DE3739415A1 - Azaindoline-spirooxazine compounds - Google Patents

Abstract

Azaindoline-spirooxazine having the general formula (I): <IMAGE> in which R1 represents an aliphatic or aromatic group; R2 and R3 in each case independently represent a hydrogen atom, an aliphatic or aromatic group or an alkoxy group, or R2 and R3, together with the carbon atom to which they are fused, represent an alicyclic group; R4 represents a hydrogen atom or an aliphatic or aromatic group; ring A contains one or more nitrogen atoms in the ring and can be non-substituted or substituted, provided that no substituent is located on a nitrogen atom in the ring; and ring B can be non-substituted or substituted by at least one substituent, provided that the 6'-position in ring B is not substituted by an amine function or a hydroxyl group. The spirooxazine compounds are suitable for imparting photochromic properties to a plastic host material, such as a plastic lens.

Description

The invention relates to spiro-oxazine compounds.

It has been found that spiro-oxazine compounds are suitable, a polymerized host material, like a plastic lens, photochromic properties to rent. Examples of typical spiro-oxazine compounds and their use are in US-PS 42 15 010, EP-A 01 41 407, GB-A 21 71 404 and 21 17 390, PCT-A 85/02619 and GB-A 86 10 709.

It has been found that certain new azaindoline Spiro-Oxazines are suitable, a polymerized Host material, such as a plastic lens, photochromism to rent.

An advantage of the azaindoline spiro according to the invention Oxazine compounds is that when in one Plastic host material are incorporated, the color, which they lend to the host material when that  Spiro-Oxazin in its lightened or inactive state located, is relatively bright compared to known ones photochromic spiro-oxazine compounds. About that In addition, the color is that of the plastic host material due to the existing spiro-oxazine compounds is awarded when this is darkened in their or activated state, also much less intense than the one you get with known photochromic spiro-oxazine compounds. As a result, the azaindoline spiro oxazine Compounds of the invention particularly suitable for Manufacture of photochromic plastic products, such as Eyeglass lenses, which have a "white" basic condition and have attractive cosmetic photochromism.

Accordingly, the invention provides azaindoline spiro Oxazines with the general formula (I) before:

wherein R₁ represents an aliphatic or aromatic group;
R₂ and R₃ each independently represent a hydrogen atom, an aliphatic or aromatic group or an alkoxy group, or R₂ and R₃ together with the carbon atom to which they are attached represent an alicyclic group;
R₄ represents a hydrogen atom or an aliphatic or aromatic group;
Ring A contains one or more nitrogen atoms in the ring and may be unsubstituted or substituted, provided that there is no substituent on a nitrogen atom in the ring; and
Ring B may be unsubstituted or substituted by at least one substituent, provided that the 6'-position in ring B is not substituted by an amine function or a hydroxyl group.

Preferably R₁ represents an alkyl, alkenyl, Phenylalkyl (such as benzyl), or a substituted one Phenyl group.

Preferably, R₂ and R₃ each set independently Hydrogen atom or an alkyl, alkenyl, phenyl, Phenylalkyl (such as benzyl), mono-, di- or tri-substituted Phenyl or alkoxy group, or R₂ and R₃ together with the carbon atom to which it is attached are an alicyclic ring like a spirocarbon, e.g. B. hexane, norbornane and adamantane.

Preferably R represents a hydrogen atom or a Alkyl, aryl or heteroaryl group, most preferred represents a hydrogen atom.  

As defined above, rings A and B can each carry one or more substituents; these substituents are preferably selected from:

• (i) a group with the formula -R, -OR, -SR, -COR, -COOR, where R is H, alkyl, aryl or Heteroaryl; with the proviso that no hydroxy group present at the 6'-position of ring B. is;
• (ii) -X, -CH₂X, -CHX₂, -CX₃, where X is halogen;
• (iii) -NO₂, -CN, -SCN;
• (iv) a ring system that condenses on ring A or B. is aromatic or heteroaromatic Rings or alicyclic or heteroalicyclic Has rings;
• (v) an amine functionality with the general Formula -NR'R '', where R 'and R' 'are each independent a hydrogen atom or an alkyl, Cycloalkyl or phenyl group or a substituted one Derivative of the same or an amine functionality, which is a cycloheteroalkyl ring, represent, wherein the ring one or more heteroatoms contains, with the proviso that no amine functionality present at the 6'-position of ring B. is.

Preferred compounds of formula (I) are represented by formula (II):  

wherein R₁, R₂, R₃ and R₄ are as defined above for the compounds of formula (I),
Ring B may be unsubstituted or substituted at the 5 'and / or 6' position, with the proviso that no hydroxy or amine functionality of the 6'-position of Ring B is present; and
Ring C may contain one or more nitrogen atoms in the ring and may be unsubstituted or substituted at one or more of the positions 7 ', 8', 9 'or 10'.

The substituents on ring C, if any, are preferred from substituents of types (i), (ii), (iii), (iv) and (v) selected as determined above.

In a preferred class of compounds according to the Invention Ring A contains a ring nitrogen atom in in the 7 position or in the 4 position. In another Group of preferred compounds contains ring A. two nitrogen atoms, one in the 4-position and one in the 7 position.

Examples of typical Ring A substituents are alkyl or alkoxy groups, such as methyl or methoxy groups, usually in the 5- or 6-position.  

In a further preferred embodiment of the invention contains in the compounds of formula (II) Ring C is a nitrogen atom in the 7'-position and / or optionally carries a substituent, usually a hydroxy or methoxy group at the 9'-position.

Preferred compounds of the invention are those with the general formula

wherein R₁, R₂ and R₃ are each a C _1-4 alkyl group, Ring A can optionally carry a C _1-4 alkyl or C _1-4 alkoxy group in the 6-position and Ring C optionally a nitrogen atom in the 7th 'Position and / or can optionally carry a C _1-4 alkoxy group in the 9' position.

The compounds with the general formula (I) can made with the general manufacturing process be described in US Pat. No. 3,578,602 and based on the following reaction scheme

wherein R₁, R₂, R₃ and R₄ and the rings A and B as above are defined.

To produce the compounds of formula (I), brings the appropriate nitroso-hydroxy derivative of the formula (IV) with the appropriate indoline of the formula (III) for Reaction. Optionally, an indolenium salt, such as a Methiodide, instead of the indoline according to formula (III) used will.

The two starting materials generally become Reacted by being in a solvent such as trichlorethylene, benzene or toluene under reflux be heated. If an indolenium salt is used, a base such as triethylamine should be present. The desired Spiro-Oxazin product is known Techniques such as chromatographic separation and Crystallization, separated and cleaned.

It will be apparent to those skilled in the art that others are known Reaction schemes can be used to control the To produce compounds of the invention. In particular is another such known reaction scheme  required when a nitrogen group is a substituent on ring C.

The azaindoline spiro-oxazine compounds of the present Invention are particularly suitable a polymerized host material, in particular a plastic eyeglass lens with photochromic properties to rent.

If the compounds of the invention are in a plastic Host material are incorporated, they produce in their lightened condition less base color than others Spiro-oxazine compounds, and the photochromic effect, which you get when the compounds are more actinic Exposure to radiation is relatively bright in comparison to the photochromic effect that is known with Receives connections. This gives the opportunity Plastic products with a "white" basic color and create an attractive cosmetic photochromism. It has also been found that the connections the present invention has good durability have and the desired photochromic Produce effects over a longer period of time can.

The invention is illustrated by the following examples explained.

Example 1

A solution of 1,3,3-trimethyl-2-methylene-7-azaindole (3.5 g; 0.02 mol) and 1-nitroso-2-naphthol (3.5 g; 0.02 mol) in benzene (50 ml) was heated under reflux for 24 hours. The benzene was removed and the oil produced was absorbed by silica and chromatographed in silica using diethyl ether-n-hexane as the eluent. When the eluent was evaporated, 1,3,3-trimethylspiro- (7-azaindoline-2-3′-3 H -naphtho- (2,1-b) (1,4) -oxazine) was formed using the formula (V ) receive. The physical data for this connection are:

Melting point 136 ° C; 'H NMR (CDCl₃); δ 1.35, S (6H), 3,3-Me₂; 2.94, S, (3H), N-Me; 6.62-8.12, m, (8H), aromatic H; 7.73, S, (1H), 2'-H; 8.55, d, (1H), 6-H.

Examples 2 to 7

Various other azaindoline spiro according to the invention Oxazine compounds were prepared using procedures which are analogous to that described in Example 1, synthetically manufactured. The connections obtained are together with their melting point, their NMR data and their structural formula given.  

Example 2

9'-methoxy-1,3,3-trimethylspiro- (7-azaindoline-2,3'- 3 H -naphtho- (2,1- b ) (1,4) -oxazine) melting point 189-91 ° C, 'H NMR (CDCl₃); δ 1.36, S (6H), 3,3-Me₂; 2.99, S, (3H), N-Me; 4.00, S, (3H), O-Me; 6.60-8.60, m, (8H).

Example 3

1,3,3-trimethylspiro- (7-azaindoline-2,3'-3 H -pyrido- (3,2- f ) - (1,4) -benzooxazine) melting point 188 ° C, 'H NMR (CDCl₃) ; δ 1.37, S, (6H), 3,3-Me₂; 2.94, S, (3H) N-Me; 6.76-8.94, m, (8H), aromatic H; 7.76, S, (1H), 2'-H.

Example 4

9'-methoxy-1,3,3-trimethylspiro- (4-azaindoline-2,3'- 3 H -naphtho (2,1, b ) (1,4) -oxazine). Melting point 151 ° C, 'H NMR (CDCl₃); δ 1.41, S, (6H), 3.3, -Me₂; 2.78, S, (3H), N-Me; 4.00, S, (3H), O-Me; 6.69-7.90, m, (8H), aromatic H; 7.72, S, (1H), 2'-H.

Example 5

9'-methoxy-1,3,3-trimethylspiro- (4,7-diazaindoline) - 2,3'-3 H -naphtho- (2,1- b ) (1,4) -oxazine). Melting point 131-3 ° C, 'H NMR (CDCl₃); δ 1.41, S, (6H), 3.3, -Me₂; 2.97, S, (3H), N-Me; 4.01, S, (3H), O-Me; 6.78-7.88, m, (7H), aromatic H; 7.71, S (1H), 2'-H.

Example 6

6-methoxy-1,3,3-trimethylspiro- (7-azaindoline-2,3'-3 H - naphtho- (2,1- b ) (1,4) -oxazine). Melting point 174-5 ° C, 'H NMR (CDCl₃); δ 1.31, S, (6H), 3,3-Me₂; 2.91, S, (3H), N-Me; 3.91, S, (3H), O-Me; 6.12, d, (1H), 4-H; 6.95-8.61, m, (7H), aromatic H; 7.72, S, (1H) 2′-H.

Example 7

1,3,3,6-tetramethylspiro- (7-azaindoline-2,3'-3 H - naphtho- (2,1- b ) (1,4) -oxazine) melting point 162-3 ° C. 'H NMR (CDCl₃); δ 1.33, S, (6H), 3,3-Me₂; 2.47, S, (3H), 6-Me; 2.94, S, (3H), N-Me; 6.52-8.61, m, (8H), aromatic H; 7.73, S, (1H), 2'-H.

Example 8

1,3,3,5-tetramethylspiro- (7-azaindoline-2,3'-3 H - naphto- (2,1- b ) (1,4) -oxazine) melting point 150 ° C. 'H NMR (CDCl₃); δ 1.33, S, (6H), 3,3-Me₂; 2.25, S, (3H), 5 Me; 2.90, S, (3H), N-Me; 6.92-8.62, m, (8H), aromatic H; 7.72, S, (1H), 2'-H.

Example 9

9'-Hydroxy-1,3,3-trimethylspiro- (7-azaindoline-2,3'- 3 H -naphtho- (2,1- b ) (1,4) -oxazine. Melting point 251 ° C, 'H NMR (CDCl₃); δ 1.35, S, (6H), 3,3-Me₂; 2.95, S, (3H), N-Me; 6.90-8.63, m, (8H), aromatic H; 7.68, S, ( 1H) 2'-H.

Claims (28)

1. Azaindoline spiro-oxazine with the general formula (I): wherein R₁ represents an aliphatic or aromatic group;
R₂ and R₃ each independently represent a hydrogen atom, an aliphatic or aromatic group or an alkoxy group, or R₂ and R₃ together with the carbon atom to which they are attached represent an alicyclic group;
R₄ represents a hydrogen atom or an aliphatic or aromatic group;
Ring A contains one or more nitrogen atoms in the ring and may be unsubstituted or substituted, provided that there is no substituent on a nitrogen atom in the ring; and
Ring B may be unsubstituted or substituted by at least one substituent, provided that the 6'-position in ring B is not substituted by an amine function or a hydroxyl group. 2. A compound according to claim 1, wherein R₁ is an alkyl, Alkenyl, phenylalkyl (such as benzyl) or a substituted one Represents phenyl group. 3. A compound according to claim 2, wherein R₁ is a methyl group is. 4. A compound according to claim 1, 2 or 3, wherein R₂ and R₃ each independently represents a hydrogen atom or a Alkyl, alkenyl, phenyl, phenylalkyl (such as benzyl), mono-, di- or tri-substituted phenyl or Alkoxy group, or R₂ and R₃ together with the carbon atom, to which they are attached, one Represent spirocarbon, norbornane or adamantane. 5. A compound according to claim 4, wherein R₂ and R₃ are each is a methyl group. 6. Connection according to one of the preceding claims, wherein R₄ is a hydrogen atom or an alkyl, aryl or heteroaryl group. 7. A compound according to claim 6, wherein R₄ is a hydrogen atom is.   8. Azaindoline spiro-oxazine according to one of the preceding claims, with the general formula (II) wherein R₁, R₂, R₃ and R₄ are as defined in any one of the preceding claims,
Ring B may be unsubstituted or substituted at the 5 'and / or 6'position; and
Ring C may contain one or more nitrogen atoms in the ring and may be unsubstituted or substituted at one or more of the positions 7 ', 8', 9 'or 10'. 9. A compound according to any one of the preceding claims, wherein each of rings A and B and ring C, if present, are substituted by one or more substituents selected from:

• (i) a group of the formula -R, -OR, -SR, -COR, -COOR, where R is H, alkyl, aryl or heteroaryl; with the proviso that there is no hydroxy group at the 6'-position of ring B;
• (ii) -X, -CH₂X, -CHX₂, -CX₃, where X is halogen;
• (iii) -NO₂, -CN, SCN;
• (iv) a ring system which is fused to ring A or B and has aromatic or heteroaromatic rings or alicyclic or heteroalicyclic rings;
• (v) an amine functionality with the general formula -NR'R '', where R 'and R''each independently represent a hydrogen atom or an alkyl, cycloalkyl or phenyl group or a substituted derivative thereof or an amine functionality which is a cycloheteroalkyl ring, represent, wherein the ring contains one or more heteroatoms, with the proviso that no amine functionality is present at the 6'-position of ring B.

10. Connection according to one of the preceding claims, wherein ring A is a ring nitrogen atom in the 7-position contains. 11. A compound according to any one of claims 1 to 9, wherein Ring A is a ring nitrogen atom in the 4-position contains. 12. Connection according to one of the preceding claims, wherein ring A contains two nitrogen atoms, one in the 4 position and one in the 7 position. 13. A compound according to any one of claims 8 to 12, in which ring C is a nitrogen atom in the 7'-position contains.   14. A compound according to any one of claims 8 to 13, in which ring C has a 9'-methoxy substituent wearing. 15. A compound according to claim 8 having the general formula where R₁, R₂ and R₃ are each a C _1-4 alkyl group, Ring A can optionally carry a C _1-4 alkyl or C _1-4 alkoxy group in the 6-position and Ring C optionally a nitrogen atom in the 7th '- have position and / or can optionally carry a C _1-4 - alkoxy group in the 9'-position. 16. A compound according to claim 8 having the general formula where R₁, R₂ and R₃ are each a C _1-4 alkyl group, Ring A can optionally carry a C _1-4 alkyl or C _1-4 alkoxy group in the 6-position and Ring C optionally a nitrogen atom in the 7th '- have position and / or can optionally carry a C _1-4 - alkoxy group in the 9'-position. 17. A compound according to claim 8 having the general formula where R₁, R₂ and R₃ are each a C _1-4 alkyl group, Ring A can optionally carry a C _1-4 alkyl or C _1-4 alkoxy group in the 6-position and Ring C optionally a nitrogen atom in the 7th '- have position and / or can optionally carry a C _1-4 - alkoxy group in the 9'-position. 18. 1,3,3-Trimethylspiro- (7-azaindoline-2-3′-3 H -naphtho- (2,1- b ) (1,4) -oxazine). 19. 9'-methoxy-1,3,3-trimethylspiro- (7-azaindoline-2-3'-3 H -naphtho- (2,1- b ) (1,4) -oxazine). 20. 1,3,3-Trimethylspiro- (7-azaindoline-2-3'-3 H -pyrido- (3,2- f ) (1,4) -benzooxazine). 21. 9'-methoxy-1,3,3-trimethylspiro- (4-azaindoline-2,3'-3 H -naphtho- (2,1- b ) (1,4) -oxazine). 22. 9'-methoxy-1,3,3-trimethylspiro- (4,7-diazaindoline) - 2,3'-3 H -naphtho- (2,1-b) (1,4) -oxazine). 23. 6-methoxy-1,3,3-trimethylspiro- (7-azaindoline- 2,3'-naphtho- (2,1-b) (1,4) -oxazine). 24. 1,3,3,6-tetramethylspiro- (7-azaindoline-2,3'-naphtho- (2,1- b ) (1,4) -oxazine). 25. 1,3,3,5-tetramethylspiro- (7-azaindoline-2,3'-3 H - naphtho- (2,1- b ) (1,4) -oxazine). 26. 9'-Hydroxy-1,3,3-trimethylspiro- (7-azaindoline-2,3'-3 H -naphtho- (2,1- b ) (1,4-oxazine). 27. Plastic host material with an incorporated Azaindoline spiro-oxazine compound or coated with the azaindoline spiro-oxazine compound according to one of the preceding claims. 28. Plastic host material according to claim 27 in the form a lens.