis.
8. A process for the preparation of a^-(benzyl-tert-butylaminoraethyl )- -hydroxy-m~xylene-a 1, a -diol which comprise reacting a-(benzyl-tert-butylaminomethyl.)- -hydroxy-benzyl alcohol with formaldehyde in the presence of sodium borate and sodium hydroxide,
9. A process as claimed in claim 1 substantially as herein defined with reference to Example 1.
10. Compounds of formula I defined in claim 1 when prepared by a process as claimed in any of claims 1 to 9.
11. A process for the preparation of a -(dibenzylamino-methyl )-½-hydroxy-m-xylene-a 1 , a*5-diol which comprises reacting a -(dibenzylaminomethyl)-¾-hydroxybenzyl alcohol with formalde hyde in the presence of sodium borate and sodium hydroxide.
12. A process as claimed in claim 1 substantially as herein described with reference to Example 2.
13. Compounds as claimed in claim 1 when prepared by the process of claim 11 or claim 12.
IL36836A 1970-06-02 1971-05-12 Preparation of phenylaminoethanol derivatives IL36836A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB26523/70A GB1298284A (en) 1970-06-02 1970-06-02 Preparation of phenylaminoethanols

Publications (2)

Publication Number Publication Date
IL36836A0 IL36836A0 (en) 1971-07-28
IL36836A true IL36836A (en) 1973-07-30

Family

ID=10244972

Family Applications (1)

Application Number Title Priority Date Filing Date
IL36836A IL36836A (en) 1970-06-02 1971-05-12 Preparation of phenylaminoethanol derivatives

Country Status (14)

Country Link
JP (1) JPS5216102B1 (en)
AT (1) AT308724B (en)
CA (1) CA989418A (en)
CH (1) CH558329A (en)
DE (1) DE2127177C3 (en)
DK (1) DK125388B (en)
ES (1) ES391800A1 (en)
FI (1) FI56823C (en)
GB (1) GB1298284A (en)
IL (1) IL36836A (en)
NL (1) NL174040C (en)
NO (1) NO130312B (en)
SE (1) SE376764B (en)
YU (1) YU34979B (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS51118737A (en) * 1975-04-10 1976-10-18 Shionogi & Co Ltd Novel process for preparation of monosubstituted aminobenzylalcohols a t o-n position
EP0259159A3 (en) * 1986-09-05 1989-08-09 Schering Corporation Method for the preparation of alpha1- [[(1,1-Dimethylethyl) amino] methyl]-4-hydroxy-1,3-benzenedimethanol, and intermediates used in its preparation
US4952729A (en) * 1986-09-05 1990-08-28 Schering-Plough Corp. Intermediates in the preparation of alpha1(((1,1-dimethylethyl) amino) methyl)-4-hydroxy-1,3-benzenedimethanol

Also Published As

Publication number Publication date
GB1298284A (en) 1972-11-29
ES391800A1 (en) 1974-11-01
DE2127177B2 (en) 1980-05-22
NL7107588A (en) 1971-12-06
DE2127177A1 (en) 1971-12-09
CA989418A (en) 1976-05-18
CH558329A (en) 1975-01-31
FI56823C (en) 1980-04-10
NO130312B (en) 1974-08-12
FI56823B (en) 1979-12-31
DE2127177C3 (en) 1981-01-29
SE376764B (en) 1975-06-09
YU127171A (en) 1979-12-31
AT308724B (en) 1973-07-25
NL174040B (en) 1983-11-16
YU34979B (en) 1980-06-30
IL36836A0 (en) 1971-07-28
DK125388B (en) 1973-02-12
NL174040C (en) 1984-04-16
JPS5216102B1 (en) 1977-05-06

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